Associations between Net Gastrointestinal Alkali Absorption, 24-Hour Urine Lithogenic Factors, and Kidney Stones

Clin J Am Soc Nephrol. 2023 Aug 1;18(8):1068-1074. doi: 10.2215/CJN.0000000000000195. Epub 2023 May 31.


Background: It is not clear whether kidney stone formers have an abnormal handling of alkali and acid precursors in the gut, which might affect urine composition and ultimately stone formation. In this study, we aimed to investigate the determinants of net gastrointestinal alkali absorption and its associations with key urinary parameters in a large group of stone formers and non-stone formers.

Methods: Data were collected from three independent cohorts with at least one 24-hour urine collection. We explored potential determinants of net gastrointestinal alkali absorption and the association between net gastrointestinal alkali absorption, urinary parameters, and stone former status. Finally, we estimated the proportion of the association between urine parameters and stone former status explained by differences in net gastrointestinal alkali absorption.

Results: The analysis included 6067 participants (1102 men and 4965 women; 698 and 1804 of whom were stone formers, respectively). Average net gastrointestinal alkali absorption values were consistently lower in stone formers across the three cohorts (from -15.0 to -4.9 mEq/d). Age was directly associated with net gastrointestinal alkali absorption, whereas body mass index and net endogenous acid production were inversely associated. Net gastrointestinal alkali absorption was inversely associated with supersaturation for calcium oxalate, uric acid, and renal net acid excretion and directly associated with supersaturation for calcium phosphate, urine pH, and citrate. The odds of being a stone former was 15% (13%-17%) lower per 10 mEq/24 hours higher net gastrointestinal alkali absorption. Differences in net gastrointestinal alkali absorption explained a modest amount of the differences between stone formers and non-stone formers for supersaturation for calcium oxalate (6.3%) and a sizable amount for supersaturation for uric acid (15.2%), urine pH (38.3%), citrate (26.2%), and renal net acid excretion (63.4%).

Conclusions: Kidney stone formers have lower net gastrointestinal alkali absorption, and this explains differences in urine composition and the likelihood of stone formation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Calcium Oxalate* / urine
  • Citrates
  • Citric Acid / urine
  • Female
  • Humans
  • Kidney Calculi* / urine
  • Male
  • Risk Factors
  • Uric Acid / urine


  • Calcium Oxalate
  • Uric Acid
  • Citric Acid
  • Citrates