title: Early markers of tubular dysfunction in antiretroviral-experienced HIV-infected patients treated with tenofovir versus abacavir.
abstract: Tenofovir disoproxil fumerate (TDF) is an effective nucleoside reverse transcriptase inhibitor for HIV infection but it is potentially nephrotoxic. A selective mithochondrial toxicity has been hypothesized. To assess early markers of renal toxicity, we evaluated a cohort of antiretroviral (ARV)-experienced HIV patients who had been switched from a thymidinic backbone to either a TDF/emtricitabine regimen (TDF; 73 patients) or an abacavir/lamivudine (ABV) regimen (28 patients). Markers of mitochondrial toxicity (cytochrome c, Cyc) or cytosolic (α-glutathione S transferase, α-GST) together with common indicators of renal damage were assessed at baseline (T0) and after 1 (T1), 3 (T2), 6 (T3), and 12 (T4) months of patient exposure to therapy. Clinical features of both groups were comparable at T0. There was no significant variation in estimated glomerular filtration rate (eGRF), median urine protein excretion, or microalbuminuria and serum phosphate levels in both groups during the study period. There was a significant increase in urinary excretion of phosphate in patients on TDF compared to those on ABV at T3 and T4. Fractional excretion of uric acid was also altered in the two treatment groups; there was no change in the ABV (constantly less than 0.10), but a progressive increase in TDF patients. Serum potassium levels were significantly lower in ABV than in TDF treated patients. Urine concentrations of α-GST showed a nonsignificant variation in both groups, while Cyc excretion was significantly higher at T1 and T3 in TDF-treated compared to ABV-treated patients. In conclusion, TDF may be associated with subclinical mitochondrial damage, inducing at a later stage increased urinary excretion of phosphate and uric acid, as markers of incipient tubular injury.
authors.affiliation: Division of Infectious Disease, University of Bari, Bari, Italy. p_maggi@yahoo.com
authors.forename: Paolo
authors.initials: P
authors.lastname: Maggi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Montinaro
authors.forename: Chiara
authors.initials: C
authors.lastname: Bellacosa
authors.forename: Stefania
authors.initials: S
authors.lastname: Pietanza
authors.forename: Anna
authors.initials: A
authors.lastname: Volpe
authors.forename: Giusi
authors.initials: G
authors.lastname: Graziano
authors.forename: Giovanni F M
authors.initials: GF
authors.lastname: Strippoli
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Angarano
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D045304:Cytochromes c / Q000652:urine*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects*; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D005919:Glomerular Filtration Rate; D005982:Glutathione Transferase / Q000652:urine*; D015658:HIV Infections / Q000188:drug therapy* / Q000652:urine; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000652:urine*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000503:physiopathology; D019259:Lamivudine / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects*; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D000068698:Tenofovir; D013997:Time Factors; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D015415:Biomarkers; D045304:Cytochromes c; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D005982:Glutathione Transferase; D019259:Lamivudine; D063065:Organophosphonates; D000068698:Tenofovir; D000099227:Abacavir; C492871:abacavir, lamivudine drug combination