Nephrology All PPTs

Acute kidney injury
Tbilisi referral hospital, Tbilisi, Georgia

Nephrologist
Nino Maglakelidze
Acute Kidney Injury
Introduction:
•Acute Kidney injury (AKI) has replaced the term Acute Renal Failure
•Universal definition and staging system has been proposed to allow

earlier detection and management of acute kidney disease;
Acute Kidney Injury
Definition:
Acute Kidney injury is a syndrome characterized by:
•Sudden decline in GFR (hours and days)
•Retention of nitrogenous wastes products
•Disturbance in extracellular volume and
•Disturbance in electrolytes and acid base homeostasis

Acute Kidney Injury
KDIGO – The Kidney Disease Improving Global Outcomes

is the most recent and preferred definition of AKI which is based on:
•Increase in serum creatinine and
• Decrees of urine output;

Acute Kidney Injury
KDIGO – definition of AKI
•Increase in serum creatinine by >0.3mg/dl (>26.5mmol/l )within

48hours, or
•Increase in serum creatinine to 1.5 times baseline, which is known

or presumed to have occurred within the prior seven days, or
•Urine volume <0.5mg/kg/hour for six hours;

Staging criteria of AKI:
Stage 1 – increase in serum creatinine to 1.5 to 1.9 times baseline

or increase in serum creatinine by 0.3mg/dl (>26.5mmol/l); or
reduction urine output to 0.5 ml/kg/hour for 6 hours;
Stage 2 - increase in serum creatinine to 2.0 to 2.9 times

baseline; or reduction urine output to 0.5 ml/kg/hour s for 12
hours;
Stage 3 - increase in serum creatinine to 3.0 to 4.0 times baseline

(>353.6mmol/l); or reduction urine output to 0.3 ml/kg/hour for 24
hours; or anuria for >12 hours; or in patients <18years, decrease in
estimating glomerular filtration rate (eGFR) to <35ml/min/1.73m2 ;
RIFLE criteria
The Acute Dialysis Quality Initiative (ADQI)group developed

diagnosis and classification of acute impairment of kidney function;
The RIFLE criteria consists of three graded levels:
Risk
Injury and
Failure
Two outcome measures:

Loss
End Stage Renal Disease

Epidemiology:
•AKI complicates approximately 5% of hospital admissions
•Up to 30% of patients in intensive care unit develop AKI defined

by RIFLE criteria;
The epidemiology of AKI tremendously differs between developed and

developing countries;
Etiologic classification of AKI:
1.Prerenal;
2. Intrinsic;
3. Post-renal;
Pre-renal causes:
•Hypovolemia
•Burns
•Cardiogenic shock
•Thromboembolism
•Sepsis/SIRS/Anaphylaxisis
•Renal artery stenosis
•Hepatorenal syndrome
Pre-renal AKI:
•Pre renal AKI is most common 55% form AKI
•Represents a physiologic response to mild to moderate renal

hypo perfusion
•Pre renal AKI is rapidly reversible upon restoration of renal blood

flow and glomerular ultrafiltration pressure;
•More sever hypoperfusion may lead to ischemic injury of renal

parenchyma and intrinsic renal AKI;
•Thus, pre renal AKI and intrinsic renal AKI due to ischemia are part
of a spectrum of manifestations of renal hypoperfusion;
Pathophysiology:
Hypovolemia leads to glomerular hypoperfusion, but filtration rate

are reserved during mild hypoperfusion through several
compensatory mechanisms
During states of more severe hypoperfusion, these compensatory

responses overwhelmed and GFR falls leading to prerenal AKI;
Intrinsic renal AKI:
•Glomerulonephritis
•ATN – acute tubular necrosis
•AIN- Acute interstitial nephritis
•Tumor lyses syndrome
Nephrotoxic drugs
•NSADs and Aspirin
•Antibiotics
Aminoglycosides
Sulfonamides
Vancomicin
Quinolones
Ripfampin
Teteracyclines
Intrinsic renal AKI:
•Chemotherapy
•Heavy metals
•Antihyperlipidemics
Statins and Gemfibrozil
•Antifungal and antiviral drugs
•ACE inhibitors
Epidemiology of intrinsic AKI :
Accounts around 40% of all AKI

Acute Kidney injury
Intrinsic AKI
•Glomerular : FSGS, Membranoprolipherative glomerulonephritis,

Rapidly progressive glomerulonephritis, Goodpasture’s disease,
IgA nephropathy and etc
• Interstitial and Tubular - ATN, ACE or AR blockers, NSADs, radio

contrast media, Tumor lyses syndrome, exogenous toxins: Cisplatin,
Cyclosporine, antibiotics and etc;
4. Vascular
Small vessels vacuities (MPA, Churg-straus syndrome -Eosinophilic
granulomatosis with polyangiitis and Wegener granulomatosis),
Sclerodermia, atheroembolic disease, TTP/HUS and etc;
Postrenal AKI
Postrenal AKI accounts 5 % of cases
•Ureteric : calculi, blood clot, cancer, external compression

(retroperitoneal fibrosis) and etc
•Bladder neck : neurogenic bladder, prostatic hypertrophy, calculi,

cancer, blood clot
•Urethra: stricture, congenital valve;

Management of patient with AKI
Careful history is essential:
Exposure of nephrotoxins and drugs;
Signs of volume depletion suggest prerenal etiology of AKI
Skin rashes may indicate acute interstitial nephritis
Blue toe suggests atheroemboli
Significant volume overload and signs of heart failure suggest

cardiorenal syndrome
Ascitis and jaundice suggest liver disease with portal hypertension

and hepatorenal syndrome;
Management of patient with AKI
Ischemia or trauma of legs may indicate rhabdomyolysis
Anuria may indicate post renal causes
A history of prostatic disease
Family history of renal diseases
Past and present use of medications
Recent surgical or radiologic procedures

Urinalysis :
Presence of few formed elements or hyaline casts is suggestive of

prerenal or postrenal azotemia
Many RBC s may suggests calculi, tumor, infection;
Eosinophiluria suggest acute interstitial nephritis;
Patient with hematuria associated with proteinuria

glomerulonephritis or vacuities should be suspected
Patients with sudden worsen of serum creatinine rapidly

progressive glomerulonephritis should be suspected and kidney
biopsy should be done
Urinalysis
Pigmented casts without erythrocytes in the sediment from urine

but with positive dipstick for occult blood indicates hemoglobinuria
or myoglobinuria
RBC and RBC cast suggests glomerular disease;

Urine and blood Chemistry
Urine osmolality and specific gravity is decreased in ATN and post-

renal AKI, while increased in pre renal AKI
Serum K+ and other electrolytes
Fractional excretion of Na+ : is ratio of urine –to plasma Na; If

sodium fractional excretion above 1% suggest prerenal AKI,
Radiography and imaging
Ultrasonography helps to see the presence of two kidneys,

evaluation of kidney size and shape,
For detecting hydronephrosis
Renal calculi
Renal vein thrombosis
Retrograde pyelography is done when obstructive uropathy is

suspected
Computed tomography CT
MRI magnetic resonance imaging MRI

Serum serologic tests:
 ANA and anti-ds-DNA
c-ANCA and p-ANCA
Anti-GBM antibodies
Anti-HCV, HBsAg; anti-HIV;
C3 and C4 complement factors
Serum and urine electrophoresis

Renal biopsy
A native kidney biopsy is mandatory in case

glomerulonephritis;
Management of AKI
Volume depletion – prerenal AKI
•In the absence of hemorrhagic shock, it is recommended using isotonic

crystalloids rather than colloids (albumin ) as initial management for
expansion of intravascular volume in patients at risk for AKI
•It is recommended the use of vasopressors in conjunction with fluids

in patients with vasomotor shock with or at risk for AKI
•It is recommended to use protocol based management of

hemodynamic and oxygenation parameters to prevent development
or worsening of AKI in high risk patients in the perioperative setting
or in patient with septic shock;
Management of AKI
Fluid overload
Hyperkalemia
Signs of uremia such as pericarditis
Sever metabolic acidosis pH<7.1

Volume overload:
Salt and fluid restriction
Loop diuretics -furosemide may be helpful in case of fluid

overload
In case of diuretic resistence hemodialysis - ultrafiltration is

recommended
Management of hyperkalemia:
Hyperkalemia – K-6.5mmol/l cardiac and neurologic complication
Restrict dietary potassium approximately 2 g a day
Give calcium gluconate 10 ml of 10% solution over 5 minutes
Glucose solution 50 ml 50% glucose plus insulin 10 units i.v
β-Agonist inhalation
Give potassium binding ion exchange resin (Resonium, Kayxelate)
Dialysis: if medical therapy fails or the patient is very toxic

Metabolic acidosis:
It is not recommended to treat metabolic acidosis unless serum

bicarbonate falls below 15mmol/l or arterial pH falls below 7.1
Severe acidosis is corrected by intravenous sodium bicarbonate

Hyperphosphatemia:
In case of severe hyperphosphatemia (P>6 mg/dl ) dietary

restriction of phosphate
Oral calcium containing binders: Calcium acetate or Calcium

carbonate is recommended
Non-calcium containing phosphor binders: lanthanum carbonate

or sevelamer is recommended ;
Nutrition of AKI patients:
It is recommended to achieve a total energy intake of

20-30kcal/kg/d in patients with any stage of AKI.
It is not recommended to avoid restriction of protein in attempt of

preventing or delaying initiation of RRT;
It is recommended administering 0.8-1.0 g/kg/d of protein intake

in noncatabolic AKI patients without need for dialysis ; 1.0-1.5g/kg/d
in patients with AKI on RRT; and up to 1.7 g/kg/d in patients on
continues renal replacement therapy (CRRT) and in hypercatabolic
patients;
Indications for dialysis therapy:
•Fluid overload that is refractory to diuretics
•Hyperkalemia, (serum potassium concentration > 6.5mmol/l or

rapidly rising potassium level, refractory to medical therapy);
•Metabolic acidosis pH<7.1 in patients in whom sodium bicarbonate

is contraindicated, such as volume overload, or those with lactic
acidosis, or ketoacidosis
•Signs of uremia such as pericarditis, neuropathy, or an otherwise

unexplained decline in mental status;
Modality of renal replacement therapy and the dose of RRT for patients
with AKI
•Continues renal replacement therapy (CRRT)
• Intermittent renal replacement therapy (IRRT)
It is recommended to use CRRT rather than standard intermittent RRT,

for hemodynamically unstable patients
Dose of dialysis in patients of AKI
•It is recommended delivering a Kt/v of 3.9 per week when using

intermittent or extended RRT in AKI.
•It is recommended delivering an affluent volume of 20-25 ml/kg/h

for CRRT in AKI;
Rhabdomyolysis
Rhabdomyolysis is a syndrome characterized by muscle necrosis and

the release of intracellular muscle constituents into the circulation.
Creatinekinase (CK) levels are typically markedly elevated,
muscle
pain and myoglobinuria .

Rhabdomyolysis
The severity of illness ranges from asymptomatic elevations in serum

muscle enzymes to life-threatening disease associated with extreme
 muscle enzyme elevations of creatininekinase CK,
electrolyte imbalances and
acute kidney injury.

CLINICAL MANIFESTATIONS
Rhabdomyolysis is characterized clinically by:
myalgias,
red to brown urine due to myoglobinuria,
and elevated serum muscle enzymes[CK]
malaise
 fever
 tachycardia
nausea and vomiting
abdominal pain
Altered mental status may occur from the underlying etiology
(eg, toxins, drugs, trauma, or electrolyte abnormalities).
Laboratory findings:
 Elevation in CK and other serum muscle enzymes.

(Serum CK levels at presentation are usually at least
Five times the upper limit of normal, but range from approximately
1500 to over 100,000 international units/L)
 Myoglobinuria observed in only half of cases.
Complete blood count (CBC), erythrocyte sedimentation rate (ESR),

and C-reactive protein (CRP);
(depends on the underlying cause of rhabdomyolysis).
Hypovolemia results from "third-spacing" due to the influx of

extracellular fluid into injured muscles and increases the risk of
acute kidney injury.
Electrolite abnormality
Hyperkalemia
Hyperkalemia is more common in patients with oliguric acute
kidney injury.
hyperphosphatemia
result from the release from damaged muscle cells
Hypocalcemia
Severe hyperuricemia
Metabolic acidosis assosiated with and an increased anion gap
Acute kidney injury (AKI, acute renal failure) common complication
of rhabdomyolysis. The reported frequency of AKI ranges from 15 to
over 50 percent
Compartment syndrome — A compartment syndrome exists when
increased pressure in a closed anatomic space threatens the viability of
the muscles and nerves within the compartment. Compartment
syndrome is a potential complication of severe rhabdomyolysis that
may develop after fluid resuscitation, with worsening edema of the limb
and muscle. Lower extremity compartment syndrome can also be a
cause of rhabdomyolysis, as may occur after tibial fractures.
Diagnosis:
Diagnosis of rhabdomyolysis is defined:
 patient with either an acute neuromuscular illness or dark urine.
A marked acute elevation in serum creatine kinase (CK).

TREATMENT
Treatment of metabolic abnormalities — Patients should be

closely followed for the development of metabolic abnormalities
including hyperkalemia, hypocalcemia, hyperphosphatemia, and
hyperuricemia.
To minimize the late occurrence of hypercalcemia as well as the

risk of calcium-phosphate precipitation, calcium supplementation
for hypocalcemia should be avoided unless significant signs and
symptoms of hypocalcemia develop or calcium administration is
required for the management of hyperkalemia.
TREATMENT
Hyperkalemia should be aggressively treated with standard medical

management.
Dialysis may be required to treat severe hyperkalemia.
Hyperuricemia should be treated with allopurinol.

