Kidney Week

Abstract: SA-PO476

The Impact of Tolvaptan on Glomerular Filtration Rate in Patients with Autosomal Dominant Polycystic Kidney Disease

Session Information

• ADPKD: Clinical Studies
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

• 1001 Genetic Diseases of the Kidney: Cystic

Authors

• Côté, Gabrielle, CHU de Quebec, Hotel-Dieu de Quebec Hospital, Quebec, Quebec, Canada

Gabrielle Côté,

• Asselin-Thompstone, Lori, CHU de Quebec, Hotel-Dieu de Quebec Hospital, Quebec, Quebec, Canada

Lori Asselin-Thompstone,

• Rene De Cotret, Paul, CHU de Quebec, Hotel-Dieu de Quebec Hospital, Quebec, Quebec, Canada

Paul Rene De Cotret,

• Mac-Way, Fabrice, CHU de Quebec, Hotel-Dieu de Quebec Hospital, Quebec, Quebec, Canada

Fabrice Mac-Way,

• Agharazii, Mohsen, CHU de Quebec, Hotel-Dieu de Quebec Hospital, Quebec, Quebec, Canada

Mohsen Agharazii,

Background

Tolvaptan, a V2 receptor antagonist that induces aquaresis, has been shown through placebo-controlled studies to slow the decline in kidney function of patients with autosomal dominant polycystic kidney disease (ADPKD). Polyuria is a significant side-effect that can be attenuated by reducing daily sodium intake. In a cohort of ADPKD on tolvaptan, we aimed to identify the determinants of polyuria, to evaluate the impact of dietary counselling on the natriuresis and to compare the decline of estimated glomerular filtration rate (eGFR) before and after tolvaptan.

Methods

Retrospective study of 29 patients with ADPKD on tolvaptan. Serum creatinine level and 24-hour urine collection with volume and natriuresis were obtained before tolvaptan initiation. Patients had individual nutrition counselling to reduce their sodium intake. Tolvaptan was introduced after the nutrition counselling with serum creatinine level and 24-hour urine collection obtained on treatment. Polyuria was arbitrary defined as a urine volume of >5L/d. We used linear regression model and generalized estimation equations to analyse the data.

Results

The average of age and eGFR were respectively 44±11 years and 60±25 mL/min/1.73m². The urinary volume increased from 2.5 to 5.2L/d (95%CI: 4.6 to 5.8) on tolvaptan. Dietetic counselling resulted in a reduction of natriuresis (147 mmol/d (95%CI: 129 to165) to 131mmol/d (95%CI: 114 to 184)) (p=0.028). For each baseline increment of 10 mmol of daily sodium intake the odds ratio of polyuria was 3.4 (95%CI: 2.7-4.5). After adjusting for tolvaptan dose, an increase in 100 mmol of sodium intake was associated with an additional urinary volume of 1.1 L/d (95%CI: 0.6 to 1.6). The annual rate of eGFR loss was -5.5 ml/min/1.73m²/year (95%CI: -8.2 to -2.7) before tolvaptan and -1.6 ml/min/1.73m²/year (95%CI: -3.5 to 0.2) on tolvaptan. This slower rate of decline was statistically significant (p=0.033).

Conclusion

Natriuresis before tolvaptan is the major determinant of the polyuria on tolvaptan, but natriuresis can be significantly reduced by dietetic counselling. In this small cohort, we observed a slower decline in renal function after tolvaptan, as compared to the annual rate of decline before treatment with tolvaptan.