Nephropathy, HIV-Associated (HIVAN)
Eric Nuermberger, MD
- Some information suggests that rates of HIVAN are lower in some African populations (e.g., Ethiopians) compared with prevalence in North America and Europe. Difference may be due to host genetic factors rather than viral subtypes or effective ART.
Studies from South Africa have found significant rates of HIVAN and immune-complex related disease in HIV+ patients.
- Generally, studies in black patients find higher rates of advanced glomerular disease (e.g., focal glomerulosclerosis) and nephrotic range proteinuria even without co-existing hypertension.
Zambia Information Author: Paul Auwaerter, M.D.
- Leading cause of chronic kidney disease and ESRD in HIV; 3rd leading cause of ESRD in all African Americans (20-64 yo)
- Vast predominance in blacks (95%). Other risk factors are low CD4 count and family history of renal disease.
- Typically, but not always, a late-stage manifestation of HIV (CD4 <200)
- Declining incidence in HAART era
- Nephrotic-range proteinuria may be massive and predates renal insufficiency
- Rapid progression to ESRD (in wks-mos) without treatment
- Other than proteinuria, urinalysis typically bland; nephritic profile suggests other Dx
- Without Bx, DDx includes: primary FSGS, immune complex glomerulonephritis (GN), GN assoc. with hepatitis B or C, drug-induced interstitial nephritis, amyloidosis, IgA nephropathy, IDV nephrotoxicity, thrombotic microangiopathy, ATN
- Renal Bx is gold standard for Dx. Other markers (eg, proteinuria, CD4 count, VL) are non-specific.
- Urgent renal Bx indicated by significant proteinuria (>1g/24h), increasing proteinuria, decreasing GFR, or unexplained acute or subacute renal failure; pathognomonic features: FSGS ("collapsing variant"), interstitial inflammation +/- fibrosis, microcystic tubular dilatation, tubuloreticular inclusions on EM
- Renal ultrasound: echogenic kidneys of normal-to-enlarged size
- SCREENING: All patients should have urinalysis and estimation of GFR at time of HIV Dx. Black pts or those with CD4 <200, VL >4000, diabetes, hypertension, hepatitis B or C, or family Hx of renal disease should be screened annually.
SCREENING: Proteinuria >1+ on dipstick, spot urine protein/creatine ratio >200 mg/g or GFR <60ml/min/1.73m2 is indication to quantify proteinuria and consider renal ultrasound, referral to nephrologist and renal Bx
- New guidelines exist (see ref. 1)
- Among treatment options, HAART most likely to reverse or stabilize renal dysfunction, prevent progression, and improve long-term renal and pt survival. Should also be considered for dialysis-dependent pts.
- BP should be kept <125/75, with preferential use of ACE inhibitors or angiotensin receptor blockers since they may reverse proteinuria and renal insufficiency and prevent progression to ESRD in absence of HAART. Calcium channel blockers should be avoided initially due to potential interactions with ARVs.
- Corticosteroids best viewed as rescue therapy or bridge to HAART +/- ACE inhibitor. Initial response may be dramatic, even reversing dialysis dependence, but transient.
- Early referral to nephrologist highly recommended
- Dialysis and placement of AV fistula should not be withheld on basis of HIV infection alone
- Observational data suggest HAART improves renal survival in patients with Bx-proven HIVAN
- Due to rapid progression, HIVAN is indication for HAART independent of CD4 count or VL
- No evident superiority of any antiretroviral class or agent, but use IDV or TDF with caution given risk of nephrotoxicity
- Greatest efficacy if initiated when serum creatinine <2.0, suggests benefit of screening for proteinuria or albuminuria
- No evident superiority of any particular agent
- May cause or exacerbate hyperkalemia
- Whether angiotensin receptor blockers have similar efficacy is unclear
- Observational data suggest corticosteroid therapy can rapidly, but transiently, reverse HIVAN
- Prednisone 1 mg/kg (up to 80 mg PO qd) for 2 mo, then tapered over 2-4 mos
- Exclude OIs before initiating corticosteroids and maintain vigilance for new OIs
- Monitor serum creatinine and spot urine protein/creatinine ratio