HIV Associated Nephropathy

HIV associated nephropathy is a collapsing form of focal segmental glomerulosclerosis, with microcystic tubular dilatation, tubulointerstitial inflammation and tubuloreticular inclusions, caused by direct infection of podocytes and tubular epithelial cells by HIV-1.

It occurs almost exclusively in people of sub-Saharan African ancestry carrying two APOL1 risk alleles (G1 or G2), who have a lifetime risk of HIV associated nephropathy of about 50% if HIV is untreated. It is typically a disease of uncontrolled viraemia and CD4 count under 200 cells/microL, but occurs at higher counts.

Incidence has fallen sharply with antiretroviral therapy, but remains a leading cause of kidney failure in African patients with HIV.

Pathophysiology. HIV infects podocytes and tubular cells; viral proteins (Nef, Vpr) promote podocyte dedifferentiation and proliferation, causing collapsing glomerulopathy; APOL1 risk variants amplify podocyte injury, and tubular dilatation follows viral replication.

• Heavy proteinuria (often more than 3.5 g daily, nephrotic range), hypoalbuminaemia, but little oedema and normal blood pressure in many patients.
• Rapid decline in kidney function over weeks to months, kidney failure within 1 to 4 years if untreated.
• Large, echogenic kidneys on ultrasound despite impaired function.
• Advanced HIV: wasting, oral candidiasis, lymphadenopathy, opportunistic infection.

Red flags

• Creatinine doubling within weeks; oliguria.
• Nephrotic syndrome with CD4 count under 200 cells/microL.
• Concurrent opportunistic infection (tuberculosis, cryptococcus, pneumocystis).
• New proteinuria after starting tenofovir disoproxil: drug toxicity.

• HIV viral load and CD4 count, creatinine, urea, electrolytes, albumin, cholesterol, urine protein:creatinine ratio (and albumin:creatinine ratio), urine microscopy (bland sediment), hepatitis B and C, syphilis, tuberculosis screening, APOL1 genotype if available.
• Renal ultrasound: enlarged echogenic kidneys.
• Kidney biopsy (when safe): collapsing glomerulopathy with glomerular tuft collapse and podocyte hypertrophy, microcystic tubular dilatation with proteinaceous casts, interstitial inflammation, and tubuloreticular inclusions on electron microscopy.

Differential diagnosis

• HIV immune complex kidney disease, tenofovir tubulopathy, thrombotic microangiopathy, hepatitis C-related glomerulonephritis, primary or secondary focal segmental glomerulosclerosis, diabetic nephropathy, drug induced interstitial nephritis (co-trimoxazole, indinavir crystals), opportunistic infection nephropathy, collapsing glomerulopathy from other causes (interferon, pamidronate, COVID-19).

First line: antiretroviral therapy for all, immediately

• Start or optimise antiretroviral therapy irrespective of CD4 count, aiming for undetectable viral load: preferred regimen dolutegravir 50 mg daily plus tenofovir alafenamide 25 mg and emtricitabine 200 mg daily (eGFR at least 30; if eGFR is 15 to 30 use dolutegravir with lamivudine dose adjusted, avoiding tenofovir disoproxil). Dolutegravir and cobicistat raise serum creatinine by 10 to 15% by blocking tubular secretion without changing true filtration; confirm with cystatin C.
• Avoid tenofovir disoproxil when eGFR is under 50 mL/min/1.73 m² or with tubulopathy; dose adjust renally cleared antiretrovirals (lamivudine, emtricitabine, abacavir has no adjustment) and avoid indinavir (crystalluria).
• Tuberculosis co-infection: start tuberculosis treatment first, then antiretrovirals within 2 to 8 weeks, according to CD4 count (within 2 weeks if CD4 under 50 cells/microL); dolutegravir 50 mg twice daily with rifampicin.

Renoprotection

• ACE inhibitor (ramipril 2.5 mg daily increased to 10 mg daily) or angiotensin receptor blocker, checking creatinine and potassium at 1 to 2 weeks; accept a creatinine rise up to 30%; stop if potassium exceeds 6.0 mmol/L (trimethoprim and pentamidine add to hyperkalaemia).
• Dapagliflozin 10 mg daily (eGFR at least 25) or empagliflozin 10 mg daily (eGFR at least 20) have limited HIV-specific data but are appropriate for proteinuric disease.
• Sodium restriction under 2 g daily; furosemide 40 to 80 mg for oedema; statin (atorvastatin 20 mg daily with dose interaction checks with protease inhibitors).

Adjunctive corticosteroids (biopsy proven disease with progressive decline or severe nephrotic syndrome, after infection is excluded)

• Prednisolone 1 mg/kg daily (maximum 60 mg) for 2 to 4 weeks, then taper over 8 to 12 weeks; monitor for infection (pneumocystis, tuberculosis, cytomegalovirus) and glucose. Benefit is observational; not for patients with uncontrolled opportunistic infection.

Prophylaxis and complications

• Co-trimoxazole 480 mg orally daily when CD4 is under 200 cells/microL (dose adjust in kidney failure; monitor potassium and creatinine); isoniazid preventive therapy 300 mg daily with pyridoxine 25 mg daily where indicated.
• Vaccination: hepatitis B (40 microg at 0, 1, 2 and 6 months in dialysis), pneumococcal, influenza.

Kidney failure. Dialysis (haemodialysis or peritoneal) at eGFR 5 to 10 or with complications; transplantation is possible with sustained viral suppression and CD4 count above 200 cells/microL for at least 3 months, with tacrolimus dose adjusted for antiretroviral interactions (protease inhibitors and cobicistat raise levels markedly).

Monitoring. Viral load every 3 months until suppressed, then every 6 months; creatinine and proteinuria every 1 to 3 months; CD4 count every 3 to 6 months.

Referral and escalation. Nephrology and HIV physician together; urgent for creatinine doubling, or hyperkalaemia above 6.5 mmol/L.

Special groups

• Children: antiretroviral therapy and ACE inhibition; early referral.
• Pregnancy: continue dolutegravir based therapy; stop ACE inhibitors; monitor for pre-eclampsia.
• People of African ancestry with HIV and two APOL1 risk alleles: yearly urine albumin:creatinine ratio screening.