To the Editor:
We read with great interest the recent report of Heida et al.1 on the impact of tolvaptan on acid−base status in autosomal dominant polycystic kidney disease (ADPKD) patients. The authors hypothesized that V2 receptor antagonism may induce a state of metabolic alkalosis by activation of V1 receptors through increased circulating vasopressin, which in turn would stimulate renal net acid excretion (NAE). The authors found no changes in plasma bicarbonate after tolvaptan administration and therefore concluded that tolvaptan does not affect renal NAE.
Recent studies2,3 indicate, however, that urinary citrate is superior to plasma bicarbonate for the detection of subtle acid−base alterations. We previously observed that ADPKD patients treated with tolvaptan exhibit a significant reduction in renal NAE, with an increase in urinary citrate.4 These changes were associated with increased net gastrointestinal alkali absorption (NGIA; a marker of alkali intake) but unaltered urinary sulfate (a marker of acid intake), suggesting that lower NAE may be due to higher alkali intake or gut alkali absorption in patients taking tolvaptan. Thus, our data suggest that tolvaptan treatment is associated with changes in renal NAE and hence acid−base homeostasis in ADPKD patients. The underlying mechanisms, however, remain to be elucidated.
References
- 1.Heida J.E., Gansevoort R.T., Meijer E. Acid-base homeostasis during vasopressin V2 receptor antagonist treatment in autosomal dominant polycystic kidney disease patients. Kidney Int Rep. 2021;6:839–841. doi: 10.1016/j.ekir.2020.12.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Gianella F.G., Prado V.E., Poindexter J.R. Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in chronic kidney disease. Kidney Int. 2021;99:208–217. doi: 10.1016/j.kint.2020.07.006. [DOI] [PubMed] [Google Scholar]
- 3.Goraya N., Simoni J., Sager L.N. Urine citrate excretion as a marker of acid retention in patients with chronic kidney disease without overt metabolic acidosis. Kidney Int. 2019;95:1190–1196. doi: 10.1016/j.kint.2018.11.033. [DOI] [PubMed] [Google Scholar]
- 4.Bargagli M., Dhayat N.A., Anderegg M. Urinary lithogenic risk profile in ADPKD patients treated with tolvaptan. Clin J Am Soc Nephrol. 2020;15:1007–1014. doi: 10.2215/CJN.13861119. [DOI] [PMC free article] [PubMed] [Google Scholar]