Allopurinol should be given orally at 300 mg if uric acid
Levels are >8 mg/dL (476 micromol/L) or if there is a 25 percent
increase from baseline.
There is no specific therapy once the patient has developed AKI. The
initiation of dialysis may be necessary for control of volume overload,
hyperkalemia, severe acidemia, and uremia.
PREVENTION
Volume administration
Correction of volume depletion if present
Prevention of intratubular cast formation

Prevention
Volume administration:
The prevention of AKI requires early and aggressive fluid

resuscitation. The goals of volume repletion are to maintain or
enhance renal perfusion, minimize ischemic injury, and
to increase the urine flow rate, which will limit intratubular cast
formation by diluting the concentration of heme pigment within the
tubular fluid, wash out partially obstructing intratubular casts, and
increase urinary potassium excretion.
Intravenous isotonic saline should be administered as soon as possible
after the onset of injury.
The optimal fluid and rate of repletion are unclear.
Bicarbonate — Patients with rhabdomyolysis may benefit from

bicarbonate therapy.
PROGNOSIS
The overall prognosis for patients with heme-induced

AKI is favorable
 recover kidney function

Dialysis independent
Or may will recover to normal or near-normal kidney function.
Chronic kidney Disease

Nephrologist
Nino Maglakelidze
Chronic Kidney Disease (CKD)
Chronic kidney disease involves progressive, irreversible loss of

kidney function
Defined as either presence of

• Kidney damage
•Pathological abnormalities
•Glomerular filtration rate (GFR) <60ml/min for 3 months or longer
CKD Chronic kidney disease is asymptomatic, clinical signs in later stages

in association with complications;
Risk factors for CKD development
Kidney damage includes pathologic abnormalities of native or
transplant kidneys;
•Microalbuminuria :
•Primary kidney disease
•Or kidney enrollment in systemic disease
•Widespread endothelial dysfunction in hypertension,
• diabetes,
• smoking,
•obesity ;
Stages of chronic kidney disease:
The albumin to creatinine ratio (ACR) in untimed ,,spot” urine:
Albuminuria stages: normal, moderately increased and severely

increased albuminuria
A1 – ACR <30 mg/g
A2 – ACR 30 to 299 mg/g
A3 – ACR >300 mg/g

Glomerular filtration rate
Decreased GFR - the hallmark of progressive kidney disease;

Measured GFR is varying by
age
Gender
protein intake and
Race and ethnicity

Glomerular filtration rate
In clinical practice GFR is typically estimated (eGFR) from the serum
concentration of creatinine;
In clinical practice individuals who have an eGFR bellow 60ml/min

are defined as having CKD;
These individuals have an increased risk of cardiovascular mortality,

ESRD, AKI and CKD progression;
Chronic Kidney disease
GFR G-stages follow the original CKD classification scheme
G1 – GFR >90ml/min per 1.73 m2
G2 – GFR 60 to 89 ml/min per 1.73 m2
G3 a – GFR 45 to 59 ml/min per 1.73 m2
G3 b – GFR 30 to 44 ml/min per 1.73 m2
G4 – GFR 15 to 29 ml/min per 1.73 m2
G5 – GFR < 15 ml/min per 1.73 m2 or treatment by dialysis

Green no risk for CKD
Yellow – moderate risk
Orange – high risk
Red – Very high risk

Causes and risk factors of CKD
•Hypertension
•Diabetes mellitus
•Cardiovascular disease
•Obesity
•Metabolic syndrome
•Kidney stones
•Polycystic kidney diaseas
•Alport’s syndrome
•Autoimmune diseases
•Glomerulonephritis
•Malignancy
•Acute kidney injury
•Family history of CKD;
Clinical signs:
Uremia:
Syndrome that incorporates all signs and symptoms seen in various

systems throughout the body;
Uremia is a serious condition and if untreated can be

life – threatening ;
Clinical signs:
Urinary system:
Polyuria:
Results from inability of kidneys to concentrate urine

Specific gravity fixed around 1010 or below
Nocturia
Oliguria:
Occurs as CKD worsens
Anuria:
Urine output less than 100 ml per 24 hours
Cardiovascular System:
Hypertension
Heart failure
Left ventricular hypertrophy
Peripheral edema
Arrhythmias
Uremic pericarditis
Respiratory system:
Dyspnea
Pulmonary edema
Pleural effusion
Predisposition to respiratory infection
Depressed cough reflex

Gastrointestinal System:
Anorexia
Vomiting, Nausea
Constipation
Dyspepsia
Gastritis
duodenitis
Peptic ulcer disease

Neurologic System:
Encephalopathy
Altered mental ability
Seizures and coma
Sleep disorders
Irritation
Sleep apnea
Restless leg syndrome
Carpal tunnel syndrome

Dermatological abnormality
Yellow gray discoloration of skin

Due to absorption/retention of urinary pigment
Pruritus
Dry pale skin
Thin nails
Ecchymoses
Petechiae
Reproductive System
Infertility
Experienced by both sexes
Decreased libido
Sexual dysfunction
Musculoskeletal System:
Weakness
Arthralgia
Myalgia
Increased bone fracture
Metabolic abnormality:
•Waste product accumulation

As GFR ↓BUN ↑Serum creatinine levels ↑
Electrolyte abnormality
•Sodium and water overload:

Sodium excretion is impaired, sodium is retained
Water is retained
Edema
Hypertension;
Potassium disorder
Hyperkalemia
Hyperkalemia mostly develops in patients who are oliguric or who

are on high potassium diet;
High potassium cause fatal arrhythmia
Acid – base abnormality
Patients with CKD have a tendency to retain hydrogen ions
Lead to metabolic acidosis

Mineral and bone disorders
•Phosphate retention – hyperphophatemia

•Hypocalcemia
•High PTH level caused by secondary hyperparathyroidism
•Low 1,25(OH)D3, calcitriol which is synthesized in kidney and begins
to fall when GFR is 40ml/min;
CKD and bone structure:
•Osteitis fibrosa
•Osteomalacia
•Adynamic bone
Hematologic system:
Anemia
Due to decrease production of erythropoietin because of
decreased of functioning renal tubular cells
Coagulation abnormality :
Platelet decreased function
Ant thrombin III deficiency
Infection
Changes in leukocyte function
Diminished inflammatory response

Laboratory tests:
Urinalysis
Urine culture
Hemoglobin
Hematocrit
Urea
Creatinine
Serum Ca, P,PTH and vit. D
Renal ultrasound
Renal scan
Urinary sediment abnormalities:
red blood cells and cast and
white blood cells and casts
Indicates the presence of glomerular injury or tubular inflammation.

Imaging abnormalities:
Polycystic kidney disease
Hydronephrosis
Small and
Echogenic kidneys;
Morphologic abnormalities:
A kidney biopsy may reveal evidence of glomerular, vascular or

tubulointerstitial disease;
Treatment and management of CKD patients
Hypertension
Antihypertensive drugs
Diuretics
β-Adrenergic blockers
Calcium channel blockers
Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin receptor blocker agents

If GFR <30ml/min it should be stopped ACE and AR blockers;
Treatment of blood pressure in CKD patients
Individualize BP targets and agents according to age, co-

existent cardiovascular disease and other co-morbidities, risk of
progression of CKD, presence or absence of retinopathy (in CKD
patients with diabetes)
LIFESTYLE MODIFICATION:
achieving or maintaining a healthy weight (BMI 20 to 25).
lower salt intake to < 90 mmol (< 2 g) per day of sodium
(corresponding to 5 g of sodium chloride);
an exercise program compatible with cardiovascular health and
tolerance, aiming for at least 30 minutes 5 times per week.
limiting alcohol intake to no more than two standard drinks per
day for men and no more than one standard drink per day for
women.
non-diabetic adults with CKD ND and urine albumin excretion >30

mg per 24 hours (or equivalent) whose office BP is consistently >
140 mm Hg systolic or > 90 mm Hg diastolic be treated with BP-
lowering drugs to maintain a BP that is consistently < 140 mm Hg
systolic and < 90 mm Hg diastolic.
non-diabetic adults with CKD ND and urine albumin excretion of
30 to 300 mg per 24 hours (or equivalent) whose office BP is
consistently > 130 mm Hg systolic or >80 mm Hg diastolic be treated
with BP-lowering drugs to maintain a BP that is consistently <130
mm Hg systolic and < 80 mm Hg diastolic.
non-diabetic adults with CKD ND and urine albumin excretion >300
mg per 24 hours (or equivalent) whose office BP is consistently >
130 mm Hg systolic or >80 mm Hg diastolic be treated with BP-
lowering drugs to maintain a BP that is consistently <130 mm Hg
systolic and < 80 mm Hg diastolic.
ARB or ACE-I be used in non-diabetic adults with CKD ND and
urine albumin excretion of 30 to 300 mg per 24 hours
an ARB or ACE-I be used in non-diabetic adults with CKD ND and
urine albumin excretion >300 mg per 24 hours
adults with diabetes and CKD ND with urine albumin excretion
<30 mg per 24 hours (or equivalent) whose office BP is consistently
>140 mm Hg systolic or >90 mm Hg diastolic be treated with
BPlowering drugs to maintain a BP that is consistently < 140 mm Hg
systolic and <90 mm Hg diastolic
adults with diabetes and CKD ND with urine albumin excretion

>30 mg per 24 hours (or equivalent) whose office BP is consistently
>130 mm Hg systolic or >80 mm Hg diastolic be treated with BP
lowering drugs to maintain a BP that is consistently <130 mm Hg
systolic and <80 mm Hg diastolic.
an ARB or ACE-I be used in adults with diabetes and CKD ND with
urine albumin excretion of 30 to 300 mg per 24 hours
an ARB or ACE-I be used in adults with diabetes and CKD ND with
urine albumin excretion >300 mg per 24 hours
Anemia
Erythropoietin
Subcutaneous is 30% effective than i.v
Side effect:
Hypertension
Iron sucrose (if serum Ferritin <100 and TSAT <20%);
Edema/Fluid overload
Sodium restriction <2 g a day
Loop diuretics
Diagnosis of anemia
Diagnose anemia in adults and children >15 years with CKD when
the Hb concentration is <13.0 g/dl (<130 g/l) in males and <12.0 g/dl
(<120 g/l) in females
Investigation of anemia
In patients with CKD and anemia (regardless of age and CKD stage),
include the following tests in initial evaluation of the anemia
Complete blood count (CBC), which should include Hb
concentration, red cell indices, white blood cell count and
differential, and platelet count
 Absolute reticulocyte count
 Serum ferritin level
Serum transferrin saturation (TSAT)
 Serum vitamin B12 and folate levels
Frequency of testing for anemia
For CKD patients without anemia measure Hb concentration when
clinically indicated.
 at least annually in patients with CKD 3
 at least twice per year in patients with CKD 4–5ND
 at least every 3 months in patients with CKD 5HD and CKD 5PD
For CKD patients with anemia not being treated with an ESA,
measure Hb concentration when clinically indicated .
at least every 3 months in patients with CKD 3–5ND and CKD 5PD
 at least monthly in patients with CKD 5HD
Treatment of anemia
For adult CKD patients with anemia not on iron or ESA therapy and
if TSAT is < 30% and ferritin is < 500 ng/ml (< 500 mg/l) treatment of
IV iron :
IRON STATUS EVALUATION :

Evaluate iron status (TSAT and ferritin) at least every 3 months
during ESA therapy,
Treatment of anemia on CKD patients
For adult CKD ND patients with Hb concentration < 10.0 g/dl

(<100 g/l)is recomeded to initiate ESA therapy and be individualized
based on the rate of fall of Hb concentration, prior response to iron
therapy, the risk of needing a transfusion, the risks related to ESA
therapy and the presence of symptoms attributable to anemia
The ESA dose depends on the patient’s Hb concentration, body

weight, and clinical circumstances. (25E/kg);
ESA ADMINISTRATION
Intravenous
subcutaneous
Hyperkalemia
IV insulin and glucose
IV 10% calcium gluconate
Sodium bicarbonate, Correct acidosis
β – agonist (Salbulamole )
Sodium polystyrene sulfonate

Kayexalate, Resonium;
Treatment of hyperphosphatemia
Phosphor diet restriction
Phosphate- binders
 Calcium containing binders
Calcium acetate; Calcium carbonate;
 Non calcium containing phosphor binders
Sevelamer hydrochloride; Renagel, Renvela;
Lanthanum carbonate
Aluminum hydroxide
Treatment of CKD-MBD
In patients with CKD stages 3–5 is suggested to maintain serum
phosphorus in the normal range .
In patients with CKD stage 5D is suggested to lower elevated
phosphorus levels toward the normal range
In patients with CKD stages 3–5D is suggested to maintain
serum calcium in the normal range
In patients with CKD stages 3–5 and 5D , is suggested to use
phosphate-binding agents in the treatment of
hyperphosphatemia.
In patients with CKD stages 3–5D and hyperphosphatemia is
recommended to restrict the dose of calcium-based phosphate
binders and/or the dose of calcitriol or vitamin D analog in the
presence of persistent or recurrent hypercalcemia
In patients with CKD stages 3–5D is recommended to avoid the
long-term use of aluminum-containing phosphate binders
Treatment and management of CKD patients:
Vit D supplements
Alfacalcidol; Rocaltrol;
Calcimimetic agents
Mimpara
Surgery – Parathyroidectomy
In patients with CKD stage 5D, is recommended to maintain iPTH

levels in the range of approximately 2-9 times the upper normal
limit for the assay
In patients with CKD stage 5D and elevated or rising PTH, is
suggested calcitriol, or vitamin D analogs, or calcimimetics, or a
combination of calcimimetics and calcitriol or vitamin D analogs to
lower PTH
In patients with CKD stages 3–5D with severe
hyperparathyroidism (HPT) who fail to respond to
medical/pharmacological therapy, we suggest parathyroidectomy
Nutrition in CKD patients
Fluid restriction
Sodium restriction 2 g a day
Protein restriction 0.6-0.8g/kg body weight
Potassium restriction 2 to 4 g a day
Phosphorus restriction 1000 mg/day

Diabetic nephopathy
Tbilisi referral hospital

Nino Maglakelidze
Diabetic nephropathy
Epidemiology:
Diabetes - leading cause of

chronic kidney disease (CKD)
end-stage kidney disease (ESKD).
The prevalence of diabetes in the United States - increased

over the last 20 years from 6 to 10 percent,
The proportion of people with diabetes who also have

CKD - remained relatively stable - 25 to 30 percent
Epidemiology
•The prevalence of persistent moderately to severely increased

albuminuria (ie, a urine albumin-to-creatinine ratio ≥30 mg/g) in
diabetic patients decreased from approximately 21 percent during
the period from 1988 to 1994 to 16 percent during the period from
2009 to 2014.
•The prevalence of decreased estimated glomerular filtration rate

(eGFR), defined as an eGFR <60 mL/min/1.73 m2, increased
from 9 to 14 percent.
United States, more than 58,000 people have ESKD attributed to

diabetes, accounting for nearly 50 percent of all patients with
ESKD.
Epidemiology
Annual incidence rates of ESKD due to diabetic kidney disease

are rising and vary from
•10 per 1 million in Romania

•67 per 1 million in Malaysia;
•the United States ranks from 10 up to 47 cases per 1 million.
The true incidence and prevalence of ESKD from diabetes is

impossible to know because kidney biopsies (the gold standard
for diagnosis of diabetic kidney disease) are infrequently
performed in diabetic patients with diabetic kidney disease.
It is unclear whether the natural history and rate of progression
of diabetic kidney disease differs according to diabetes type.
The vast majority of people with type 2 diabetes, disease onset

is after the age of 40 years, and other factors such as
age-related senescence of the kidney

hypertension
Obesity , high BMI
can participate in kidney function decline to varying degrees.

