Tolvaptan treatment is associated with altered mineral metabolism parameters and increased bone mineral density in ADPKD patients

Nephrol Dial Transplant. 2023 Jun 30;38(7):1645-1654. doi: 10.1093/ndt/gfac298.

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a unique bone and mineral phenotype. The impact of tolvaptan treatment on mineral metabolism and bone mineral density (BMD) is unknown.

Methods: We conducted an analysis in the Bern ADPKD Registry, a prospective observational cohort study. Mineral metabolism parameters were measured at baseline and every 12 months thereafter. BMD was determined by dual-energy X-ray absorptiometry at baseline and after 3 years. Multivariable mixed-effects regression models were applied to assess changes in mineral metabolism parameters and BMD associated with tolvaptan treatment.

Results: A total of 189 participants (122 without and 67 with subsequent tolvaptan treatment) were included in the analysis. During follow-up, tolvaptan treatment was associated with increased BMD at the femoral neck {β = 0.092 [95% confidence interval (CI) 0.001-0.183], P = .047}. In addition, tolvaptan treatment was associated with higher plasma magnesium [β = 0.019 (95% CI 0.001-0.037), P = .037], bicarbonate [β = 0.972 (95% CI 0.242-1.702), P = .009] and urine pH [β = 0.214 (95% CI 0.056-0.372), P = .008] and lower parathyroid hormone [β = -0.191 (95% CI -0.328 to -0.053), P = .006], 1,25(OH)D3 [β = -0.126 (95% CI -0.235 to -0.164), P = .024] and fractional urinary magnesium excretion [β = -0.473 (95% CI -0.622 to -0.324), P < .001].

Conclusions: Chronic tolvaptan treatment is associated with increased femoral BMD and significant changes in both mineral metabolism and acid-base parameters in ADPKD patients.

Keywords: ADPKD; bone mineral density; mineral metabolism; tolvaptan.

Publication types

  • Observational Study

MeSH terms

  • Antidiuretic Hormone Receptor Antagonists / therapeutic use
  • Bone Density
  • Humans
  • Magnesium
  • Polycystic Kidney, Autosomal Dominant* / complications
  • Polycystic Kidney, Autosomal Dominant* / drug therapy
  • Prospective Studies
  • Tolvaptan / therapeutic use

Substances

  • Tolvaptan
  • Antidiuretic Hormone Receptor Antagonists
  • Magnesium