Addis Ababa University አዲስ አበባ ዩኒቨርሲቲ

College of Health Sciences የሕክምና ትምህርት ቤት

Department of Internal Medicine የውስጥ ደዌ ሕክምና ክፍል

Nephrology
Lectures
 Kidneys
• Kidney-shaped retroperitoneal organs
• 12 cm long
Kidney Function
 Nephrons
• The functional and
structural unit of kidney
• Glomerulus = filtration
• Renal tubule =
excretion, reabsorption,
secretion
• About 1 million
nephrons per kidney
 Nephrons

15% nephrons located in deeper

85% nephrons located in outer cortex
Long LH → concentrating and salt
Short LH
conserving nephrons
 Glomerulus
• Tuft of capillaries
enveloped by Bowman’s
capsule
 Gloms
• Capillary endothelial cells = fenestrated
• Visceral epithelium (podocytes) =
interdigitated foot processes with slit
diaphragm
• Parietal epithelium = interior of Bowman’s
capsule
• Mesangial cells = supportive cells
• Juxtaglomerular cells = renin producing
smooth mm cells
 Filtration membrane
• Glomerular Endothelium, GBM, podocytes
• Glom endothelium = fenestra (70-100 nm)
• GBM = charge barrier
• Podocytes = diaphragm slit (25 nm)
– Slits bridged by nephrin
• Particles are selectively filtered by size (<70
kDa) and charge (negative charge repelled)
• Filtration 180 L/day
Filtration membrane
 Renal tubules
• Tubes of transporting epithelia in sequence
• Proximal convoluted tubule
• Loop of Henle
– Thin descending limb,
– Thin ascending limb
– Thick ascending limb
• Macula densa = connects TALH to DCT
• Distal convoluted tubule
• Collecting duct
Renal tubule
Renal tubular transport
Proximal = gross, bulk transport
Distal = more regulated, selective process
 Renal hemodynamics
• RBF = 20% CO (1L/min)
• GFR = 120 ml/min
• Reabsorption = 99% of filtration
• The starling forces govern the GFR.
 Renal diseases
1. Glomerular diseases
2. Tubulointerstitial diseases
3. Vascular diseases of the kidney
 Glomerular diseases
Primary GN
1. MCD
2. FSGS
3. Membranous Nephropathy
4. Membrano-proliferative
GN
5. Acute post-infectious GN
6. IgA nephropathy
Hereditary GN
1. Alport syndrome
2. Fabry disease
Secondary GN
1. DM nephropathy
2. Lupus nephritis
3. Small vessel vasculitis (GPA,
EGPA, MPA), HSP
4. Thrombotic microangiopathy
5. Goodpasture syndrome
6. Postinfectious GN (SBE, HIV,
HCV, HBV, syphilis …)
7. Amyloidosis
8. Lymphoproliferative d/os
 Glomerular syndromes
1. Acute Nephritic Syndrome
2. Nephrotic Syndrome
3. Glomerular vascular syndromes
4. Basement membrane syndromes
5. Pulmonary-renal syndromes
6. Infectious disease-associated syndromes
Glomerular syndromes
Proteinuria
Hematuria
 Tubulointersitial diseases
• ATN
• Tubulointerstitial Nephritis is inflammatory
diseases of the kidneys that primarily involve
the interstitium and tubules
• Drug-Induced Interstitial Nephritis
• Acute Pyelonephritis
• Chronic Pyelonephritis and Reflux
Nephropathy
Vascular diseases of the kidney
Acute Kidney Injury
 AKI definition
• A clinical syndrome Characterized by the
sudden impairment of kidney function
resulting in the retention of nitrogenous and
other waste products normally cleared by the
kidneys.
 AKI: KDIGO definition
1. ↑sCr ≥0.3 mg/dl within 48hrs, Or
2. ↑sCr ≥1.5x baseline within the prior 7 days, or
3. ↓Urine Output ≤0.5 ml/Kg/h for >6 Hours.
 AKI aetiopathogenesis

50 – 60% → prerenal
30 – 40% → intrinsic renal (90% is ischemic ATN)
5% → postrenal
 Prerenal azotemia
1. Hypovolemia
– Hemorrhage
– GI loss - ↓ intake, vomiting, diarrhea, GI bleeding
– Renal loss – polyuria – diuretics, osmotic diuresis
– Insensible loss – skin, respiratory – sweat
– Third space loss – burn, crush injury, acute pancreatitis, intestinal
obstruction
2. Hypotension – different types of shock
3. Decreased effective circulating volume – edematous states
– CHF
– Hepatic failure: hepatorenal syndrome
– Nephrotic syndrome
4. Selective renal ischemia – Impaired renal autoregulation
– NSAIDs: block prostaglandin-mediated afferent arteriolar relaxation
– ACE-I/ARB: block angiotensin II mediated efferent arteriolar vasoconstriction
– Cyclosporine
 Intrinsic AKI
• Glomerular – Microvascular causes
– AGN
– Malignant hypertension
– Vasculitis, Collagen vascular diseases – SLE, scleroderma renal crisis
– thrombotic microangiopathies: TTP-HUS, DIC; preeclampsia; antiphospholipid
antibody syndrome, radiation nephritis, malignant nephrosclerosis,
• Tubular - ATN
– Ischemic – severe prerenal causes
– Nephrotoxic:
• Exogenous: AG, AmphB, tenofovir, cisplastin, contrast nephropathy (iodinated contrasts)
• Endogenous: hemolysis, rhabdomyolysis, myeloma, intratubular crystals, TLS
• Tubulointerstitial – interstitial nephritis
– Infectious/sepsis, inflammatory, infiltrative, allergic
• Renovascular – Large vessel diseases
– ATH, thrombosis, thromboembolism, renal artery dissection
– renal vein compression e.g abdominal compartment syndrome: elevated
intraabdominal pressures >20 mmHg
Postrenal AKI

