HIV-Associated Nephropathy and Collapsing Glomerulopathy
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Direct answer
HIV-associated nephropathy is a collapsing variant of focal segmental glomerulosclerosis, seen mainly in people with untreated HIV, that causes heavy proteinuria and progressive kidney failure. It is strongly linked with APOL1 risk variants, common in people of recent African ancestry, and it is more frequent with low CD4 counts and high viral loads. Early antiretroviral therapy together with ACE inhibition or ARB therapy can lead to remission of proteinuria.
What you must remember
- Histology: collapsing focal segmental glomerulosclerosis, with collapsed capillary tufts, podocyte hyperplasia and microcystic tubular dilatation.
- Ultrastructure: tubuloreticular inclusions in glomerular endothelial cells on electron microscopy, reflecting an interferon effect.
- Clinical picture: nephrotic-range proteinuria with rapidly falling renal function, often with enlarged, echogenic kidneys on ultrasound.
- APOL1: two copies of the G1 or G2 risk variants greatly increase the risk in people of recent African ancestry.
- Risk factors: untreated HIV, a low CD4 count and a high viral load.
- Treatment: early antiretroviral therapy, with ACE inhibitor or ARB therapy to reduce proteinuria.
- Corticosteroids: have a limited role, and immunosuppression is not the mainstay of management.
- Collapsing glomerulopathy: the same collapsed-tuft pattern occurs in other settings, including with interferon, pamidronate and parvovirus B19 infection.
A man with heavy proteinuria at HIV diagnosis
A 36-year-old man newly diagnosed with HIV has oedema, heavy proteinuria and a rising creatinine. His CD4 count is low and his viral load is high, so the kidney question is whether this is HIV-associated nephropathy.
- Confirm the immune status: CD4 count and viral load show the degree of immune suppression, and low counts with high load raise the likelihood of kidney disease.
- Quantify the proteinuria: A urine protein-creatinine ratio shows whether the proteinuria is in the nephrotic range, and urinalysis may show haematuria.
- Image the kidneys: Ultrasound often shows enlarged, echogenic kidneys, a helpful but non-specific clue.
- Biopsy when the picture is unclear: Renal biopsy confirms collapsing focal segmental glomerulosclerosis and tubuloreticular inclusions, and it excludes other HIV-related glomerular diseases.
- Consider APOL1 testing: Genetic testing for APOL1 risk variants helps stratify risk in patients of African ancestry, though it is used in some centres rather than routinely.
- Start antiretroviral therapy and RAS blockade: ART is started promptly, with an ACE inhibitor or ARB for proteinuria, and kidney function is followed closely.
- Monitor for tenofovir toxicity: Tenofovir disoproxil can injure proximal tubules, so renal function and serum phosphate are checked during treatment.
Where the examiner tests the wrong pathway
Most errors come from treating the kidney as a simple infection problem or from missing a drug cause.
- Trap: treating HIV-associated nephropathy with cyclophosphamide or heavy immunosuppression as first line Correct: ART and RAS blockade are the mainstay, because HIV gene expression in renal epithelial cells drives the injury.
- Trap: labelling every nephrotic syndrome in HIV as HIV-associated nephropathy Correct: HIV is also linked with membranous nephropathy, IgA nephropathy and immune complex glomerulonephritis, so biopsy is needed.
- Trap: assuming kidney injury in a patient on ART is always from HIV itself Correct: tenofovir can cause tubular injury, so the drug is a common and treatable cause of decline.
Frequently asked questions
What is the typical histology of HIV-associated nephropathy?
HIV-associated nephropathy typically shows collapsing focal segmental glomerulosclerosis, with collapsed capillary tufts and podocyte hyperplasia. The tubules show microcystic dilatation, and electron microscopy reveals tubuloreticular inclusions in glomerular endothelial cells.
Which genetic factor increases the risk of HIV-associated nephropathy?
APOL1 risk variants, the G1 and G2 alleles, markedly increase the risk of HIV-associated nephropathy in people of recent African ancestry. Two copies of these variants carry the highest risk, and the same variants are linked with other kidney diseases.
How does antiretroviral therapy help HIV-associated nephropathy?
Antiretroviral therapy suppresses HIV replication in renal epithelial cells, and it can lead to remission of proteinuria and recovery of kidney function when started early. It is combined with ACE inhibitor or ARB therapy, which reduces proteinuria and slows progression of the disease.
Which antiretroviral drug can cause kidney injury?
Tenofovir disoproxil fumarate can cause proximal tubular injury, including Fanconi-type features such as phosphaturia and low-molecular-weight proteinuria. Renal function and serum phosphate are therefore monitored in patients taking tenofovir disoproxil fumarate.
Which other nephropathies occur in people with HIV?
Membranous nephropathy, IgA nephropathy and immune complex glomerulonephritis also occur in people with HIV, so biopsy is needed when the picture is unclear. Their management differs from HIV-associated nephropathy, which is why the histological pattern matters.