HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy

Abstract

The classic kidney disease of human immunodeficiency virus (HIV) infection, HIV-associated nephropathy, is characterized by progressive acute renal failure, often accompanied by proteinuria and ultrasound findings of enlarged, echogenic kidneys. Definitive diagnosis requires kidney biopsy, which shows collapsing focal segmental glomerulosclerosis with associated microcystic tubular dilatation and interstitial inflammation. Podocyte proliferation is a hallmark of HIV-associated nephropathy, although this classic pathology is observed less frequently in antiretroviral-treated patients. The pathogenesis of HIV-associated nephropathy involves direct HIV infection of renal epithelial cells, and the widespread introduction of combination antiretroviral therapy has had a significant impact on the natural history and epidemiology of this unique disease. These observations have established antiretroviral therapy as the cornerstone of treatment for HIV-associated nephropathy in the absence of prospective clinical trials. Adjunctive therapy for HIV-associated nephropathy includes angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, as well as corticosteroids in selected patients with significant interstitial inflammation or rapid progression.

Figure 1

The glomerular capillary lumina are globally obliterated by collapse of glomerular basement membranes with hypertrophy and hyperplasia of overlying podocytes (Jones methenamine silver, x400). [COLOR PRINT/ ONLINE]

Figure 2

The podocytes surrounding the collapsed tuft form a corona of hypertrophied cells with numerous protein resorption droplets. Some of the podocytes appear detached from the tuft and suspended in the urinary space (Jones methenamine silver, x400). [COLOR PRINT/ ONLINE]

Figure 3

The podocyte hyperplasia forms pseudocrescents that obliterate the urinary space, (Jones methenamine silver, x400). [COLOR PRINT/ ONLINE]

Figure 4

Overlying the collapsed tuft, the enlarged podocytes contain abundant trichromred protein resorption droplets (Masson trichrome, x400). [COLOR PRINT/ ONLINE]

Figure 5

There are focally distended tubules forming microcysts that contain loose proteinaceous casts. Adjacent cortical tubules display degenerative changes (H&E, x200). [COLOR PRINT/ ONLINE]

Figure 6

The collapsed capillaries have wrinkled glomerular basement membranes and are surrounded by hyperplastic visceral epithelial cells that obliterate the urinary space, in continuity with adjacent parietal epithelial cells (electron micrograph, x3000).

Figure 7

A high power view shows podocyte hypertrophy with open-appearing cytoplasm and complete effacement of foot processes. One of the podocytes contains prominent intracytoplasmic protein resorption droplets (electron micrograph, x5000).

Figure 8

A large tubulo-reticular inclusion is seen within a glomerular endothelial cell (electron micrograph, x40,000).

Figure 9

A tubule is lined by hyperplastic epithelial cells with enlarged regenerative nuclei containing prominent nucleoli (electron micrograph, x4000).

Figure 10

In an area of back-to-back tubular microcyst formation, the lining epithelial cells of 2 individual microcysts appear flattened and compressed by the voluminous proteinaceous electron dense cast material, (electron micrograph, x3000).