HIV Immune Complex Kidney Disease

HIV immune complex kidney disease is a group of glomerular diseases in people with HIV in which immune complex deposits, rather than direct viral podocyte injury, produce glomerular inflammation. It has become more common than HIV associated nephropathy in the antiretroviral era and is found in all ancestry groups.

Histological patterns include immune complex membranoproliferative glomerulonephritis, lupus like glomerulonephritis (full house immunofluorescence without lupus), IgA nephropathy, membranous nephropathy, proliferative glomerulonephritis and, less often, post-infectious glomerulonephritis. HIV-related antigens, co-infections (hepatitis C, hepatitis B, syphilis, tuberculosis) and B-cell dysregulation drive the immune complexes.

Epidemiology. Accounts for about 30 to 40% of kidney biopsies in HIV in high income settings; most patients have controlled or only moderately active HIV, with CD4 count above 200 cells/microL.

• Proteinuria (nephrotic range in about 40%), haematuria, hypertension, oedema, variable kidney function from normal to rapid decline.
• Low complement (C3 and/or C4) in membranoproliferative and lupus like patterns.
• Symptoms of co-infection: jaundice (hepatitis), rash and neuropathy (cryoglobulinaemia, syphilis), cough and weight loss (tuberculosis).
• Slower course than HIV associated nephropathy; kidney failure in about 25 to 30% over 5 years.

Red flags

• Rapid decline in eGFR or crescents.
• Cryoglobulinaemia (purpura, neuropathy, low C4).
• Severe nephrotic syndrome with albumin under 20 g/L.
• Active hepatitis B or C or tuberculosis requiring treatment before immunosuppression.

• HIV viral load, CD4 count, creatinine, urea, electrolytes, albumin, lipids, urine microscopy (dysmorphic red cells), protein:creatinine ratio, C3 and C4, antinuclear antibodies, anti-dsDNA, cryoglobulins, rheumatoid factor, hepatitis B and C (antibody and RNA/DNA), syphilis serology, tuberculosis screen, serum protein electrophoresis.
• Kidney biopsy: immune complex deposits on immunofluorescence (IgG, IgM, IgA, C3, C1q; full house in lupus like disease), mesangial or capillary wall deposits on electron microscopy, tubuloreticular inclusions (frequent in HIV, not specific), the patterns listed in the overview.

Differential diagnosis

• HIV associated nephropathy (collapsing FSGS, negative immune deposits), tenofovir tubulopathy, thrombotic microangiopathy, lupus nephritis, hepatitis C- or B-related glomerulonephritis, infection related glomerulonephritis, amyloid, diabetic nephropathy.

First line: control HIV and treat co-infections

• Antiretroviral therapy to undetectable viral load: dolutegravir 50 mg daily plus tenofovir alafenamide 25 mg and emtricitabine 200 mg daily (eGFR at least 30); avoid tenofovir disoproxil with reduced eGFR; creatinine rises 10 to 15% on dolutegravir through secretion block.
• Hepatitis C: glecaprevir and pibrentasvir 300 mg and 120 mg daily for 8 weeks; hepatitis B: entecavir 0.5 mg daily (renal dose adjustment) or tenofovir alafenamide 25 mg daily; syphilis: benzathine benzylpenicillin 2.4 million units intramuscularly weekly for 3 weeks (late disease); tuberculosis: multi-drug regimen with dose adjustment.

Renoprotection

• Blood pressure below 130/80 mmHg; ramipril 2.5 mg daily increased to 10 mg daily (stop if potassium exceeds 6.0 mmol/L; accept a creatinine rise up to 30%); dapagliflozin 10 mg daily (eGFR at least 25) or empagliflozin 10 mg daily (eGFR at least 20); sodium restriction under 2 g daily; furosemide 40 to 80 mg for oedema; statin.

Immunosuppression (nephrotic syndrome or progressive disease after infections are controlled)

• Membranoproliferative or proliferative disease with progression: prednisolone 0.5 to 1 mg/kg daily (maximum 60 mg) tapered over 6 months, or rituximab 375 mg/m² weekly for 4 doses (or 1 g on days 1 and 15) with careful infection surveillance.
• Crescentic disease: methylprednisolone 500 mg to 1 g intravenously daily for 3 days, then prednisolone 1 mg/kg daily with cyclophosphamide 15 mg/kg intravenously (reduced to 12.5 mg/kg at age 60 to 70 and 10 mg/kg over age 70) every 2 weeks for 3 doses, then every 3 weeks, if infections are controlled.
• Prophylaxis: co-trimoxazole 480 mg daily, proton pump inhibitor, hepatitis B screening before rituximab.

Kidney replacement therapy. Dialysis at eGFR 5 to 10 with symptoms or complications; transplantation with sustained viral suppression and CD4 count above 200 cells/microL; antiretroviral tacrolimus interactions need dose adjustment and level monitoring.

Monitoring. Viral load every 3 months until suppressed; creatinine, protein:creatinine ratio and complement every 1 to 3 months; repeat biopsy for unexplained decline.

Referral and escalation. Nephrology and HIV specialists together; hepatology for viral hepatitis; urgent for rapid decline or crescents.

Special groups

• Children: antiretroviral therapy and ACE inhibition; limited immunosuppression data.
• Pregnancy: dolutegravir based therapy continues; avoid ACE inhibitors, mycophenolate and cyclophosphamide.
• Co-infection with tuberculosis: rifampicin lowers dolutegravir exposure (use 50 mg twice daily).