Viral DNA in microdissected renal biopsy tissue from HIV infected patients with nephrotic syndrome

Abstract

Focal glomerulosclerosis (FGS) has been considered as HIV-associated nephropathy, a specific renal complication of infection. To determine whether renal disease in HIV infected patients has one highly prevalent pathologic expression, and whether renal parenchymal viral genomic incorporation affects pathologic outcome, we reviewed renal biopsies performed at our center. Twenty-eight HIV infected patients with nephrotic range proteinuria underwent renal biopsy for diagnosis of renal disease: 85.7% led homosexual or bisexual lifestyles; 10.7% admitted to intravenous drug use; and 85.7% were Black. Only 53.6% had FGS; 28.6% had glomerulonephritis. Two patients had diabetic renal disease; 93.3% of patients with FGS and 87.5% of patients with glomerulonephritis were Black. Paraffin slides of twenty-two of the patients' renal biopsies were evaluated by polymerase chain reaction (PCR) for the presence of HIV DNA, using primers and probes to the gag gene, detected by liquid hybridization and polyacrylamide gel electrophoresis. Twenty-one of the twenty-two evaluated tissue specimens showed the presence of HIV DNA. Microdissection studies of glomeruli, tubules, interstitial cells and infiltrating inflammatory cells showed the presence of HIV genome in all but interstitial cells. HIV infected patients without renal disease also had positive PCR evaluations of microdissected tissue, while non-infected patients were all negative. We conclude that although focal glomerulosclerosis is the most common renal pathologic lesion in patients with HIV infection and nephrotic range proteinuria, glomerulonephritis is a relatively frequent finding. HIV genome is present in renal tissue in HIV infected subjects with nephrotic range proteinuria, but is also found in HIV infected subjects without nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Emerging Paradigms in the Renal Pathology of Viral Diseases

“…Cohen et al (1) first reported the presence of HIV RNA in podocytes as revealed by in situ hybridization (ISH) in 1989, a finding that was supported by microdissection studies of Kimmel et al (2). These studies were difficult to validate because of the failure of others to replicate these findings using conventional techniques of ISH, the inability to demonstrate the presence of viral peptides in renal parenchymal cells by immunohistochemistry, and the inability to demonstrate appropriate receptors for viral entry into cells, namely CD4 and the chemokine receptors CXCR4 or CCR5, on renal parenchymal cells (3).…”

HIV-1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas upregulation.

“…Acute renal failure secondary to tubular injury is also frequent in AIDS (6). In cases of HIVAN, viral antigens and genome have been demonstrated in microdissected renal tissues (8), but the permissiveness of renal cells to replication of HIV-1 is still controversial (9)(10)(11)(12)(13)(14). The finding of apoptotic cells in glomeruli and especially in tubuli of HIV patients may suggest a possible mechanism of HIV-induced renal damage (15).…”

Mapping a locus for susceptibility to HIV-1-associated nephropathy to mouse chromosome 3

“…Clinically, it is characterized by the development of proteinuria usually followed by rapid progression to renal failure; pathological features include focal and segmental glomerulosclerosis with characteristic glomerular collapse, podocyte hyperplasia, pronounced tubulo-interstitial inflammation and microcystic tubular dilation, and epithelial dedifferentiation, proliferation, and apoptosis (6)(7)(8)(9). HIVAN results from direct epithelial infection (10)(11)(12)(13); however, the mechanisms underlying disease susceptibility and progression remain unknown.…”