HIV-Associated Nephropathy: Clinical Presentation and Natural Course
HIVAN does NOT cause rapidly progressive glomerulonephritis (RPGN) within days after starting antiretroviral therapy; rather, ART dramatically slows disease progression and may improve renal function. 1, 2, 3
Signs and Symptoms of HIVAN
Classic HIVAN presents with:
- Heavy proteinuria (often nephrotic-range) with extensive podocyte foot process effacement 4
- Rapid decline in kidney function without treatment 2, 5
- Occurs predominantly in Black patients between ages 20-64 years 5, 6
- Strongly associated with severe immunosuppression and low CD4+ counts 2
- Majority of patients have AIDS-defining conditions at diagnosis 5
- Requires APOL1 high-risk genotypes (G1 and G2 variants) plus a "second-hit" event for disease manifestation 2
Natural Course Without Treatment
HIVAN is one of the most aggressive forms of kidney disease:
- Progression to end-stage renal disease occurs within weeks to months without treatment 2, 5
- Average time to ESRD is 3.9 months in untreated patients 2
- GFR declines at 4.3 mL/min/month without antiretroviral therapy 2, 6
- Renal survival is only 12.5% without treatment 2
Effect of Antiretroviral Therapy on Disease Course
ART dramatically improves outcomes rather than causing acute deterioration:
- Time to ESRD increases from 3.9 months to 18.4 months with ART 2
- GFR decline slows from 4.3 mL/min/month to 0.08 mL/min/month with treatment 2, 6
- Renal survival improves from 12.5% to 18.1% with ART 2
- ART should be initiated immediately in all patients with biopsy-proven HIVAN, regardless of CD4 count 4, 1, 3
- Achieving HIV RNA suppression to <200 copies/mL is associated with improved outcomes 2
HIVAN Does Not Present as RPGN After Starting ART
The evidence clearly demonstrates that ART improves rather than worsens HIVAN. The disease naturally progresses rapidly over weeks to months when untreated, but this is the natural course of the disease itself, not a complication of starting therapy 2, 5. ART dramatically slows this progression and may even improve kidney function 6, 3.
Histopathology
Classic HIVAN is defined by:
- Collapsing glomerulopathy with glomerular basement membrane collapse 4, 2
- Hypertrophy and hyperplasia of glomerular epithelial cells forming "pseudocrescents" 4
- Tubular microcyst formation 4, 2
- Interstitial inflammation and tubular injury 4, 2
- Diffuse podocyte foot process effacement on electron microscopy 4, 2
Critical Diagnostic Considerations
Kidney biopsy is essential because:
- Up to 50% of HIV-positive patients with glomerular disease have lesions other than classic HIVAN 2, 7
- The spectrum has shifted post-ART era toward immune complex glomerulonephritis, diabetic nephropathy, and non-collapsing FSGS 4, 7
- Biopsy differentiates HIVAN from ART nephrotoxicity, immune complex disease, and comorbid conditions 4, 8
- Classic HIVAN has the poorest 5-year kidney survival compared to other HIV-related kidney diseases 7
Common Pitfall to Avoid
Do not delay or withhold ART due to concerns about worsening kidney function. The evidence overwhelmingly demonstrates that early ART initiation benefits kidney outcomes in HIVAN, and modern antiretroviral regimens have improved safety profiles 1. The rapid progression seen in HIVAN is the natural course of untreated disease, not a consequence of starting therapy 2, 5.