BOO
 Clinical features
• Hemorrhage, vomiting, diarrhea, polyuria
• prostatic disease, nephrolithiasis, or pelvic or
paraaortic malignancy
• Medications: diuretics, NSAIDs, ACE inhibitors,
and ARBs
• Complications of AKI

• Signs of dehydration/hypovolemia
– Orthostatic hypotension, tachycardia, reduced JVP
– Decreased skin turgor, and dry mucous membranes
 Clinical features
• Oliguria/Anuria
• Fatigue
• Peripheral edema, pulmonary edema, pleural
effusion or ascites, Pericardial effusion
• Decreased appetite, nausea and vomiting
• Hiccups
• Mucocutaneous bleeding
• Change in mental status/flapping tremor/seizure
 Work up
• Urinalysis
• BUN and creatinine
• Serum electrolytes
• ECG – to look for evidence of hyperkalemia
• Renal ultrasound to exclude urinary tract
obstruction and assess kidney size
• Renal biopsy-when glomerulonephritis is
suspected, cause is not clear
• Other investigation should be done based on the
suspected specific etiologies
 AKI complications
1. Acute renal failure – Uremia
2. Hypervolemia, hypovolemia
3. Serum electrolyte and acid base disturbance
a. Hyponatremia
b. Hyperkalemia
c. Hyperphosphatemia
d. Hypocalcemia
e. Metabolic acidosis
4. Cardiac – arrhythmia, pericarditis, pericardial effusion
5. Hematologic – anemia, bleeding
6. Infections – the commonest cause of death in AKI
7. Malnutrition
 AKI – management principles
• Treat correctable causes
1. Prerenal → hydration
2. Postrenal → relieve obstruction
3. Intrinsic → etiologic specific e.g DC nephrotoxic drugs or dose
adjustment
• Supportive care: symptomatic Rx, Treat & prevent complications
1. ABCs with monitoring (VS, fluid balance, cardiac monitor, serial sCr)
2. Volume management – fluid restriction, diuretics
3. Correct electrolyte and acid derangements – hyperkalemia
4. Correct anemia; treat CHF, hypertensive crisis
5. Antibiotics
6. GI prophylaxis, DVT prophylaxis
7. Nutritional support
• Renal replacement therapy (RRT) – dialysis
 AKI Rx – general issues
1. Optimization of systemic and renal
hemodynamics through volume resuscitation
and judicious use of vasopressors
2. Elimination of nephrotoxic agents (e.g., ACE
inhibitors, ARBs, NSAIDs, aminoglycosides) if
possible
3. Initiation of renal replacement therapy when
indicated
AKI Rx – specific issues
 Renal replacement therapy
• Dialysis
• Kidney transplantation
CKD
 CKD definition
A kidney damage for ≥3 months as defined by
1. GFR ≤60 mL/min/1.73m2
2. Abnormal blood or urine tests
3. Abnormal pathologic findings
4. Abnormal imaging sturdies
 Pathophysiology of CKD
• Kidney injury → destruction of nephrons →
↓renal function & GFR
• Adaptation causes ↑nephron size &
↑glomerular pressure
• ↑glom pressure causes further loss of
nephrons
Progressive dysfunction
 CKD causes
• Prerenal causes
– Hypertensive nephrosclerosis
– Renal aa stenosis
• Renal cause
– Glomerular = chronic GN of any cause
– Tubulointerstitial nephropathy
• Post-renal cause
– Obstructive uropathy
 CKD causes
1. Diabetic nephropathy
2. Hypertension-associated CKD (hypertensive
nephropathy + vascular and ischemic kidney
disease)
3. Chronic Glomerulonephritis
4. Tubulointerstitial nephropathy
5. Cystic kidney diseases – ADPKD
6. Congenital kidney diseases – CAKUT
CKD staging
 Clinical features
• Volume overload
• Hypertension
• Electrolyte disturbance
• Acid-base disturbance
• Uremia
• Anemia
• Bone-mineral disorders
• Cardiovascular disease
 Uremia
• A clinical syndrome accompanying renal
failure
• Due to accumulation of urea (azotemia) and
other toxic waste products
 Uremia
1. Renal excretory dysfunction → accumulation
of toxins including products of protein
metabolism
2. Metabolic and endocrine failure
3. Progressive systemic inflammation →
vascular and nutritional consequences
Uremia features
 Work up
• CBC, RBC indices
• Urinalysis
• BUN, Creatinine and estimated GFR
• Electrolytes
• Calcium, Phosphate, PTH, ALP, DEXA
• Fasting blood glucose, Fasting lipids
• Renal imaging
 CKD management
• Dietary modification
• Rx reversible causes
– Avoid nephrotoxic drugs
• Prevent or slow progression
– ACE inhibitors, ARBs
• Rx comorbidities
– Glycemic control, BP control ≤130/80 mmHg, Statins
– Quit smoking/alcohol
• Rx complications
• RRT

ሜልክዮር MD
CKD management

ሜልክዮር MD
 Dietary modification
• Nutritional support – adequate calorie
• Calcium supplement
• Salt and water restriction
– 2 – 3 L/d, sodium individualized
• Potassium restriction <60meq/day
• ?Protein restriction <1g/kg
– Slows progression of disease
• Phosphorus restriction <1g/d

ሜልክዮር MD
 Dialysis
• ESRD with eGFR <15 ml/min
• Refractory hyperkalemia
• Refractory fluid overload
• Refractory metabolic acidosis
• Uremic encephalopathy, pericarditis, gastritis