Year 4 Module C

Medicine
Nephrology
Done by
Elaf BaharethaHatimialmagrabi
TABLE OF CONTENTS
Introduction to Nephrology ................................ 3
Investigations ............................................................. 3
CBC ........................................................................ 3
Glomerular filtration rate (GFR) ............................ 3
Urinalysis ............................................................... 3
Proteinuria ................................................................. 4
Benign proteinuria ................................................. 5
Acute Kidney Injury ............................................ 7
Causes of AKI .............................................................. 8
Pre-renal AKI .......................................................... 8
Renal (Intrinsic) AKI ............................................... 9
Post-renal AKI ...................................................... 11
Chronic Kidney Disease .................................... 15
Dialysis ..................................................................... 20
Uremia ..................................................................... 21
Glomerular Diseases......................................... 22
Nephrotic syndrome ................................................ 24
Nephritic Syndrome ................................................. 26
Additional topic ........................................................ 31
Acute Interstitial nephritis ................................... 31
Lupus nephritis .................................................... 32
IgA nephropathy (Berger disease) ....................... 33
Electrolyte Imbalance ....................................... 34
Sodium Disorders (Na+) ........................................... 34
Hyponatremia ...................................................... 35
Syndrome of inappropriate antidiuretic hormone
secretion (SIADH) ...................................................... 36
Hypernatremia ..................................................... 37
Diabetes Insipidus ................................................ 38
Potassium (K+) ......................................................... 39
Hyperkalemia ....................................................... 39
Hyperkalemic emergency .................................... 42
Hypokalemia ........................................................ 43
Acid-Base Balance Disorders ............................. 48
Metabolic acidosis.................................................... 48
Metabolic alkalosis ................................................... 49
Respiratory acidosis ................................................. 49
Respiratory Alkalosis ................................................ 49
Additional Topics ............................................. 50
Renal artery stenosis ................................................ 50
Polycystic kidney disease ......................................... 51
Hydronephrosis ........................................................ 52
Introduction to Nephrology
Investigations for the patient with renal disease and chronic kidney disease
Typical range for serum creatinine is:
For adult men, 0.74 to 1.35 mg/dL (65.4 to 119.3 micromoles/L)
For adult women, 0.59 to 1.04 mg/dL (52.2 to 91.9 micromoles/L)
Blood urea nitrogen (BUN) test:
Around 6 to 24 mg/dL (2.1 to 8.5 mmol/L)

CBC
Normocytic normochromic anemia: associated with chronic kidney disease due to decreased erythropoietin
Iron Deficiency anemia
Hemolytic anemia: TTP, HUS. And SLE
Pancytopenia: associated with SLE

Glomerular filtration rate (GFR)

Most accurate test to determine kidney function and stage the chronic kidney disease
GFR may be measured directly by injecting and measuring the clearance of compounds such as inulin or radio
labeled ethylenediaminetetracetic acid which are completely filtered at the glomerulus and are not secreted or
reabsorbed by the renal tubules
Normal GFR is more or equal to 90
Symptoms of renal failure starts from grade 3 to 5

Urinalysis
Screening for the presence of blood, protein, glucose, ketones, nitrate and leukocytes and to assess pH and
osmolality of urine can be achieved by dipstick testing

Proteinuria
Microalbuminuria 30 - 300 mg/day

Trace proteinuria 300 - 1000 mg/day

Mild proteinuria (from here we can detect it in urine dipstick) 1 g/day

Nephrotic range proteinuria 3.5 g/day

Note about the table

Albumin-creatinine ratio is the best test for Microalbuminuria
Annual screening for diabetic patients

Urine dipstick positive for hematuria

It is present in nephritic syndrome
Bladder origin: Intact RBCs
Kidney origin: Dysmorphic RBC or RBC cast
Others:
WBC; infection
Abnormal epithelial cells; tumor
Haemoglobinuria; in intravascular hemolysis
Myoglobinuria (brown urine); Rhabdomyolysis
Casts on urinalysis
Cast Indicates

Dehydration or accumulation of normal protein tubule

Hyaline casts
History of AKI; pre-renal cause

RBC cast Glomerular disease

Acute Tubular necrosis (ATN)

Muddy brown granular, dirty cast
Patient presents with AKI, oliguria

Acute interstitial nephritis

White blood cell cast
History of new drug administrations

Ethylene glycol (suicide attempt)

Calcium oxalate crystals
AKI-crystals induced

Tumor lysis syndrome

Uric acid crystal
Known case of lymphoma that started on chemotherapy

Broad cast Chronic kidney disease

Proteinuria
It is defined as a urinary protein excretion of >150 mg/day.
In a healthy adults individuals, normally 150mg/day of protein can be excreted on the urine

Diagnostics
Urinalysis
Urine dipstick: repeat to rule out transient proteinuria (primarily detects albumin), single test is not enough
to know the amount of protein in urine due to some factors that can affect the quantity such as
hypertension, hydration status and exercise. Findings of urine dipstick:
+ 1g

++ 2g

+++ 3g

++++ 4g or more
Sulfosalicylic acid test: sulfosalicylic acid is added to urine to measure total urine proteins (not specific for
albumin)
24-hour urine collection or urine protein-to-creatinine ratio (albumin-creatinine ratio) in a spot urine
sample to rule out orthostatic proteinuria
Urine sediment to rule out glomerular disease
Electrophoresis to rule out tubulointerstitial diseases and multiple myeloma
Proteinuria can cause foamy urine

Important note
24-hour urine collection is the most accurate and best modality for proteinuria
Albumin-creatinine ratio is the best screening modality of microalbuminuria; the urinalysis is taken by a single
test
Classification
Urine albumin excretion of 30 300
mg/day
Microalbuminuria Diagnosis is made if two out of three
(All Diabetic patients must be screened once tests are positive.
per year by albumin-creatinine ratio test) Early symptom of diabetic
nephropathy and hypertensive
According to quantity nephropathy

Urine albumin excretion >300 mg/day

Overt proteinuria (formerly
"macroalbuminuria")
Standard urine dipstick tests can be used
for detection.
Nephrotic syndrome: massive proteinuria
(>3.5 g/24 h), hypoalbuminemia, edema,
and hyperlipidemia

(e.g., minimal change disease,

IgA nephropathy)
Glomerular proteinuria Non-
(e.g., rapidly
progressive glomerulonephritis, lupus
nephritis, amyloid nephropathy)

Tubulointerstitial nephritis, analgesics

Tubular proteinuria
nephropathy, acute renal failure
According to origin
Found in diseases that affect both the
Mixed proteinuria glomeruli and the tubules (e.g., chronic
renal failure)

Prerenal proteinuria (or overflow Hemoglobinuria (in hemolysis)

proteinuria) Myoglobinuria (in rhabdomyolysis)

Proteins that are being produced in the

Postrenal proteinuria tubules (Tamm-Horsfall protein)
(e.g., trauma or inflammation)

Benign proteinuria (Important)

Defined as isolated proteinuria <3.5 g/day
Very common; mostly affects younger individuals
No treatment necessary

Types of benign proteinuria

Orthostatic proteinuria (postural proteinuria): increased protein excretion only in the upright position
(standing)
Happens with fever or exercise
Women can present with mild proteinuria due to vaginal discharge
Transient proteinuria
Most common cause of isolated proteinuria in children, Causes:
Heavy exertion/stress
Fever
Seizures
Exposure to cold temperatures
 High grade
proteinuria (more Do renal biopsy for further investigation
or equals 1g)
A repeated
Does the patient have:
proteinuria If yes: do renal biopsy
Abnormal renal
on dipstick If no: do urine analysis, blood pressure
Moderate or low function test?
and creatinine (GFR) every 6-12 months
grade (less than 1g) HTN or DM?
with evaluation if anything happen
Family history of renal
(close follow-up)
diseases?

Reminder of hematuria presents in:

Causes:
Infections (e.g., pyelonephritis, urethritis, cystitis)
Stones (calcifications)
Renal cell carcinoma, they present with (Triad):
Painless hematuria (most common)
Flank pain
Palpable flank mass
Trauma
To know the cause of hematuria, we do:
Urine sample investigation, Findings:
Casts of dysmorphic RBCs (Glomerular origin)

They present with change in urine color (dark red or pink)

Acute Kidney Injury
Sources: AMBOSS ( video included), Boards and Beyond, Step-up to Medicine, The slides,

Objectives (of acute and chronic kidney injury)

Knowledge
1. Identify the causes of acute and chronic kidney injury.
2. Explain the pathophysiology of the different causes of acute
and chronic kidney injury.
3. Describe the pathogenesis of different clinical changes in
chronic kidney disease.
4. Differentiate clinically between acute kidney injury and
chronic kidney disease.
5. Describe different stages of chronic kidney disease.
6. Describe the principle of hemodialysis in the management of
chronic kidney disease.
7. Recognize the indications and types of renal replacement
therapy (RRT).
Cognitive Skills
1. Choose the most appropriate investigations to diagnose acute
kidney injury and chronic kidney disease (blood, urine, and
imaging) based on the available clinical data
2. Interpret blood tests (CBC, renal function, electrolytes), and
urine tests.
3. Formulate and prioritize a differential diagnosis for the causes
of acute kidney injury and chronic kidney disease
4. Develop an evidence-based pharmacological and
nonpharmacological management plan for acute kidney injury
and chronic kidney disease
5. Appropriately prioritize referral for Nephrology service
6. Demonstrate the appropriate skills patient education

Definition
When there is a sudden, sustained and acute reversible loss of the kidney function that happens over a few days
leading to a retention of urea & nitrogenous waste product (e.g., Ammonia and uric acid) and dysregulation of
extracellular volume & electrolytes

Risk factors for AKI

1. Age >75 years old 7. Hypotension
2. Chronic kidney disease (Acute on top of chronic) 8. Sepsis
3. Previous episode of AKI 9. Hypovolemia
4. Heart failure 10. Nephrotoxins
5. Liver disease 11. Debility and dementia
6. Diabetes mellitus

General clinical features of AKI

1. Signs and symptoms from loss of kidney function
a. Low urine output, edema, hypertension or discolored urine
b. Weakness and easy fatigability
c. Anorexia and vomiting
d. Mental status changes or seizures
2. Asymptomatic
a. Elevation in the plasma creatinine
b. Abnormalities on urinalysis
3. Sign and symptoms from a primary disease
a. Systemic manifestation
b. Arthralgias
c. Rash
Diagnostic criteria for AKI is (kidney disease: Improving Global Outcomes or KDIGO guidelines) or RIFLE criteria
The RIFLE criteria of AKI is
1. Risk of getting the disease is considered stage 1 or Class R
2. Injury
3. Failure
4. Persistent AKI or Loss of renal function for more than 4 weeks (requires dialysis)
5. End stage renal disease and his loss of kidney function is for more than 3 months (requires dialysis)

The KDIGO guidelines define AKI as

An increase in serum creatinine of at least 0.3mg/dL within 48 hours
Or as an increase in serum creatinine by 1.5 times the baseline serum creatinine within the last 7 days
Or when the urine volume has been less than 0.5 mL/Kg/hr for six hours.

Based on this criteria, there are 3 stages of AKI:

1. Stage 1 (is mild type of AKI)
a. Serum creatinine is >1.5 to 1.9 times the baseline serum creatinine (folds)
b. Urine output is below 0.5 mL/Kg/hrs for 6 to 12 hours.
2. Stage 2
a. Serum creatinine is >2 to 2.9 times the baseline serum creatinine (folds)
b. Urine output is less than 0.5 mL/Kg/hrs for more than or equal to 12 hours.
3. Stage 3 (is severe type of AKI)
a. Serum creatinine is up to 3 times the baseline serum creatinine (folds)
b. Urine output is less than 0.3 mL/Kg/hrs for more than or equal to 24 hours
c. Anuria (<100mL/day) for more than 12 hours or during renal replacement therapy.
d. Initiation of renal replacement therapy

Note
The numbers are not very important to memorize
Any kidney injury they will have oliguria (urine output is <400mL/day or 20mL/hr)
If a patient with Acute kidney injury with high creatinine level but he has polyurea then he is in a recovery stage.

Important note
Glomerular filtration rate: is the rate at which fluid is filtered by the kidneys
Normal GFR range
Male: 95 145 mL/min/1.73m2
Female: 75 125 mL/min/1.73m2
The GFR is used to estimate kidney function and to stage chronic kidney disease.