Risk factors
In addition, type 2 diabetes can be asymptomatic for years,

resulting in a delay in diagnosis;
Therefore, the true time of onset of the hyperglycemic exposure

is usually unknown.
Risk factors for diabetic kidney
Risk factors for diabetic kidney disease — Diabetic kidney

disease is a complex disease with multiple phenotypes:
Risk factors:
Age
Race /ethnicity
Sex/gender
Low socio economic status
Obesity
Smoking
Hypertension
Hyperglycemia
Genetic factors
Acute kidney injury
Risk factors
Age — Increasing age is directly related to the prevalence of

diabetic kidney disease with decreased eGFR.
Rising from:
8 percent in the 5th decade
19 percent in the 6th decade
35 percent in the 7th decade of life
Race/ethnicity — Compared with their white counterparts,

African American, Latino, and American Indian populations
have higher rates of albuminuria, decreased eGFR, and ESKD.
Risk factors
Sex/gender — Both CKD in general and diabetic kidney disease

in particular are more common in women.
Men have a significantly higher risk of progression from late-stage

CKD to ESKD (hazard ratio [HR] 1.37;
The reasons for greater CKD prevalence in women, but higher

risk of progression in men, are uncertain, but differences in
genetic architecture, sex hormone exposure, body composition
(eg, muscle mass), and lifestyle factors (eg, smoking, obesity,
physical activity, and diet) have been proposed as possible
mediators.
Risk factors
Low socioeconomic status - Albuminuria and decreased

eGFR (<60mL/min/1.72 m2) is more common among individuals
with lower education level, even after controlling for
sociodemographic and clinical factors.
After controlling for race, the incidence rate of ESKD in one

study was 4.5-fold higher among populations in which more than
25 percent lived below the poverty level as compared with
populations in which fewer than 5 percent lived below the poverty
level.
Socioeconomic status in people with type 1 diabetes is also

associated with pathogenic factors involved in diabetic kidney
disease, including glomerular hyperfiltration and levels of
certain cytokines.
Risk factors
Mediators of the association between low socioeconomic

status and diabetic kidney disease are numerous.
Obesity — Even in the absence of diabetes, obesity leads to

a form of secondary focal segmental glomerulosclerosis.
40 percent of these patients have features of diabetic kidney

disease (mesangial expansion, glomerular basement membrane
thickening, and nodular glomerulosclerosis), even in the absence
of diabetes.
Obesity is a significant risk factor for type 2 diabetes.

Risk factors
Smoking — in the absence of diabetes, smoking can

result in nodular sclerosis of the kidney that is indistinguishable
from diabetic glomerulosclerosis.
Smoking triggers many of the same pathogenic pathways that

are active in diabetic kidney disease:
endothelial dysfunction,
oxidative stress,
inflammation.
Risk factors
Hyperglycemia — restoration of normal glycemic

control with pancreatic transplantation in patients with type 1
diabetes can improve kidney disease in the long term.
In both type 1 and type 2 diabetes lower HbA1c levels are

associated with reversal of hyperfiltration, increased albuminuria
regression, reductions in worsening albuminuria, rapid eGFR
decline, and the development of stage 3 CKD.
Hypertension — A systolic blood pressure greater than 140

mmHg has consistently been found to increase the risk for the
development of severely increased albuminuria and stage 3
CKD.
Risk factors
Genetic factors - APOL1 variants are associated with an

increased risk for progression of diabetic kidney disease in
African Americans.
Acute kidney injury - diabetic kidney disease, AKI-induced

injuries involve the podocyte and endothelium of the glomerulus
and induce myofibroblast transformation of tubular cells.
As a result, both the glomerulopathy and tubulointerstitial fibrosis

associated with diabetic kidney disease may be accelerated
by AKI.
Pathogenesis
Glomerular hemodynamics - Hyperglycemia in diabetic

patients results in production of advanced glycation end-products
(AGE) and reactive oxygen species. These aberrant metabolic
products activate intercellular signaling for proinflammatory and
profibrotic gene expression with production of a host of mediators
for cellular injury.
While hyperglycemia undoubtedly plays a central role,

hyperinsulinemia and insulin resistance also may incite
pathogenic mechanisms, possibly accounting for variation in
histopathology between type 1 and type 2 diabetes.
Pathogenesis
The diabetic mellitus activates the renin-angiotensin-aldosterone

system (RAAS) and numerous other downstream mediators,
triggering kidney hypertrophy, increased renal plasma flow (RPF),
and increased filtration fraction (FF), which together result in
an abnormally elevated glomerular filtration rate (GFR)
Increased circulating vasodilators, such as atrial natriuretic
peptide, nitric oxide, and prostanoids, and a relative deficiency
or resistance to insulin have a preferential impact on reducing
afferent arteriole resistance. The imbalance in tone between
afferent and efferent arterioles increases intraglomerular pressure
that, over time, triggers a sclerotic response in diabetic kidney
disease.
Pathogenesis
Glomerular hyperfiltration — Hyperfiltration can be defined at

the level of the single nephron, wherein the ratio between GFR
and effective RPF (ie, FF) is elevated due to either altered
glomerular hemodynamics or glomerular damage with hypertrophy
of remnant nephrons.
Oxidative stress and inflammation — Hyperglycemia, insulin

resistance and dyslipidemia cause increased formation of
NF-kappaB, Protein kinase C, endothelial nitric oxide (eNOS) and
endothelin 1 and vascular endothelial growth factor (VEGF),
which promotes endothelial instability and NF-kappaB stimulated
cytokine production.
Mesangial cell hypertrophy and matrix accumulation, hallmarks
of diabetic glomerulosclerosis, are mediated by the transforming
growth factor-beta (TGF-beta) system ; Vascular proliferation and
endothelial permeability are increased in diabetic kidney disease
and are thought to be mediated by VEGF;
Pathogenesis
Interstitial fibrosis and tubular atrophy (IFTA) — As diabetic

kidney disease progresses, there is a clear relationship between
the degree of interstitial fibrosis/tubular atrophy (IFTA) and decline
in eGFR ;
Diagnosis
The term "diabetic nephropathy" was historically defined by the

presence of albuminuria accompanied by retinopathy in patients
with type 1 diabetes.
Kidney biopsy revealed in the diabetic glomerulopathy:
thickening glomerular basement membrane,

endothelial damage,
mesangial expansion and nodules,
and podocytes loss.
Kidney biopsy
(A)Normal glomerulus.
(B) Diffuse mesangial
expansion with mesangial
cell proliferation.
(C) Prominent mesangial
expansion with early
nodularity and
mesangiolysis.
(D) Accumulation of
mesangial matrix forming
Kimmelstiel–Wilson nodules.
(E) Dilation of capillaries
forming microaneurysms,
with subintimal hyaline
(plasmatic insudation).
(F) Obsolescent glomerulus.
Kidney biopsy
) Structural changes in diabetic glomerulopathy found with electron microscopy. C indicates

arked expansion of the mesangium. D indicates marked diffuse thickening of capillary basement
embranes (to 3 times the normal thickness in this case). E indicates segmental effacement of the
sceral epithelial foot processes. Original magnification, ×3500.
) Normal glomerulus.
Renal Pathology Society classification:
•Class I – Isolated glomerular basement membrane thickening.

Basement membranes are greater than 430 nm in males and
395 nm in females over the age of nine years. There is no
evidence of mesangial expansion, increased mesangial matrix,
or global glomerulosclerosis involving >50 percent of glomeruli.
•Class II – Mild (Class IIa) or severe (Class IIb) mesangial

expansion. A lesion is considered severe if areas of expansion
larger than the mean area of a capillary lumen are present in >25
percent of the total mesangium.
•Class III – At least one Kimmelstiel-Wilson lesion (nodular

intercapillary glomerulosclerosis) is observed on biopsy, and
there is <50 percent global glomerulosclerosis.
Renal pathology Sociaty classification:
Class IV – Advanced diabetic glomerulosclerosis. There is

>50 percent global glomerulosclerosis that is attributable to
diabetic nephropathy
Clinical features:
The most common clinical abnormalities of diabetic kidney

disease are:
•persistently elevated urine albumin excretion

•and/or persistently decreased estimated glomerular filtration rate
(eGFR).
In severe cases, albuminuria levels can be above the nephrotic

threshold of 3.5 g per 24 hours, often resulting in the nephrotic
syndrome .
Clinical features:
These manifestations are typically asymptomatic and are therefore

usually detected through routine, periodic testing.
Urine albumin excretion can be estimated using a spot urine

sample and the albumin-to-creatinine ratio, or measured using the
more traditional approach of a timed (24 hours or other) urine
collection.
Testing is recommended to commence in patients with type 1

diabetes five years after diagnosis. In patients with type 2 diabetes,
testing for kidney disease is recommended to be undertaken at
the time of diagnosis.
Clinical features:
Albumin excretion in urine in diabetic kidney paitents can be:
Moderately increased albuminuria (30 to 300 mg/g or mg/day) —

Previously termed "microalbuminuria," moderately increased
albuminuria is defined as either an estimated or a measured urine
albumin excretion between 30 and 300 mg/g creatinine or mg/day ;
Severely increased albuminuria (>300 mg/g or mg/day) —

Previously termed "macroalbuminuria," severely increased
albuminuria is defined as either an estimated or a measured urine
albumin excretion >300 mg/g or mg/day
Clinical features:
GFR can be estimated using several different creatinine-based

equations; however, the Chronic Kidney Disease Epidemiology
(CKD-EPI) and Modification of Diet in Renal Disease (MDRD)
equations are most commonly used.
The urine sediment in diabetic kidney disease may reveal the

following:
microscopic hematuria,
In patients with nephrotic-range proteinuria - oval fat bodies or
lipid droplets.
Dysmorphic red blood cells and red blood cell casts.
Treatment
Main goals of treatment in diabetic kidney disease:
Blood pressure control

Glycemic control
Lifestyle modification
Lipid lowering
Blood pressure control — It is recommended intensive blood
pressure lowering in patients with DKD. In general, more intensive
versus less intensive blood pressure lowering in patients with
chronic kidney disease (CKD) reduces mortality and prevents
cardiovascular morbidity; in addition, more intensive blood
pressure lowering may prevent end-stage kidney disease (ESKD)
in patients with severely increased albuminuria.
Initial antihypertensive therapy in patients with DKD typically

consists of either an angiotensin-converting enzyme (ACE)
inhibitor or angiotensin receptor blocker (ARB) but not both
simultaneously.
Combination antihypertensive therapy will be required for most

individuals with DKD. In such cases, the combination of an ACE
inhibitor or ARB plus a dihydropyridine calcium channel blocker
is often preferred or diuretic may be preferred.
Glycemic control — In patients with type 1 diabetes, intensive
blood glucose control may prevent the development of DKD.
The glycemic control target in patients with type 1 diabetes and

DKD is ideally a glycated hemoglobin (A1C) of 7 percent or less.
The approach (to target an A1C of 7 percent or less, if tolerated)

is similar in patients with type 2 diabetes.
A separate issue is that certain glucose-lowering medications

should be avoided or used at a reduced dose in patients with DKD,
depending upon the degree of reduced kidney function.
Treatment
Glycemic control – The short-acting sulfonylureas, glipizide

(initial dose 2.5 mg/day) or glimepiride (initial dose 1 mg/day), are
the preferred agents among nondialysis CKD patients who have an
estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2.
Glyburide and other long-acting sulfonylureas are generally not
recommended in any CKD patient with type 2 diabetes, because of
the risk of hypoglycemia.
Treatment
Glycemic control :
Metformin, which is a preferred agent in patients without kidney

disease, should not be used among CKD patients with an eGFR
of <30 mL/min/1.73 m2 because of an increased risk of lactic
acidosis.
Other agents including thiazolidinediones, alpha-glucosidase

inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors are
generally not considered first-line agents among CKD patients,
because of limited data regarding long-term safety and efficacy.
Treatment:
Glycemic control :
Patients who fail therapy with oral agents are treated with insulin.
The indications for initiating insulin therapy and the principles
underlying insulin therapy are the same for nondialysis CKD
patients as for the general diabetic population.
No dose adjustment is required if the GFR is >50 mL/min.

The insulin dose should be reduced to approximately 75 percent
of baseline when the GFR is between 10 and 50 mL/min.
The dose should be reduced by as much as 50 percent when
the GFR is <10 mL/min.
Treatament
Lifestyle modification – Diabetic patients, regardless of the

presence of kidney disease, should be counseled on healthy
eating, regular exercise, and if needed, weight loss and smoking
cessation.
Lipid lowering – Most patients with DKD are at high

cardiovascular risk and should therefore be treated with a
statin, atorvastatin or fluvastatin are often preferred because
they do not require dose adjustment based upon the GFR.
Treatment
Type 2 diabetes: SGLT2 inhibitors - Patients with type 2

diabetes and DKD with a sodium-glucose co-transporter 2
(SGLT2) inhibitor. Initiating SGLT2 inhibitors should generally be
avoided among patients with an eGFR <30 mL/min/1.73 m2 and
among those with a prior lower extremity amputation or current
threat of amputation;
SGLT2 inhibitors can be continued among patients whose eGFR

falls below 30 mL/min/1.73 m2. If canagliflozin is used, the target
dose is 100 mg once daily. Starting doses of other SGLT2
inhibitors (eg, 10 mg once daily of empagliflozin or 5 mg once
daily of dapagliflozin) are reasonable as treatment of DKD in
patients with type 2 diabetes.
Glomerulonephritis
Tbilisi referral hospital, Tbilisi,

Georgia
Nephrologist
Nino Maglakelidze
Glomerulonephritis which causes nephrotic syndrome
•Minimal change disease
•Membranous nephropathy
•Focal segmental glomerulosclerosis
•Membranoproliferatove glomerulonephritis
Minimal change glomerular disease
Epidemiology
•Children under age 6 minimal change glomerular disease( MCD)

is around 90%;
•Among adults is around 15%

Diagnosis:
Kidney biopsy is gold standard for diagnose
glomerulonephritis
Morphology of minimal change disease
Glomeruli appear normal on light microscope

There are no complement or immunoglobulin on
immunoflourescence microscope
Diffuse foot effacement on Electron microscope is seen in MCD
Morphology
Normal glomerular on electron microscope
Pathogenesis of minimal change glomerulonephritis
T cell dysfunction
•T – cell dysfunction increase permeability factor

•Permeability factor affects glomerular capillary wall
•Increase foot process fusion and proteinuria
•Remission can be induced by meseals, an infection known to modify
T - cell mediated immunity
•In children with MCD relapse were associated with decrease

T regulatory cells
•The lesion of MCD occurs more frequently in patients with Hodgkin
lymphoma than general population
•Atopic individuals are high risk for developing MCD
B cell dysfunction
•Favorable effect on MCD of rituximab - monoclonal antibody

that depletes CD20+ B cell population;
Glomerular permeability factor
•Circulating immune origin factor alerts glomerular permeability in MCD;

•A T cell hybridoma made from a patient with MCD released a substance,
when injected into rats induce foot process effacement and
•In an in vitro assay using isolated rat glomeruli increased permeability
to albumin was noted after incubation with sera collected from a patient
with MCD and Hodgkin lymphoma;
•Two kidney from a patient with MCD were transplanted into to
recipients without significant baseline proteinuria ; In both recipients
proteinuria developed at the time of grafting and diminished rapidly in
six weeks;
Glomerular basement membrane
Glomerular basement membrane consists:

