The Efficacy and Safety of N-acetylcysteine and Taurine (Nefrosave®) in Chronic Kidney Disease: A Double-Blind, Multicenter, Placebo-Controlled Trial (DELAY-CKD)

Background and objective Chronic kidney disease (CKD) is a progressive disorder with declining renal function and an elevated risk for end-stage renal disease (ESRD) and mortality. While oxidative stress is implicated in its pathogenesis, treatment using antioxidants remains uncertain. This study aimed to evaluate the effectiveness of the combination of N-acetylcysteine (NAC; 150 mg) and taurine (500 mg) in CKD. Methods A multicenter, double-blind, randomized, placebo-controlled trial was conducted across India between February 2021 and October 2023. Consenting adults aged 18-65 years with CKD stages 1-3 and serum creatinine <3.0 mg/dL were enrolled. Participants received NAC+taurine (Nefrosave®) or an identical placebo twice daily for 180 days, in addition to standard of care (SOC) and a low-protein diet. Primary endpoints included mean changes in urinary albumin-creatinine ratio (uACR), serum cystatin C, and estimated glomerular filtration rate (eGFR) from baseline to day 180. Secondary endpoints included time to event (hemodialysis, renal transplantation, treatment escalation). Safety was analyzed on the basis of adverse events (AEs). Results Efficacy analysis was conducted in 80 of the 100 randomized participants (NAC+taurine+SOC: 42; placebo+SOC: 38). Early-stage CKD (stages 1 and 2) was identified in 11 (26.19%) and 11 (28.95%) participants in the test and control arms, respectively. Microalbuminuria was observed in 10 (23.81%) participants in the NAC+taurine+SOC arm and 14 (36.84%) in the placebo+SOC arm. An overall 18.57% reduction in uACR at day 180 was observed with NAC+taurine supplementation compared with placebo, including a 34.09% reduction in microalbuminuria and a 19.34% reduction in macroalbuminuria; the between-group difference reached statistical significance for microalbuminuria (p=0.043). Overall, cystatin C decreased by 21.46% in the NAC+taurine+SOC arm, representing a 39.17% greater reduction than in the placebo+SOC arm (p=0.079). The increase in serum creatinine was lower in the NAC+taurine+SOC arm (0.03 mg/dL (1.78%)) compared with placebo+SOC (0.19 mg/dL (11.52%)), resulting in an overall relative reduction of 9.74% in the test arm. Comparable relative reductions were observed in CKD stages 1 and 2 (27.43%) and among participants with microalbuminuria (20.41%) in the NAC+taurine+SOC arm compared with placebo+SOC. Modest increases in mean eGFR were observed with NAC+taurine supplementation in CKD stage 3a, although overall changes were comparable to placebo+SOC. No clinically significant events were reported. Mild AEs were reported in five participants in the test arm. Conclusions Adjunctive NAC+taurine (Nefrosave®) therapy was well tolerated and was associated with favorable trends in albuminuria and other renal biomarkers as compared to SOC. The between-group difference in uACR reached statistical significance in participants with microalbuminuria and early CKD, supporting the need for further evaluation of this adjunctive strategy in larger trials.