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

Abstract

Purpose: Tenofovir 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 methods: We 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.

Results: The 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.

Conclusion: These data suggest that clinically meaningful renal injury can develop in HIV-infected Koreans receiving long-term TDF.

Keywords: HIV; anti-retroviral therapy; cystatin-C; eGFR; renal toxicity; tenofovir.

Fig. 1. Characteristics of 50 HIV-infected individuals in a prospective cohort whose eGFR measured by plasma cystatin-C declined between 0, 12, 24, and 48 wks. (A) 17 individuals who had the decline of ≥10 mL/min and spontaneous recovered. All data are expressed as symbols. Lines within boxes are mean values, and upper and lower horizontal lines of boxes are upper and lower values of SD, respectively. Error bars and vertical lines are ranges of total value showing maximum and minimum levels. (B) Four participants with continuously declining eGFR. Δ=subtraction of eGFR at 48 wks from eGFR at 0 wk. eGFR, estimated glomerular filtration rate.

Fig. 2. Changing patterns of eGFR by CKD-EPI (A) or MDRD (B), and SCr (C). Changing patterns of eGFR by CKD-EPI or MDRD and Scr over 3 years in a prospective cohort (n=50). Upper lines of histograms are mean values, and error bars indicate upper and lower values of SD. p-values by linear mixed model are at the bottom. ^*p<0.01, ^†p<0.05 by Post-hoc test using paired t-test with Bonferroni correction. eGFR, estimated glomerular filtration rate; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; MDRD, Modification of Diet in Renal Disease; SCr, serum creatinine.

Fig. 3. Changes in eGFR by CKD-EPI (A) or MDRD (B), and SCr (C). Change in eGFR by CKD-EPI or MDRD and SCr level in first-line tenofovir-backbone ART and ART-naïve groups in a retrospective cohort. Symbols in each line indicate median value. ^*p<0.05 by Mann-Whitney U test. eGFR, estimated glomerular filtration rate; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; MDRD, Modification of Diet in Renal Disease; SCr, serum creatinine; ART, antiretroviral therapy; TDF, tenofovir disoproxil fumarate.