•the fenestrated endothelial cells;
•the glomerular basement membrane and
•the epithelial cell foot with a slit diaphragm
Glomerular basement is strongly anionic and glomerular permeability
factor diminishes the anionic properties of GBM and increase protein
excretion in urine;
Slit Diaphragm
Defects of slit diaphragm are visible by light
microscope- foot process effacement
Etiology of minimal change glomerulonephritis
Drugs
Neoplasm
Infections
Allergy
Etiology
Drugs:
•NSADs
•Antimicrobial drugs; (ampicilin, cephalosporins,
rifampicin);
•Lithium
•D-penicilamine
•Pamidronate and other bisphsophonates
•Sulfasalazine
•Immunizations
•Gamma interferon
Etyiology
Malignancy:
Hematologic malignancies, Hodgkin lymphoma and leukemia;
Infections:
•Syphilis,
•Tuberculosis,
• Mycoplasma;
•Echinococcuse
• Borreliosis (Lyme disease)
Clinical signs:
Sudden onset over days or a week symptoms of nephrotic

syndrome
Sometimes followed after respiratory or systemic infection

Treatment:
Imunosupresion therapy:
•Prednisone 1.0 mg/kg during 4 weeks (maximum dose 80mg);

Or alternative day prednisone 120 mg every other day
•Or oral cyclophsphamide 2-2.5 mg/kg for 8 weeks
•Cyclosporine 3-5mg/kg /d;

•Tacrolimus 0.05-0.1 mg/kg/d;
•Micophenolate Mofetile 500-1000 twice a day;
•Rituximabe 500 mg weekly 4 doses in a year;

Focal Segmental Glomerulosclerosis
Epidemiology
•In United States focal segmental glomerulosclerosis accounts 35% in

kidney biopsy cases and in afro-americans are 50%;
•In Europe focal segmental glomerulosclerosis accounts 15%;

Focal segmental glomerulosclerosis:
Histology variants of focal segmental glomerulosclerosis
•FSGS not otherwise specified (NOS); formally called classical form
•Collapsing variant
•Tip variant
•Perihilar variant
•Cellular variant
Morphological variants of FSGS
FSGS not otherwise specified (NOS);
classical form
Mesangial collapse and sclerosis is seen but not total glomeruli;

Sclerotic changes occur in juxtamedullary, mild hypercellularity and
partial occlusion of the capillary lumen by hyaline deposits are common;
Collapsing variant
This is characterized by collapse and sclerosis the entire glomerular tuft;

Tip variant
The tip variant is characterized by epithelial cell injury and foam cell
accumulation.
Perihilar variant
Perihilar variant consists of perihilar sclerosis and hialynosis in more than
50% of glomeruli;
Immunofluorescence and electron microscope findings is similar to
other forms of FSGS.
Cellular variant
Is characterized segmental and capillary hypercellularity that occludes
capillary lumen
Immunofluorescence microscope usually reveals no immune

deposits; very rare it reveals IgM or complement C3 in sclerotic
areas and mesangium;
Electrone microscope:
Diffuse foot effacement on Electron microscope is seen in
FSGS
Pathogenesis of FSGS
Injury of the visceral epithelial cell or podocyte which attaches to the

glomerular basement membrane by discrete foot processes is
responsible for the pathogenesis of primary focal segmental
glomerulosclerosis;
Circulating permeability factors – suPAR which acts via activation of

alphavbeta3 which plays important role in regulation of mature of foot
processes and adhesion to glomerular basement membrane;
Circulating permeability factors
•Proteinuria recurs rapidly after kidney transplantation within hours to

weeks
•In patient with recurrent FSGS treatment with plasmapheresis is

effective
•Administration of serum from patients with FSGS into rats induces

proteinuria
•Transplacental transmission of permeability factors from mother to

child causes neonatal proteinuria
•Proteinuria and histological changes resolve when transplanted kidneys

with recurrent FSGS are reimplanted in patients with end-stage renal
disease due to disease other than FSGS
Classification of focal segmental glomerulosclerosis
Idiopathic
Secondary
Genetic FSGS
Secondary focal segmental glomerulosclerosis
Obesity
Reflux nephropathy
Diabetic nephropathy
Sickle cell anemia
Drugs (Heroin, Interferon, Biphosphonates, anabolic steroids, Lithium);
Virus (HIV, Hepatitis C, parvovirus B19, Cytomegalovirus,

Epstein-Barr virus);
Genetic causes of FSGS
NPHS 1 gene which encodes nephrin; (Finnish Type);
NPHS 2 gene encodes podocin;

Treatment :
•Prednisone 1.0 mg/kg during 4 weeks (maximum dose 80mg);
•Or alternative day prednisone 120 mg every other day
•Cyclosporine 3-5mg/kg /d;
•Tacrolimus 0.05-0.1 mg/kg/d;

Membranous glomerulonephritis
Epidemiology
• 30% of cases of nephrotic syndrome in adults;
•1-2% of cases in children
Classification of Membranous glomerulonephritis:

•Idiopathic 70-80%;
•And secondary 20-30%
Morphology of membranous glomerulonephritis
Light microscope:
•Thickening of glomerular capilary wall,
•Glomerular basement membrane spikes
•Subepitelial glomerular deposits
Imminohistology:
Diffuse granular pattern of imunoglobuline of IgG along GBM
Diffuse granular pattern of complement factor C3 along GBM
Electron microscope
Sub epithelial electron-dense deposit outer of GBM
Foot process effacement and spikes;
Pathogenesis:
Circulating antibodies targeting magalin on podocyte
Subepithelial immune deposits activates complement and C5-9

(membrane attack factor)
Its insertion into the podocyte plasma membrane;
Antigens implicated in the pathogenesis MN:

•Phospholipase A2 receptor – M type PLAR2
•Thrombospondine type 1 domain
•Neutral endopeptidase
Secondary membranous glomerulonephritis:
•Systemic lupus erythematosus
•Drugs (NSADs, D-penicilamin, captopril);
•Malignancy; (colon cancer, breast cancer, prostate, lung

cancer, bladder and etc);
•Virus (Hepatitis C and B)
•syphilis
Clinical signs:
Membranous glomerulonephritis is characterized with nephrotic

syndrome
Treatment:
Immunosupresion therapy
Prednisone 0.5 mg/kg during 6 months and oral cyclophsphamide

2-2.5 mg/kg for 8 weeks
Or Cyclosporine 3-5mg/kg /d with combination steroids 16mg

methylprednizone
Or without steroids;
Tacrolimus 0.05-0.1 mg/kg/d with combination steroids 16mg
methylprednizone
Or without steroids;
Micophenolate Mofetile 500-1000 twice a day;
Rituximabe 500 mg weekly 4 doses in a year;

Membranoproliferative glomerulonephritis
Hystorical classification:
Type I is characterized with mesangial proliferation, discrete

immune deposits in mesangium and duplication of GBM –
double tram; Messangial and subendotelial electrone dense
deposits
Type II – Dense deposit disease – Messangial and

intramembranous dense deposits
Type III – Mesangial, subepithelial and subendothelial dense

deposits
Classification by immunohistology
•Immune complex –mediated MPGN
Characterized by positive staining for immune globulins and
complements (C3, IgM, IgG and C1q; kappa and lambda light chains);
Infections - Hepatitis C, hepatitis B,
Autoimmune diseases : Lupus erythematosus, Shogren syndrome and
systemic sclerosis;
Monoclonal gammopathy – excluded by serum protein electrophoresis,
serum free light chains and urine electrophoresis;
•Complement mediated MPGN

Characterized by positive staining for complements - C3 and no or
minimal staining with immunglobulins
Dense Deposit disease, C3 glomerulonephritis;
Light
microscope MPGN
Immunofluorescence
microscope
Immune
complex Complement
mediated mediated
MPGN MPGN
Monoclonal
gammopathy Dense Deposit
Autoimmu disease, C3
Infections
ne disease glomerulone-
phritis;
Membranoprolipherative glomerulonephritis
Morphology of membranoprolipherative gn
Light microscope:
•Thickening of glomerular capillary walls
• Mesangial expansion and hypercelularity
•Masangial ,,double tram”

Morphology of membranoprolipherative gn
Immunohistology:
Diffuse subendothelial and mesangial staining with imunoglobuline
IgG , IgM, or complement factors C1q and C3;
Electrone microscope :
MPGN type I is characterized by discrete immune deposits in the
mesangium and subendothelial space;
MPGN type II (dense deposit disease, or DDD) is characterized by
messangial and intramembranous dense deposits ;
Type III – Mesangial, subepithelial and subendothelial dense deposits

Clinical signs:
•Nephritic syndrome
•Nephrotic syndrome
•Rapidly progressive glomerulonephritis

Treatment:
•Steroids 1.0 mg/kg

•Plasmapheresis 3l three times a week for 2-3weeks;
•Cyclophsphamide 2.0 mg /kg
•Mycofenolat mofetil 2000 g/day
•Rituximab 375mg/m2 4 doses;
Antiviral treatment HCV and HBsAg related glomerulonephritis

Hematuria

Nephrologist
Nino Maglakelidze
Definition of Hematuria
•Visible by naked eye (macrohematuria/gross hematuria)
•Detectable only on examination (microhematuria);
•Urine sediment is gold standard for the detection of microscopic

hematuria (3 RBC or more per high – power field);
•Dipstick is more sensitive and detects 1 to 2 RBCs per high power

field;
Dipstick false positive tests:
•Semen, which is present in the urine after ejaculation may cause a

positive heme reaction on the dipstick
•An alkaline urine with a pH greater then 9
•The presence of myoglobinuria or hemoglobinuria;

Classification of hematuria
• Non glomerular hematuria;
•Glomerular hematuria;
Glomerular hematuria:
•Isomorphic RBCs
•Dysmorphic RBCs more than 40%;
•Acantocytes 5%
•>1 erythrocytic casts;

Non glomerular hematuria:
•Isomorphic erythrocytes
•Dysmorphic erythrocytes less than 40%;

Glomerular diseases and hematuria
•Immunoglobulin A nephropathy (IgA)
•Thin glomerular basement membrane
•Membranoprolipherative glomerulonephritis
•Alport ‘s syndrome
Transient hematuria
• Postinfective glomerulonephritis
•Exercise
IgA nephropathy
Epidemiology
IgA nephropathy is accounts 45% of renal biopsies in East Asian and
Caucasian people;
Diagnosis:
Kidney biopsy is gold standard;
Morphology of IgA nephropathy:
Light microscope: Mesangial expansion, mesangial and

endocapillary proliferation and hypercellularity;
Immunohistology:
Dominant mesangial deposits of IgA alone or with IgM or IgG;
Subendothelial capillary wall IgA deposts may also occur;
Electron microscope:
Mesangial electrone dense-deposit are seen on electrone
microscope;
Clinical Features:
•40-50% of patients present with one or recurrent hematuria, often

accompanying upper respiratory infection, ,, synpharyngitic
hematuria”
•30-40% microscopic hematuria with mild proteinuria;
•Less than 10% nephritic syndrome or an acute rapidly progressive

glomerulonephritis characterized by arterial hypertension, edema
and renal insufficiency;
Treatment:
Long term treatment with ACE or ARB when proteinuria <1g;
If proteinuria >1g treatment with corticosteroids during 6 month
Cyclophsphamide 2.5mg/kg in combination with steroids during 3

months;
Then followed with Azathioprine 1.5 mg/kg;
Treatment with fish oil in case if proteinuria >1 g;
Mycophenolat mophetile - MMF?
Cyclosporine 3-5 mg/kg ?

Alport’s Syndrome
Hereditary X-link disease
Mutation of genes which encodes alpha – 3; alpha-4 and alpha 5

chains of IV collagen;
IV collagen alpha chains are located in glomerular basement

membrane, eye and ear;
Alport syndrome can be autosomal recessive

COL4A3 or COL4A4 genes and accounts around 15%.
It can be also autosomal dominant , which arise from heterozygous

mutations ofCOL4A3 or COL4A4 genes and accounts 20- 30%;
Alport’s Syndrome
Epidemiology
Alport ‘s syndrome account 3% in children with ESRD

and 0.2% in adults with ESRD
Alport’s Syndrome
Clinical signs:
Renal manifestation:
•Asymptomatic persistent hematuria
•Recurrent episodes of gross hematuria
•Over time patient develops proteinuria,
•arterial hypertension and
•renal insufficiency;
Alport’s Syndrome
Extra renal manifestation:
Ear
•Hearing loss occur in 85% of affected boys and 15% in females;
Ocular manifestation:
•Lens – regular conical protrusion

•Retinal changes, white and yellow granulation;
•Corneal changes, corneal erosion cause corneal pain;
Arterial disease:
•Aneurisms of the aortic or abdominal aorta;

Alport’s Syndrome
Diagnosis:
•Renal or skin biopsy
•Molecular genetic test
•Positive family history of persistent hematuria
•Presentation with chronic kidney disease and sensor neural defense

and or characteristic ocular findings regardless of family history;
Morphology of Alport syndrome
Light microscopy : Podocyte hypertrophy specimen. Segmental

glomerular sclerosis. Irregular thickening of the glomerular
basement membrane.
Immunofluorescence: Distribution of the α5(IV) chain in the kidney
and the skin basement membranes
Electron microscope:
Longitudinal splitting of the lamina densa of the glomerular
basement membrane;
Alport’s syndrom
Treatment:
•Annual monitoring of microalbuminuria and proteinuria as soon as

the diagnosis of Alport syndrome is diagnosed;
•ARB is initiated when patient develop overt proteinuria;
•Over time patient will develop End Stage Renal Disease;
•Renal transplantation is preferred for the patients who develops

ESRD;
•Insignificant risk of developing anti-GBM disease after kidney

transplantation; (<3%);
Thin basement membrane
Epidemiology:
Thin basement membrane accounts around 1 % in the
population;
Clinical signs:
•Microhematuria
•Gross hematuria and flank pain;
•Blood pressure and urinary protein excretion are typically

normal;
Pathogenesis of thin basement membrane
It has been suspected that the genetic defect in thin basement

membrane nephropathy (TBMN) would be similar to that in
hereditary nephritis (Alport syndrome).
This hypothesis was confirmed in families in which TBMN was

associated with heterozygous defects in COL4A3 or COL4A4, the
genes that encode the alpha-3 and alpha-4 chains of type IV
collagen.
Patients with TBMN can be considered "carriers" of autosomal

recessive Alport syndrome.
Morphology of thin basement membrane:
Light microscopy of thin basement membrane syndrome showing

minor abnormalities
Very rare it has been seen sclerotic changes of glomeruli
Morphology of thin basement mambrane
Results from immunofluorescence microscopy are negative for IgG,
IgA, IgM, Clq, C3 and fibrinogen.
Electron microscopy: irregular thinning of glomerular basement

membrane;
Thin basement membrane
Treatment:
•No randomized controlled studies have evaluated the efficacy of

therapy in patients with thin basement membrane;
•In case of proteinuria ARB is beneficial for patients with thin

basement membrane
Prognosis:
•Excellent long-term prognosis ;

•Or slowly progressive renal insufficiency can occur
Nutcracker syndrome:
Compression of the renal vein between aorta and proximal superior

mesenteric artery;
Clinical signs:
•Microhematuria
•Gross hematuria
•Microhematuria may be associated with pain in left flank.

