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

Authors

Pietro Manuel Ferraro, U.O.S. Terapia Conservativa della Malattia Renale Cronica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.
Eric N. Taylor, Maine Medical Center
John R. Asplin, Litholink Corporation, Laboratory Corporation of America® Holdings, Itasca, IL, USA.
Gary C. Curhan, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Document Type

Article

Publication Date

5-31-2023

Institution/Department

Nephrology & Transplantation

Journal Title

Clinical journal of the American Society of Nephrology : CJASN

Abstract

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 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 6,067 participants (1,102 men and 4,965 women; 698 and 1,804 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 BMI 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 (CaP), urine pH and citrate. The odds of being a stone former were 15% (13 to 17%) lower per 10 mEq/24h higher net gastrointestinal alkali absorption. Differences in net gastrointestinal alkali absorption explained a modest amount of the 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.

Recommended Citation

Ferraro PM, Taylor EN, Asplin JR, Curhan GC. Associations between Net Gastrointestinal Alkali Absorption, 24-Hour Urine Lithogenic Factors, and Kidney Stones [published online ahead of print, 2023 May 31]. Clin J Am Soc Nephrol. 2023;10.2215/CJN.0000000000000195. doi:10.2215/CJN.0000000000000195