Causes of AKI
Pre-renal AKI
a. There is decreased in systemic arterial blood flow into the kidneys (impaired perfusion) leading to renal
ischemia due to:

o Prolonged hypotension causes acute tubular necrosis

e.g.,
Hypovolemic states like an
o Acute hemorrhage
o Gastrointestinal losses (diarrhea and vomiting)
o Renal losses (like taking diuretics or osmotic diuresis in hyperglycemia)
 o Hypercalcemia
o Dermal losses (e.g., burns)
o Sequestration of fluid (also known as third-spacing) like with acute pancreatitis or sepsis.
b. Azotemia with Increased BUN: creatinine ratio (>20:1)
c. Fractional excretion of Na <1% (the amount of sodium that leaves the body through urine compared to the
amount filtered and reabsorbed by the kidney)
d. Some medications such as NSAIDs, ACE-inhibitors, ARBs, cyclosporine and iodinated contrast can damage
renal blood vessels leading to ischemia and causing prerenal AKI.
e. Prolonged prerenal injury leads to intrinsic renal injury, as decreased renal perfusion causes tubular necrosis.
f. Clinical features of pre-renal AKI
Tachycardia (A reflex tachycardia that is caused by the hypotension)
Postural Hypotension
o Definition: A 20 mm Hg drop in systolic blood pressure or 10 mm Hg drop in diastolic blood pressure
that occurs within 5 minutes after rising from a supine or seated position.
Reduced skin turgor (elasticity of the skin)
o Often used as a way to check for dehydration.
Signs of volume depletion (e.g., Weak rapid pulse, flattened neck veins and the other features mentioned
in this part).
Cool extremities
Delayed capillary return
Metabolic acidosis (could be alkalosis secondary to vomiting)
Hyperkalemia
Oliguria/Anuria
The renin-angiotensin-aldosterone system is activated, leading to water and sodium retention.
Weight gain and edema due to positive water and sodium balance

o
cardiorenal syndrome causing signs of heart failure, like hypotension, fatigue, dyspnea, and
peripheral edema.
o
hepatorenal syndrome causing individuals to have hypotension and signs of liver disease like
splenomegaly, cirrhosis, caput medusae, ascites and peripheral edema.
Important Notes
Elevated BUN seen with: Taking catabolic drugs (Steroids), GI/soft tissue bleeding (Due to RBC digestion and
reabsorption of urea) and dietary protein intake.
Elevated creatinine seen with: Increased muscle breakdown and various drugs.

Renal (Intrinsic) AKI

a. Damage to the tubules, the glomerulus, or the kidney interstitium (which is the space between tubules) or
vascular damage. So, glomerular filtration and tubular function are significantly impaired. Thus, the kidneys
are unable to concentrate urine effectively.
b. Decreased BUN: creatinine ratio (<20:1)
c. Fractional excretion of Na >2%
d. It is caused by:
Acute tubular necrosis (ATN)
o Ischemia due to prolonged hypotension or prolonged prerenal azotemia
o Nephrotoxic drugs: e.g., radiographic contrast agents, and new drugs used such as:
a. Aminoglycoside (Gentamicin): it is a nephrotoxic, ototoxic and neurotoxic
o Endogenous toxins: (e.g., hemoglobin in intravascular hemolysis, myoglobin in rhabdomyolysis)
o Muddy brown granular casts
 Acute interstitial nephritis
o Medication (e.g., antibiotics (especially amoxicillin), phenytoin, interferon, PPIs, NSAIDs,
cyclosporine)
o Infection (Bacterial, fungi and viral)
o Infiltrative diseases: (e.g., sarcoidosis, amyloidosis)
o Consider a type I or type IV hypersensitivity reaction and the early symptoms include fever, rash and
eosinophilia.
Acute Glomerulonephritis
o Usually will need to perform renal biopsy
o Treatment depends on the disease but generally involve immunosuppressive therapy and steroids.
Vascular diseases such as
o Small vessel vasculitis
o Hemolytic uremic syndrome (HUS)
o Thrombotic thrombocytopenic purpura (TTP)
Contrast-induced nephropathy
o It is an AKI after IV administration of iodinated contrast medium
o Risk factors
a. Chronic kidney disease (CKD): in patients with diabetes mellitus, multiple myeloma
b. Congestive heart failure, arterial hypotension
c. Nephrotoxic drugs: NSAIDs
d. Anemia
e. Dehydration
o Course
a. It occurs after more than 24 hours post exposure to contrast, and the creatinine peaks the
highest after 3 5 days after injury and usually falls back to the baseline level within 1 week.
b. The course is typically mild because end-stage renal disease usually only occurs in patients with
pre-existing CKD.
c. Non-oliguric, FENa <1%
o Prevention of contrast-induced nephropathy
a. Always evaluate kidney function before administering a contrast agent.
b. Use a low dose and low concentration of contrast medium.
c. The patient should discontinue nephrotoxic substances before administration.
d. Ensure hydration: isotonic NaCl before and after administration of contrast medium
e. N-Acetylcysteine (old method)
Studies investigating acetylcysteine showed that it has NO effectiveness in preventing
contrast-induced nephropathy
e. Clinical features
Hematuria and proteinuria (which are symptoms of glomerular diseases)
Clinical manifestation of underlying disease such as SLE which will cause lupus nephritis or systemic
vasculitis
Cause signs of nephrotic syndrome, such as peripheral or periorbital edema even ascites.

Important note: What is Rhabdomyolysis?

It is a skeletal muscle breakdown commonly caused by trauma (crush injuries). Thus, it releases the muscle fiber
content (myoglobin) which is a toxic substance to the kidneys which can lead to AKI via tubular damage and
obstruction
Diagnose with high serum CK, urine dipstick (+) for myoglobinuria, without RBCs on microscopy and pigmented

metabolic acidosis
 Clinical features:
Classic triad
Myalgia
Generalized weakness
Darkened urine
Nonspecific symptoms: nausea, vomiting
Signs of complications: AKI, compartment syndrome, cardiac arrhythmias

Post-renal AKI
a. Any condition that results in bilateral obstruction of urinary flow (with intact kidney) from the renal tubule to the
urethra which causes a buildup of urine and pressure that backs up into the kidney (Tubules).
b. Obstruction to urine flow will cause:
Increased tubular pressure
Vasoconstriction
Decreased renal blood flow
c. Both BUN and creatinine are elevated
Both kidneys must be obstructed (e.g., prostatic enlargement) for creatinine to rise
d. Decrease GFR
e. Decreased BUN: Creatinine ratio (<20:1)
f.
g. Renal function can be restored if obstruction is relieved before the kidneys are damaged but if left untreated it
can lead to ATN
h. It is caused by
Benign prostatic hyperplasia (BPH) causes urethral obstruction
Urinary calculi or nephrolithiasis
Tumors: e.g., bladder, prostate (in male), cervical cancer (in female) or intra-abdominal tumors that
compress the ureter
o can present with unintentional weight loss and fatigue.
Urethral stricture or congenital malformations such as posterior urethral valves
Meatal stenosis or phimosis
Retroperitoneal fibrosis
i. Clinical features will be
On physical examination, Abdominal distension is present, suprapubic tenderness, bladder enlargement
and dullness on percussion
When inserting a foley catheter a large amount of urine will be out and symptoms will be relieved
An Ultrasound KUB confirms the diagnosis by looking for the obstruction and hydronephrosis or
hydroureter
Loin pain of stones are present
Hematuria
Obstructive ureteral kidney stones, the individual has renal colic along with anuria if both ureters are
completely obstructed
Urethral stones, the individual has pain in the urethra and anuria

Important note
If only one ureter is obstructed (called unilateral obstruction) and the other kidney is working fine, then renal
function is usually preserved
But if both ureters are obstructed like when there are stones in both ureters (called bilateral obstruction) or if
Complication of AKI
ECF volume expansion and causing pulmonary edema
Treat with diuretic (furosemide)
Hyperkalemia
Due to low excretion of the potassium and the movement of potassium from ICF to ECF due to tissue
destruction and acidosis
Metabolic acidosis
Increased anion gap
If severe, treat with sodium bicarbonate
Hypocalcemia
Loss the ability to form active vitamin D
Rapid development of PTH resistance
Hyponatremia (If water intake is greater than body losses or if a volume depleted patient consumes excessive
hypotonic solution) or hypernatremia (In hypovolemic states)
Hyperphosphatemia and hyperuricemia
Volume overload
Uremia (Toxic end product of metabolism accumulation), leading to:
Platelet dysfunction
Immune dysfunction
Uremic pericarditis
Uremic encephalitis
Infection
Pneumonia, UTI, wound infection and sepsis

Investigations in AKI
Blood urea nitrogen and serum creatinine
If a patient came with high creatinine look for previous creatinine level reading to know if this is AKI or CKD.
Serum electrolytes especially potassium, calcium and phosphate
Patients with AKI can develop hyperka
Calcium can be decreased in rhabdomyolysis and increase in multiple myeloma
Patients with secondary hyperparathyroidism they have chronic kidney disease which will cause the calcium
to decrease but in the tertiary hyperparathyroidism is it due to prolonged CKD and it will lead to increase in
calcium levels than in the secondary type (Autonomy)
Tumor lysis syndrome: it will cause AKI, the patient will have a history of taking chemotherapy. The
chemotherapy breaks down the cancer cells and other cells causing its content to flush out such as
potassium and uric acid will increase but calcium will decrease
Albumin which is a negative phase reactant (Any inflammation it will be decreased)
Will decrease in either nephrotic syndrome or sepsis
Full blood count and clotting screen
Low platelet could indicate DIC especially in case of sepsis
Acute blood loss can cause AKI due to decrease in the blood flow to the kidneys
Urinalysis
To see nitrite in the urine, Normally the urine contains Nitrates but if a bacteria enters the urinary tract it will
turn the nitrate into nitrite and it will be a sign of urinary tract infection (UTI)
Hematuria indicates glomerulonephritis, tumor in the urinary tract (Bladder cancer) or bleeding disorder
A dipstick positive test for protein (3+, 4+) suggests intrinsic renal failure due to glomerular insult
Urine microscopy (we need to see the cast type to make the diagnosis)
Dysmorphic red cells indicates glomerulonephritis
Muddy brown or Sediment with coarse granular casts in ATN
Hyaline cast can be seen in pre-renal causes
 WBC cast indicates renal parenchymal inflammation (pyelonephritis) or infection
WBC casts + Hansel stain indicates Acute Interstitial Nephritis
Crystal indicates drug-induced, uric acid nephropathy or presence of stones
Waxy cast in chronic kidney disease
Fatty cast indicates nephrotic syndrome
Urine culture to rule out infection
Urine chemistry (FENa or FEUrea, osmolality, urine Na, urine Cr and urine BUN) used to distinguish between
different forms of AKI
Renal ultrasound
For any patient with AKI to rule out obstruction or post renal cause
Hydronephrosis/hydroureter or enlarged bladder will be seen
Asymmetric kidney in renovascular or developmental (congenital) disease
Small kidney in chronic kidney disease
Important note: Diabetic patients with CKD their kidney will be preserved not small, that's why we
exclude CKD for them
HIV, Amyloidosis and cystic kidney with CKD will not have small kidneys
Chest X-Ray
In CKD patient or acute on top of chronic renal disease
Pulmonary edema in fluid overload
Globular heart in pericardial (uremic) effusion
Serology
For HIV and hepatitis for patients who will perform dialysis
Autoimmune profile if indicated
Renal biopsy if you suspect acute GN or acute allergic interstitial nephritis
Renal arteriography for renal artery occlusion but only performed for specific therapy
ECG; indicated if
Patient is more than 40 years old
Electrolytes abnormalities (e.g., hyperkalemia)
Risk of cardiovascular disease (CKD is an independent risk factor for cardiovascular disease)
Uremic pericarditis

Important note: FENa is most useful if oliguria is present

FENa<1% indicates pre-renal AKI
It can be high in selected cases:
Pre-existing CKD: FENa 2-3 even without tubular injury
Poor sensitivity with diuretics use
FENa>1% indicates intrinsic causes of AKI
It can be low in selected cases:
Contrast-induced nephropathy
Acute GN
Myoglobin induced ATN

General treatment of AKI

AKI management is primarily supportive. Currently, there are no specific pharmacotherapies for AKI
Avoid medications that decrease blood flow (NSAIDs) and nephrotoxic medications (e.g., Aminoglycosides) and
reduce doses of therapeutic drugs according to the level of renal function
Avoid co-administering RAAS inhibitors and NSAIDs in patients with reduced renal perfusion (e.g., in
congestive heart failure, renal artery stenosis) because doing so can significantly decrease their GFR.
Match fluid intake to urine output (with additional 500 ml to cover insensible losses once patient is euvolemic
Measure body weight on regular basis as a guide to fluid requirements and the see overload development
 Correct fluid imbalance
If volume is depleted, Give IV fluids. However, many patients with AKI are volume overloaded (especially if
they are oliguric or anuric) so diuresis is necessary.
BUT be sure from cardiac history of the patient, do not give excessive fluid to a patient with CHF
Avoid pulmonary edema by monitoring the central venous pressure
Correct electrolytes disturbance
Correct hyperkalemia (if >6.5 mmol/L) by glucose and insulin
Correct acidosis if pH is <7 by sodium bicarbonate
Order dialysis if symptomatic uremia, intractable acidemia, hyperkalemia or volume overload develop.
Indication for urgent dialysis (AEIOU):
Acidosis, Electrolytes, Intoxication (overdoses), Volume Overload, Uremia

Treatment of pre-renal AKI

Treat underlying disorder (Hypovolemic or cardiogenic shock)
Fluids to maintain euvolemia and restore blood pressure (not given for patients with edema or ascites), NS is
preferred unless acidemia is present (may worsen with hyperchloremia) so give ringer lactate to avoid the
hyperchloremic acidosis
Discontinuation of antagonizing medications (NSAIDs, RAAS blockers or diuretics)
Treatment of Intrinsic renal AKI
Supportive therapy if ATN develops and the renal function generally recovers
Elimination of the causing agent
If oliguric, a trial of furosemide may help to increase urine flow
Treatment of post-renal AKI
Bladder catheterization to decompress the urinary tract (diagnostic and therapeutic)

Indications for renal replacement therapy (hemodialysis) in AKI

Refractory hyperkalemia
Refractory volume overload
Refractory metabolic acidosis
Uremic encephalopathy
Uremic pericarditis
Certain intoxications such as in CKD patients who got overdosed or acute poisoning by ethylene glycol
Modalities include:
Hemodialysis and/or hemofiltration (i.e., by CRRT or intermittent hemodialysis)
Peritoneal dialysis

Recovery from AKI

1. Gradual return of urine output
2. Steady improvement in plasma biochemistry
3. Be aware of diuretic phase (Recovery phase)
a. Patient may need sodium chloride, sodium bicarbonate, potassium chloride and phosphate to compensate
for increased urinary losses (it happens due to fluid overload)
Chronic Kidney Disease
Sources: AMBOSS ( video included), Boards and Beyond, Step-up to Medicine, Davidson, The slides,

Definition
It is defined as either decreased kidney function (GFR<60 mL/min) or an abnormality of kidney structure or function
that persists for > 3 months regardless of the cause.