Polycystic Kidney disease
•Autosomal recessive polycystic kidney disease (ARPKD) is a recessively

inherited disease characterized by cystic dilations of the renal collecting
ducts and developmental defects of hepatobiliary ductal plate
remodeling, which result in varying degrees of congenital hepatic
fibrosis;
•Autosomal dominant polycystic kidney disease (ADPKD) is a dominantly

inherited characterized by cystic dilations in all part of the nephron;
•Cyst in liver, pancreas and other organs is also common;
Genetics:
ARPKD is caused by mutations in the PKDH1 gene located on

chromosome 6P21;
ADPKD is caused by mutation in the PKD1 gene which is located on

chromosome 16 and PKD2 gene which is located on chromosome 4;
Diagnosis:
•Family history of ADPKD
•Multiple cysts on ultrasonography or CT scanning
•Cysts may also be seen in the liver or pancreas
•Genetic testing for PKD1 and PKD2

Diagnosis
Ultrasound of polycystic kidney disease

Diagnosis
CT scan of polycystic kidney disease

Autosomal dominant polycystic disease
Clinical signs :
•Hematuria (rupture of cyst in collecting duct)

•Mild proteinuria
•Urinary tract infection
•Concentrating defect (increased thirst, polyuria, nocturia and
urinary frequency);
•Arterial hypertension
•Progressive renal insufficiency
•Nephrolithiasis (Uric acid stones, rare calciumoxalate)
•Flank and abdomen pain
•Renal cancer – renal cell carcinoma;
Treatment:
•Sodium restriction
•Increased fluid intake
•ACE or ARB blockers
•Statins
Vasopressin receptor antagonist – TENPO trial – Tolvaptan

1157 patients
Annual decline of kidney function was better in Tolvaptan group
(2.61 vs3.81mg/ml);
Adverse events 0.5 in Tolvaptan group
Liver enzymes elevation, chest pain, headache;
mTOR inhibitor
SIRENA trial
Rapamycin stabilize cyst growth
No deference in decrease eGFR
Autosomal recessive polycystic kidney disease
Diagnosis:
Ultrasound of kidney and liver

•Kidney of ARPKD on ultrasound are characterized by bilateral large
echogenic kidneys with poor corticomedullary differentiation;
•Liver – hepatomegaly , increased echogenicity and dilation of

peripheral intrahepatic ducts and main bile ducts;
CT scan or MRI of kidney and liver;
Molecular genetic tests of PKDH1 gene mutation;

Clinical manifestation
Disease presentation:
•One third before 1 year
•Two third between 1 to 20 year
•One third after 20 year
Renal manifestation:
•Polyuria and polydipsia due to reduced concentration ability
•Recurrent episodes of urinary tract infection
•Urinary abnormality, proteinuria, glucosuria, hyperphsphaturia
•Metabolic acidosis due to decreased urinary acidification capacity
•Progressive renal impairment
Liver:
•Portal hypertension due to congenital fibrosis

•Ascites
•Splenomegaly
•Esophageal variceal hemorrhage
Other findings:
•Feeding difficulties
•Thrombocytopenia
•Growth impairment
•Hyponatremia
Management and treatment of patients of ARPKD
•Hypertension – ACE or ARB

•Hyponatremia – fluid restriction
•Supplemental nasogastric feeding to obtain adequate caloric
intake
Renal management – ESRD renal replacement therapy
•Hemodialysis
•Peritoneal dialysis
Hepatic complications:
•Bacterial cholangitis – empiric antibacterial treatment
•Progressive portal hypertension

Renal raplacment therapy
Hemodyalisis

Nephrologist
Nino Maglakelidze
Hemodialysis
•Falling kidneys may reach a point when they no longer excrete water
and ions at rates that maintain body balances of these substances, nor
can they excrete waste products as fast as they are produced;
•An elevation waste products, as measured in the blood, is called

,,azotemia”. When waste products accumulate they cause sick feeling
throughout the body called ,,Uremia”.
For patients with ESRD renal replacement therapy is achieved by
•Hemodialysis
•Peritoneal dialysis
•Kidney transplantation
Creatinine clearance < 10 ml/min patient needs dialysis

Hemodyalisis
Hemodialysis uses special filters to remove excess waste products

and water from the body
Hemodialysis
The apparatus used to conduct hemodialysis consists of the

following components:
Dialyzer
Dialysis solutions
Tubing for transport blood and dialysis
Machine to power and mechanically monitor the procedure

Hemodialysis modalities:
Hemodialysis
Hemofiltration
SLEDD – slow low-efficiency daily dialysis
CRRT-continues renal replacement therapy
CVVH – continues venovenous hemofiltration
CVVHD –continues venovenous hemodialysis
CVVHDF –continues venovenous hemodiafiltration

Solute clearance
Solute is cleared from the intravascular compartment inside dialyzer

by:
diffusive and
convective transport;
Blood flow/dialysate flow:
Blood flow 300-450 ml/min
Dialysate flow 500ml/min

Dialyzers
Types of dialyzers:
Hollow fiber dialyzers – contains thousands of hollow fibers

similar to human capillary;
Parallel plate Dialyzers – operates similarly to the hollow fiber and

are fashioned with flat sheets of membrane
Dialyzer
Type of membrane
Blood volume capacity
Surface area
Ultrafiltration coefficient
Clearance of various substances
Sterilization requirement
Types of membrane
•Unmodified cellulose – cuprophan is polysaccharide – based

membrane obtained from pressed cotton
•Substituted cellulose membrane obtained by chemical bonding

of the free hydroxyl groups at the surface of the cellulose
polymer.
•Cellulosynthetic membrane are modified by the addition of a

synthetic material to liquid cellulose during its formation and
have higher permeability and compatibility than cellulose
membrane.
Blood volume capacity
Is the priming blood volume required to fill dialyzers fiber

•Hollow –fiber dialyzer volume capacity is less than parallel –plate
dialyzers
•Blood volume capacity of hollow – fiber dialyzer is fixed and will not
increase with increasing transmembrane pressure.
•Priming volume depends on upon dialyzer surface area and ranges
from 60 to 120 ml;
Surface area
Dialyzers differs by surface areas

•And ranges from 0.8 to 2.1 m2
Clearance:
Clearance of various solutes from blood is a function of dialyzer
efficiency
Dialyzer clearance are routinely reports as urea or creatinine

clearance (small solutes) and vitamin B12 and beta – 2
microglobulines(large solutes)
The dialyzer mass transfer – area coefficient (KoA) quantitative

measure of dialyzer efficiency of clearance depends on membrane
porosity and thickness, solute size and blood and dialysate flow;
High efficiency : high KoA urea >600 ml/min;
High flux – high ultrafiltration (convenction) capacity

High clearance beta-2 microglobulines : 11 800 and vit. B12
Ultrafiltration coefficient:
The ultra filtration coefficient correlates directly with its

permeability
The volume of fluid that is transferred across the membrane per

mmHg of pressure gradient is called ultra filtration coefficient. (KUf)
A low KUf denotes a low permeability to water. The lower

permeability to water the higher TMP is needed to achieve ultra
filtration.
Sterilization and reuse:
Dialyzers are sterilized with ethylene oxide

Gamma irradiation
Steal autoclaving
Dialysate composition:
Water: ultrapure water, no bacteria and endotoxin should not be

detected;
These can be reached by reverse osmosis, deionization resins and
activated charcoal;
Dialysate composition:
Na+ - 135-142 mmol/l;
K+ - 0-4mmol/l;
Ca ++ - 1.25-1.75mmol/l;
Mg ++ - 0.25-1mmol/l;
Cl – 112mmol/l;
HCO3 – 28-35mmol/l;
Acetate – 2.5-10mmol/l;
Glucose – 0-200 mg/dl;

Anticoagulation during hemodialysis:
Heparin; control aPTT;
Low molecular heparin
Citrate
Evodialmembrane – heparin coated membrane
Xa factor inhibitor – Fondaparunix, Arixtra;
Refludan – Hirudin
No anticoagulation, saline infusion

GI bleeding, Hemorrhagic stroke and etc.
Vascular access
•Native arteriovenous fistula
•AV graft
•Temporary catheter
•Permanent tunneled catheter
Dialysis dose:
•Adequate dialysis dose Kt/v -1.4 per session; eKt/v 1.2;

K- dialyser clearance of urea; t-time for treatment in minutes;
volume of distribution of urea in the body;
•Urea reduction rate URR >65%
Dialysis machines:
Dialysis machines contains blood pump, which moves blood from

patient to dialyzer and back;
Dialysis monitors:
temperature monitor
air detector
arterial and vein blood line pressure monitors
dialysate conductivity monitor
Complications during dialysis sessions:
Hypotension
Cramps
Disequilibrium syndrome: headache, vomiting,
Allergy to the membrane, first use syndrome
Heparin induced thrombocytopenia
Airembolism , hemolysis
Nephritic and Nephrotic
syndrome

Nephrologist
Nino Maglakelidze
Nephrotic syndrome
•Heavy proteinuria (urinary protein excretion greater >3.5g/day)
•Hypoalbuminemia – Serum albumin less than 2.5 g/l;
•Edema
•Hyperlipidemia
•Lipiduria
Etiology of nephrotic syndrome
Glomerulonephritis which causes nephrotic syndrome:
•Minimal change disease
•Membranous nephropathy
•Focal segmental glomerulosclerosis
•Membranoproliferatove glomerulonephritis
•Amyloidosis (AL and AA – amyloidosis)
•Lupus Erythematosus
•IgA nephropathy
Mechanism of proteinuria
Proteinuria is due to increased filtration of macromolecules across

glomerular capillary wall;
Normally filtration of macromolecules is restricted:
charge – selectivity and
size selectivity;
Glomerular capillary wall consists: the fenestrated endothelial cells;
the glomerular basement membrane and the epithelial cell foot
proceses;
The pores between foot processes are closed by slit membrane;
In MCD and FSGS charge selectivity is lost due to foot effacement;
In other cases size selectivity is lost (membranouse

glomerulopathy; membranoproliferative gn and etc);
Mechanism of development nephrotic syndrome
Urinary loss of more than 3.5 g/day of albumin and other proteins
Hypoalbuminemia less than 2.5 g/l;
Decrease of oncotic pressure
Increase of secretion of cholesterole and triglyceride
Decrease of effective blood volume
Activation of neurohumoral system activation(increase of aldosterone,
catecholamines and etc)
Retention of water and sodium
Increase of plasma volume
Increase of capillary hydraulic pressure
Water accumulation in interstitial
 Edema
Complications of nephrotic syndrome
Edema (periorbital and pretibial edema)
Protein malnutrition (loss of lean body mass, which can be masked

weight gain because of edema, secondary anorexia and vomiting)
Hypovolemia (volume depletion is caused volume movement into

the intestitium)
Acute kidney injury (Hypovolemia, interstitial edema, ischemic

tubular injury and use of NSADs);
Thromboembolism (pulmonary emboli and rare cerebral vein

thrombosis);
Infection (pneumococcal infection in MCD children);

Diagnosis
•Protein excretion in 24 hour > 3.5g/day;

Alternative :
•protein to creatinine ratio in urine sample;
•Urine protein electrophoresis and immunofixation
•Serum protein elecrophresis

Serology :
Antinuclear antibodies (ANA);
Anti-ds-DNA
Anti-GBM antibodies
Complement factors – C3 and C4;
Serum free light chains ;
Serum AA amyloid – SAA;
Hepatitis B and C serology;
HIV – serology;
Patients with nephrotic syndrome -
Kidney biopsy
is gold standard in clinical nephrology

Treatment:
•Sodium restriction (approximately 2 g a day)
•Diuretics (loop diuretics and etc)
•ACE or AR –blockers to decrease preoteinuria (serum kreatinin and

potassium should be monitored)
•HMG CoA reductase inhibitors and dietary modification (treatment

of Hyperlipidemia)
•Serum albumin below 2,5g/l treatment with heparin then followed

with varfarin is recomended (treatment and prevention of
hypercoagulation);
Nephritic syndrome
Definition of nephritic syndrome
Acute nephritis is sudden onset of:

•Haematuria (macroscopic/microscopic ) with red cell casts or
dysmorphic RBCs
•Proteinuria in the non-nephrotic range ( <3.5g)
It is often accompanied by:

Hypertension
Edema, (peri orbital, leg and sacral)
Temporary oliguria and
Decrease glomerular filtration rate or sudden increase serum
creatinine
Pathegeneses
Acute nephritic syndrome comprise of a specific set or renal diseases

where an immune mechanism triggers inflammation causing damage
to the basement membrane, messangium or capillary endothelium
of the glomerulus.
Acute nephritic syndrome is often caused by an immune response

triggered by an infection or other disease.
Causes of nephritic syndrome in children and adolescents:
•Hemolitic uremic syndrome (disorder that occurs when an infection

In the digestive system produces toxic substances that destroy
red blood cells and cause kidney injury)
•IgA nephropathy
•Post-streptococcal glomerulonephritis (kidney disorder that occurs

after infection with certain strains of streptococcus bacteria)
•Goodpasture syndrome (disorder in which the immune system attacks

the glomeruli)
Causes of nephritic syndrome in children and adolescents:
•Endocarditis (inflammation of the inside lining of the heart chambers

and heart valves caused by a bacterial or fungal infection)
•Membranoproliferative glomerulonephritis (disorder that involves
inflammation and changes to kidney cells)
•Rapidly progressive (crescentic) glomerulonephritis (a form of
glomerulonephritis that leads to a rapid loss of kidney function)
•Lupus nephritis (kidney complication of systemic lupus erythematosus)
•Vasculitis (inflammation of the blood vessels)
Poststreptococcal glomerulonephritis
Poststreptococcal glomerulonephritis (PSGN) is caused by prior

infection with specific nephritogenic strains of group A beta-hemolytic
streptococcus.
Epidemiology:
PSGN is the most common cause of acute nephritis in children,
it primarily occurs in developing countries.
•new annual cases of PSGN worldwide, 97 percent occur in regions of

the world with poor socioeconomic status, with an annual incidence that
ranges from 9.5 to 28.5 per 100,000 individuals
•In more developed and industrialized countries, the incidence has

continued to decrease; the estimated annual incidence was 0.3 per
100,000 individuals between 2005 and 2015
PATHOGENESIS:
PSGN appears to be caused by glomerular immune complex disease

induced by specific nephritogenic strains of group A beta-hemolytic
streptococcus (GAS). The resulting glomerular immune complex disease
triggers complement activation and inflammation.
Mechanisms for the immunologic glomerular injury induced by

beta-hemolytic streptococcus infection:
●Deposition of circulating immune complexes with streptococcal
antigenic components.
●In situ immune complex formation resulting from deposition of
streptococcal antigens within the glomerular basement membrane
(GBM) and subsequent antibody binding.
●In situ glomerular immune complex formation promoted by
antibodies to streptococcal antigens that cross-react with glomerular
components (molecular mimicry).
Morphology of postinfective glomerulonephritis:
Light microscope:
•Light microscopy shows prominent endocapillary proliferation and

hypercelluraty with neutrophils
Immunofluorescence microscopy
Immunofluorescence (IF) microscopy reveals :
A characteristic pattern of deposits of immunoglobulin G (IgG) and C3
distributed in a diffuse granular pattern within the mesangium and
glomerular capillary walls;
Electron microscopy :
The most characteristic feature detected by
electron microscopy (EM) are the dome-shaped subepithelial
electron-dense deposits that are known as humps.
CLINICAL MANIFESTATIONS:
●Edema − Generalized edema is present in approximately two-thirds

