Effect of sodium bicarbonate supplementation on the renin-angiotensin system in patients with chronic kidney disease and acidosis: a randomized clinical trial

Dominique M. Bovée, Lodi C.W. Roksnoer, Cornelis van Kooten, Joris I. Rotmans, Liffert Vogt, Martin H. de Borst, Robert Zietse, A. H.Jan Danser, Ewout J. Hoorn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: Acidosis-induced kidney injury is mediated by the intrarenal renin-angiotensin system, for which urinary renin is a potential marker. Therefore, we hypothesized that sodium bicarbonate supplementation reduces urinary renin excretion in patients with chronic kidney disease (CKD) and metabolic acidosis. Methods: Patients with CKD stage G4 and plasma bicarbonate 15–24 mmol/l were randomized to receive sodium bicarbonate (3 × 1000 mg/day, ~ 0.5 mEq/kg), sodium chloride (2 × 1,00 mg/day), or no treatment for 4 weeks (n = 15/arm). The effects on urinary renin excretion (primary outcome), other plasma and urine parameters of the renin-angiotensin system, endothelin-1, and proteinuria were analyzed. Results: Forty-five patients were included (62 ± 15 years, eGFR 21 ± 5 ml/min/1.73m2, plasma bicarbonate 21.7 ± 3.3 mmol/l). Sodium bicarbonate supplementation increased plasma bicarbonate (20.8 to 23.8 mmol/l) and reduced urinary ammonium excretion (15 to 8 mmol/day, both P < 0.05). Furthermore, a trend towards lower plasma aldosterone (291 to 204 ng/L, P = 0.07) and potassium (5.1 to 4.8 mmol/l, P = 0.06) was observed in patients receiving sodium bicarbonate. Sodium bicarbonate did not significantly change the urinary excretion of renin, angiotensinogen, aldosterone, endothelin-1, albumin, or α1-microglobulin. Sodium chloride supplementation reduced plasma renin (166 to 122 ng/L), and increased the urinary excretions of angiotensinogen, albumin, and α1-microglobulin (all P < 0.05). Conclusions: Despite correction of acidosis and reduction in urinary ammonium excretion, sodium bicarbonate supplementation did not improve urinary markers of the renin-angiotensin system, endothelin-1, or proteinuria. Possible explanations include bicarbonate dose, short treatment time, or the inability of urinary renin to reflect intrarenal renin-angiotensin system activity. Graphic abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)1737-1745
Number of pages9
JournalJournal of Nephrology
Issue number5
Early online date31 Dec 2020
Publication statusPublished - Oct 2021

Bibliographical note

Funding Information:
We thank all patients who participated in this trial, our colleagues who helped with the inclusion of patients, the research physicians and nurses who helped with data collection (E.F.E. Wenstedt, M.A. De Jong, B.M. Voorzaat, B. Nome and N. Scheper-Van den Berg). This study was organized as part of the Dutch NOVO platform and was funded by a research grant from the Dutch Kidney Foundation (14OK19 to EJH).

Publisher Copyright:
© 2020, The Author(s).


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