Risk Factors of CKD

1. Diabetes mellitus is the most common cause (Diabetic nephropathy)
2. Hypertension (Hypertensive nephropathy)
3. Glomerular disease (Glomerulonephritis)
4. Interstitial disease
5. Obesity
6. Advanced age (>60 years of age)
7. Substance use (smoking, alcohol, recreational drugs)
8. Acute kidney injury
a. Any of the causes of AKI can lead to CKD if prolonged or if treatment is delayed
9. Family history of CKD
10. Renovascular disease
11. Systemic inflammatory disease (SLE, vasculitis)
12.
a. is a genetic condition that is characterized by kidney disease, hearing loss (deafness) and
eye abnormalities. They experience a progressive loss of kidney function and they could have hematuria.

Clinical features of CKD

Patients are often asymptomatic and their typical presentation is raised urea and creatinine (which are found incidentally
during routine blood tests) until later stages due to the exceptional compensatory mechanisms of the kidneys
If the case got worse and GFR falls below 30, the uremic symptoms will show up (Encephalitis, pericarditis or
volume overload)
Early symptom is Nocturia (increase urination during night)
Tiredness and breathlessness (due to anemia or fluid overload)
Advanced renal failure: Kussmaul breathing (due to acidosis), muscular twitching, fits (due to encephalitis),
drowsiness and coma.
In details:
1. Cardiovascular
a. Hypertension: Secondary to salt and water retention
i. Decreased GFR will stimulate renin-angiotensin system and aldosterone secretion to increase which
leads to an increase in BP
ii. Renal failure is the most common cause of secondary hypertension
b. Congestive heart failure due to volume overload, HTN and anemia
c. Pulmonary (interstitial pulmonary edema) and peripheral edema
d. Pericarditis (uremic)
i. Clinical features: chest pain worsened by inhalation
ii. Physical examination findings:
1. Friction rub on auscultation
2. ECG changes normally seen in nonuremic pericarditis (e.g., diffuse ST-segment elevation) are
not usually seen
iii. Pleuritis
 2. GI (due to uremia)
a. Nausea, vomiting and anorexia (loss of appetite)
b. Uremic fetor: characteristic ammonia- or urine-like breath odour
3. Neurologic
a. Lethargy, confusion, peripheral neuropathy, somnolence (drowsiness) and uremic seizures
b. Weakness, asterixis (tremor of the hand and best seen when the person attempts to extend their wrists)
and hyperreflexia
c. Restless legs sign: Neuropathic pain in the legs that is only relieved by movement.
d. Hypocalcemia (from decreased vitamin D conversion) can cause lethargy, confusion and tetany
4. Hematologic
a.
destruction of RBCs)
b. fection
c. Bleeding due to platelet dysfunction (due to uremia)
i.
5. Endocrine/Metabolic
a. Calcium-phosphorus disturbance
i. Decreased renal clearance of phosphate leads to hyperphosphatemia which results in decreased
renal production of 1,25-dihydroxy vitamin D leads to hypocalcemia which causes secondary
hyperparathyroidism.
ii. Long-standing secondary hyperparathyroidism can cause hypercalcemia due to a parathyroid gland
secreting excess PTH without responsiveness to plasma calcium levels, known as tertiary
hyperparathyroidism.
iii. Secondary hyperparathyroidism causes renal osteodystrophy, causing weakness of the bones and
fractures.
iv. Hyperphosphatemia causes phosphate and calcium to precipitate which causes vascular
calcification (Calciphylaxis) resulting in necrotic skin lesions.
v. Uremic frost where urea crystals can deposit in the skin and they look like powdery snowflakes.
vi. When the kidney starts to sense a lower than normal amount of fluid getting filtered, they respond
by releasing the renin hormone to increase blood pressure (hypertension)
b. Hypothalamic-pituitary disturbance and gonadal response to sex hormone
i. In men: Decreased testosterone
ii. In women: Amenorrhea, infertility and hyperprolactinemia
c. Pruritus
i. Uremic frost: uremia leads to high levels of urea secreted in the sweat, the evaporation of which
may result in tiny crystallized yellow-white urea deposits on the skin.
6. Fluid and electrolytes problems
a. Volume overload - Can cause pulmonary edema
b. Hyperkalemia - due to decreased urinary secretion and can cause cardiac arrythmias
c. Hypermagnesemia - Secondary to decrease urinary loss
d. Hyperphosphatemia
e. Metabolic acidosis - Loss of renal mass it will lead to decreased production of ammonia which the
kidney use t
7. Immunologic
a. Uremia inhibits cellular and hormonal immunity

In conclusion: Kidney OUTAGES: hyperKalemia, renal Osteodystrophy, Uremia, Triglyceridemia, Acidosis (metabolic),
Growth delay, Erythropoietin deficiency (anemia), Sodium/water retention (consequences of chronic kidney disease)
Diagnostic criteria
Criteria for irreversible chronic kidney disease (CKD) include the persistence of eGFR < 60 mL/min/
and/or of any of the following markers of kidney damage for > 3 months:
Albuminuria: e.g., urine albumin-to-
Urine sediment abnormalities: e.g., hematuria
Abnormalities due to tubulointerstitial dysfunction, e.g.:
Electrolyte and acid-base imbalances
Retention of nitrogenous wastes
Reduced production of erythropoietin, 1,25-dihydroxyvitamin D, and/or renin
Histological abnormalities on biopsy
Imaging showing structural abnormalities: e.g., polycystic kidney disease
History of renal transplant

Note: CKD progression is the presence of either of the following:

A decline in renal function, leading to a change in eGFR category
A sustained decline in eGFR of > 5 mL/min/1.73 m2 per year

CGA classification of chronic kidney disease

CKD is classified according to the cause, eGFR category, and albuminuria category; this is referred to as the CGA
classification and normally the GFR is >90
1. Stage 1 (GFR>90): Structural kidney impairment but GFR is intact
2. Stage 2 (GFR 80-60)
3. Stage 3A (GFR 59-45)
4. Stage 3B (GFR 44-30)
5. Stage 4 (GFR 29-15)
6. Stage 5 (GFR<15): Hemodialysis is required for these patients
a. End-stage renal disease (ESRD): Irreversible kidney dysfunction with eGFR <15 mL/min/1.73 m2
b. AND manifestations of uremia requiring chronic renal replacement therapy with either dialysis
(hemofiltration or hemodiafiltration) or renal transplantation
Some clinical importance: Diabetic patients who are already on metformin and they are stage 3B they can
continue on metformin, BUT if they have never taken metformin and they are stage 3B DO NOT give metformin.
Diabetic patients who are on metformin and they are at stage 4, stop the metformin.

Diagnosis of CKD
Urea and creatinine
To assess progression/stability of the disease but compare it with previous results.
Urinalysis
Level of proteinuria is high alongside with GFR as it is associated with more rapid progression of CKD
Hematuria and proteinuria can indicate glomerular disease and need for biopsy.
Measure creatinine clearance to estimate GFR
CBC
Serum electrolytes (K, Ca, PO4 and protein)
Calcium, phosphate, PTH and 25(OH)D
Assessment of renal osteodystrophy
Albumin (hypoalbuminemia)
Consider malnutrition, inflammation or nephrotic syndrome
OR Albuminuria (ACR >= 3mg/mmol)
Lipid, glucose and HbA1c
To assess cardiovascular risk
Hepatitis and HIV serology: if dialysis or transplant is planned.
 Renal ultrasound
Size of the kidney and to rule out obstruction
Small kidney are suggestive of chronic renal insufficiency with little chance of recovery (EXCEPT in DM,
HIV, PCKD and amyloidosis)
Asymmetric renal size suggests renovascular or developmental disease
Presence of normal or large sized kidney does not exclude CKD
Persistent hematuria and positive family history of polycystic kidney disease or progressive CKD
Renal biopsy - to look for changes like glomerulosclerosis (hardening, scarring and diminishes the nephrons
ability to filter the blood in cases such as hypertension and diabetes mellitus)

Complications of CKD
In patients with CKD, symptomatic volume overload and severe hyperkalemia are the most common
complications.
Pulmonary edema secondary to volume overload - look for recent weight gain
Infection (UTI, Sepsis and Pneumonia)
Obtain an ECG for hyperkalemic patients

Treatment for CKD

Monitoring of renal functions:
Every 6 months in patients with stage 3 CKD but more frequently in patients who are deteriorating rapidly or
have stage 4 or 5 CKD.
1. Diet
a. Low protein, low salt diet (if HTN, CHF or oliguria are present) daily water intake of 2L and restricted
potassium, phosphate and magnesium intake
2. ACE inhibitors - to dilate efferent arteriole of glomerulus or ARBs
a. Prescribed to all patients with diabetic nephropathy and patients with CKD and proteinuria (even if not
hypertensive)
b. Consistent high BP can cause thickening of the vessel walls and causing protein deposition (Hyaline
arteriosclerosis)
c. If ACEI used early, they can reduce the risk of progression to End-stage renal disease (ESRD) because they
slow the progression of proteinuria and control hypertension
d. BUT be caution because they can cause hyperkalemia
i. If baseline potassium >5.5 mmol/L DO NOT start ACEI or ARBs
ii. If serum potassium is >6: the dose of ACEi or ARBs should be reduced or discontinue entirely but only
after trying all other measure to treat high K
e. Monitor renal function within first 7-10 days if reduction in GFR is greater than 25% discontinue the
medication
3. Control BP
a. ACEI and diuretics may be required
4. Glycemic control (if the patient is diabetic)
a. Prevents worsening of proteinuria
5. Lipid management
a. cerides are common)
b. Start on Statin therapy
6. Smoking cessation
7. Correction of electrolytes abnormalities
a. Correct hyperphosphatemia with calcium citrate (a phosphate binder)
b. Patients with CKD are treated with long-term oral calcium and vitamin D to prevent secondary
hyperparathyroidism and uremic osteodystrophy
c. Acidosis - treat the underlying cause (renal failure) and may require oral sodium bicarbonate supplements
 d. Persistent hypercalcemia (tertiary hyperparathyroidism) -> Perform parathyroidectomy, if unsuccessful or
not possible -> Calcimimetic agents (cinacalcet which bind to calcium-sensing receptor in the parathyroid
glands and reduce PTH secretion)
e. Hyperkalemia - low K diet and give Ca or Na resonium
8. Anemia
a. Causes of anemia in CKD
i. Deficiency of erythropoietin
ii. Toxic effect of uremia on marrow precursor cells
iii. Reduced RBC survival
iv. Blood loss due to capillary fragility and poor platelet function
v. Reduced intake, absorption and utilisation of iron
b. Consider erythropoietin-stimulating agents (ESAs): for patients with Hb < 10.0 g/dL
i. Treatment target: usually Hb concentration between 11 and 12 g/dL
ii. Treatment with ESAs is not recommended for patients with Hb level
been associated with increased mortality, stroke, and venous thromboembolism.
c. Avoid blood transfusions: particularly in patients eligible for renal transplantation (risk of alloimmunization)
9. Pulmonary edema
a. Dialysis if the condition is unresponsive to diuresis
10. Pruritus - Capsaicin cream or cholestyramine and UV light
11. Dialysis
12. Transplantation is the only cure

Important note:
Reduction of rate of progression is mainly dependent on
Control BP, targets for BP: ACE inhibitors and ARBs are favored to reduce proteinuria and retard the progression
of CKD
No proteinuria: 140/90mmHg
Moderately proteinuria: 130/80mmHg
Heavy proteinuria: 125/75mmHg
Diet: moderate protein restriction (to 60g protein/day)

