Acute kidney disease among Zambian adults initiating tenoforvir disoproxil fumarate-based antiretroviral therapy

Tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy ART is the commonest first-line regimen worldwide; however, it causes nephrotoxicity that primarily occurs in the first three to six months following initiating therapy. The TDF-associated nephrotoxicity can manifest as AKI that may lead to direct complications including permanent loss of kidney function, chronic kidney disease (CKD), end-stage kidney disease (ESKD) requiring dialysis and to indirect complications such as cardiovascular diseases.Tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy ART is the commonest first-line regimen worldwide; however, it causes nephrotoxicity that primarily occurs in the first three to six months following initiating therapy. The TDF-associated nephrotoxicity can manifest as AKI that may lead to direct complications including permanent loss of kidney function, chronic kidney disease (CKD), end-stage kidney disease (ESKD) requiring dialysis and to indirect complications such as cardiovascular diseases.

We prospectively followed 205 ART-naïve Zambian adults at the adult infectious disease research centre (AIDC) in Lusaka for three months from the day of initiating TDF-based therapy to determine the incidence of TDF-associated nephrotoxicity. We defined TDF-associated nephrotoxicity as meeting any of the following criteria: 1) An episode of estimated glomerular filtration rate (eGFR)< 60ml/ min/1.73m2 for< 3 months, 2) reduced eGFR by> 35% for< 3 months or 3) increased serum creatinine by> 50% in 3 months.

A total of 45 (22%) developed TDF-associated nephrotoxicity; but there was no statistically significant difference in the demographics, clinical and laboratory parameters between the patients that did and those that did not suffer nephrotoxicity. We concluded that a mere assessment of baseline clinical and laboratory characteristics was not enough to distinguish or classify patients’ risk for TDF-associated nephrotoxicity.

Methods
Participants were systematically randomly sampled to include every other Antiretroviral-naive adult that clinicians initiated on tenofovir disoproxil fumarate based therapy. The study was a prospective observational cohort of 205 participants. The study was done within the confines of standard clinical practice, where only candidates that the clinicians initiated on TDF-based therapy were invited to participate in the study. The investigators had no control over whom the clinicians initiated on therapy; they initiated participants based on the Zambian national ART treatment guidelines and their expert clinical discretion of the risk for TDF-associated nephrotoxicity.