HIV-associated nephropathy: links, risks and management

Figures & data

Figure 1 HIV-associated nephropathy.

Notes: (A) Collapsing glomerulopathy. The glomerular tuft is collapsed and marked podocyte hypertrophy is observed. Podocytes show marked protein overload. Light microscopy, silver-stained section, 200× magnification. (B) Diffuse podocyte injury with complete foot process effacement and focal microvillous transformation. A tubuloreticular inclusion is observed in an endothelial cell (box). Scanning electron microscopy, 6000× magnification.

Table 1 Differential diagnosis of HIV-associated nephropathy

• HIV-associated immune complex kidney disease

• Membranoproliferative glomerulonephritis (associated with concurrent hepatitis C infection)

• Classic FSGS

• Amyloidosis

• Minimal change disease

• Post-infectious glomerulonephritis

• Thrombotic microangiopathy

• Diabetic nephropathy

• Immunoglobulin A nephropathy

• Membranous glomerulopathy

Abbreviations: FSGS, focal segmental glomerulosclerosis; HIV, human immunodeficiency virus.

Figure 2 Spectrum of APOL1-associated kidney diseases.

Abbreviations: ESRD, end-stage renal disease; FSGS, focal segmental glomerulosclerosis; HIVAN, human immunodeficiency virus-associated nephropathy.

Table 2 Risk factors and predictors of HIV-associated nephropathy

• Black race^Citation5,Citation6

• G1/G2 high-risk alleles for APOL1^Citation7^–^Citation9

• CD4 count <200/mL, high viral load >400 copies/mL^Citation29,Citation32^–^Citation34

• Proteinuria >3 g/day^Citation20,Citation21

• eGFR <90 mL/min, serum creatinine elevated from baseline^Citation20,Citation30,Citation31

Abbreviations: eGFR, estimated glomerular filtration rate; HIV, human immunodeficiency virus.

Table 3 Summary of previous studies regarding management

Management	Author, journal, year of study	Patient population	Type of study	Outcome	Reference
cART	Atta MG, Gallant JE, Rahman MH, et al. Nephrol Dial Transplantat. 2006	263 consecutive HIV-infected patients	Retrospective	Renal survival was significantly better in the group receiving ART by both univariate (p=0.025) and multivariate analyses (p<0.05), compared with no treatment	^Citation40
	Lucas GM, Eustace JA, Sozio S, Mentari EK, Appiah KA, Moore RD. AIDS. 2004	4000 HIV-positive patients, clinical diagnosis of HIVAN	12-year cohort study	The HIVAN risk was reduced to 60% (95% CI, −30% to −80%) by use of HAART	^Citation39
ACE inhibitors/ARB	Kimmel PL, Mishkin GJ, Umana WO. Am J Kidney Dis 1996	18 patients with biopsy-proved HIVAN	Case-control study	Renal survival was significantly enhanced in patients treated with captopril vs controls (mean renal survival 156±71 vs 37±5 days, respectively; p<0.002)	^Citation42
	Wei A, Burns GC, Williams BA, et al. Kidney Int 2003	44 patients with biopsy-proven HIV	Prospective study	Longer renal survival for HIV-positive patients treated with fosinopril as compared to untreated patients (relative risk: 0.003; p<0.0001)	^Citation43
Corticosteroids	Eustace JA, Nuermberger E, Choi M, Scheel PJ, Jr, Moore R, Briggs WA. Kidney Int. 2000	21 patients with biopsy-proved HIVAN	Retrospective cohort	The relative risk (95% CI) for progressive azotemia with corticosteroid treatment at 3 months was 0.20 (0.05, 0.76, p<0.05). A limited course of corticosteroid therapy in selected patients was beneficial and safe	^Citation45
	Laradi A, Mallet A, Beaufils H, et al. J Am Soc Nephrol. 1998	102 patients with biopsy-proven HIVAN	Retrospective study	Delay in the initiation of hemodialysis was observed. The proportion of patients free of dialysis at 0.5, 1 and 3 years was 73%±5%, 60%±7% and 18%± 10%, respectively	^Citation46
Kidney transplantation	Stock PG, Barin B, Murphy B, et al. N Engl J Med 2010	150 HIV-positive patients	Multicenter, prospective non-randomized, 3-year trial	A higher-than-expected rejection rate was observed, with 1- and 3 year estimates of 31% (95% CI, 24–40) and 41% (95% CI, 32–52), respectively	^Citation53
	Waheed S, Sakr A, Chheda ND, et al. PLoS ONE. 2015	11 patients with biopsy-proven HIVAN	Retrospective analysis	Delayed graft function: 64%; required postoperative dialysis within 1 week of transplant: 54%. Graft survival rates at 1 and 3 years were 100% and 81%, respectively, and acute rejection rates at 1 and 3 years were 18% and 27%, respectively	^Citation54
	Muller E, Barday Z, Mendelson M, et al. N Engl J Med. 2015	27 HIV-positive patients	Prospective non-randomized study	Rejection rates were 8% at 1 year and 22% at 3 years	^Citation55
	Muller E, Barday Z. J Am Soc Nephrol. 2018	43 kidneys from 25 HIV-positive deceased donors transplanted into HIV-positive patients	Prospective, non-randomized study	Since 2008, 43 kidneys from 25 HIV-positive deceased donors have been transplanted into patients who are HIV positive in Cape Town, South Africa Only one recipient experienced an increased viral load after the transplant, which was related to a period of noncompliance on her medication	^Citation57

Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ART, active antiretroviral therapy; cART, combined active antiretroviral therapy; HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus; HIVAN, HIV-associated nephropathy.

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