of patients due to sodium and water retention. In severe cases, fluid
overload leads to respiratory distress due to pulmonary edema.
●Gross hematuria − is present in approximately 30 to 50 percent of

patients. The urine looks smoky and tea or colacolored.
●Hypertension − Hypertension is present in 50 to 90 percent of

patients and varies from mild to severe. It is primarily caused by salt
and fluid retention.
CLINICAL MANIFESTATIONS:
●Subclinical cases of PSGN are primarily characterized by microscopic

hematuria. Such patients were often detected during epidemics.
●Some patients present with clinical symptoms related to hypertensive

crisis or edema with minor urine abnormalities.
Renal function — PSGN is associated with a variable decline in

glomerular filtration rate (GFR) that is detected by a rise in serum
creatinine. Acute renal failure requiring dialysis is uncommon.
Urinalysis and urinary protein excretion — in patients

with PSGN reveals hematuria (some of the red cells are typically
dysmorphic) with or without red blood cell casts, varying degrees of
proteinuria, and often pyuria. Nephrotic range proteinuria is
uncommon and occurs in approximately 5 percent of cases at
presentation.
Laboratorial finding
Complement Factors :
In approximately 90 percent of patients, C3 and
C4 are significantly depressed in the first two weeks of the disease
course.
Serology:
•Anti-streptolysin (ASlO)
•Anti-hyaluronidase (AHase)
•Anti-streptokinase (ASKase)
•Anti-nicotinamide-adenine dinucleotidase (anti-NAD)
•Anti-DNase B antibodies.
Indications for renal biopsy
Kidney biopsy is usually performed in patients in whom other

glomerular disorders are being considered.
•Persistently low C3 levels beyond six weeks are suggestive of a

diagnosis of membranoproliferative glomerulonephritis as C3 levels
typically normalize in patients with PSGN by this timeframe.
•Recurrent episodes of hematuria are suggestive of IgA nephropathy

and are rare in PSGN.
•A persistent or progressive increase in serum creatinine is

uncharacteristic of PSGN, but there are occasional patients whose renal
function does not fully recover.
ACUTE MANAGEMENT
Supportive care :
•No specific therapy is indicative for PSGN.
•Management is supportive and is focused on treating the clinical

manifestations of the disease, particularly complications due to
volume overload.
•General measures include sodium and water restriction and loop

diuretics.
•Loop diuretics generally provide a prompt diuresis with reduction

of blood pressure and edema.
ACUTE MANAGEMENT
•Infrequently, patients have hypertensive encephalopathy due to severe

hypertension.
These patients should be treated urgently to reduce the blood pressure.
Oral nifedipine or parenteral nicardipine are effective.
•angiotensin-converting enzyme (ACE) inhibitors should be used with

caution due to the risk of hyperkalemia.
•Patients with PSGN have variable reductions in renal function and some
patients require dialysis during the acute episode.
Dialysis indications:
•For patients with serious renal impairment
•Life-threatening fluid overload (pulmonary edema, heart failure,

and hypertension) that is refractory to medical therapy.
•Hyperkalemia (serum or plasma potassium >6.5 mmol/l) unresponsive

to medical therapy
Prognosis:
Most patients have an excellent outcome.
This patients who present with acute renal failure and may have
crescents on the initial renal biopsy their kidney function recovers
totally.
anti-GBM antibody (Goodpasture's) disease
Anti-GBM antibody disease is a disorder in which circulating antibodies

are directed against an antigen intrinsic to the glomerular basement
membrane (GBM), thereby resulting in acute or rapidly progressive
glomerulonephritis that is typically associated with crescent formation.
PATHOGENESIS
There is short-lived production of circulating autoantibodies, which are

directed against an antigen intrinsic to the glomerular basement
membrane (GBM), in response to an unknown inciting stimulus.
The development of anti-GBM antibodies may precede the onset of

clinical signs and symptoms by many months. The principal target for
the anti-GBM antibodies (which are typically immunoglobulin G
(IgG) 1 and 3 but sometimes IgA or IgM) is the NC1 domain of the
alpha-3 chain of type IV collagen (alpha-3(IV) chain), one of six
genetically distinct gene products found in basement membrane
collagen.
The epitope of type IV collagen specifically recognized by anti-GBM

antibodies may correlate with the prognosis of the disease.
EPIDEMIOLOGY
Acute glomerulonephritis due to anti-GBM antibody disease is rare,

estimated to occur in fewer than one case per million population;
Crescentic glomerulonephritis due to anti-GBM antibody disease

accounted for fewer than 3 percent of all kidney biopsies.
EPIDEMIOLOGY
The diagnosis of anti-GBM disease is made in older children and in

adults of all ages. However, younger patients (<30 years) are more
likely to present with the full constellation of Goodpasture's syndrome
(eg, with pulmonary hemorrhage), and older patients (>50 years)
with isolated glomerulonephritis.
There appears to be a slight male predominance in the younger age

group, and a female predominance in the older age group.
CLINICAL PRESENTATION
•Hematuria
•Nephritic range proteinuria
•Nephritic sediment - dysmorphic red blood cells, red blood cell casts.
•Rapidly progressive renal failure over weeks
•With or without pulmonary hemorrhage

Pulmonary manifestation:
•Pulmonary involvement, generally consisting of alveolar hemorrhage,
•affects approximately 40 to 60 percent of patients;
•Pulmonary manifestations include shortness of breath,
•cough,
•sometimes overt hemoptysis,
•pulmonary infiltrates on chest x-ray.

Pulmonary CT scan of Goodpasture syndrome
CLINICAL PRESENTATION
Iron deficiency anemia, possibly due to prolonged pulmonary bleeding,

may be seen.
A rare variant of anti-GBM antibody disease, known as "atypical

anti-GBM nephritis," has been reported in a series of 20 patients who
presented with hematuria, proteinuria, and mild renal insufficiency,
without pulmonary hemorrhage.
Renal biopsy in these patients demonstrated bright linear

immunoglobulin G (IgG) deposition along the GBM but without features
of crescentic glomerulonephritis.
These atypical cases accounted for approximately 12 percent of

anti-GBM patients.
DIAGNOSIS
The presence of anti-GBM antibody disease should be

suspected in any patient with acute glomerulonephritis, particularly if
accompanied by rapid progression and/or pulmonary (alveolar)
hemorrhage.
The diagnosis of anti-GBM antibody disease requires demonstration

of anti-GBM antibodies either in the serum or the kidney biopsy.
Kidney biopsy
Light microscopy usually shows crescentic glomerulonephritis.

Kideny biopsy
Immunofluorescence microscopy demonstrates the virtually

pathognomonic finding of linear deposition of immunoglobulin G (IgG)
along the glomerular capillaries and occasionally the distal tubules.
Kidney biopsy
Electron microscope show granular deposits of antigen-antibody

complexes along the glomerular basement membrane.
Serologic testing
•anti-GBM antibodies; (using a direct enzyme-linked immunoassay

ELISA)
•In 10 and 50 percent of patients with anti-GBM antibody disease

also test positively for ANCA
Treatment:
•it is recommended to begin treatment with high-dose corticosteroids

1.0 mg/kg maximum dose 60-80mg per day;
•in combination with cyclophosphamide 0.5 -1.0 mg/m2 monthly
•plus plasmapheresis 14 sessions or until serum anti-GBM antibodies

become undetectable in serum;
•It is not recommended no maintenance immunosuppressive therapy

for anti-GBM GN;
PROGNOSIS
Renal and patient survival correlates closely with the degree of renal
impairment at presentation.
Patients with moderate to severe disease who do not require dialysis

upon presentation generally respond to therapy
Patients who require immediate dialysis at presentation does not

escape the need for maintenance dialysis.
Hemolytic - uremic syndrome
The hemolytic uremic syndrome (HUS) is defined by the simultaneous

occurrence of
hemolytic anemia,
thrombocytopenia,
and acute kidney injury.

Classification of hemolytic uremic syndrome:
HUS had been divided into:
diarrhea-positive (resulted from Shiga toxin-producing Escherichia coli

(STEC) infections and less frequently from Shigella dysenteriae
type 1 infection).
and diarrhea-negative HUS. (such as cases due to complement

dysregulation (also referred to as atypical HUS)
Complement gene mutations

Antibodies to complement factor H
Gene affected gene for non-STEC-HUS cases
Complement factor H (CFH, 20 to 30 percent)
CD46, previously known as membrane cofactor protein

(5 to 15 percent)
Complement factor I (CFI, 4 to 10 percent)
Complement factor 3 (C3, 2 to 10 percent)
Complement factor B (CFB, 1 to 4 percent)
Thrombomodulin gene (THBD, 3 to 5 percent)

Thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura (TTP) is due to deficient

activity of the Von Willebrand factor cleaving protease.
TTP can be congenital and acquired.
TTP is usually due to mutations of the ADAMTS13 gene.
Affected children usually present at birth with hemolytic anemia and

thrombocytopenia. Nervous system is affected, the patient may have
Confusion, seizures and etc. Renal involvement often occurs.
TTP is distinguished from HUS by abnormally low ADAMTS13 activity.

DIAGNOSIS — The diagnosis of hemolytic uremic syndrome (HUS)
is clinically based on the presence of the classical triad of
microangiopathic hemolytic anemia, thrombocytopenia and acute
kidney injury.
•The microangiopathic hemolytic anemia is established by a

hemoglobin level less than 8 g/dL with a negative Coomb's test and a
peripheral blood smear demonstrating a large number of schistocytes
(up to 10 percent of red cells).
•Thrombocytopenia is characterized by a platelet count below

140,000/mm3 and is usually approximately 40,000/mm3. Despite the
low platelet count, there is typically no purpura or active bleeding.
The degree of thrombocytopenia is unrelated to the severity of renal
dysfunction.
DIAGNOSIS
•Elevated lactate dehydrogenase level and low level of haptoglobine.
•Acute kidney injury − The severity of renal involvement ranges from

hematuria and proteinuria to severe renal failure (usually identified by
abnormally elevated serum creatinine and blood urea nitrogen [BUN]
levels) and oligoanuria. Severe renal failure occurs in one-half of cases.
•Hypertension is common, particularly after the administration of excess

fluids or blood transfusions.
•Most patients have microscopic hematuria on urinalysis, although

macroscopic hematuria may be observed. Red blood cell casts are
occasionally seen, but are not a typical feature.
DIAGNOSIS
•Screening for Shiga toxin-producing bacterial strains to differentiate

STEC HUS from other forms of HUS. This includes testing for Shiga toxins
(eg, ELISA) in the stool, stool cultures, and serologic testing for IgM and
anti-lipopolysaccharide antibodies against the most frequent STEC
serotypes.
•Assessing ADAMTS 13 function to differentiate HUS from thrombotic

thrombocytopenic purpura (TTP).
Kidney biopsy
Renal histology typically demonstrates glomerular thrombotic
microangiopathy in patients with STEC HUS, characterized by a thickening
of the capillary walls, with a double-contour appearance due to a
widening of the subendothelial space. In patients with complement-
mediated HUS, the renal histological lesion is most often arteriolar
thrombotic microangiopathy.
TREATMENT
The management of hemolytic uremic syndrome (HUS) is supportive.
Use of the following interventions is primarily based on data from
observational studies of patients with Shiga toxin-producing
E. coli (STEC) HUS.
•Red blood cell transfusions for anemia when clinically indicated;

(eg, hemoglobin level reaches 6 to 7 g/dL or hematocrit <18 percent).
•Platelet transfusion for patients who have significant clinical bleeding.

•Appropriate fluid and electrolyte management to maintain adequate
intravascular volume and correct/avoid electrolyte abnormalities.
•Initiation of dialysis therapy in patients with symptomatic uremia,

severe fluid overload, or electrolyte abnormality that is refractory
to medical therapy.
•Provision of adequate nutrition.

TREATMENT
Treatment of complement-mediated HUS
•Plasma exchange or infusion
•Eculizumab, a monoclonal antibody to C5 that blocks the terminal

complement cascade
•Renal or combination renal-hepatic transplantation.

Treatmemt of Thrombotic thrombocytopenic purpura
 Fresh frozen plasma infusion
Plasma exchange
Steroids
Renal replacement therapy
Peritoneal dialysis

Nephrologist
Nino Maglakelidze
Peritoneal dialysis
•Peritoneal dialysis (PD) is a treatment for patients with chronic

kidney disease, stage V – ESRD
•A dialysis technique that uses the patient’s own body tissue –

peritoneal membrane inside the abdominal cavity as a filter.
Goals of peritoneal dialysis:
Remove toxic substances and metabolic wastes
Reverse the symptoms of uremia
Reestablish normal fluid and electrolyte balance
Maintain a positive nitrogen balance
Prolong life
Have a maximal level of quality of life

Contra indications
Absolute contraindications
•Peritoneal fibrosis and adhesions following intra abdominal operations

•Inflammatory gut disease
Relative contra indications

•Hernias
•Significant loin pain
•Diverticulitis
•Colostomy
•Obesity
•Significant decrease lung function
Principles underling peritoneal dialysis
Three processes take place simultaneously
Diffusion
Osmosis
Ultrafiltration
Types of peritoneal dialysis
•Continuous ambulatory peritoneal dialysis (CAPD)

•Automated peritoneal dialysis (APD)
Continuous ambulatory peritoneal dialysis (CAPD)
Carried out during day time, manually by patients or

caregivers
Dialysis fluid is infused to the peritoneal cavity
Dwell time between 4-8 hours

Automated peritoneal dialysis:
Is performed through a cycler machines
During the night when the patient sleep
Types of automated peritoneal dialysis
•Continuous cycling peritoneal dialysis (CCPD)

•Tidal peritoneal dialysis (TPD)
•Nocturnal (night) intermittent peritoneal dialysis (NIPD)
Automated peritoneal dialysis (APD)
Continuous cycling peritoneal dialysis (CCPD)
•CCPD has a long daytime dwell
•Several cycles over night
•Minority of patients do not have a day time dwell
•Some patients have ,,midday exchange” to achieve adequate

ultrafitration
Nocturnal (night) intermittent peritoneal dialysis (NIPD)
•Noctural intermittent peritoneal dialysis have treatments periods
,,wet abdomen” altering with times during which peritoneal cavity has
been drained of dialysate ,,dry abdomen”.
Tidal peritoneal dialysis (TPD)

•TPD is modification of cycler therapy in which exchange consists of
partial drain. (Usually 80 - 90% of instilled volume plus ultra filtration
from the body)
•The peritoneal cavity always contains 250 – 400ml dialysate
•The patients may or may not have a day time dwell
PD catheters
An internal section with numerous openings and an
open tip to let dialysate flow freely
A subcutaneous section
An external section for connection to dialysate
section;
Types of peritoneal catheters
Straight Tenckhoff
Curled Tenckhoff
Swan-neck
T-fluted
Types of peritoneal membrane
Four types peritoneal membrane
High transporter
Low transporter
High average transporter
Low average transporte

