4511 TOLVAPTAN DOSE ADJUSTMENT IN ADPKD BASED ON URINARY OSMOLALITY: SIMILAR EFFICACY AND LOW DROPOUT RATE

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. Tolvaptan is the only treatment that has been shown to slow disease progression. The current recommendation is to reach the maximum tolerated dose while controlling side effects such as hepatotoxicity. There are data suggesting a marked decrease in tolerability at high doses of the drug. We explored the possibility of an individualized tolvaptan dose adjustment, based on urinary osmolality (Uosm), as an indirect indicator of treatment efficacy. Method Single-center prospective cohort study of tolvaptan in patients with ADPKD and rapid progression, with dose adjustment according to Uosm, with dose increase if Uosm > 200 mOsm/kg. Glomerular filtration rate (GFR) estimated by CKD-EPI, Uosm, adverse effects and dropouts were analyzed. Results 40 patients: 35 patients with more than 2 years treatment, mean follow-up 30± 6 months. Mean age 45± 7 years, 82% hypertensive and 47% male. Evolution: mean annual fall in GFR during the previous 3 years without treatment -7.24 ± 1.5 ml/min/year. Baseline GFR 51.05±12.5 mL/min and baseline Uosm 391±87 mOsm/kg. Average annual drop in GFR over 3 years with treatment -3.18±1.3 mL/min/year. Average Uosm achieved during treatment 171 ± 47 mOsm/kg. Maximum tolvaptan dose reached 60 mg (90%) and 90 mg (10%). The adverse events recorded highlight that there were no cases of hepatotoxicity (0%). The most frequent alterations were hyperuricemia (18%) and hypernatremia (11%), but in all cases asymptomatic. Polyuria was recorded in all our patients (100%), with a median diuresis 6000 ml/day (7000-5500), but the dropout rate due to aquaretic effects was minimal, only 2 patients (5%). Conclusion In our series of patients, treatment with tolvaptan at a dose adjusted to Uosm, seems to show similar efficacy to the reference studies in the annual fall of GFR, with a low rate of adverse events and very low dropout rate.