HIV-associated nephropathy (HIVAN) is a major renal complication in patients with HIV , particularly those who are not on antiretroviral therapy (ART) . It is characterized by a rapidly progressive kidney disease and is more common among individuals with advanced HIV or those noncompliant with ART .
Epidemiology
- HIVAN occurs almost exclusively in individuals of African descent , accounting for ~90% of HIVAN-related end-stage renal disease (ESRD) cases.
- Risk is significantly reduced with early and sustained ART .
- A strong association exists between HIVAN and APOL1 gene polymorphisms , particularly among individuals of West African ancestry.
Pathogenesis
- Direct infection of renal epithelial cells (podocytes and tubular cells) by HIV plays a critical role.
- Systemic immune dysregulation and genetic susceptibility (especially APOL1 variants) contribute to disease progression.
- HIVAN is histologically identified as a collapsing form of focal segmental glomerulosclerosis (FSGS) with prominent tubulointerstitial inflammation and microcystic dilation .
Clinical Presentation
Patients with HIVAN often present with features of nephrotic syndrome and rapidly declining renal function.
Key Features:
| Clinical Feature | Description |
|---|---|
| Proteinuria | Nephrotic-range (>3.5 g/day) |
| Renal Function | Elevated serum creatinine (azotemia) |
| Serum Albumin | Hypoalbuminemia |
| Lipids | Hyperlipidemia |
| Urinalysis | Microhematuria, leukocytes, hyaline casts, oval fat bodies |
| Blood Pressure | Typically normal or low , not hypertensive |
| Kidney Ultrasound | Normal to enlarged kidneys, high echogenicity |
| CD4 Count | Often <200 cells/μL |
| Electrolytes | Hyponatremia, hyperkalemia (due to nephrotic state or SIADH) |
| Complement Levels | Usually normal |
Differential Diagnosis
The spectrum of HIV-related kidney disease includes:
1. Glomerular-Dominant Nephropathies
- HIVAN (collapsing FSGS)
- HIV Immune Complex Kidney Disease (HIVICK)
2. Tubulointerstitial-Dominant Nephropathies
- ART-induced acute tubular injury
- Drug-induced interstitial nephritis (non-ART)
- Opportunistic infections (bacterial, viral, fungal)
- Tubulointerstitial injury related to HIVAN
3. Vascular-Dominant Nephropathies
- Thrombotic microangiopathy
- HIV-associated atherosclerosis
4. Other Nephropathies in HIV
- Diabetic nephropathy
- Age-related nephrosclerosis
Diagnosis
- Renal biopsy is the gold standard: shows collapsing glomerulopathy, microcystic tubular dilation, and interstitial inflammation.
- HIV viral load , CD4 count , and APOL1 genotyping may support diagnosis and risk stratification.
- Imaging (renal ultrasound): typically reveals large, echogenic kidneys .
Management
1. Antiretroviral Therapy (ART)
- Cornerstone of treatment : slows progression, may reverse HIVAN in early stages.
- Early initiation of ART improves renal and overall survival outcomes.
2. Adjunctive Therapies
| Therapy | Role |
|---|---|
| ACE inhibitors/ARBs | Reduce proteinuria and slow CKD progression (e.g., captopril, losartan) |
| Corticosteroids | Considered in progressive disease unresponsive to ART; used cautiously due to side effects |
| Blood pressure control | Target <130/80 mmHg if proteinuric |
⚠️ Note: Long-term ART is associated with other nephrotoxic risks such as arterionephrosclerosis , diabetic nephropathy , and non-collapsing FSGS .
Prognosis
- Without treatment, HIVAN progresses rapidly to end-stage renal disease (ESRD) .
- With ART , kidney function can be stabilized or even improved, especially if treatment begins early.
- ESRD secondary to HIVAN is a leading cause of dialysis in HIV-positive patients in some regions.
Key Takeaways for Exams and Clinical Practice
- HIVAN is more common in African descent due to APOL1 gene variants.
- Presents with nephrotic-range proteinuria , normal blood pressure , and echogenic enlarged kidneys .
- Initiate ART immediately upon diagnosis.
- Add ACE inhibitors or ARBs to reduce proteinuria.
- Consider renal biopsy for definitive diagnosis if clinical suspicion is high.
- Monitor renal function and proteinuria closely in HIV-positive patients, especially if ART adherence is poor.
