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finding, as well as findings of increased podocyte swelling, intracytoplasmic protein resorption
droplets, and diminished hyalinosis serve to distinguish HIVAN from idiopathic FSGS and from
heroin nephropathy.[927,928]
Tubulointerstitial changes are prominent and may be more severe than glomerular disease
in HIVAN. The most prominent feature is microcystic tubulointerstitial disease, which accounts
for the renal enlargement. Other changes may include tubular epithelial cell simplification, loss
or attenuation of the brush border, enlarge hyperchromatic nuclei with nucleoli, numerous
proximal tubular intracytoplasmic protein droplets, and lipid resorption droplets. The amount of
interstitial, microcystic change, atrophy, edema, fibrosis, and inflammation is variable. The
presence of tubular degenerative changes and tubular microcyst formation is more likely in
HIVAN than heroin nephropathy. The tubuloreticular inclusions seen with HIVAN by electron
microscopy are similar to the “myxovirus-like” particles of lupus nephritis.[927,928]
A subset of HIVAN cases have the predominant feature of collapsing glomerulopathy
(CG) which is characterized by focal, segmental, or global glomerular capillary collapse with
wrinkling of the basement membranes, obliteration of capillary lumens, disappearance of
endothelial and mesangial cells, and hypertrophy and hyperplasia of adjacent visceral epithelial
cells. Cases of CG are seen independent of HIV infection. CG appears to be more aggressive
than the FSGS pattern seen with HIVAN. The HIV-associated form of CG appears to occur
more commonly in blacks and on biopsy have more tubuloreticular inclusions in glomerular
endothelial cells and more cast nephropathy than cases of CG in non-HIV infected persons.[930]
HIV directly infects renal tubular cells and podocytes. The HIV nef gene appears
important for the development of the HIVAN phenotype. The nef-induced activation of Stat3 and
RAS-MAP kinase via a Src kinase-dependent pathway is responsible for podocyte proliferation
and differentiation.[928]
HIV-related immune complex disease encompasses four entities: immune complex–
mediated glomerulonephritis, immunoglobulin A (IgA) nephritis, mixed sclerotic/inflammatory
disease, and lupus-like disease. The p24 antigen contributes to immune complex formation. A
proliferative glomerulonephritis ensues and patients can present with proteinuria and renal
failure.[931] In general, renal diseases other than HIVAN in HIV infected persons progress
more slowly to renal failure.[929]

ACUTE INTERSTITIAL NEPHRITIS (AIN).-- In one study of renal biopsies in HIV-
infected persons, AIN was found in 11%. Only a fourth of cases had a classic presentation triad

of fever, rash,and pyuria. Only a fourth had significant proteinuria. Over half of the patients
were men, were of Black race, had concomitant hepatitis C infection, and were on antiretroviral
therapy. A causative drug was identified in three fourths of cases, most often a nonsteroidal anti-

inflammatory drug or sulfamethoxazole/trimethoprim. An antiretroviraldrug was the cause in
only three cases.[932]

TENOFOVIR TOXICITY.-- The antiretroviral drug tenofovir is associated with Fanconi
syndrome and declining renal function in a small number of patients. Renal tubular impairments
characteristic for Fanconi syndrome include glycosuria, aminoaciduria, hyperphosphaturia, and
hypophosphatemia. Osteomalacia may occur from impairment of renal production of vitamin
D3 (calcitriol). If tenofovir is discontinued, the Fanconi syndrome will typically abate.
However, some patients may continue to have decreased creatinine clearance. Pathologic
findings can include tubular degenerative changes, including luminal ectasia, simplification and