Long-term renal survival in HIV-associated nephropathy with angiotensin-converting enzyme inhibition.

BACKGROUND: Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the most common cause of end-stage renal disease (ESRD) in HIV-infected patients. Angiotensin-converting enzyme (ACE) inhibition has previously shown a short-term benefit in HIVAN. This study examines the long-term effects of ACE inhibition on renal survival in HIVAN. METHODS: In this single-center prospective cohort study, 44 patients with biopsy-proven HIVAN were enrolled prior to the onset of severe renal insufficiency (serum creatinine or=two antiviral drugs for >or=30 consecutive days, CD4 lymphocyte count, initial median serum creatinine concentration, or proteinuria. Risk of renal failure was reduced with ACE inhibitors (RR = 0.003, P < 0.0001). Exposure to antiretroviral therapy did not have a significant impact on the risk of renal failure. Of the ACE inhibitor-treated group, 87.5% survived compared with 21.4% of the control group (P < 0.001). CONCLUSION: ACE inhibition initiated prior to severe renal insufficiency may offer long-term renal survival benefits in HIVAN. Diagnosis should be sought early in patients with clinical signs suggestive of HIVAN.

Renal epithelium is a previously unrecognized site of HIV-1 infection.

The striking emergence of an epidemic of HIV-related renal disease in patients with end-stage renal disease provided the rationale for the exploration of whether HIV-1 directly infects renal parenchymal cells. Renal glomerular and tubular epithelial cells contain HIV-1 mRNA and DNA, indicating infection by HIV-1. In addition, circularized viral DNA, a marker of recent nuclear import of full-length, reverse-transcribed RNA, was detected in the biopsies, suggesting active replication in renal tissue. Infiltrating infected leukocytes harbored more viral mRNA than renal epithelium. Identification of this novel reservoir suggests that effectively targeting the kidney with antiretrovirals may be critical for patients who are seropositive with renal disease. Thus, renal epithelium constitutes a unique and previously unrecognized cell target for HIV-1 infection.