#2845 tolvaptan treatment for three years significantly improved renal prognosis in autosomal dominant polycystic kidney disease (adpkd) patients

Abstract Background and Aims Vasopressin receptor antagonist, tolvaptan, is the first specific treatment approved for ADPKD. Long-term real clinical results with this drug are not yet available. We present the results regarding renal function, cyst-kidney volume and renal prognosis in patients with rapidly progressive disease after three years of tolvaptan treatment. Method Forty-one ADPKD patients who remained in tolvaptan treatment, without adverse reactions for 3 years, were included in the study. Total kidney volume (TKV) was measured using Magnetic Resonance Imaging (MRI), before and after three years of treatment. The Mayo Clinic Imagining Category (MCIC) and the prediction of End Stage Renal Disease (ESRD) based on the Mayo Clinic formula (Irazabal MV et al, JASN, 2015) were also calculated for all patients, before and 3 years post treatment. Using the same formula the expected estimated-glomerular filtration rate (e-GFR) at 3 years without treatment was calculated and compared to the e-GFR found after three years of treatment. The expected TKV increment at 3 years was calculated (5.3% increment per year) and was compared to the TKV measured in the second MRI. Finally, the expected renal prognosis at the time of treatment initiation (i.e. minus 3 years at the end of the study) was compared to the prognosis calculated based on real patients’ data found after 3 years of treatment. The dose of tolvaptan was adjusted according to the urine osmolarity (< 200 mOsm/Kg). In the third year of treatment, 15, 13 and 13 patients were treated with 90/30, 60/30, and 45/15 mg/day of tolvaptan respectively Paired t-test and Wilcoxon signed-rank test were used for statistical analysis. Results Forty-one patients (18 females, 23 males), mean (SD) age 42.5 (8.6) years old were treated with tolvaptan for 3 years. According to MCIC, 41% of the patients were classified as 1C, 44% as 1D, and 15% as 1E. Pre-treatment mean (SD) e-GFR was 61.8 (24.6) ml/min while 15% of the patients were on stage 1 of Chronic Kidney Disease, 42% on stage 2, 12% on stage 3a, 24% on stage 3b, and 7% on stage 4 (>25 ml/min). The expected mean (SD) TKV at 3 years without treatment was 2717 (1839) ml, while the measured TKV found after 3 years of treatment was 2773.3 (2086.9) ml (p = 0.44). The expected e-GFR at 3 years without treatment was calculated at 51.1(25.2) ml/min while the measured e-GFR after 3 years of treatment was 57.3 (30.2) ml/min (p = 0.001). Finally, while the expected mean (SD) ESRD prediction at the time of treatment initiation was 10 (6.9) years, the calculated ESRD prediction after 3 years of tolvaptan treatment was 12 (8) years (p<0.001). Conclusion Tolvaptan treatment for three years slowed down the clinical course of ADPKD in terms of renal function decline and ESRD prediction, but had no impact on total kidney volume.