End-stage kidney and renal failure

1. Functions of the Kidney

• Excretion of metabolic waste
• Regulation of salt + water balance
• Maintenance of acid-base balance
• Secretion of hormones (EPO, renin, active vitamin D)

4 functional components: glomeruli, tubules, interstitium, blood vessels. Damage to any one secondarily affects the others → chronic disease → end-stage kidney.

2. End-Stage Kidney

Definition

• Complete / near-complete loss of kidney function (GFR < 15 mL/min, <10 % of normal).
• No longer removes wastes, concentrates urine, or regulates endocrine function.
• Most common causes: DM (40 %) and hypertension (30 %).
• Incompatible with life → dialysis or transplantation required.

Morphology

• Symmetrically shrunken kidneys, red-brown granular surface.
• Glomerular obliteration (hyalinic sclerosis) — protein leak → trapping → compression → sclerosis.
• Interstitial fibrosis with tubular atrophy and loss of peritubular capillaries.
• Lymphocytic interstitial infiltrate.
• Thyroid-like appearance (“thyroidization”) of atrophic tubules.

3. Renal Failure

Kidneys fail to excrete toxins and metabolic waste. Clinical manifestation = azotemia + uremia.

A) Azotemia (biochemical)

• BUN > 9 mmol/L (normal 2–9)
• Creatinine > 120 µmol/L
• Reflects ↓ GFR.

Type	Mechanism	Example
Pre-renal	Renal hypoperfusion, no parenchymal damage	Shock, dehydration
Renal (intrinsic)	Parenchymal damage (glomeruli/tubules/vasc.)	Glomerulonephritis, ATN
Post-renal	Obstruction below kidney	Urolithiasis, BPH

B) Uremia (clinical syndrome)

Azotemia + systemic manifestations from accumulated waste + ↑ PTH.

1. Fluid / electrolyte / acid-base
   • Tubular disease → polyuria → dehydration.
   • Glomerular → ↓ filtration → salt & water retention → edema, cardiac failure.
   • Metabolic acidosis from failed waste excretion.
2. Ca²⁺ / PO₄³⁻ metabolism
   • ↑ PO₄³⁻ → ↓ Ca²⁺ → ↑ PTH → bone resorption → renal osteodystrophy.
   • Compensatory ↑ Ca²⁺ → metastatic calcifications in soft tissues.
3. Cardiopulmonary
   • Uremic (fibrinous) pericarditis = “bread-and-butter” pericarditis (↑ vascular permeability → fibrinogen leak).
   • Uremic pneumonitis — hyaline membrane-like changes.
4. Hematopoietic
   • Anemia — ↓ erythropoietin synthesis.
   • Bleeding tendency — platelet dysfunction.
5. GI
   • Uremic gastritis, colitis.
6. Neuromuscular
   • Uremic neuropathy.

4. Acute Renal Failure

• Sudden ↓ renal function with oliguria / anuria.
• 3 types:
  • Pre-renal → reversible, hypoperfusion (hypotension, dehydration, salt depletion).
  • Renal (parenchymal) — acute GN, pyelonephritis, cystic diseases, ATN.
  • Post-renal — urinary tract obstruction.

Morphology

• ↓ + maldistributed cortical blood flow → local ischemia.
• Large, pale pink kidney; thick pale cortex, dark hyperemic pyramids.
• Histology: dilated DCT with flattened epithelium; glomeruli normal.

5. Chronic Renal Failure

• Prolonged uremia; end result of all chronic kidney diseases.

Causes (frequency)

Cause	%
Diabetes mellitus	40 %
Hypertension	30 %
Glomerulonephritis	15 %
Polycystic kidney disease	10 %
Other (pyelonephritis)	5 %

💡 High-yield: End-stage kidney = GFR <15, granular shrunken kidneys, #1 causes = DM + HTN. Azotemia (biochemical ↑BUN/Cr) split into pre-renal (hypoperfusion) / renal (parenchymal) / post-renal (obstruction). Uremia (clinical) → fibrinous “bread-and-butter” pericarditis, renal osteodystrophy, metastatic Ca²⁺, EPO-deficiency anemia, bleeding, uremic neuropathy.