#2841 AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) PATIENT CHARACTERISTICS ASSOCIATED WITH BETTER RESPONSE TO TOLVAPTAN TREATMENT
Authors: Gkika Vasiliki , Evangelou Eirini , Gkalitsiou Dimitra , Liaveri Paraskevi , Louka Michaela , Drakopoulos Angelos , Tigka Eirini , Vasileiou Kyriaki , Tsagkatakis Mihail , Tsirpanlis George 
Published: June 2023

Background and Aims

Tolvaptan treatment is indicated in patients with rapidly progressive ADPKD. The factors associated with a favorable medication response are not completely analyzed. We looked into the characteristics of ADPKD patients who responded better to tolvaptan treatment after three years of treatment.

Method

Forty-one (41) patients, 18 females, 23 males, with rapidly progressive ADPKD (Mayo Clinic Imaging Category, MCIC, 1C, 1D and 1E, mean (SD) age 42.5 (8.6) years and estimated-glomerular filtration rate (e-GFR) &gt; 25 ml/min) who completed three years treatment with tolvaptan, were included in the study. Total kidney volume (TKV) was measured using Magnetic Resonance Imaging at the initiation of the study and 3 years post treatment. The expected e-GFR decline at 3 years without treatment was calculated using the Mayo Clinic formula (Irazabal MV et al., JASN, 2015) and compared to the e-GFR found after three years of tolvaptan treatment (e-GFR measured after 3 years of treatment versus expected e-GFR). Based on the same formula, the End Stage Renal Disease (ESRD) prediction was calculated, before and after 3 years of treatment (i.e. we focused on the difference between the ESRD prediction calculated prior to treatment initiation and the prediction calculated with the data measured after 3 years of treatment). The above mentioned differences in e-GFR and ESRD prediction were used as response to treatment markers and correlated with a series of patient characteristics (age, sex, age at ADPKD diagnosis, presence of hypertension (HTN) and age at HTN onset, age at ESRD of the affected parent, TKV, MICI, etc) using univariate and multivariate statistical analysis.

Results

The median (IQR) difference between e-GFR measured after three years of tolvaptan treatment and the expected without treatment was 5.3 (-1.3, 8.7) ml/min (i.e. more than the expected at 3 years without treatment). The median (IQR) prediction of ESRD had been prolonged by 1 (0, 2) years (more than the expected prediction calculated prior to treatment initiation). In univariate analysis, the baseline e-GFR (immediately before treatment) and the age at which the affected parent had developed ESRD were both positively associated with the e-GFR improvement and ESRD prediction prolongation (p = 0.02, 0.047, 0.01, and 0.02, respectively). In multivariate analysis, e-GFR improvement was associated with the age of the patient at treatment initiation (β = -0.9, 95%CI: -1.52 - 0.29, p = 0.006), the age of the patient at hypertension diagnosis (β = 0.88, 95%CI: 0.25 - 1.52, p = 0.008) and the age at which the affected parent had developed ESRD (β = 0.57, 95%CI: 0.16 - 0.98, p = 0.008). In addition, ESRD prediction prolongation was associated with the initial e-GFR (p = 0.001), the age at which the affected parent had developed ESRD (p = 0.013) and the MCIC (β = 1.93, 95%CI 0.46 – 3.39, p = 0.013) (i.e. greater ESRD prediction prolongation for patients at MCIC 1E than at 1C).

Conclusion

Tolvaptan treatment seems to be more efficient in younger patients with rapidly progressing ADPKD, well-preserved renal function, a less severe family history, and a shorter chronicity of hypertension.