PET – peritoneal equilibration test evaluates:
Type of peritoneal membrane

Ultrafitration capacity of peritoneal dialysis
Types of peritoneal solutions
Dextrose solutions:
1,5% dextrose solution 2000-2500 ml;
7.5% 2000ml Icodextrine solution;

Complications of peritoneal dialysis
Dialysate leakage
Ceased peritoneal dialysis
Drainage problems
Kinking in tubes
Constipation
Fibrin formation – Heparin or streptokinase
administration
Malpositioned catheter
Shoulder pain
Following infusion of fresh dialysate
Resolve within 20min after instillation, analgesics can
be given
Hemoperitoneum
Occurs in female;
Management :
Heparin administration;
Transfer to HD
Peritonitis
Abdominal pain
Cloudy effluent
Tenderness,
Identification of micro organism, culture or gram
staining
 Treatment -antibiotics ;
Remove PD catheter if unresolved in 4 days;
Exit site infection

The presence of purulent drainage with or without
erythema of the skin
Tunnel infection
Swelling, pain and redness over the subcutaneous
tunnel may be observed
Management:
Drainage culture and
Antibiotic therapy
Thank you for
your attention
Kidney transplantation

Nephrologist
Nino Maglakelidze
•Kidney transplantation is the treatment of choice for end-stage renal
Disease
•A successful kidney transplant improves the quality of life and
•Reduces the mortality risk for most patients when compared with
maintenance dialysis
•Kidney transplant patients require close follow-up after transplantation

since they are on complex immunosuppressive regimens that render
them susceptible to infection, (Bacterial, viral and fungal), malignancy
and cardiovascular disease (CVD).
Recipients of a solid organ transplant receive immunosuppressive

therapy in order to prevent rejection of the allograft.
Immunosuppressive therapy can be divided into
•induction and
•maintenance regimens.
Induction therapy
Induction therapy is administered at or around the time of

transplantation and is associated with greater immunosuppression than
maintenance therapy.
The goals of induction therapy are to prevent acute rejection and to

permit minimization or avoidance of maintenance immunosuppressive.
Induction therapy typically consists with biologic antibodies:
•Rabbit antithymocyte globuline (ATG)

•Basiliximab (CNI receptor inhibitor)
Maintenance immunosuppression
Maintenance immunosuppression is usually initiated at the time of

transplantation and continued long-term for the duration of the allograft.
Maintenance regimens can include:
•glucocorticoids,
•calcineurin inhibitors (CNIs: tacrolimus or cyclosporine)
•antimetabolic agents (mycophenolate mofetil, enteric coated

mycophnolat sodium or azathioprine)
•mTOR inhibitors, sirolimus or everolimus
•or costimulatory blockade agents - belatacept

Routine follow –up and laboratory monitoring after kidney
transplantation
•Serum creatinine, glucose, bicarbonate, and electrolytes (sodium,

potassium, calcium, magnesium, and phosphorus)
•Monitoring tacrolimus, cyclosporine, everolimus, or sirolimus levels for
patients who are taking these agents (some centers follow peak levels)
•Complete blood count and differential
•Urinalysis with, if available, a sediment examination
•Spot urine protein-to-creatinine ratio
•Fasting blood glucose
•Complete fasting lipid profile
•Parathyroid hormone (PTH) and 25-hydroxyvitamin D levels
•Urine and/or blood tests to screen for BK virus
•PCR testing for cytomegalovirus (CMV)
Transplant kidney biopsy
Allograft biopsies are usually performed in the setting of some

Evidence
•of allograft dysfunction,
•an elevated serum creatinine,
•decreased urine output,
•or worsening proteinuria

Toxicity associated with immunosuprressive agent
Many of the drugs used for maintenance immunosuppression have

well-described side effects that vary in severity.
•CNIs – Hirsutism and gingival hyperplasia (cyclosporine), alopecia

(tacrolimus), neurologic disturbances, insomnia, hypertension,
acute and chronic renal dysfunction, electrolyte abnormalities,
PTDM, hyperlipidemia, malignancies, and anemia.
•Mycophenolate – Gastrointestinal disturbances, particularly

diarrhea. Leukopenia;
•Sirolimus/everolimus – Pulmonary edema, hypertension, poor

wound healing, joint pain, anemia, edema, and
hypertriglyceridemia/hypercholesterolemia.
Azathioprine – Leukopenia, hepatitis, and anemia

Infection complications after kidney transplantation
Transplant patients are susceptible to both common and

opportunistic infections.
Common infections:
•Upper respiratory infections
•Urinary tract infection
opportunistic infections:
Cytomegalovirus (CMV).
Polyomavirus (BK and John Cunningham [JC] virus)..)
Nocardia asteroides.
Listeria monocytogenes.
Infection complications after kidney transplantation
opportunistic infections:
•Aspergillus fumigatus.
•Pneumocystis jirovecii (formerly carinii) pneumonia (PCP).
•Hepatitis B and C viruses.
•Herpes simplex virus.
•Varicella-zoster virus.
•Epstein-Barr virus.
•Mycobacterium tuberculosis
Cardiovascular complications:
•Dyslipidemia
•Obesity
•Coronary artery disease

Bone metabolism and disease
Bone disease is common among patients with chronic kidney disease

and often persists following renal transplantation.
Factors that contribute to posttransplant bone disease include:
•pretransplant renal osteodystrophy,
•glucocorticoids, calcineurin inhibitors (CNIs),
•persistent hyperparathyroidism
•calcium and
•vitamin D deficiencies.
Osteoporosis:
•Bone loss occurs rapidly following kidney transplantation.
Risk factors for osteoporosis that are specific to renal transplant

recipients include:
•the long-term use of glucocorticoids
•CNIs, and
•persistent hyperparathyroidism.
Malignancy after kidney transplantation
Renal transplant recipients are approximately three times more likely

to develop cancers than the general population.
Risk factors specific to the transplant population include:
 the type, extent and duration of immunossuppression
 viral infections (Ebshtein –bar virus)
 and pretransplant dialysis.

Malignancy after kidney transplantation
•Skin cancers
•Lip cancers
•Posttransplant lymphoproliferative disorder (PTLD)
•Anogenital cancers
•Kaposi sarcoma
•Renal carcinomas
Acute allograft rejection
Acute renal allograft rejection is a major cause of allograft dysfunction.
Acute renal allograft rejection is defined as an acute deterioration in

allograft function associated with specific pathologic changes in the
graft. There are two principal histologic forms of acute rejection:
•Acute T cell-mediated (cellular) rejection (TCMR), which is

characterized by lymphocytic infiltration of the tubules, interstitium
and, in some cases, the arterial intimae.
•Acute antibody-mediated rejection (ABMR), the diagnosis of which

requires morphologic evidence of acute tissue injury, circulating
donor-specific alloantibodies, and immunologic evidence of an
antibody-mediated process (such as C4d deposition in the allograft).
•ABMR and acute TCMR may coexist at the same time in the allograft.
Acute T-cell mediated rejection
The Banff classification of acute TCMR is divided into the following

Grades
•Borderline – Mild interstitial inflammation (<25 percent of nonsclerotic

cortical parenchyma; i0 or i1) plus any tubulitis (t1, t2, or t3)
Or significant interstitial inflammation (>25 percent of nonsclerotic
cortical parenchyma; i2 or i3) plus foci of mild tubulitis (t1)
•Type IA – Significant interstitial inflammation (>25 percent of

nonsclerotic cortical parenchyma; i2 or i3) and foci of moderate
tubulitis (t2)
•Type IB – Significant interstitial inflammation (>25 percent of

nonsclerotic cortical parenchyma; i2 or i3) and foci of severe tubulitis
(t3)
Acute T-cell mediated rejection
Type IIA – Mild-to-moderate intimal arteritis (v1) with or without

interstitial inflammation and tubulitis
Type IIB – Severe intimal arteritis comprising >25 percent of the luminal
area (v2) with or without interstitial inflammation and tubulitis
Type III – Transmural arteritis and/or arterial fibrinoid change and

necrosis of medial smooth muscle cells with accompanying
lymphocytic inflammation (v3)
Acute antibody mediated rejection
The diagnosis of ABMR requires three components:
•Histologic evidence of acute tissue injury
•Evidence of antibody interaction with vascular endothelium

(eg, C4d staining in peritubular capillaries);
•Serologic evidence of circulating donor specific Antibodies

Clinical signs of acute rejection
Most patients who have acute rejection episodes are asymptomatic.
Patients with acute allograft rejection present with an acute rise in

the serum creatinine.
Pyuria or new or worsening proteinuria may also be present
Acute rejection is confirmed by renal allograft biopsy

Treatment:
T-cell mediated rejection
•Puls-steroid 500 mg during 3-5 days - standard care for

Banff 1a, some 1b rejection;
•Consider switch CsA to > tacrolimus
•Treatment of 2a, 2b some 1b rejection with rATG

(antithymocitic globuline) 1.5mg /kg X5-14 doses;
Treatment of antibody mediated rejection
•Puls-steroid 500 mg during 3-5 days
•Plasma exchange 5-6 session followed by IVIG

(human imunoglobuline) 200mg/kg;
•+/- with rituximab 500 mg 2 doses;

Cytomegalovirus disease in kidney transplant recipients
Cytomegalovirus (CMV) is a globally widespread virus that becomes

latent following primary infection but reactivates frequently and, in the
setting of immunocompromise, causes disease in solid organ transplant
patients.
Cytomegalovirus disease in kidney transplant recipients
CMV can present in kidney transplant recipients as either active

CMV infection or CMV disease.
•Active CMV infection is defined as the presence of CMV replication

in blood regardless of whether signs or symptoms are present.
•CMV disease is defined as the presence of detectable CMV in a

clinical specimen accompanied by other clinical manifestations.
Epidemiology:
The primary risk factor for CMV infection or disease is the CMV
serostatus of the donor/recipient pair. Among United States
kidney transplant recipients, approximately 18 percent are
CMV-seronegative recipients of kidneys from CMV-seropositive
donors (CMV D+/R-), 61 percent are CMV-seropositive patients
(CMV R+), and 21 percent are CMV D-/R-
Both CMV D+/R- and CMV R+ patients are at substantial risk of CMV
reactivation, but CMV D+/R- patients are at higher risk of developing
CMV disease than CMV R+ patients.
CLINICAL MANIFESTATIONS — Active CMV infection in kidney
transplant recipients can manifest as CMV syndrome or
tissue-invasive CMV disease.
CMV syndrome is defined as the presence of detectable viral

replication in blood accompanied by attributable symptoms and signs
(eg, fever, malaise, arthralgia, leukopenia, thrombocytopenia) in the
absence of tissue-invasive disease.
Patients with tissue-invasive CMV disease have clinical symptoms and

signs of end-organ disease (eg, enteritis, colitis, hepatitis, nephritis,
pneumonitis, meningitis, encephalitis, retinitis).
Clinical presentation
Patients with tissue-invasive CMV disease may present with any of the
following syndromes:
•Enteritis and/or colitis – Nausea, vomiting, diarrhea, and/or

abdominal pain
•Hepatitis – Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) elevation with CMV viremia in the absence of
any other cause.
•Pancreatitis – Abdominal pain with elevated amylase and lipase in
the setting of CMV viremia.
•Pneumonitis – Cough, shortness of breath, and pulmonary infiltrates
on radiographic imaging plus CMV in bronchoalveolar lavage fluid.
•Meningoencephalitis – Headache, nuchal rigidity, mental status
changes, or paralysis, plus CMV in cerebrospinal fluid.
•Retinitis – Retinal edema or hemorrhage as reported by an

ophthalmologist. CMV retinitis can present with one or more
discrete foci of retinal edema or necrosis, with or without retinal
hemorrhage or inflammatory sheathing of retinal vessels on
funduscopic examination.
•Nephritis – Renal dysfunction in the presence of microbiologic and

histologic features of CMV infection in a kidney biopsy specimen.
Diagnose:
•Serologic tests : The detection of CMV-specific IgM and IgG antibodies
•Polymerase chain reaction (PCR) for the detection of CMV DNA is

the diagnostic modality of choice for most transplant clinicians.
•Very rare histopathologic examination of biopsied tissue – transplant

kidney biopsy may be necessary to diagnose tissue-invasive CMV disease
in patients who have localizing signs or symptoms .
Treatment :
•Antiviral therapy with ganciclovir, 5 mg/kg IV every 12 hours

(adjusted for renal function) for 21 days.
•But therapy can range from 14 to 28 days or longer
•Then switch to valgancilovir 900 mg once a day during 3 months ;
•Reduction of immunossupresion is mandatory (sometimes is

recommended to stop MMF);
•Patients who do not respond to reduction of immunosuppression and

to antiviral therapy may require an alternative regimen, further
reduction of immunosuppression, and/or adjunctive treatment
with cytomegalovirus immune globulin
Urinary tract infection

Nephrologist
Nino Maglakelidze
Urinary tract
infection
Upper urinary tract infection: Lower urinary tract infection:
Acute peylonphirits Cystitis,

Chronic pyelonephritis Urethritis
Renal abscess Protatitis
Perirenal abscess
Both of them can be complicated

and uncomplicated;
UTI terminology
Uncomplicated: UTI without underling renal or neurologic disease;
Complicated: UTI with underling structural, medical and neurologic

disease;
Recurrent: >3 symptomatic UTIs within 12 months following clinical

therapy;
Reinfection: recurrent UTI caused by a different pathogen at any

time
Relapse: recurrent UTI caused by same species causing original UTI

within 2 weeks after therapy.
Urinary tract infection
Cystitis
Definition:
Cystitis is inflammation of urinary bladder, caused by infection,

which can be alone or in combination with pyelonephritis.
Cystitis: Complicated and uncomplicated;

Cystitis
Classification of cystitis
Uncomplicated cystitis is limited lower urinary tract and the patient

has no underling medical problems or anatomic or physiologic
abnormalities;
Complicated cystitis is defined by coexisting upper UTI,

multiple drug resistant uropathogens, or host with special
considerations;
Cystitis
Risk factors of cystitis:
•Female sex
•Lack of circumcision is risk factor for UTI in males
•Sexual activity
•Abnormalities of the urinary system:
•Bladder stones
•Bowel and bladder dysfunction
•Neurogenic bladder
•Indwelling bladder catheter
•Immunodeficiency
Cystitis
Lower urinary tract symptoms:
Dysuria
Frequency
Urgency
New onset incontinence
Hematuria (microscopic hematuria or gross hematuria with cloth

formation)
Fever very rare

Cystitis
Laboratory evaluation
Urinalysis: dipstick
Urinary sediment microscopic examination
Urine culture
Ultrasound or CT scan
Cystitis
Bacterial infections in children and adolescence

may be caused by:
E. Coli; Klebsiella spp; Enterobacter spp and

Pseudomonas aeruginosa
Viral culture
Adenovirus, cytomegalovirus, polyomaviruses (BK
and JC);
Method: polymerase chain reaction;
Fungal culture:
Vast majority are caused by Candida spp;
Cystitis
Treatment:
Antibiotics: Trimethoprime-sulfamethoxasole; amoxicilline-

clavunate, second or third generation cephalosporines,
nitrofurantoin;
Duration of therapy:
3 days with antibiotics uncomplicated
7-14 days with antibiotics complecated;
Prostatitis
Risk factors: Acute prostatitis can occur in the setting of cystitis,

urethritis, or other urogenital tract infections.
The pathogens associated with acute prostatitis reflect the spectrum

of organisms causing cystitis, urethritis, and deeper genital tract
infections.
Protatitis
Prostatitis most frequently is caused by:
•E. coli – 58 to 88 percent
•Proteus species – 3 to 6 percent

•Other Enterobacteriaceae (Klebsiella, Enterobacter, and
Serratia species) – 3 to 11 percent
•Pseudomonas aeruginosa – 3 to 7 percent
•gram-positive cocci including Staphylococcus aureus, streptococci
and enterococci
Prostatitis:
Clinical signs:
fever, chills,
malaise,
myalgia,
dysuria,
irritative urinary symptoms (frequency, urgency, urge incontinence),
pelvic or perineal pain,
and cloudy urine.
Swelling of the acutely inflamed prostate can cause voiding symptoms.
Prostatitis
Complications:
Bacteremia
Epididymitis
Chronic bacterial prostatitis
Prostatic abscesses
and metastatic infection (eg, spinal or sacroiliac infection)

Prostatitis:
Treatment:
Patients with gram negative rods levofloxacin or ciprofloxacin may be

given with or without an aminoglycoside (gentamicin or tobramycin
5 mg/kg daily, if the creatinine clearance is normal).
Gram-positive cocci treatment with amoxicillin or ampicillin .