In conclusion for acute and chronic kidney disease

Favors Chronic kidney disease Favors Acute kidney injury

History if kidney disease, HTN, Abnormal urinalysis, edema -

Small kidney size on renal ultrasound -

- Return of renal function to normal with time

Hyperkalemia, acidemia, hyperphosphatemia, anemia

- Urine output <500mL/day without uremic symptoms

Urinalysis with broad casts (more than 2 or 3 WBCs in diameter) -

Important note: CRAB indicates organ damage: Calcium increased, Renal insufficiency, Anemia, and Bone lesions.
Dialysis in couple of sentences and a table
There are 2 major methods of dialyzing a patient are: hemodialysis and peritoneal dialysis
Indication for dialysis (AEIOU):
Refractory Acidosis
Electrolytes - severe, persistent hyperkalemia
Intoxication - methanol, ethylene glycol, lithium, aspirin
Overload - hypervolemic (Pulmonary edema, refractory hypertensive)
Uremia (severe) - based on clinical presentation and not on laboratory findings (e.g., uremic pericarditis or
uremic encephalitis are absolute indication for dialysis)
When to consider dialysis?
CKD: A permanent treatment when the patient is not a transplantation candidate or serves as a bridge to
renal transplantations.
AKI: A temporary measure until the patient's renal function improves often due to absolute indications for
dialysis.
Overdose of medications or ingestions of substances cleared by the kidney, but not all medications and
toxins can be dialyzed
Nonemergent indication:
Cr and BUN levels are not absolute indication for dialysis; however, some nephrologist will decide to
initiate dialysis once a CKD GFR drop below a certain level.
Hemodialysis Vs. Peritoneal dialysis

Hemodialysis Peritoneal dialysis

Four exchange per day, each taking 30-60mins

4 hours, three times per week (continuous ambulatory peritoneal dialysis) or 8-10hrs
each night (automated peritoneal dialysis)

2-3 days between treatments A few hours between treatments

Requires visits to the hospital Performed at home

Requires an intact peritoneal cavity without major

Requires venous circulation for vascular access
scarring from previous surgery

Careful adherence to diet and fluid restrictions

Diet and fluid are less restricted
between treatment

Fluid removal compressed into treatment periods, may

Slow continuous fluid removal, usually asymptomatic
cause symptoms and hemodynamic instability

Infections related to vascular access may occur Peritonitis and catheter-related infection may occur

Patients can take care full responsibility for their

Patients are dependent on others
treatment
For more detailed explanation: Step-Up to medicine; Dialysis
Uremia
Definition: accumulation of toxic substances due to decreased renal excretion. These toxic substances are

Symptoms:
Constitutional symptoms
Fatigue
Weakness
Headaches
Gastrointestinal symptoms
Nausea and vomiting
Loss of appetite
Dermatological manifestations
Pruritus
Uremic frost: uremia leads to high levels of urea secreted in the sweat, the evaporation of which may
result in tiny crystallized yellow-white urea deposits on the skin.
Neurological symptoms
Asterixis
Signs of encephalopathy
Seizures
Somnolence
Coma
Hematologic symptoms

Uremic pericarditis: a complication of chronic kidney disease that causes fibrinous pericarditis
Clinical features: chest pain worsened by inhalation
Physical examination findings
Friction rub on auscultation
ECG changes normally seen in nonuremic pericarditis
Glomerular Diseases
Sources: AMBOSS, Boards and Beyond, Step-up to Medicine, The slides,

Objectives
Knowledge
1. Define nephrotic and nephritic syndrome
2. Classify the different causes of glomerular diseases (nephritic
and nephrotic syndrome)
3. Recognize the different clinical features associated with
nephritic/nephrotic syndrome
4. Describe the prognosis of major types of glomerular Diseases
5. Identify the red flag clinical features and major complications
of acute onset glomerular diseases
Cognitive Skills
1. Choose the most appropriate investigations to diagnose
glomerular diseases (blood, urine, kidney biopsy, imaging) based
on the available clinical data
2. Interpret blood tests for (renal function, serology,
autoimmune markers) and urine for (microscopy, albumin and
protein excretion) in glomerular diseases
3. Formulate and prioritize a differential diagnosis for nephrotic
and nephritic syndrome
4. Develop an evidence-based management plan for nephrotic
and nephritic syndrome depending on the cause of glomerular
disease
5. Appropriately prioritize referral for Nephrology service

Definitions
Primary: a kidney disease specifically affecting the glomeruli (e.g., minimal change glomerulonephritis)
Secondary: a disease affecting the glomeruli in the context of a systemic disease (e.g., lupus nephritis in SLE) or a
disease affecting another organ (e.g., diabetic nephropathy)
Diffuse: > 50% of glomeruli affected (e.g., diffuse proliferative glomerulonephritis)
Focal: < 50% of glomeruli affected (e.g., focal segmental glomerulosclerosis)
Global: entire glomerulus is affected
Segmental: only part of the glomerulus is affected

Other definitions
Proliferative: an increased number of cells in the glomerulus
Membranous: thickening of the glomerular basement membrane (e.g., membranous nephropathy)
Sclerosing: scarring of the glomerulus
Necrotizing: cell death within the glomerulus
Crescentic: accumulation of cells such as macrophages, fibroblasts, and epithelial cells in Bowman space

Causes of glomerular disease

Immunological injury such as cryoglobulinemia
Cryoglobulin-mediated vasculitis that is characterized by temperature-dependent deposition of
immunoglobulins/immune complexes (IgG and IgM) in blood vessel walls and subsequent inflammation of
involved vessels and surrounding tissue

Metabolic disease such as diabetes mellitus

Deposition of abnormal proteins such as amyloidosis

The kidney is the most commonly affected organ in systemic amyloidosis.

 General concept, all can cause:
Proteinuria
Hematuria: dysmorp
Edema (Everywhere including the eyes)
Reminder: Congestive heart failure: the edema will be seen in the dependent area (Lower limbs)
Best initial test for all: urine analysis
To check for protein and RBCs (with its morphology)
Most accurate test: Renal biopsy
Clinically: is not always performed

Glomerular disease (focus on the one in this lecture)

Glomerular

Wegner (Granulomatosis with polyangiitis) Goodpasture syndrome

Churg strauss syndrome IgA nephropathy

Henoch-Schonlein purpura (immunoglobulin A vasculitis) Post streptococcal glomerulonephritis

Thrombotic thrombocytopenic purpura Rapidly progressive glomerulonephritis

Hemolytic uremic syndrome

Cryogobinemia DM and HTN

Amyloid deposition

Difference between nephritic and nephrotic syndromes

Nephritic syndrome Nephrotic syndrome

Proteinuria (<3.5 g/day)

Heavy proteinuria (>3.5 g/day)
Hematuria with acanthocytes
Hypoalbuminemia
RBC casts in urine
Generalized edema
Edema
Presentation Hyperlipidemia
Hypertension
Azotemia
Hypertension
Sterile pyuria

Poststreptococcal glomerulonephritis
IgA nephropathy (Berger disease)
Granulomatosis with polyangiitis
Due to primary or secondary podocyte damage
Microscopic polyangiitis
Minimal change disease
Causes Eosinophilic granulomatosis with polyangiitis
Focal segmental glomerulosclerosis
Goodpasture syndrome (anti-GBM disease)
(focus on the Membranous nephropathy
Alport syndrome (hereditary nephritis)
ones within this Due to secondary podocyte damage
Thin basement membrane disease
lecture which are Diabetic nephropathy
Rapidly progressive glomerulonephritis (RPGN)
mentioned below) Amyloid light-chain (AL) amyloidosis, light chain deposition
Lupus nephritis
disease
Most common causes of nephritic-nephrotic
Lupus nephritis
syndrome:
Membranoproliferative glomerulonephritis
Diffuse proliferative glomerulonephritis

Pathogenesis Inflammatory response within glomeruli Damage to podocytes

Prognostic Indicators (poor prognosis)
Male gender
Pre-existing Hypertension
Severe and persistence of proteinuria
Rapid decline on renal function
Tubulo-interstitial fibrosis on renal biopsy

Note
When the criteria for both syndromes are fulfilled, the findings are referred to as mixed nephritic-nephrotic
syndrome
All glomerular diseases can lead to acute and chronic kidney failure

Note of definitions from the table

Acanthocytes: A type of dysmorphic red blood cell characterized by irregular, thorn-like cytoplasmic projections.
Oliguria: The production of an abnormally small amount of urine that is quantitatively defined as urine output of
< 400 mL per 24 hours in adults (less than 0.5 mL/kg/h in children)
Azotemia: An increase in the level of nitrogenous waste (both urea and creatinine)
Sterile pyuria: The presence of significant leukocyturia that is not accompanied by evidence of bacteria in the
urine on standard microscopy or urine culture
Presents in Acute tubulointerstitial nephritis, nephritic syndrome, Urogenital tuberculosis, stones,
malignancy, UTI with atypical organism what does not appear on media culture and recent or incomplete
antibiotic use (partially treated infection)

Nephrotic syndrome
Etiology
Primary (idiopathic) forms and they are commonly associated with other conditions.
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Membranoproliferative glomerulonephritis (can manifest as nephrotic or nephritic syndrome)
Secondary forms
Diabetic nephropathy
Amyloid nephropathy
Lupus nephritis (can manifest as nephrotic or nephritic syndrome)

Clinical features
Massive proteinuria (> 3.5 g/24 hours)
Edema
Typically starts with periorbital edema
Peripheral edema (pitting)
Hypoalbuminemia
Hyperlipidemia
Hypercoagulable state with increased risk of thrombosis and embolic events
Increased susceptibility to infection
Hypertension
frothy urine
 Diagnostics
Confirmation of nephrotic-range proteinuria
Urine dipstick (commonly used for screening)
Quantitative assessment of urine protein excretion
24-hour urine protein (test of choice): > 3.5 g/24 hours
Spot urine protein/creatinine ratio: > 3.5 g/g
Urine sediment microscopy
Renal biopsy (when the etiology of nephrotic syndrome is unclear)
Additional laboratory studies

Hyperlipidemia

Differential diagnosis of nephrotic syndrome

Disease Epidemiology Associations Findings Treatment

High-dose of glucocorticoid
therapy (prednisone)
Fusion/effacement If glucocorticoid-resistance or
Minimal change disease Most common in
Tumors (e.g., Hodgkin lymphoma) of podocyte foot relapses: Maintenance
(lipoid nephrosis) children
processes glucocorticoid or cytotoxic
therapy + renal biopsy
Does not progress to CKD

Primary
o Apolipoprotein L1
Primary FSGS: High-dose
(APOL1) gene variant segmental
glucocorticoid therapy PLUS
Secondary sclerosis
other immunosuppressants
o Heroin use Possibly IgM,
Focal segmental In adults, Secondary FSGS: Treat
o HIV infection C1, and C3
glomerulosclerosis especially in underlying cause + reduce
o Massive obesity deposits
(FSGS) (black population) proteinuria by RAAS inhibitors
o Chronic hypertension inside the
Usually leads to End-stage
o Sickle cell disease sclerotic
renal disease (ESRD) if left
o Previous HUS regions
untreated
o Cholesterol embolism
o Vasculitis

Primary
Primary: High-dose
o Autoantibodies against
glucocorticoid therapy
M-type phospholipase
Spike and dome (Prednisone) PLUS
A2 receptor 1 (anti-
appearance due to immunosuppressants (e.g.,
Membranous In adults of white PLA2R antibodies)
deposits of IgG cyclophosphamide) in severe
nephropathy population Secondary
and C3 (dense disease
o Infections (HBV, HCV,
deposits) Secondary: treat underlying
malaria, syphilis)
cause + RAAS inhibitors
o Autoimmune diseases
Usually leads to ESRD if left
(e.g., SLE)
untreated
o Tumors (Lymphoma)

Stringent glycemic control

ACE inhibitors or ARBs
Eosinophilic
Most common Additional signs of other organ Annual measurement of
nodular
secondary cause system complications (e.g., albumin-creatinine ratio:
Diabetic nephropathy glomerulosclerosis
leading to ESRD in retinopathy, neuropathy) that's o Type 1 DM: beginning will
(Kimmelstiel-
adults why we do fundoscopy be 5 years after diagnosis
Wilson nodules)
o Type 2 DM: At the time of
diagnosis

Amyloid nephropathy Seen in elderly patients.

Treatment
Management of symptoms and complications of nephrotic syndrome
Edema
Dietary sodium restriction
Diuretic therapy
Proteinuria
reduction of proteinuria; can lead to increased serum albumin, decreased edema; and slowing the
progression of chronic kidney disease or any underlying renal disease (e.g., diabetic nephropathy)
Antiproteinuric therapy
RAAS inhibitor: ACEI (ramipril) or ARB (losartan) are commonly used.
Effects
Reduces proteinuria
Treats hypertension
Dietary protein: avoid very high-protein diet
Hypercoagulability
Prophylactic anticoagulation
Infectious risk
Preventive measures
Pneumococcal vaccination
Annual vaccination for influenza

Disease-specific measures
Primary forms of nephrotic glomerulopathies: often treated with immunosuppressive therapy
Immunosuppressive therapies may include:
Glucocorticoids (often used initially)
Additional immunosuppressants (e.g., cyclophosphamide, calcineurin inhibitors) in patients with steroid-
resistant nephrotic syndrome or severe disease
Secondary forms of nephrotic glomerulopathies: Treat the underlying cause.

