The spectrum of kidney disease in patients with AIDS in the era of antiretroviral therapy

Abstract

With prolonged survival and aging of the HIV-infected population in the era of antiretroviral therapy, biopsy series have found a broad spectrum of HIV-related and co-morbid kidney disease in these patients. Our study describes the variety of renal pathology found in a prospective cohort of antiretroviral-experienced patients (the Manhattan HIV Brain Bank) who had consented to postmortem organ donation. Nearly one-third of 89 kidney tissue donors had chronic kidney disease, and evidence of some renal pathology was found in 75. The most common diagnoses were arterionephrosclerosis, HIV-associated nephropathy and glomerulonephritis. Other diagnoses included pyelonephritis, interstitial nephritis, diabetic nephropathy, fungal infection and amyloidosis. Excluding 2 instances of acute tubular necrosis, slightly over one-third of the cases would have been predicted using current diagnostic criteria for chronic kidney disease. Based on semi-quantitative analysis of stored specimens, pre-mortem microalbuminuria testing could have identified an additional 12 cases. Future studies are needed to evaluate the cost-effectiveness of more sensitive methods for defining chronic kidney disease, in order to identify HIV-infected patients with early kidney disease who may benefit from antiretroviral therapy and other interventions known to delay disease progression and prevent complications.

Figure 1. HIV-associated nephropathy

On blinded review of kidney tissue obtained at the time of rapid autopsy, 15 of the 89 MHBB kidney tissue donors had findings consistent with HIV-associated nephropathy (HIVAN). (a) Low power view illustrates many glomerular microcysts and collapsed glomeruli with dilatation of the urinary space (PAS, original magnification × 100). (b) A segment of the glomerular tuft is obliterated by matrix material with capping of the overlying podocytes (PAS, original magnification × 600). (c) There is global tuft collapse with podocyte vacuolation and dilatation of the urinary space (PAS, original magnification × 400).

Figure 2. Membranoproliferative glomerulonephritis

Another common pathologic diagnosis in MHBB kidney tissue donors was membranoproliferative glomerulonephritis (MPGN). Among the 7 cases of MPGN, 3 were associated with hepatitis C virus coinfection. (a) There is global mesangial expansion by increased mesangial cell number and matrix. The glomerular capillary lumina are narrowed by extensive duplication of glomerular basement membranes (PAS, original magnification × 400). (b) Membranoproliferative pattern with thrombotic microangiopathy. There are many fibrin thrombi on a background of endothelial swelling and double contouring of glomerular basement membranes (PAS, original magnification × 400).

Figure 3. Other renal pathology identified in MHBB kidney tissue donors

(a) Diabetic glomerulosclerosis. There is global mesangial sclerosis with segmental nodule formation. Glomerular basement membranes and Bowman’s capsule are also thickened (PAS, original magnification × 400). (b) Chronic interstitial nephritis. There is diffuse lymphocytic interstitial inflammation, fibrosis, and tubulitis, with sparing of glomeruli (PAS, original magnification × 200). (c) Indinavir nephrotoxicity. The tubules contain many intraluminal clear crystals with mononuclear reaction (PAS, original magnification × 400). (d) Cryptococcus. Large rounded yeast forms dilate several glomerular capillaries. (PAS, original magnification × 400). (e) Candidiasis. Hyphal forms infiltrate the interstitium and tubules (PAS, original magnification × 400). (f) Amyloidosis. The glomerular tuft is obliterated by pale amorphous material that also occupies the renal interstitium (PAS, original magnification × 400).