REAL-WORLD USE OF TOLVAPTAN AND ITS IMPACT ON EGFR IN A NORTH EAST UK COHORT

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is a cause of progressive chronic kidney failure (CKD) and end stage kidney disease (ESKD). Tolvaptan has been shown within clinical trials to slow down decline of kidney function in patients with ADPKD at risk of rapid progression. We performed a retrospective review of a cohort of ADPKD patients who had been established on tolvaptan therapy to determine its efficacy in a real- world clinic setting. Method Subjects who had a clinical diagnosis of ADPKD and who had been established on tolvaptan for a period of >18 months were reviewed retrospectively in terms of their eGFR. Subjects were between the ages of 18-65 years old and both males and females were included in this study. Other inclusion criteria involved a pre-treatment slope of <-2.5 ml/min/1.73m2 based on readings for a 3 year period, a pre-treatment eGFR of 30-90 ml/min/1.73m2 and ability to tolerate tolvaptan treatment and be maintained on treatment for at least12 months. We calculated based on eGFR slopes, predicted time to reach CKD stage 5 with and without tolvaptan therapy. Given this was a retrospective review, eGFR were estimated during clinic visits whilst on tolvaptan treatment, rather than after a drug washout period. Results The cohort of patients included 20 from Newcastle upon Tyne Hospitals and 2 from Sunderland Royal Infirmary. The mean rate of eGFR decline prior to treatment was -5.92 ml/min/1.73m2 per year for the cohort. Following tolvaptan treatment, the average decline in eGFR was reduced to -2.57 ml/min/1.73m2 per year. Therefore, tolvaptan lessened average eGFR decline within this cohort by 3.35 ml/min/1.73m2 per year, gaining 7 years and 9 months delay until CKD stage 5. The majority of patients (n=19) received full dose tolvaptan (90mg/30mg). At an individual level, 3 patients failed to respond at all to tolvaptan, with no improvement in decline of GFR and 2 others had a very mild improvement only (change in eGFR slope of <0.5 ml/min/1.73m2 per year). 6 patients had a dramatic improvement in eGFR slope (>5 ml/min/1.73m2 per year). Conclusion The real life use of tolvaptan seemed to give a dramatic improvement in eGFR slopes, much more than the previously reported clinical studies have shown. This may be in part due to patient selection and only including patients who tolerated therapy, a “tolvaptan clinic” effect where great personal care is given to these patients and to excellent compliance with medication. Reasons for both non-response and exaggerated response need to be evaluated carefully to determine how individualisation of tolvaptan therapy can be best used.