Kidney Week

Abstract: TH-PO424

Effects of Salt and Protein Intake on Polyuria in Tolvaptan-Treated ADPKD Patients: A Randomized Controlled Trial

Session Information

• Genetic Diseases: Cystic - Therapeutic Investigations and Prognosis
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Geertsema, Paul, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Paul Geertsema,

• Koorevaar, Iris Willianne, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Iris Willianne Koorevaar,

• Ipema, Karin, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Karin Ipema,

• Kramers, Bart J., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Bart J. Kramers,

• Casteleijn, Niek F., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Niek F. Casteleijn,

• Gansevoort, Ron T., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Ron T. Gansevoort,

• Meijer, Esther, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Esther Meijer,

Background

The only renoprotective treatment in Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a vasopressin V2-receptor antagonist (V2RA). However, aquaresis-associated side effects limit tolerability. We investigated whether salt and protein intake influence urine volume and aquaresis-related endpoints in V2RA-treated ADPKD patients.

Methods

In this randomized, controlled, double-blind, crossover trial, ADPKD patients treated with a maximally tolerated dose of a V2RA were included. While on a low salt (≈6 g/24h) and low protein (≈0.8 g/kg/24h) diet, patients were given additional salt and protein during a baseline study period to mimic regular intake, which was replaced by placebo during four 2-week periods: low salt/low protein, low salt/regular protein, low protein/regular salt and regular protein/regular salt intake in random order. Primary endpoint was change in 24h urine volume. Secondary endpoints were change in quality of life, measured glomerular filtration rate (mGFR), blood pressure and copeptin level.

Results

Twelve patients (49±8 years, 25.0% male, mGFR 59±23 mL/min/1.73m²) were included. Baseline salt- and protein intake was 10.8±1.3 g/24h and 1.2±0.2 g/kg/24h. During the low salt and low protein treatment periods, intake significantly decreased to 5.8±1.6 g/24h and 0.8±0.1 g/kg/24h respectively. Baseline 24h urine volume (5.9±1.2 L) diminished to 5.2±1.1 L (-11%, p=0.004) on the low salt & low protein and to 5.4±0.9 L (-8%, p=0.04) on the low salt intake. Reduction in 24h urine volume tended to be greater in patients with lower urine osmolality (-16 vs -7%, p=0.1). Polyuria QoL scores improved with changes in urine volume. mGFR decreased on the low salt & low protein intake, while mean arterial pressure did not change during the study periods. Plasma copeptin decreased significantly during low salt and low protein periods.

Conclusion

Changes in intake of salt and protein have only a minor effect on urine volume in V2RA-treated ADPKD patients. In subjects with most complete vasopressin blockade, i.e. those with the lowest baseline urine osmolarity, this antipolyuric effect tended to be most pronounced. Reduction of osmolar intake decreased plasma copeptin and might therefore improve the renoprotective effect of a V2RA.

Funding

• Private Foundation Support