Complications
Thrombotic complications
Venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism)
Renal vein thrombosis: thrombus formation in the renal veins or their branches
Cause: hypercoagulable state
Chronic kidney disease: FSGS and membranous nephropathy in particular may progress to chronic kidney disease
and ESRD
Atherosclerotic complications

Nephritic Syndrome
Clinical features (It is an inflammatory process)
Hematuria with acanthocytes
Intermittent gross hematuria (red or brown urine, i.e., cola-colored urine)
RBC casts in urine
Proteinuria (< 3.5 g/24 h)
Hypertension

Azotemia
 Diagnostics
Urinalysis: nephritic sediment
Hematuria
Acanthocytes
Red blood cell casts
Mild to moderate proteinuria of >150 mg/24 h but < 3.5g/24h
Sterile pyuria and sometimes WBC casts
Blood tests

Complement, ANA, ANCA, and anti-GBM antibodies

Important note:
Glomerular hematuria: is a typical finding in nephritic syndrome. It is characterized by acanthocytes, RBC casts,
and mild to moderate proteinuria.
Nonglomerular hematuria: is characterized by bright red or pink urine, the occurrence of blood clots, normal
RBC morphology, and the absence of RBC casts.

Diseases associated with mild nephritic syndrome

Disease Epidemiology Associations Findings Treatment

IgA nephropathy (Berger Commonly in
disease)
Asymptomatic microhematuria
with intermittent gross hematuria
during or directly after one or
more of the following:
male Upper respiratory tract infections
Gastrointestinal infections
Note: must be within the first few
days ONLY
Control blood pressure
Normal C3 complement
RAAS inhibitors
levels
High dose of glucocorticoid
mesangial IgA immune
treatment in those at high-
complex deposits
risk of progressive disease

Bloody diarrhea
Petechial rash typically
affecting buttocks and
lower legs Supportive treatment
Abdominal pain due to Has a spontaneous
Most commonly Infection with E. coli
Henoch-Schonlein vasculitis involving GIT resolution
occurs in Systemic vasculitis in response to
purpura (IgA vasculitis) Arthralgia (pain in a joint) Relapses are common
children an infectious trigger
Renal disease with or Progress to develop ESRD in
without hematuria and some patient
proteinuria
Mesangial IgA immune
complex deposits

Most commonly nephritic, but

severe forms can also be nephrotic
IG-mediated (type 1) IG-mediated (type 1)
Immunoglobulin (IG)-mediated
o subendothelial and o Treat underlying cause
membranoproliferative
mesangial IgG o Immunosuppressive
glomerulonephritis (type 1 MPGN)
immune complex drugs
o Associated with SLE,
deposits with Complement-mediated
monoclonal gammopathy
granular appearance (type 2)
Complement-mediated
Membranoproliferative o o Eculizumab
membranoproliferative
glomerulonephritis complement levels o Anti-c5 inhibitor
Mainly in glomerulonephritis (type 2 MPGN
(MPGN) = Complement-mediated In general:
children o associated with dense
Mesangiocapillary (type 2) o RAAS inhibitors
deposit disease (C3 nephritic
glomerulonephritis o Intramembranous C3 o Prednisone
factor, cause a persistent
deposits (dense (glucocorticoid) alone
complement activation,
deposit disease) on or in combination with
leading to a depletion of C3)
basement membrane other
Both associated with HBV, HCV
o immunosuppressants
and cryoglobulinemia
complement levels
May manifest with concomitant
Tram-track appearance
nephrotic-range proteinuria
(nephritic-nephrotic syndrome)
Rapidly progressive glomerulonephritis (RPGN)
Renal function declines rapidly over days to weeks
Poor prognosis: can progress to ESRD within weeks to months
Crescent formation (moon-shaped) made of plasma proteins (e.g., C3b) and fibrin
Renal biopsy: Crescentic lesions often associated with necrotizing lesions within the glomerulus particularly in
small vessel vasculitis
Non-visible hematuria + proteinuria + red cell casts and dysmorphic red cells on urine microscopic associated
with hypertension and edema

Disease presenting with rapidly progressive glomerulonephritis (RPGN)

They might require dialysis

Disease Epidemiology Associations Findings Treatment

Poststreptococcal Affects children Occurs weeks after Positive Supportive

glomerulonephritis 3 12 years of - antistreptococcal
age and elderly hemolytic antibodies (ASO,
patients streptococcal ADB)
infections
Pharyngitis/tonsillit complement levels
is (most common): (due to
1 2 weeks after consumption)-
infection Granular
Skin infections: 3 4 subepithelial
weeks after immune complex
infection depositions (IgG,
Periorbital and IgM, C3) = (humps)
peripheral edema
Hypertension
Usually self-limiting
in children
May lead to rapidly
progressive
glomerulonephritis

insufficiency in
adults

Anti Glomerular 20 30 years Caused by Pulmonary Plasma exchange

Basement Membrane (Male) antibodies against infiltrates on chest (plasmapheresis) +
antibody disease 60 70 years the alpha-3 of type x-ray glucocorticoids +
(Goodpasture (Female) 4 collagen which is Pulmonary immunosuppression
syndrome) present in the hemorrhage and Early diagnosis is
basement hemoptysis essential! As it can
membrane of Linear deposition of require dialysis
glomeruli and the immunoglobulin
lungs only (IgG) along the
Anti-GBM glomerular
glomerulonephritis: basement
glomerulonephritis membrane (and the
in the presence of alveolar basement
anti-GBM membrane in the
antibodies without lung)
lung involvement

Small vessel vasculitis 3 Types: Granulomatosis with polyangiitis (formerly Wegener granulomatosis), Microscopic
(no need to know) polyangiitis, Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
Other diseases that are involved with nephritic syndrome
Alport syndrome (Hereditary nephritis)
X-linked dominant (Commonly in male)
Mutation in gene encoding type IV collagen
CKD + Hearing loss + abnormalities of the eye
Diffuse proliferative glomerulonephritis (DPGN)
Most common and severe manifestation of lupus nephritis in systemic lupus erythematosus (SLE)
Seen with IgA nephropathy

Important note: Low serum C3 levels are seen in:

Poststreptococcal glomerulonephritis
Lupus nephritis
Membranoproliferative glomerulonephritis (Mesangiocapillary glomerulonephritis)

Important note: (conclusion)

Primary glomerular disorder
IgA nephropathy (Is the most common cause of glomerular hematuria)
Minimal change disease
Focal segmental glomerulosclerosis
Membranous glomerulonephritis
Alport syndrome
Secondary glomerular disorder
Diabetic nephropathy
Hypertensive nephropathy
Lupus
Membranoproliferative GN
Poststreptococcal GN
Goodpasture syndrome

What we need to know (Overview-conclusion)

Disease Description Tests Treatment

Renal symptoms associated with cough,
hemoptysis and SOB (Lower respiratory
tract) Best initial: Anti-basement
Goodpasture Renal + Lung only disease membrane antibody Plasma exchange + steroid
syndrome Can lead to rapid prgressive Most accurate: Renal biopsy and immunosuppression
glomerulonephritis (Liner deposition)
Common in young patients
Early discover = saves the kidney function

Renal symptoms associated with upper

Wrgner respiratory tract (cough, hemoptysis and Steroid and
(Granulomatosis SOB) and sinus symptoms (history of recent Best initial test: c-ANCA cyclophosphamide
with polyangiitis) sinusitis) Most accurate: Renal biopsy (Antineoplastic Agents)
Multi-organ involvement (Join, GIT, eyes
and skin)

Churg strauss
syndrome
Renal symptoms associated with history of Best initial test: CBC
(Eosinophilic
bronchial asthma (cough), eosinophilia and High eosinophils -
granulomatosis
atopy Most accurate: Biopsy
with polyangiitis)
 Renal symptoms mainly painless recurrent Renal biopsy is necessary to Steroid and ACEI
hematuria confirm (unlike the above) (reduces the progression
IgA nephropathy
History of upper respiratory tract infection o IgA deposition on the of proteinuria)
(Berger disease) 1-2 days before onset of renal symptoms kidney (serum IgA is not Fish oil (can reduce the
useful to look for) progression)
Can lead to End stage renal disease
Level of IgA is not high in all cases

Penicillin to eradicate
History of dark color urine (tea, cola) and the infection (BUT it
Best initial test: ASO titer
Post streptococcal Edema after 1-2 weeks of upper respiratory does not reverse the
Low complement level (C3)
glomerulonephritis tract infection or skin infection disease)
Biopsy is the most accurate
Hypertension Diuretics to control
hypertension

Renal symptoms with muti-organ

involvement such as skin (purpuric skin
Hench-Schonlein rash) and GI also joint
purpura Systemic deposition of IgA
Associated with bleeding sometimes
Abdominal pain, hematochezia or melena
No need to treat (self-
No need to investigate, it is a clinical
limiting) unless it is severe
suspicion
case so steroid is given

Renal symptoms with systemic vasculitis

Abdominal pain, hemorrhage, purpuric skin Diagnosis: Sural nerve biopsy
Polyarteritis rash and stroke - A peripheral nerve that arises in
-
nodosa Associated with hepatitis B the posterior compartment of
Can affect every organ in the body except the leg (calf or sural region)
the lungs

Congenital disease affecting the eyes and

- -
ears with renal involvement
Hearing loss (sensory-neural hearing loss)

need to treat
Anti-double strand DNA (ANAs) Mild or non-
proliferative: steroid
History of patient: known case of SLE progression Proliferative or severe
Lupus nephritis
Renal biopsy most definitive disease: Mycophenolate
test and is used for staging Cyclophosphamide
(NEEDED) is given for SLE
when there is CNS
involvement

Both TTP and HUS have:

Hemolytic anemia (high LDH, high
reticulocytes, high indirect bilirubin)
Uremia (kidney involvement)
Fever is present:
Thrombocytopenia
TTP and HUS Only TTP has the triad PLUS:
Thrombocytopenia
Fever (fragmentocytes)
CNS symptoms
Plasma exchange
There could be a history of E. coli infection
and already treated by antibiotic
TTP it is caused by: ADAMTS13
deficiency/inhibition

Secondary to chronic infection or

inflammation
Steroid and treat the
Amyloidosis Amyloid protein deposition on the kidney Biopsy is needed
underlying cause
Cardiac, muscle and gut
It causes restrictive cardiomyopathy
 What we need to know about primary renal disorder (Overview)
Classified as their response to steroid therapy
All diagnosed by biopsy

Disease Description

Minimal change disease (Nil lesion) In Children

Good response to steroid

Membranous glomerulonephritis Adult individuals

Associated with cancer, endocarditis, lupus

Associated with hepatitis C

Membranoproliferative Treat hepatitis
Low complement level

HIV patient or IV drug user

Focal segmental Poor response to steroid
Rapid progressed to ESRD

Reminder from cardiology: Causes of restrictive cardiomyopathy

Cancer
Hemochromatosis (Iron overload disease): abnormal iron deposition in specific organs.
Amyloidosis
Sarcoidosis
Fibrosis

Remember:
NephrItic syndrome is characterized by presence of hematuria in association to hypertension, oliguria, fluid
retention and decrease of renal function
NephrOtic syndrome is characterized by proteinuria of more than 3.5g/day and hypoalbuminemia with edema
and fluid retention BUT no hematuria.

Additional topic

Acute Interstitial nephritis

Definition
An acute inflammation of the renal interstitium (tissue that surrounds glomeruli and tubules) and tubules that
causes a decline in renal function over a period of days to several weeks

Etiology
Acute allergic reaction to medication is the most common cause
RSVP Rifampin, Sulfa drugs and the V (5) Ps (Proton pump inhibitors, Pain killers
P Penicillins, and Phenytoin).
Others: Cephalosporins (cefazolin) and anticoagulant
Infection (especially in children)
Streptococcus spp. and Legionella pneumophila
Collagen vascular disease - Sarcoidosis
Autoimmune disease - SLE
Clinical features
Causes intrinsic AKI and its associated symptoms
Rash, fever and eosinophilia (common)
Pyuria and hematuria may be present
Flank pain and costovertebral angle tenderness
Arthralgia

Diagnosis
Blood: elevated serum creatinine, eosinophilia
Urine: pyuria (typically eosinophiluria), proteinuria, microscopic hematuria, WBC and white cell casts
Renal biopsy: may show diffuse interstitial T-cell and monocyte infiltration
Eosinophilic parenchymal infiltration that spares glomeruli may also be present.
This is the only way to distinguish it from Acute tubular necrosis (ATN)

Treatment
Removing the offending agent
If creatinine continues to increase after stopping the offending agent, steroids may help
Treat infection if present
Administer IV fluids

Acute versus chronic interstitial nephritis

Acute: causes a rapid deterioration in renal function and is associated with interstitial eosinophils or
lymphocytes
Chronic: has more indolent course and is associated with tubulointerstitial fibrosis and atrophy

Lupus nephritis
Inflammation of the kidneys from having Lupus (found in around 50% of patients with SLE)
Can manifest in nephrotic or nephritic syndromes

Clinical features
Hypertension and edema
Hematuria

Diagnostics
Urinalysis: proteinuria, hematuria, cellular casts (RBCs, hemoglobin, granular, tubular, or mixed)
Anti-dsDNA (marker that reflects progression of disease)
Kidney biopsy: immune complex-mediated glomerulonephritis (used for staging)

Classification of lupus nephritis

Class 1 Minimal mesangial disease
Class 2 Mesangial proliferative disease
Class 3 Focal glomerular disease
Class 4 Diffuse glomerular disease
Class 5 Membranous glomerular disease
Class 6 Advanced sclerosing disease

Management
IV glucocorticoids (e.g., methylprednisolone)
PLUS other immunosuppressants (e.g., mycophenolate or cyclophosphamide)
Note: patients with class 1,2, or 5 lupus nephritis do not usually require specific immunosuppressive therapy
IgA nephropathy (Berger disease)
It is the most common primary glomerulonephritis in adults, they are usually triggered by upper respiratory tract or
gastrointestinal infections and include gross hematuria and flank pain. In some cases, it may present as rapidly
progressive glomerulonephritis (RPGN).

