Spectrum of Renal Injury with Antiretroviral Therapy.
Christine A VanBeek, Arthur H Cohen, Mark Haas, Cynthia C Nast. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Antiretroviral therapy (ART) agents are associated with various forms of renal injury. Nucleotide reverse transcriptase inhibitors (NtRTI) tenofovir (T), adefovir (Ad) and cidofovir (Cd) cause tubular mitochondrial injury; T is used in HIV while Ad and Cd are given for other viral infections. Nucleoside reverse transcriptase inhibitors (NsRTI) also may induce mitochondrial injury, while protease inhibitor indinavir (IDV) causes crystal deposition and rarely interstitial nephritis. We sought to assess the range of renal injury in biopsies from patients on ART.
Design: From 2000-2010, 101 biopsies from 101 patients on ART had adequate material and were included. Biopsies were evaluated by light (LM), immunofluorescence and electron (EM) microscopies, and available clinical and laboratory data were reviewed. Abnormal (A) tubular cell mitochondria (TCM) were defined as >1000 nm in width, with broken, absent or distorted cristae, and irregular non-uniform shape.
Results: Of 101 biopsies, 54 had ATCM. This included 38 of 57 (67%) patients on T with tubular cell damage (TCD) by LM and serum creatinine (Cr) from 1.5 to 14 (mean 4.7) mg/dl. Of those with available data, 53% had glycosuria with normal serum glucose. In patients taking ART other than T, 16 of 44 (29%) demonstrated ATCM and TCD with Cr from 1.5 to 8.5 (mean 3.5)mg/dl. One of these patients discontinued T 4 months prior to biopsy for nephrotoxicity, but had persistent renal failure. Other medications in this group included Cd for CMV retinitis (1), Ad for hepatitis B (2), NsRTIs for HIV (9) and 3 were on regimens without Ns- or NtRTIs. Ultrastructurally, affected tubular cells contained from a single to > 50% ATCM. Each involved tubule had from one to many (up to 70%) affected cells. By LM, tubules with TCD were clustered, and comprised from < 5% to > 50% of tubules. Other ART associated lesions included 2 cases of IDV-induced crystal-containing casts. The remaining 45 cases (18 on T, 27 not on T) had normal TCM and diagoses of ATN (24), ATN with interstitial nephritis (10), interstitial nephritis (9) and 2 without tubulo-interstitial injury.
Conclusions: ATCM are found in 54% of biopsies from patients receiving ART; of these, 30% occur in the absence of T treatment. Patients receiving Cd and Ad for non-HIV viral infections and those on ART other than NtRTI may develop this form of tubular damage. ATCM may occur in small numbers in few tubular cells, and patients with progressive renal failure may have only few affected cells. Therefore, careful ultrastructural evaluation is required in all patients receiving ART for identification of this lesion.
Category: Kidney (does not include tumors)
Monday, February 28, 2011 1:30 PM
Platform Session: Section H, Monday Afternoon