Nephropathy, HIV-Associated (HIVAN)

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Nephropathy, HIV-Associated (HIVAN)

Eric Nuermberger, MD
09-28-2009

Zambia Specific Information

Studies from South Africa have found significant rates of HIVAN and immune-complex related kidney disease in HIV+ patients.
Glack patients have higher rates of advanced glomerular disease (e.g., focal glomerulosclerosis) and nephrotic range proteinuria, even without co-existing hypertension.
Renal insufficiency prevalent in Zambia population at initiation of ART (see Mulenga ref): approximately 1/3 had some renal insufficiency. Of these 73.5% had mild (GFR 60-89 ml/min), 23.4% moderate (30-59 ml/min) and 3.1% severe (<30ml/min) disease.
Since TDF is a component of initial ART regimens in Zambia, consider screening patients prior to initiation of ART with serum creatinine +/- urine protein.
Renal disease estimated to be 3-4x more common in Africa than developed countries. Estimate of nephropathy in Zambia is that it affects 12.4% of diabetic population.

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

Approach to therapy

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

HAART

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

Angiotensin converting enzyme (ACE) inhibitors

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

Corticosteroids

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

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Abbreviations