End Stage Kidney Disease

End stage kidney disease is irreversible loss of kidney function to the point where survival requires kidney replacement therapy (dialysis or transplantation), conventionally eGFR below 15 mL/min/1.73 m2 with uraemic symptoms or complications. It is the terminal stage of any progressive kidney disease.

Leading causes worldwide are diabetic kidney disease, hypertensive nephrosclerosis, chronic glomerulonephritis (IgA nephropathy, focal segmental glomerulosclerosis), polycystic kidney disease, chronic tubulointerstitial disease and obstructive uropathy. In sub-Saharan Africa, HIV-related kidney disease, APOL1-associated disease, schistosomiasis and untreated hypertension contribute substantially, and many patients first present already at this stage.

Progression is driven by hyperfiltration, glomerulosclerosis, tubulointerstitial fibrosis, persistent proteinuria and uncontrolled blood pressure. The disease carries a cardiovascular mortality many times that of the general population, driven by vascular calcification, left ventricular hypertrophy, anaemia, mineral bone disorder and chronic inflammation.

Uraemic symptoms usually appear when eGFR falls below 10 mL/min/1.73 m2 and include anorexia, nausea, metallic taste, fatigue, pruritus, restless legs, sleep inversion and impaired concentration.

• Volume: oedema, resistant hypertension, pulmonary oedema, pleural effusion
• Cardiovascular: left ventricular hypertrophy, heart failure, uraemic pericarditis with friction rub, accelerated atherosclerosis
• Haematological: normochromic normocytic anaemia, platelet dysfunction with bruising and bleeding
• Metabolic: hyperkalaemia, metabolic acidosis, hyperphosphataemia, hypocalcaemia, secondary hyperparathyroidism
• Neurological: asterixis, peripheral neuropathy, encephalopathy, seizures
• Skin: uraemic frost (rare), pallor, calciphylaxis

Red flags demanding urgent dialysis: pericardial friction rub or effusion, encephalopathy, intractable vomiting, refractory hyperkalaemia (potassium above 6.5 mmol/L), pH below 7.15, pulmonary oedema unresponsive to diuretics, uraemic bleeding.

Diagnosis is by eGFR below 15 mL/min/1.73 m2 for more than 3 months with imaging or biochemical evidence of chronicity.

• Creatinine, urea, electrolytes, bicarbonate, calcium, phosphate, PTH, 25-hydroxyvitamin D, albumin, haemoglobin, ferritin, transferrin saturation, lipids, HbA1c
• Urine albumin:creatinine ratio and urinalysis
• Ultrasound: small echogenic kidneys (below 9 cm) with loss of corticomedullary differentiation; preserved or enlarged kidneys in diabetes, amyloid, polycystic disease, HIV-associated nephropathy
• Hepatitis B surface antigen and antibody, hepatitis C antibody and HIV serology before starting dialysis
• Echocardiography for left ventricular hypertrophy and effusion

Differentials: acute kidney injury (documented prior function, rapid change), acute kidney disease, and acute-on-chronic disease with a reversible component (obstruction, volume depletion, nephrotoxins, hypercalcaemia). Always exclude reversible factors before labelling the stage.

Decision making. Offer, with shared decision making: haemodialysis, peritoneal dialysis, pre-emptive transplantation, or conservative kidney management with symptom directed palliation. Conservative management is appropriate in frail older patients with high comorbidity, where dialysis is unlikely to extend survival or quality of life.

Starting dialysis. Start for uraemic symptoms, refractory fluid overload, refractory hyperkalaemia or acidosis, or declining nutritional status, usually at eGFR 5 to 10 mL/min/1.73 m2. Asymptomatic early initiation at higher eGFR offers no survival benefit.

Haemodialysis. Usually three sessions weekly of 3.5 to 5 hours, blood flow 300 to 400 mL/min, dialysate flow 500 mL/min. Adequacy: single pool Kt/V at least 1.2 for each session, or urea reduction ratio at least 65%. Prefer an arteriovenous fistula, created 3 to 6 months before anticipated start; avoid non-tunnelled catheters beyond 2 weeks.

Peritoneal dialysis. Continuous ambulatory exchanges of 1.5 to 2.5 L, three to four exchanges daily, or automated overnight cycling. Preserves residual urine output. Contraindications: extensive abdominal adhesions, large uncorrected hernia, active inflammatory bowel disease, severe peritoneal fibrosis.

Transplantation. Pre-emptive living donor transplantation gives the best survival. Refer when eGFR is below 20 mL/min/1.73 m2 or earlier if declining rapidly.

Complication management

• Anaemia: target haemoglobin 100 to 120 g/L. Replace iron first (ferritin below 200 microg/L or transferrin saturation below 20%): iron sucrose 100 mg intravenously at each of 10 consecutive dialysis sessions. Then epoetin alfa 50 to 100 units/kg intravenously or subcutaneously three times weekly, adjusting by 25% every 4 weeks. Avoid haemoglobin above 130 g/L.
• Hyperphosphataemia: dietary phosphate 800 to 1000 mg daily; sevelamer carbonate 800 mg three times daily with meals, titrated every 2 to 4 weeks to phosphate 1.1 to 1.7 mmol/L; alternatively calcium carbonate 500 mg elemental calcium with meals, limited to 1.5 g elemental calcium daily.
• Secondary hyperparathyroidism: alfacalcidol 0.25 to 0.5 microg daily; cinacalcet 30 mg daily titrated to 180 mg daily when calcium is above 2.2 mmol/L.
• Hyperkalaemia: dietary potassium restriction to 2 g daily; sodium zirconium cyclosilicate 5 to 10 g daily.
• Acidosis: sodium bicarbonate 500 mg to 1 g two to three times daily to keep bicarbonate at least 22 mmol/L.
• Hypertension: salt below 5 g daily, ultrafiltration to dry weight, then amlodipine 5 to 10 mg daily, ACE inhibitor if residual function and potassium permit.
• Cardiovascular risk: atorvastatin 20 mg daily; aspirin 75 mg daily for established vascular disease.
• Vaccination: hepatitis B (double dose, 40 microg at 0, 1, 2 and 6 months), influenza annually, pneumococcal.

Special groups

• Older adults: balance dialysis burden against benefit; conservative care with scheduled symptom review is a legitimate option.
• Renally cleared drugs: avoid metformin, NSAIDs, magnesium containing laxatives and gadolinium based contrast of higher risk; reduce gabapentin to 100 to 300 mg after dialysis and halve metoclopramide.
• Pregnancy is rare and high risk; intensive dialysis (at least 20 hours weekly) improves foetal outcome.