Tolvaptan delays kidney failure in polycystic kidney disease
Long-term efficacy of tolvaptan used to treat patients with autosomal dominant polycystic kidney disease (ADPKD), a common cause of kidney failure showed a slower rate of kidney function decline compared with historical controls, according to the findings of a study recently published in the Clinical Journal of the American Society of Nephrology (CJASN).
ADPKD is the fourth leading cause of end-stage kidney disease which is triggered by the hormone vasopressin. Two similar trials; the three-year TEMPO 3:4 and in the one-year REPRISE phase 3 clinical trials, showed that tolvaptan (a vasopressin receptor antagonist) slowed the decline of kidney function in patients with ADPKD at early and later stages of chronic kidney disease, respectively. The results suggest that tolvaptan might delay the need for dialysis or kidney transplantation, provided that its effect on kidney function decline is sustained and cumulative over time, beyond the relatively short duration of TEMPO 3:4 and REPRISE.
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Vicente Torres, MD, Ph.D. (Mayo Clinic) and his associates retrospectively analyzed information on 97 ADPKD patients treated with tolvaptan for up to 11 years at the Mayo Clinic. Kidney function was measured as estimated glomerular filtration rate (eGFR).
- Patients treated with tolvaptan had lower eGFR slopes compared with controls (-1.97 vs -3.50 ml/min per 1.73 m2 per year) and a lower risk of a 33% reduction in eGFR from baseline.
- Also, the annualized eGFR slopes of patients treated with tolvaptan did not change with the duration of follow-up.
- The investigators also compared the eGFR values observed at the last follow-up in the tolvaptan-treated patients to the anticipated last follow-up eGFR values, estimated using a previously validated predictive equation. Differences between observed and predicted eGFRs at last follow-up increased with duration of treatment, suggesting that the beneficial effect of tolvaptan on the eGFR accumulates over time.
"The results of the study suggest that the effect of tolvaptan on eGFR in patients with ADPKD is sustained, cumulative, and consistent with potentially delaying the need of kidney replacement," said Dr. Torres.
The study concluded that follow-up for up to 11.2 years (average 4.6 years) showed a sustained reduction in the annual rate of eGFR decline in patients treated with tolvaptan compared with controls and an increasing separation of eGFR values over time between the two groups.