Clinical features
Asymptomatic
Patients only have laboratory abnormalities, e.g., microhematuria.
Recurring episodes of:
Gross or microscopic hematuria
Flank pain
Low-grade fever
And/or nephritic syndrome (including hypertension)
Usually during or immediately following a respiratory or gastrointestinal infection
Renal function is usually normal
Can progress to RPGN and/or nephrotic syndrome
Some patients can progress to end-stage renal disease within 20 25 years.

Diagnostics
Urinalysis of asymptomatic patients often shows persistent microhematuria and minor proteinuria
More severe cases may manifest with recurrent episodes of nephritic syndrome.
Kidney biopsy is indicated in patients with signs of severe or progressive disease including:
Urinary protein > 0.5 1 g/24 h

Hypertension
Laboratory tests
Serum IgA level is elevated.
Complement levels (e.g., C3 level) are generally normal.

Treatment
Patients with proteinuria or hypertension: ACE inhibitors/angiotensin II receptor blockers
For severe/rapidly progressive disease: glucocorticoids
Electrolyte Imbalance
Sources: AMBOSS ( video included), Boards and Beyond, Step-up to Medicine, The slides,

Objectives
Knowledge Cognitive Skills
1. Identify the clinical features of hypo/hypernatremia and 1. Choose the most appropriate investigations to diagnose
hypo/hyperkalemia electrolyte imbalance (serum osmolality, serum electrolytes,
urine electrolytes and osmolality, ECG) based on the available
clinical data.
2. Develop a clinical approach for hypo/hypernatremia and 2. Interpret serum electrolyte and osmolality, urine electrolytes
hypo/hyperkalemia and osmolality
3. Define SIADH (syndrome of inappropriate ADH secretion) and 3. Formulate and prioritize a differential diagnosis for
its diagnostic criteria hypo/hypernatremia and hypo/hyperkalemia
4. Describe Diabetes Insipidus 4. Construct a diagnostic approach to hypo/hypernatremia and
hypo/hyperkalemia
5. Outline diabetes insipidus types, and pathophysiology 5. Develop an evidence-based management plan for
hypo/hypernatremia and hypo/hyperkalemia and their
underlying cause

Sodium Disorders (Na+)

General information about sodium
Potassium is an intracellular ion, while sodium is an extracellular ion
The most common electrolyte imbalance is hyponatremia, and the most common dangerous is
hyperkalemia
Any Na+ disturbance will cause Neurologic problems, and K+ disturbance causes cardiac problems

Regulation of Sodium level:

Decreases Na+: ADH, RAAS system, Aldosterone, and Sympathetic stimulation
Increases Na+: Dopamine, ECF Na+ and volume, Natriuretic peptide
Serum osmolality is: the amount of water compared to solutes in the blood
Plasma osmolality: (2Na+) +(Glucose/18) + (BUN/2.8)
Normal (270-300)
Urine osmolality is: the amount of water compared to solute in the urine
Normal (400-500)

Serum osmolality Urine osmolality

Factors that increase it (>300) Factors that increase it (>1400)

1- Free water loss 1- Low fluid volume
2- Diabetes insipidus 2- SIADH
3- Na overload 3- Increase ibuprofen use

Factors that decrease it (<280)

1- SIADH Factors that decrease it (<50)
2- Renal failure 1- Increase fluid volume
3- Diuretic use 2- Diabetes insipidus
4- Adrenal insufficiency
Hyponatremia
Defined as plasma level of sodium < 135 mEq/L
The most common electrolyte disturbance
Occurs in up to 22% of hospitalized patients

Clinical features
Hyponatremia can be classified into:

Serum sodium level

Classification Clinical features
(mmol/L)

Mostly asymptomatic but can present with headache,

Mild hyponatremia 130-134
nausea, vomiting, fatigue, confused, anorexia, muscle cramps

Non-specific symptoms: Gait disturbance, headache,

Moderate hyponatremia 125-129
vomiting, fatigue, confused, muscle cramps

Delirium, restlessness, agitation or lethargy, seizures,

Severe hyponatremia <120
brainstem herniation, respiratory arrest, coma, death
Important note: the severity is assessed using clinical features, Na levels are less reliable to assess severity

Diagnosis
Approach:
1. Confirm hyponatremia: repeat basic metabolic
panel (BMP)
2. Exclude hyperglycemia: check serum glucose
3. Check serum osmolality (first step to evaluate
confirmed hyponatremia). Interpretation:
a. Low serum osmolality: hypotonic
hyponatremia (true hyponatremia; most
common and most important)
b. High serum osmolality: hypertonic
hyponatremia
c. Normal serum osmolality: isotonic
hyponatremia or pseudo hyponatremia

Management
Mild hyponatremia: Fluid restriction
Moderate: 0.9% saline with loop diuretics (slow correction)
Severe: 3% hypertonic saline (rapid correction)

Rapid correction Slow correction

When? 1- Acute (<24h) severe (<120 mEq/L)
Hyponatremia to Prevent/treat brain
swelling or brain edema
2- Symptomatic Hyponatremia (Seizures,
coma, etc.) to alleviate symptoms
Once rapid Rx has resolved symptoms and
brought serum Na up to 120 mEq/L
OR Asymptomatic, mild, chronic hyponatremia
 How? 3% normal saline 1-2 mEq/l/h until:
- Symptoms resolve
- 3 to 4 elapsed and/or serum Na has
reached 120 mEq/L
Then slow down correction to 0.5 mEq/Lh
with 0.9% NS or simply fluid restriction. The
aim for overall 24h correction to be <8-12
mEq/L/d to prevent Central pontine
myelinolysis
With the use of 0.9% NS at a rate of 0.5 mEq/L/h
until desired Na level is achieved
To correct hyponatremia with euvolemia or
hypervolemia:
- Fluid restriction alone
- For patients with SAH, HI, post-neurosurgery: do
not give IV and PO salt

Central pontine demyelination

-12 mEq/L per day

Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

The most common cause of euvolemic hypotonic hyponatremia, caused by increased antidiuretic hormone
(ADH) secretion in the pituitary gland leading to free water retention
Etiology
Associated with small cell lung cancer (ectopic ADH secretion)
Other causes include infections, drugs (SSRIs, chlophosphomide), hypothyroidism and brain damage
Clinical features
Symptoms of hyponatremia mentioned above
SIADH patients are usually euvolemic, normotensive, and have no edema. A hyponatremic patient with
edema should raise suspicion for other conditions (e.g., congestive heart failure).
Symptoms of the underlying condition
Diagnosis
Diagnostic approach is the approach to hyponatremia
Diagnostic criteria
Hyponatremia (Serum sodium < 135 mEq/L)
Hypoosmolality (Serum osmolality < 275 mOsm/kg)
Euvolemia (No signs of hypovolemia or hypervolemia)
Concentrated urine (urine osmolality > 100 mOsm/kg)
Elevated urinary sodium (urine sodium concentration >20-30 mEq/L)
No alternative cause (other causes have been excluded)
Treatment
Restrict all fluid, and do not limit salt or protein intake
If initial management fails, consider pharmacology:
Demeclocycline
Vaptans
Urea
Low-dose loop diuretics
Manage the underlying cause
Psychogenic polydipsia
Patients present with history of increased urination and drinking a lot of fluid (can be confused with diabetes
insipidus, look for the following hints)
Patient is often a known case of psychiatric illness
Diagnosis
Hyponatremia (Serum sodium < 135 mEq/L)
Positive water deprivation test (polyuria disappears when the patient does not drink a lot of water)
The patient often has no night symptoms (e.g., nocturnal enuresis)

Hypernatremia
Defined as plasma level of sodium > 145 mEq/L
Relative deficit of water in relation to Na, can be due to:
Increase in Na loading (rare)
Free water deficit (loss of water without the loss of Na)

Causes
Unreplaced water loss
o Sweat loss
o Gastrointestinal loss
o Central or nephrogenic diabetes insipidus
o Osmotic diuresis
o Hypothalamic lesions impairing thirst or osmoreceptor function
Water loss into cells
o Severe exercise or seizures
Sodium overload
o Intake or administration of hypertonic sodium solutions

Clinical features
Mild symptoms Moderate symptoms Severe symptoms
(Dehydration) Confusion and lethargy Focal neurologic deficit
Decreased saliva Weakness Coma
Dry mucous membranes Neuromuscular Seizures
and skin irritability

Diagnosis
Treatment
Hypovolemic patients: volume resuscitation
Identify and treat the underlying cause
Hypernatremia correction
Replace the free water deficit orally with water or IV via an effective hypotonic solution (typically D5W, or
hypotonic saline)
Note: to calculate free water deficit: ((Serum Na/140) - 1) x Total body water (TBW)

Diabetes Insipidus
Condition where the kidneys are unable to concentrate urine
Has two types
Central (most common): insufficient secretion of ADH from the posterior pituitary gland
Nephrogenic (rare): defective ADH receptors in the distal tubules and collecting ducts of the kidneys

Causes of central diabetes insipidus (CDI) Nephrogenic diabetes insipidus (NDI)

Primary
Hereditary (X-linked recessive)
Most cases are idiopathic
Acquired
Thought to be autoimmune
Renal disease
Secondary
Adverse effect of medications (lithium,
Space occupying lesion
demeclocycline)
Neurosurgery
Hypokalemia, hypercalcemia
Traumatic brain injury

Clinical features
Polyuria with dilute urine
Polydipsia (excessive thirst)
sleepiness
Severe dehydration and hypotension

Diagnosis
Hypernatremia (serum sodium > 145 mEq/L)
Low urine osmolality and high serum osmolality
Water deprivation test is negative (polyurea despite no water intake)
To differentiate central from nephrogenic diabetes insipidus:
In central, giving antidiuretic hormone will improve symptoms. While there will be no response in
nephrogenic

Treatment
Treat the underlying condition, ensure sufficient fluid intake, and initiate a low-sodium, low-protein diet.
Central diabetes insipidus:
Desmopressin (DDAVP) is the primary therapy
Chlorpropamide increases ADH secretion and enhances effect of ADH
Nephrogenic diabetes insipidus
Sodium restriction and thiazide diuretics
Potassium (K+)
It is the most abundant intracellular mineral which is involved in cellular electrolyte balance, fluid balance, cellular
membrane transport, and pH balance.

It is a main cation and any delicate balance even the slightest acute compartmental shift can be fatal
Regulation of serum (K+) involves appropriate distribution between intracellular & extracellular compartments
and a balance between dietary, supplemental intake and bodily excretion
Kidneys role in K+ regulation:
In healthy individuals, 90% of daily ingested K+ is excreted through urine and about 10% is excreted through
colon
Aldosterone plays a key role in K+ elimination via the kidneys by increasing density and activity of sodium-
potassium ATPase pumps in the basolateral membrane.
It is critical for the normal function of muscles, heart and nerves. Moreover, it is important for normal
transmission of electrical signals through nervous system
Blood potassium level is 3.6 to 5.2 mmol/L (3.5-5.0 mEq/L)

Hyperkalemia
Common and potentially life-threatening disorder of potassium balance when a serum potassium level>5 mEq/L

Etiology
Potassium excess: due to altered K+ metabolism or intake
Reduced excretion: acute and chronic kidney disease
Endocrine causes: hypocortisolism, hypoaldosteronism
In Addison disease (primary adrenal insufficiency), the lack of mineralocorticoids leads to
hyperkalemia.
Drugs: potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), NSAIDs, and
trimethoprim-sulfamethoxazole (TMP-SMX)
Especially in HIV patients who are taking high-dose TMP-SMX
Type 4 renal tubular acidosis
Increased intake
High potassium diet, e.g., fresh fruits, dried fruits and legumes, vegetables, nuts, seeds, bran products,
milk, and dairy products
K+ containing IV fluids

Extracellular shift

Hyperosmolality
Insulin deficiency (manifests with hyperglycemia)
Insulin stimulates the Na+/K+-ATPase pump. Therefore, a lack of insulin causes decreased Na+/K+-
ATPase activity with K+ remaining extracellular.
Drugs
Beta blockers
-mediated stimulation of the Na+/K+-ATPase pump
Succinylcholine: (esp. when given with preexisting burns and/or muscle trauma)
Digoxin: inhibits the Na+/K+-
Extracellular release
Pathological cell lysis:
Rhabdomyolysis
Tumor lysis syndrome
Hemolysis
 High blood cell turnover: e.g., thrombocytosis, erythrocytosis, leukocytosis
Pseudohyperkalemia: resulting from iatrogenic red blood cell lysis
Blood drawn from the side of IV infusion or a central line without previous flushing
Prolonged use of a tourniquet
Fist clenching during blood withdrawal
Delayed sample analysis
Others
Potassium-sparing diuretics (amiloride)
direct inhibition of the epithelial sodium channels (ENaC) in the distal convoluted tubule and the

Important Note
Errors in blood-drawing technique may lead to red blood cell lysis and a falsely elevated serum potassium
concentration (pseudohyperkalemia)!
When K+ shifts out of the cell, it's a BAD LOSS! Beta blockers, Acidosis, Digoxin, Lysis, hyperOsmolality, high
Sugar, Succinylcholine

Note of definition
Type 4 renal tubular acidosis: a condition caused by impaired sodium reabsorption in the distal tubule, usually
due to hypoaldosteronism. Manifests with a normal anion gap, hyperchloremic metabolic acidosis as well as
hyperkalemia and low urine pH.
Hyperosmolarity: a condition in which the blood is more concentrated (e.g., with sodium, glucose, and other
substances) than normal. Occurs during diabetic ketoacidosis and hyperglycemic.
Iatrogenic: a descriptor for a condition or injury caused by treatment or a diagnostic procedure.