Of note, these regimens are not active against most Enterococcus
faecium or other ampicillin-resistant strains.
Gram-positive cocci - due to Staphylococcus

aureus or coagulase-negative staphylococci
effective oral antibiotics are cephalosporins cephalexin or
penicillinase-resistant penicillins dicloxacillin; cefazolin or nafcillin.
If there are risk factors of methicillin-resistant S. aureus, vancomycin
can be used.
Pyelonephritis
Clinical signs
•Fever
•Chills
•Flank pain
•Nausea/vomiting
•Costovertebral angle tenderness

Pyelonephritis
Complications:
•Bacteriemia
•Sepsis
•Multiple organ system dysfunction
•Shock
•Acute renal failure
•Abscesses
•Emphysematous pyelonephritis,
Pyelonephritis
Diagnosis:
•Urinalysis
•Urine culuture
Imaging :
Renal ultrasound;
MRI imaging
CT scanning
Pyelonephritis
Management :
Empiric antibacterial treatment promptly taking into account

risk factors, including previous antimicrobial use and results of
recent culture results, with antimicrobial susceptibility data.
Treatment:
•Ceftriaxone
•Piperacillin –tazobactam
•Vancomycin , Linesolid - MRSA
•Ciprofloxacin, levofloxacin
•Imepenem, meropenem and doripenem
Urinary tract obstruction
Etiology :
The causes of urinary tract obstruction vary in part based upon the
location of the obstruction
Kidney:
•Stones
• Renal cell carcinoma
Ureter:
•Stones
•Renal cell carcinoma
•Extrinsic tumors
•Retroperitoneal fibrosis
•Infection
•Obstructed stent
•Blood cloth
•Trauma
•Ectopia
Bladder:
•Blood cloth
•Edema/inflammation
•Bladder dysfunction
•Posterior urethral valve
Urethra:
•Prostatic enlargement
•Stones
•Stricture
Clinical signs:
•Pain
•Change in urine output
•Hypertension
•Hematuria and pyuria
•Increased serum creatinine
•Hyperkalemic renal tubular acidosis
Diagnosis:
•Ultrasound
•CT – computed tomography
•MRI – Magnetic Resonance Imaging
Urinary incontinence
Definition:
It is defined as involuntary or uncontrolled urination from the bladder

sufficient to cause a social or hygienic problem.
Classification of urinary incontinence:
•Stress urinary incontinence-increased Intra abdominal pressure

•Urgency incontinence – overactive bladder
•Overflow incontinence – detrusor muscle under activity
•Overflow incontinence – urinary outlet obstruction
Stress incontinence
1. Urethral hypermobility – is thought to stem from insufficient support

of the pelvic floor musculature and vaginal connective tissue to the
urethra and bladder neck. This causes the urethra and bladder neck to
lose the ability to completely close against the anterior vaginal wall.
Which increases in intra-abdominal pressure, coughing or sneezing ,the
Musculature of the urethra fails to close, leading to incontinence;
Stress incontinence
2. Intrinsic sphincteric deficiency – Intrinsic sphincteric deficiency (ISD)

is a form of stress urinary incontinence that results from a loss of
intrinsic urethral mucosal and muscular tone that normally keeps the
urethra closed. In general, ISD results from neuromuscular damage and
can be seen in women who have had multiple pelvic or incontinence
surgeries. ISD can occur in the presence or absence of urethral
hypermobility and typically results in severe urinary leakage even with
minimal increases in abdominal pressure. Treatment is aimed at
improving urethral blood flow with vaginal estrogen and with pelvic
muscle exercise or surgery.
Urgency incontinence:
1. Women with urgency incontinence experience the urge to void

immediately preceding or accompanied by involuntary leakage of
urine. "Overactive bladder" is a term that describes a syndrome of
urinary urgency with or without incontinence, which is often
accompanied by nocturia and urinary frequency.
2. Urgency incontinence is more common in older women and may be

associated with comorbide conditions that occur with age. It is believed
to result from detrusor overactivity, leading to uninhibited (involuntary)
detrusor muscle contractions during bladder filling. This may be
secondary to neurologic disorders (eg, spinal cord injury), bladder
abnormalities, or may be idiopathic.
Overflow incontinence — Overflow incontinence typically presents

with continuous urinary leakage or dribbling in the setting of incomplete
bladder emptying. Associated symptoms can include weak or
intermittent urinary stream, hesitancy, frequency, and nocturia.
When the bladder is very full, stress leakage can occur or low-amplitude
bladder contractions can be triggered resulting in symptoms similar to
stress or urgency incontinence.
Overflow incontinence is caused by detrusor underactivity or

bladder outlet obstruction.
●Detrusor underactivity – Detrusor underactivity may be caused by

impaired contractility of the detrusor muscle. Impaired urothelial
sensory function may also contribute. Studies suggest that detrusor
contractility and efficiency decrease with age. Severe detrusor
underactivity occurs in about 5 to 10 percent of older adults. Other
etiologies of detrusor underactivity include smooth muscle damage,
fibrosis, low estrogen state, peripheral neuropathy (due to diabetes
mellitus, vitamin B12 deficiency, alcoholism), and damage to the spinal
detrusor efferent nerves by pathologies affecting the spinal cord .
A subset of women with this condition can have detrusor hyperactivity

with impaired contractility (DHIC). The bladder does not
effectively contract to empty and also has low-amplitude hyperactivity,
resulting in urgency as well as overflow incontinence. DHIC is
particularly difficult to treat as any therapy for over activity results in
increased urinary retention and overflow incontinence.
●Bladder outlet obstruction – Bladder outlet obstruction in women is

generally caused by external compression of the urethra. This can occur
with fibroids that obstruct the urethra, advanced pelvic organ prolapse
(ie, beyond the hymen), or overcorrection of the urethra from prior
pelvic floor surgery. Less common causes include external masses or
tumors at the level of the bladder outlet, urethral stricture, or uterine
incarceration of a retroverted uterus
Risk factors:
•Age
•Obesity
•Mode of delivery
•Family history
•Ethnicity/race
•Others – smoking, diabetes, depression, radiation, hormone

replacement therapy, cognitive impairment;
Evaluation
•History
•Urinalysis and urine culture
•Clinical tests
Bladder stress test – In patients with suspected stress incontinence, we
perform the bladder stress test to confirm the diagnosis. This test is
performed with the patient in the standing position with a full bladder.
While the examiner visualizes the urethra by separating the
labia, the patient is asked to Valsalva and/or cough vigorously. The
clinician observes directly whether or not there is leakage from the
urethra.
Postvoid residual – measuring the PVR can be helpful when diagnosis is
uncertain, initial therapy is ineffective, or in patients where there is
concern for urinary retention and/or overflow incontinence.
Urodynamic testing ;
Management:
Behavioral
Pharmacological
Surgical
Behavioral:
• Bladder training
• Schedule voiding
•Pelvic floor exercises – Kegel Exercises
•Biofeedback – placement of vaginal pressure sensor within the

vagina that masseurs pressure and provides an audible and visual
feedback of strength of pelvic floor contraction.
Pharmacological :
1. Oestrogen
Decrease obstruction of urine flow by restoring mucosal, vaginal
and muscular integrity – quinstrediol, estrol;
2. Anticholinergic agents
Decrease spasticity of bladder, inhibit bladder contraction –
Oxybutynine
3. Alpha adrenergic blocker

Decrease Spasticity of bladder neck – Prazocine
Surgical:
1. Lifting and stabilizing the bladder or urethra to restore the

normal urethra vesicle angle
2. Periurethral bulking agents (periurethral injection of collagen,
silicon or fat)
3. Chronic catheterization
Strategies for managing UI:
•Increase our awareness of amount, timing of all fluid intake

•Reduce amount and timing of fluid intake
•Avoid blather stimulants (caffeine)
•Avoiding taking diuretics after 4pm
•Avoid constipation
•Void regularly 5-8 times
•Stop smoking
•Weight loss
Nephrolithiasis
Structure of kidney stones :
80% of renal stones composed of
•Calcium oxalate
•Calcium phosphate
20% are composed of
•Struvite
•Uric acid
•Cystine
Struvite stones
•Struvite stone compose of Magnesium amoniaphosphat and

calcium carbonate
•3-4 times more frequent in women
•Associated with urinary tract infection

Uric acid stones
Gout
Increased serum uric acid level
Acid urine
Inherited condition
Cystine stones
•Genetic autosomal recessive disease
•Urine acid
•Genetic defect of absorption of cystine in proximal tubules of kidney
Diagnosis:
•Genetic analysis SLC3A1 and SLC7A9
•To detect cystine in urine, cystine level in urine >400mg/day
•Screening for cianidpruside

Calcium oxalate stones
Primary hyperoxaluria :
•Type I 80%
•Type II 10%
•Type III 5%
Primary hyperoxaluria is genetic autosomal recessive
Diagnosis:
Genetic test
Measure oxalates in 24 hour urine sample

Pathogenesis of primary hyperoxaluria
High production of oxalates causes oxalate storage in different

organs – kidneys;
Kidney stone formation risk factor :
Hypercalciuria
Hyperoxaluria
Low level of citrate in urine

Clinical signs of renal calculi
Pain
Hematuria
Nausea, vomiting
Hydronephrosis
Clinical laboratory analysis
•Measurement of iPTH
•Microscopic analysis of renal stone if evaluable
•Urine pH
•Calcium in urine
•Oxalate in urine
•Uric acid
•Cytrite in urine
•Sodium in urine
•Potassium in urine
Diagnosis of renal calculi
Ultrasound
CT scan
MRI
Intravenous pyelography
Preventive measures
Avoid protein intake; usually preotein is restricted to 60 g; it

decreases urinary excretion of calcium and uric acid
A sodium intake of 3 to 4 g/day is recommended. High sodium

food should be reduced because sodium competes with calcium
reabsorption in the kidneys.
Avoid intake of oxalate – containing foods (Strawberries, spinach,

tea, peanuts and etc)
During the day drink fluid every 1 to 2 hours;

Treatment of uric acid stones:
I. Alopurinol
II. Thiasides
III. Potassium citrate

Management of renal calculi:
Pain killers:
NSAds
Analgetics
 Opioide analgetics
Surgical management:
Laser lithotripsy
Rigid and elastic uretheroscope (URS)
Thank you for
your attention

Nephrology All PPTs

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Acute kidney injury

Tbilisi referral hospital, Tbilisi, Georgia

•Universal definition and staging system has been proposed to allow

Acute Kidney injury is a syndrome characterized by:

•Sudden decline in GFR (hours and days)

•Retention of nitrogenous wastes products

•Disturbance in extracellular volume and

•Disturbance in electrolytes and acid base homeostasis

KDIGO – The Kidney Disease Improving Global Outcomes

•Increase in serum creatinine and

• Decrees of urine output;

KDIGO – definition of AKI

•Increase in serum creatinine by >0.3mg/dl (>26.5mmol/l )within

•Increase in serum creatinine to 1.5 times baseline, which is known

•Urine volume <0.5mg/kg/hour for six hours;

Stage 1 – increase in serum creatinine to 1.5 to 1.9 times baseline

Stage 2 - increase in serum creatinine to 2.0 to 2.9 times

Stage 3 - increase in serum creatinine to 3.0 to 4.0 times baseline

The Acute Dialysis Quality Initiative (ADQI)group developed

The RIFLE criteria consists of three graded levels:

Two outcome measures:

End Stage Renal Disease

•Up to 30% of patients in intensive care unit develop AKI defined

The epidemiology of AKI tremendously differs between developed and

•Renal artery stenosis

•Pre renal AKI is most common 55% form AKI

•Represents a physiologic response to mild to moderate renal

•Pre renal AKI is rapidly reversible upon restoration of renal blood

•More sever hypoperfusion may lead to ischemic injury of renal

Hypovolemia leads to glomerular hypoperfusion, but filtration rate

During states of more severe hypoperfusion, these compensatory

•Antifungal and antiviral drugs

Accounts around 40% of all AKI

•Glomerular : FSGS, Membranoprolipherative glomerulonephritis,

• Interstitial and Tubular - ATN, ACE or AR blockers, NSADs, radio

Postrenal AKI accounts 5 % of cases

•Ureteric : calculi, blood clot, cancer, external compression

•Bladder neck : neurogenic bladder, prostatic hypertrophy, calculi,

•Urethra: stricture, congenital valve;

Careful history is essential:

Exposure of nephrotoxins and drugs;

Signs of volume depletion suggest prerenal etiology of AKI

Skin rashes may indicate acute interstitial nephritis

Blue toe suggests atheroemboli

Significant volume overload and signs of heart failure suggest

Ascitis and jaundice suggest liver disease with portal hypertension

Ischemia or trauma of legs may indicate rhabdomyolysis

Anuria may indicate post renal causes

A history of prostatic disease

Family history of renal diseases

Past and present use of medications

Recent surgical or radiologic procedures

Presence of few formed elements or hyaline casts is suggestive of

Many RBC s may suggests calculi, tumor, infection;

Eosinophiluria suggest acute interstitial nephritis;

Patient with hematuria associated with proteinuria

Patients with sudden worsen of serum creatinine rapidly

Pigmented casts without erythrocytes in the sediment from urine

RBC and RBC cast suggests glomerular disease;

Urine osmolality and specific gravity is decreased in ATN and post-

Serum K+ and other electrolytes

Fractional excretion of Na+ : is ratio of urine –to plasma Na; If

Ultrasonography helps to see the presence of two kidneys,

For detecting hydronephrosis