In addition to slowing cyst growth and kidney function decline, tolvaptan promotes favorable changes in urinary composition that may curb stone formation in patients with autosomal dominant polycystic kidney disease (ADPKD), according to new study findings.
Large kidney volume and urinary abnormalities contribute to stone formation in up to 36% of patients with ADPKD. Untreated patients have a higher frequency of uric acid stones and, to a lesser extent, calcium oxalate monohydrate stones than other stone formers, according to background information provided by the investigators.
Daniel G. Fuster, MD, of Bern University Hospital in Bern, Switzerland, and colleagues studied 24-hour urine compositions from 38 patients treated with tolvaptan, a vasopressin V2 receptor antagonist, and 87 untreated patients from the Bern ADPKD registry. Thirteen percent of patients had a history of symptomatic stones. By design, none received renal replacement therapy.
In multivariable analysis, tolvaptan use was associated with significantly lower urine relative supersaturation ratios for calcium-oxalate (-0.56), brushite (-0.33), and uric acid (-0.62) at 1 year, the investigators reported in the Clinical Journal of the American Society of Nephrology.
The investigators also observed significantly higher excretion of urine citrate (0.25 mmol/mmol creatinine/d) and calcium (0.31 mmol/mmol creatinine/d). Hypocitraturia and hyperoxaluria appeared to be the most common prolithogenic abnormality in patients with ADPKD, in line with previous studies, Dr Fuster’s team noted.
In addition, tolvaptan was associated with a significantly lower net acid excretion (-0.54 mEq/mmol creatinine/d) and a significantly higher net gastrointestinal alkali absorption (0.57 mEq/mmol creatinine/d). The researchers suggested that tolvaptan users may have higher alkali intake.
Tolvaptan treatment is associated with a significantly improved urinary lithogenic risk profile in patients with ADPKD,” Dr Fuster and his collaborators concluded.
Disclosure: This clinical trial was supported by Otsuka Pharmaceutical, the makers of tolvaptan (Jynarque™). Please see the original reference for a full list of authors’ disclosures.
Bargagli M, Dhayat NA, Anderegg M, et al. Urinary lithogenic risk profile in ADPKD patients treated with tolvaptan. Clin J Am Soc Nephrol. July 2020;15(7):1007-1014. doi: 10.2215/CJN.13861119