Abstract

Background and Aims

Nephrolithiasis is a common health problem in autosomal dominant polycystic kidney disease (ADPKD) and significantly contributes to patient morbidity. In observational studies, prevalence rates of up to 36% have been reported. Kidney stones of ADPKD patients are typically composed of uric acid (UA) or calcium oxalate (CaOx), and hypocitraturia and low urinary pH have been reported as the main prolithogenic abnormalities. Recently, Tolvaptan has been introduced for the treatment of ADPKD, but its impact on the lithogenic risk profile in ADPKD patients remains unknown.

Method

We conducted a retrospective analysis of patients enrolled in the Bern ADPKD registry, an observational cohort study. Inclusion criteria were age ≥ 18 years, clinical diagnosis of ADPKD, and informed consent. The main exclusion criterion was need for renal replacement therapy. 24-h urine analyses were performed at baseline and then at yearly follow-ups. Relative supersaturation ratios (RSS) for CaOx, calcium phoshate (CaP) and UA were calculated with EQUIL2. Univariate and multivariate mixed-effects linear regression models, adjusted for age, sex, BMI, eGFR and endogenous acid production, estimated by net acid excretion, were used to assess the impact of Tolvaptan treatment on urinary composition.

Results

38 patients received Tolvaptan treatment (39.5% females) and were included in the analysis. Six patients (15.8%) had a history of symptomatic stone events. In multivariate analysis, Tolvaptan treatment was significantly associated with reductions of CaOx, CaP and UA RSS (p < 0.01) and increased urinary citrate (p = 0.015) and calcium (p < 0.01) excretion. In contrast, Tolvaptan treatment was not associated with alterations in urinary oxalate excretion or urinary pH.

Conclusion

Tolvaptan significantly reduces RSS for CaOx, CaP and UA. Future studies are needed to assess the impact of Tolvaptan treatment on stone recurrence in ADPKD patients.

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