The following is a summary of ”Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies,” published in the June 2023 issue of the Kidney Medicine by Chebib et al.
Tolvaptan is indicated for treating patients at risk for accelerated progression of autosomal dominant polycystic kidney disease (ADPKD). A modest proportion of participants in the Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trial were aged 56 to 65. Researchers evaluated the effects of tolvaptan on the decline in estimated glomerular filtration rate (eGFR) in participants older than 55 years. This was an aggregated analysis of tolvaptan or non-tolvaptan standard of care (SOC) data from eight studies. ADPKD patients older than 55 years were included.
To reduce confounding, data from >1 studies were linked longitudinally for maximal follow-up duration, with participants matched for age, sex, eGFR, and chronic kidney disease (CKD) stage. Interventions include Tolvaptan or non-tolvaptan SOC.m Using mixed models with fixed effects for treatment, time, treatment-by-time interaction, and baseline eGFR, the impact of treatments on the annualized eGFR decline was compared. At baseline, 230 tolvaptan-treated and 907 SOC participants in the aggregated studies were older than 55. Ninety-five participant pairs from each treatment group were matched, with all participants in CKD G3 or G4 and aged 56 to 65 (tolvaptan) or 55 to 67 (SOC). Over 3 years, the eGFR annual decline rate was reduced by 1.66 mL/min/1.73 m2 (95% CI, 0.43-2.90; P = 0.009) in the tolvaptan group compared to SOC (-2.33 versus -3.99 mL/min/1.73 m2).
There is a potential for bias due to differences in the study population (bias risk was reduced through matching and multiple regression adjustment); vascular disease history data was not collected uniformly and was therefore not adjusted; and the natural history of ADPKD prevents the evaluation of specific clinical endpoints within the study time frame. Tolvaptan was associated with efficacy similar to that observed in the overall indication in patients aged 56 to 65 years with CKD G3 or G4, compared to a SOC group with a mean GFR rate of decline 3 mL/min/1.73 m2/year.
Source: sciencedirect.com/science/article/pii/S2590059523000493