Clinical features
Symptoms usually occur if serum potassium levels are > 7.0 mEq/L or they change rapidly.

Cardiac arrhythmias (e.g., atrioventricular block, ventricular fibrillation)

Muscle weakness, paralysis, paresthesia

Nausea, vomiting, diarrhea

Bradycardia

Important note
Hyperkalemia (and hypokalemia) can cause cardiac arrhythmia and lead to ventricular fibrillation!

Diagnostics
Laboratory studies
High serum K+ levels
Glucose: If very high, consider spurious hyperkalemia secondary to hyperglycemic crisis.
These patients require K+ replacement during treatment of hyperglycemia

N
K+: Repeat to confirm the diagnosis and rule out pseudohyperkalemia.
Renal function tests: often show renal impairment
Hyperkalemia (prevalence is up to 50% in patients with CKD)
CBC: can show hemolytic anemia or thrombocytosis
Liver chemistries: may be abnormal in hemolysis or tumor lysis syndrome
Blood gases (venous or arterial): often show metabolic acidosis
Note:
In hemolytic anemia, pseudohyperkalemia is a result of the release of intracellular K+ from RBCs.
In thrombocytosis, it is due to the release of intracellular K+ from platelet granules during coagulation.

Investigation of underlying causes

Depending on symptoms and risk factors, further testing may be appropriate, particularly if renal function is normal.

ECG findings in hyperkalemia

Mild hyperkalemia: 5.5 6.4 mEq/L
Tall, peaked T waves
Moderate hyperkalemia: 6.5 8.0 mEq/L
Widening and flattening of P wave, which eventually disappears
Lengthening of QRS interval (QRS complex widening)
Severe hyperkalemia: > 8.0 mEq/L
Absent P wave
Wide QRS complex that merges with the T wave; a marker of impending V-Fib and asystole
Sine wave pattern: a sinusoidal pattern with absent P waves and a wide QRS complex that merges with
the T wave
Cardiac arrhythmias (e.g., V-tach, V-fib), asystole
Can show cardiac manifestations such as:
Conduction abnormalities (e.g., RBBB, LBBB and AV block)
Arrhythmias (e.g., sinus bradycardia, sinus arrest, VT/VF and asystole)

Risk stratification
Hyperkalemic emergency is an acute severe elevation that requires urgent lowering and occurs if any of the
following are present:
Clinical manifestations: e.g., ECG changes in hyperkalemia, muscle weakness, paralysis
Serum K+ >6.0 6.5 mEq/L
Comorbidities that affect ongoing K+ influx and elimination: e.g., AKI, ESRD, GI bleeding, rhabdomyolysis,
Tumor lysis syndrome
Less urgent hyperkalemia (typically chronic elevations that can be lowered more slowly)
Patient is asymptomatic
Serum K+ is 5.5 6.0 mEq/L
Patient has no high-risk comorbidities

Treatment
In patient with potassium concentration <6.5 mmol/L in the absence of neuromuscular symptoms or ECG changes:

Reduction of potassium intake

Correction of predisposing factors
Hyperkalemic emergency: Patients require immediate management.
If there are ECG changes: Stabilize the cardiac membrane first with IV calcium gluconate.
Important note: It does NOT reduce potassium level
Initiate treatment to shift potassium intracellularly, e.g.:
Short-acting insulin with IV glucose
Given together to prevent hypoglycemia
Consider the addition of inhaled SABAs.
Ventolin (nebulizer dose or 2 puffs)
IV sodium bicarbonate to induce alkalosis and treat the acidosis
Remove potassium from the body treatment, e.g.:
Cation-exchange resins (Calcium resonium)
Excrete by GI not kidneys, causes diarrhea
Diuretics (IV furosemide)
If renal function is not severely impaired
Dialysis for refractory hyperkalemia

More information about the treatments:

Treatment Options Indications

10% calcium gluconate
Cardiac membrane stabilization ECG changes in hyperkalemia
10% calcium chloride

Insulin and glucose (short-acting insulin Preferred acute noninvasive K+-lowering

combined with 50% dextrose) treatment

Intracellular potassium shifting Consider it as an adjunct to insulin (not

Inhaled SABAs (nebulized albuterol)
effective as a monotherapy).

Considered as an adjunct treatment only

Sodium bicarbonate
in patients with severe metabolic acidosis

These drugs release Na+ or Ca2+ ions in

Cation-exchange medications (Cation-
Enhanced potassium elimination the gut, which are exchanged for K+,
exchange resins; Calcium resonium)
thereby enhancing enteral K+ elimination

Preferred option in patients with end-

stage renal failure (particularly if already Most effective definitive therapy for
Hemodialysis
receiving renal replacement therapy), or refractory hyperkalemia
oliguria

Loop diuretics IV Furosemide For patients with volume overload

Important note:
Cardiac arrhythmias due to hyperkalemia can cause sudden death.
Calcium salts have no influence on serum K+ levels and therefore should be paired with a K+-lowering agent.
Loop diuretics increase urinary K+ excretion because they increase the distal delivery of sodium and urine flow
rate

Conclusion
To remember K+-lowering treatments, think C BIG K Die (if you see a big serum K+, your patient may die!): Calcium
salts, Beta-agonists/Bicarbonate, Insulin + Glucose, Kation exchange medication, Dialysis/Diuretics
Hypokalemia
It is a common electrolyte disorder that is typically caused by potassium loss (e.g., due to diarrhea, vomiting, or
diuretic medication) happens when serum potassium (K+) level is <3.5 mEq/L

Etiology
Causes
Primary losses due to gastrointestinal diseases/symptoms
Vomiting
Gastrointestinal loss (Urine K+ is Diarrhea
<20-30 mmol/L) Villous adenoma of the colon
Secondary losses due to medication or other causes
Laxatives

Primary losses due to renal diseases

Renal loss (Urine K+ is >20-30
mmol/24 hours)
Type I (distal) and II renal tubular acidosis (proximal)
Cushing syndrome
Renin-secreting tumors
Genetic disorders (associated with hypertension and alkalosis)
Congenital adrenal hyperplasia
Bartter syndrome
Gitelman syndrome
Liddle syndrome
Secondary losses due to medication or other cause
Diuretics: thiazides, loop diuretics, and osmotic diuretics
Beta-2 adrenergic agonists: beta-2 receptor-mediated stimulation of the
Na+/K+-ATPase pump (e.g., albuterol, terbutaline)
Glucocorticoids
Catecholamines
Endocrine causes: hyperaldosteronism ( e), hypercortisolism
Hypomagnesemia: can lead to refractory hypokalemia!

Alkalosis
Insulin: stimulation of the Na+/K+-ATPase pump, which transports potassium into
Intracellular shift the cell
Hyposmolality
Diabetic ketoacidosis

Clinical features
Patients may be asymptomatic, particularly if the deficiency is mild. Symptoms usually occur if serum K+ levels are <
3.0 mEq/L
Symptoms of cardiac arrhythmias (e.g., palpitations, irregular pulse, syncope)
Hypotension
Muscle cramps and spasms
Muscle weakness, paralysis
Respiratory failure secondary to paralysis of the respiratory muscles
Decreased deep tendon reflexes
Nausea, vomiting
Constipation or paralytic ileus (functional bowel obstruction)
Paralytic ileus: Temporarily impaired peristalsis (hypomotility) of the gastrointestinal tract in the absence of
mechanical obstruction
Fatigue
Hyperglycemia
Polyuria
Long-standing hypokalemia -> renal tubular damage (hypokalemic nephropathy) and can interfere with the
tubular response to vasopressin (acquired nephrogenic diabetes insipidus) resulting in polyuria and polydipsia
 Diagnostics
Laboratory studies
Low serum K+ levels
Serum calcium, magnesium, phosphate, bicarbonate

Blood gas (venous or arterial): may show metabolic alkalosis

Urinary potassium findings:
Renal loss: spot urine >15 20 mEq/L (24-hour collection >15 mEq/L)
Extrarenal loss: spot urine <15 20 mEq/L (24-hour collection <15 mEq/L)
Urinary calcium excretion, Findings:

cemia)
Urine chloride
A low urine chloride <30 mmol/L due to vomiting

To differentiate between them screen urine for diuretic drugs, if high then they are on diuretic
therapy.
If diagnosis remain unclear check for plasma renin
It is involved in the differential diagnosis of hypokalemia associated with hypertension

ECG findings in hypokalemia

Mild to moderate hypokalemia
T-wave flattening or inversion
ST depression
Prolonged PR interval
Moderate to severe hypokalemia
Presence of U waves: small waveform following the T wave that is often absent but becomes more
pronounced in hypokalemia or bradycardia and it is seen in lead V2 & V3
T and U wave fusion
QT prolongation
Dysrhythmias
Premature atrial and ventricular complexes
Diuretic use (Most common)
Investigate for
Renin-secreting tumor
High PRA causes of secondary Renovascular hypertension
High PAC hyperaldosteronism Malignant hypertension
Coarctation of the aorta

Low PRA
Check for
High PAC
Hypertension Plasma renin activity
and (PRA) Congenital adrenal hyperplasia
hypokalemia Plasma aldosterone Cushing syndrome
concentrations (PAC)
Glucocorticoid resistance
Low PRA Investigate for > Altered aldosterone
Low PAC
metabolism
11-beta-HSD deficiency
Doc producing tumor
Exogenous mineralocorticoid
Remember: renin is the precursor of aldosterone
Treatment
Most patients require potassium chloride (KCl) repletion
Treatment of the underlying cause
Severe hypokalemia (< 2.5 mEq/L) and/or high risk of recurrent severe hypokalemia (E.g., patients with DKA on
IV insulin therapy)
KCl: IV repletion PLUS oral repletion if tolerated
Rate of repletion should not exceed 10 20 mEq/hour through a peripheral IV
Concentrations of K+> 10 20 mEq/hour infused into a small peripheral vein can cause significant
phlebitis, which can lead to localized pain, inflammation, and venous scarring.
Higher doses (up to 40 mEq/hour) must be administered through a central line.
Moderate hypokalemia (2.5 2.9 mEq/L)
KCl: Oral repletion is preferred unless the patient is unable to tolerate PO, has severe symptoms, or has ECG
changes in hypokalemia.
Start oral or IV magnesium for patients with hypomagnesemia.
Potassium supplementation will be ineffective if concurrent hypomagnesemia is left untreated
Patients with a continued source of potassium loss (e.g., those on diuretics) may require long-term potassium
supplementation.
If hypokalemia is associated with systemic acidosis give potassium bicarbonate per oral
In DKA patients do not start insulin infusion if there was hypokalemia (Always treat hypokalemia first)

Important note: High concentrations of IV potassium can cause local venous irritation and potentially lead to
cardiac arrhythmias. Limit the rate of infusion according to the type of IV access and place patients on a continuous
cardiac monitor
Conclusion of hyperkalemia and hypokalemia
Hyperkalemia Hypokalemia

Definition Serum potassium level >5 mEq/L Serum potassium (K+) level is <3.5 mEq/L

Artefactual (not true hyperkalemia)

