Physiological Effects of End-stage Renal Dysfunction

Fluid, electrolytes and blood pressure

• Na⁺ and water: ↓ GFR / nephron mass → impaired Na⁺ and water excretion → extracellular volume expansion → oedema, hypertension and pulmonary oedema. Impaired concentrating/diluting ability also limits adaptation to changes in water intake.
• K⁺: ↓ renal K⁺ excretion → hyperkalaemia → weakness, conduction disturbance and arrhythmias.
• Blood pressure: volume expansion plus RAAS / sympathetic activation and increased vascular resistance contribute to hypertension and LV hypertrophy.

Acid–base balance

• ↓ functioning nephron mass → ↓ ammoniagenesis, NH₄⁺ excretion and net acid excretion.
• Retention of sulfate, phosphate and other non-volatile acids → metabolic acidosis.
• Consequences include compensatory hyperventilation, worsened hyperkalaemia, protein catabolism and bone buffering.

Excretion of metabolic waste

• ↓ GFR → accumulation of urea, creatinine, urate, phosphate and other uraemic toxins.
• Uraemia may cause encephalopathy / neuropathy, anorexia, nausea, platelet dysfunction and bleeding, pericarditis, weakness and myopathy.

Calcium, phosphate and bone

• ↓ phosphate excretion → hyperphosphataemia.
• ↓ renal 1α-hydroxylase activity → ↓ calcitriol → ↓ intestinal Ca²⁺ absorption → hypocalcaemia.
• Hypocalcaemia + hyperphosphataemia + ↓ calcitriol → ↑ PTH → secondary hyperparathyroidism → renal osteodystrophy, bone pain/fractures and vascular/soft-tissue calcification.

Endocrine and haematological effects

• Erythropoietin: ↓ viable renal tissue and impaired renal oxygen-sensing response → ↓ EPO production → ↓ erythropoiesis → normocytic normochromic anaemia.
• Uraemia also shortens RBC survival; iron deficiency, blood loss and inflammation may contribute.
• Impaired renal insulin degradation may reduce insulin requirements in advanced renal failure.

Drug handling and systemic consequences

• ↓ filtration ± ↓ tubular secretion → ↓ renal drug/metabolite clearance → prolonged half-life and accumulation; maintenance dose or interval may need adjustment.
• Uraemia may also alter protein binding, volume of distribution and non-renal metabolism.
• Chronic acidosis, inflammation and uraemia contribute to protein catabolism, muscle wasting and malnutrition.