Change in Renal Function among HIV-Infected Koreans Receiving Tenofovir Disoproxil Fumarate-Backbone Antiretroviral Therapy: A 3-Year Follow-Up Study

Abstract

PurposeTenofovir disoproxil fumarate (TDF) is commonly prescribed as a fixed-dose, co-formulated antiretroviral drug for HIV-1 infection. The major concern of long-term TDF use is renal dysfunction. However, little is known about the long-term patterns of changes in renal function in HIV-infected Koreans receiving TDF.Materials and MethodsWe prospectively followed 50 HIV-infected Koreans, performing laboratory tests every 3 months during the first year and every 6 months for the next 2 years. Urine N-acetyl-β-D-glucosaminidase (NAG) and plasma cystatin-C were measured using samples collected in the first year. Data on renal function were retrospectively collected on HIV-infected patients receiving first-line TDF (n=40) and in antiretroviral therapy (ART)-naïve patients (n=24) for 3 years. Renal function was evaluated as estimated glomerular filtration rate (eGFR) from serum creatinine [Modification of Diet in Renal Disease (MDRD)] and cystatin-C.ResultsThe eGFR (cystatin-C) showed significant changes from 0 to 48 wks (p=0.002), with the lowest levels at 24 wks (84.3±18.8 mL/min vs. 90.3±22.5 mL/min, p=0.021 by post hoc test). Urine NAG levels did not differ at 0, 12, 24, and 48 wks, although eGFR (MDRD) significantly decreased from 0 (98.7±18.9 mL/min/1.73 m2) to 144 wks (89.0±14.7 mL/min/1.73 m2) (p=0.010). The first-line TDF group had significantly lower eGFR (MDRD) than the ART-naïve group at 144 wks (89.7 mL/min/1.73 m2 vs. 98.4 mL/min/1.73 m2, p=0.036). Thirteen (26%) participants experienced a decrease in renal impairment of 10 mL/min/1.73 m2 in eGFR (MDRD) at 144 wks.ConclusionThese data suggest that clinically meaningful renal injury can develop in HIV-infected Koreans receiving long-term TDF.

A study of renal dysfunction among HIV-infected patients on tenofovir based ART regimen in the Northeast part of India

“…This acquired renal tubular mitochondriopathy eventually drives epithelial cells cells to apoptosis, resulting in proximal tubular damage and renal injury. 13 The prevalence of tenofovir-related renal dysfunction found in this study was higher than previously reported randomized controlled trials and cohort studies from western countries which showed a prevalence ranging from 4% to 11%. 14,15 However, retrospective cohort studies from Asian region have shown similarly high rates of renal dysfunction.…”

“…22 This contradicting result is supported by a study conducted by Kyoung HL et al which showed that tenofovir-related renal dysfunction had no relationship to BMI. 13 This study found a high prevalence of renal dysfunction among HIV patients receiving tenofovir-based ART regimen. Old age, low CD4 cell count, HCV co-infection, and advanced HIV infection were found to be important risk factors for the development of renal dysfunction.…”

“…14,15 However, retrospective cohort studies from Asian region have shown similarly high rates of renal dysfunction. 13,16,17 A study conducted by Kyuong HL et al among HIV infected Koreans found a prevalence of 27%. 13 One of the postulated explanations for this is the lower BMI of the patients in Asia as well as genetic predisposition.…”

“…13,16,17 A study conducted by Kyuong HL et al among HIV infected Koreans found a prevalence of 27%. 13 One of the postulated explanations for this is the lower BMI of the patients in Asia as well as genetic predisposition. 17 Polymorphism in the genes encoding proximal tubular transportes, such as the ABCC2 and ABCC4 genes, have been postulated to increase the plasma concentration of tenofovir and hence an increased risk of nephrotoxicity.…”

Reduced Kidney Function in Tenofovir Disoproxil Fumarate Based Regimen and Associated Factors: A Hospital Based Prospective Observational Study in Ethiopian Patients

“…Several studies revealed fall greater than 25% and mean change in estimated glomerular filtration rate (eGFR) relative to baseline in TDF based antiretroviral regimen. The prevalence of fall greater than 25% in eGFR in those studies varied from country to country and it was found in the range of 6% to 40.8% [9, 15–20]. There is no study in Africa as well as in Ethiopia to show the extent of fall in eGFR greater than 25% relative to baseline.…”