Reduced intake
Hemolysis during venipuncture
Dietary deficiency
Hemolysis in vitro (Lab)
Potassium free IV fluid
Thrombocytosis/leukocytosis
Diuresis (most common)
Increased intake
Loop diuretics - thiazides
Dietary potassium
Recovery from acute tubular
Potassium-containing IV fluid (Iatrogenic
necrosis
cause)
Recovery from renal obstruction
Redistribution from cell (kicks the K+ out)
Redistribution into cells
Acidosis
Alkalosis
Insulin deficiency
Insulin
Severe hyperglycemia
Catecholamines
DKA
Beta-adrenergic agonist
Beta blockers
Hypokalemic periodic paralysis
Hyperkalemic periodic paralysis
Increased urinary excretion (urine K+
Rhabdomyolysis
>20 mmol/24 hours)
Severe hemolysis
Activation of mineralocorticoid
Etiology Tumor lysis syndrome (chemotherapy
receptor: Conn's syndrome, cushing
destroying the normal cells)
syndrome, glucocorticoid excess
Reduced urinary excretion
, liquorice
Reduced glomerular filtration: AKI and
Genetic disorder (associated with
CKD (K+ is being reabsorbed instead of
hypertension and alkalosis)
getting secreted)
Reduced mineralocorticoid receptor
activations: Addison disease (Aldosterone
deficiency), Congenital adrenal
(hypomagnesemia)
hyperplasia, isolated aldosterone
Renal tubular acidosis type 1 and
deficiency, ACE inhibitors, ARBs,
type 2
calcineurin inhibitors, spironolactone,
Increased gastrointestinal loss (Urine K+
eplerenone, heparin and digoxin
<20 mmol/L)
Inhibitors of renin production: NSAIDs and
Upper GI tract: vomiting,
beta blocker
nasogastric aspiration (associated
Tubulointerstitial disease: interstitial
with metabolic alkalosis)
nephritis, diabetic nephropathy, obstructive
Lower GI tract: Diarrhea, laxative
uropathy
abuse, villous adenoma
Others: Potassium sparing diuretic (Amiloride)

Asymptomatic until potassium levels become Symptoms usually occur if serum K+

Clinical more than >6.5 mmol/L levels are < 3.0 mEq/L
features Progressive muscle weakness Muscle weakness
Paresthesia Constipation or paralytic ileus
Cardiac arrhythmias Hypokalemic nephropathy

Tall, Peaked T waves (Early sign)

Flattening and inversion of T waves
Shortened QT interval
ECG changes Prolonged QT interval
Loss of P wave
Visible U wave
Progressive widening of QRS complex
ST depression
Sine wave pattern
 Low serum K+ levels
If diagnosis remain unclear check for
plasma renin
High serum K+ levels
Serum calcium, magnesium etc.
Glucose, Serum electrolytes, Renal function
Diagnostic Urine chloride
tests, Blood gases (for metabolic acidosis)
Low (<30mmol/L) = vomiting
High (>40 mmol/L) = Diuretic
insufficiency
therapy, genetic disease next step
to differentiate by screening urine
for diuretics drugs

In patient with potassium concentration <6.5

mmol/L in the absence of neuromuscular
symptoms or ECG changes: Reduction of
Treat the underlying cause
potassium intake and Correction of
Slow release of potassium chloride
predisposing factors
tablets
Hyperkalemic emergency:
Be caution when you give IV
IV calcium gluconate for heart
potassium chloride in a peripheral
Treatment stabilization
vein as it can cause phlebitis (do not
Either using what shifts K+ into cells:
exceed 10 mmol/hour)
insulin with IV glucose
Higher concentration must be
SABA
infused via central vein with
IV sodium bicarbonate
continuous cardiac monitoring (up
Or what removes K+ from body
to 40mmol/L)
IV furosemide
Cation-exchange resins
Dialysis for refractory hyperkalemia
Acid-Base Balance Disorders
Sources: AMBOSS ( video included), Boards and Beyond, Step-up to Medicine, The slides,

Normal values of ABG

pH: 7.35-7.45
PaCO2: 35-45
PaO2: 10-13
HCO3: 22-26
Anion gap: 8-12

Acid-base balance is kept by

1. Pulmonary system: quick and effective compensation
a. Works by increasing or decreasing loss of CO2 through ventilation (which is considered as an acid)
2. Renal system: slow and less effective compensation
a. Works by absorbing or secreting HCO3 (which is considered as a base)
3. Buffering system (first to respond)

Disorders of Acid-Base system

Metabolic (renal) acidosis or alkalosis
Respiratory acidosis or alkalosis

Steps to read ABG

1. Acidosis or Alkalosis?
a. Acidosis: pH<7.35
b. Alkalosis: pH<7.45
2. Respiratory (PaCO2) or Metabolic (HCO3)?
a. If the patient has acidosis, it can be a result of:
Respiratory: high PaCO2
Metabolic: low HCO3
b. If the patient has alkalosis, it can be a result of:
Respiratory: low PaCO2
Metabolic: high HCO3
3. Is it compensated or not?

Metabolic acidosis
We calculate the anion gap
(Na+K) - (Cl+HCO3)
Na and K are positive, while Cl and HCO3 are negative
Normal anion gap: 8-12

Note: the effect of potassium is minimal and we could not be provided with its value in the exam.
Normal anion gap metabolic acidosis
Diarrhea or renal tubular acidosis
High anion gap metabolic acidosis
DKA, lactic acidosis, kidney disease (uremia), aspirin poisoning (Salicylates), methanol poisoning and
ethylene glycol poisoning
Low anion gap metabolic acidosis
Decrease Albumin, lithium
Important note: All compensated by hyperventilation (Respiratory alkalosis: decrease the level of PaCO2)
Normal anion gap metabolic acidosis
To know if the cause is RTA or diarrhea, urine anion gap should be measured (urine Na + urine K) - urine Cl
Positive urine anion gap: RTA
Negative urine anion gap: Diarrhea

Renal tubular acidosis

Type 1 (Distal RTA)
Distal tubule function is reabsorption of HCO3, when it dysfunctions: Urine pH is high (alkaline urine, which
is associated with stones), presented with hypokalemia
Type 2 (Proxima RTA)
Proximal tubule function is reabsorption of H+, when it dysfunctions: acidic urine, associated with
hypokalemia but no stones
Type 4
Associated hyperkalemia

Lactic Acidosis
Pathophysiological classification of lactic acidosis

Hypoxic Non-hypoxic

Ischemia Delayed clearance

Shock, severe anemia, cardiac arrest Renal or hepatic dysfunction

Global hypoxia Pyruvate dehydrogenase dysfunction

Sepsis, thiamine deficiency, catecholamine excess, alcoholic and

Carbon monoxide poisoning
diabetic ketoacidosis

Respiratory failure Uncoupling of oxidative phosphorylation

Cyanide, salicylate, methanol & ethylene glycol metabolites, anti-

Severe asthma, COPD, asphyxia
retroviral drugs, valproic acid, biguanides, INH

Regional hypoperfusion Accelerated aerobic glycolysis

Limb or mesenteric ischemia Increased effort, sepsis, seizures, large fructose loads, malignancies

Metabolic alkalosis
Increase level of HCO3 and compensated by hypoventilation (respiratory acidosis: PaCO2 retention)
Causes
GI loss of bicarbonate: vomiting or NGT
Diuretics
Increase aldosterone: primary hyperaldosteronism (Conn syndrome), cushing syndrome
Milk-Alkai syndrome: high volume of liquid anti-acid, associated with calcium disorders

Respiratory acidosis
High PCO2 compensated by increased level of HCO3 (metabolic alkalosis)
Causes
Any cause of hypoventilation or respiratory failure type 2, such as chest wall injury, COPD, paralysis or opiate
overdose
Note: Ventilation is necessary to treat the underlying cause

Respiratory Alkalosis
Decrease in PCO2, compensated by decrease level of bicarbonate (metabolic acidosis)
Causes
Any cause of hyperventilation: anxiety, anemia or pain
Additional Topics
Sources: AMBOSS ( video included), Boards and Beyond, Step-up to Medicine, The slides,

Renal artery stenosis

It is the narrowing of one or both renal arteries which is most commonly caused by atherosclerosis. The decreased
renal blood flow due to renal artery stenosis causes activation of the renin-angiotensin-aldosterone system, which in
turn results in secondary hypertension

Etiology
Atherosclerosis: occurs more often in men >50 years of age; increased risk in smokers
Fibromuscular dysplasia: mostly affects women <50 years of age

Pathophysiology
ischemia
activation of the renin-angiotensin-

hypertension (secondary hypertension)

Clinical features
Hypertension
Features of atherosclerosis in other parts of the body
Family history of hypertension is often absent.
Abdominal bruit heard over the flank or epigastrium: present during both systole and diastole
Flash pulmonary edema

Diagnostics
Indications for imaging:
Onset of hypertension before the age of 30 years
Severe hypertension after the age of 55 years
Hypertension resistant to a 3-drug antihypertensive regimen
New- initiating ACE inhibitors or ARBs
ACE inhibitors and ARBs can induce or worsen renal insufficiency, particularly in patients with severe
bilateral renal artery stenosis or high-grade unilateral stenosis.
Unexplained renal atrophy or asymmetry of >1.5 cm between the kidneys
Unexplained acute pulmonary edema
Modalities
First-line (screening) tests
Renal dysfunction present: duplex ultrasonography (US) or MR angiography without contrast
Normal or near-normal renal function: duplex US, CT angiography, or MR angiography with gadolinium
contrast
Second-line test: catheter angiography
Additional imaging (not recommended for establishing a diagnosis)
Renal vein renin measurement can help lateralize the most affected kidney (the ischemic kidney secretes
higher levels of renin compared to the normal or less affected kidney).

Important note: In patients with renal dysfunction, there is a risk of contrast-induced nephropathy with
CT/catheter angiography and a risk of nephrogenic systemic fibrosis with MR angiography with gadolinium contrast.
Polycystic kidney disease
It is an inherited disorder characterized by the development of multiple cysts in the kidneys. It is classified into two
distinct disorders: autosomal recessive PKD (ARPKD) and autosomal dominant PKD (ADPKD).
ADPKD is the most common inherited cause of chronic kidney disease which manifests with flank pain, arterial
hypertension, and progressive kidney disease with onset in adulthood.
ARPKD manifests with severe pulmonary insufficiency and progressive renal failure with onset during infancy or
early childhood. If left untreated, it is typically lethal before adolescence.
Early diagnosis and treatment may prevent or delay end-stage renal disease in both conditions.

Etiology
ADPKD
Autosomal dominant inheritance
Mutation in:
PKD1 on chromosome 16
PKD2 on chromosome 4
Positive family history
ARPKD
Autosomal recessive inheritance
Mutation in PKHD1 gene on chromosome 6

Clinical features
ADPKD; Symptoms usually occur after 30 years of age, but the disease may also manifest during childhood.
Renal manifestations (Important)
Gross hematuria
Flank or abdominal pain
Recurrent urinary tract infections
Nephrolithiasis
Kidneys might be palpable and enlarged on abdominal exam (they are usually normal at birth)
Signs of chronic kidney disease (e.g., hypertension, fluid overload, uremia)
Extrarenal manifestations
Multiple benign hepatic cysts
Cysts may also occur in the pancreas
Cerebral berry aneurysm
Cardiovascular
arterial hypertension (e.g., morning headaches); through increased renin production
Heart valve defects (particularly mitral valve prolapse)
Left ventricular hypertrophy (hypertrophic cardiomyopathy); mid systolic click and murmur which
increases with valsalva maneuver
Colon diverticula (diverticulosis)
ARPKD; Symptoms most commonly manifest in infancy or childhood.
Renal manifestations
Protruding abdomen; bilateral renal enlargement and/or hepatomegaly
Chronic renal failure: frequently hematuria, proteinuria, and oliguria
Severe in-
sequence (craniofacial abnormalities, clubbed feet, and pulmonary hypoplasia)
Extrarenal manifestation
Hypertension

hypertension
Diagnostics
Ultrasound
ADPKD
enlarged kidneys with multiple cysts bilaterally of varying sizes (anechoic masses)
In children: evidence of cysts in combination with a family history positive of ADPKD
Hepatic, pancreatic, and/or splenic cysts
ARPKD
Enlarged kidneys with multiple cysts bilaterally of equal size
Diffuse increased echogenicity, despite the presence of liquid-filled cysts (anechoic)
Hepatic cysts
Pathology
ADPKD
Progressive cystic dilatation of the kidney tubular system
ARPKD
Cystic dilatation of the collecting ducts
Treatment
Treatment/prevention of renal dysfunction
ACE-inhibitors (ACEIs) or angiotensin receptor blockers (ARBs): to prevent/treat hypertension as well as to
slow proteinuria and ESRD progression
Tolvaptan
Slows down the growth of kidney cysts in ADPKD patients
Avoid nephrotoxic substances
In severe cases: e.g., ESRD
Kidney transplantation is the only curative option

Hydronephrosis
Definition: dilation of the renal pelvis and calyces
Etiology: dilation of the urinary tract occurs proximal to the site of the underlying pathology
Urinary tract obstruction
Lower UTO can cause bilateral hydronephrosis.
Mild hydronephrosis (particularly right-sided) is a normal finding in pregnancy.
Urinary tract obstruction: e.g., due to retroperitoneal fibrosis
Vesicoureteral reflux
Retroperitoneal fibrosis
Clinical features
May be asymptomatic
Isolated hydronephrosis is almost always asymptomatic; it is the presence of associated conditions such as a
UTI or the underlying cause of hydronephrosis (such as a stone) that cause the symptoms below.
Flank/back pain and/or abdominal pain
Oliguria
Fever and features of UTI if infected (pyonephrosis)
Diagnosis
Ultrasound: hypoechoic dilation of the renal pelvis and calyces distending the healthy parenchyma
Renal parameters (e.g., creatinine) may be elevated and might indicate renal failure (if bilateral obstruction is
present or obstruction of a solitary kidney)
Important note
Women with gynecological malignancies may present with hydronephrosis.
Cervical, uterine, and ovarian cancers should therefore always be considered in nonpregnant women with new
onset hydronephrosis!