{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:06:00Z","timestamp":1791461160333,"version":"4.3.4"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Tricida, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epidemiological studies demonstrate an association between kidney stones and risk of chronic kidney disease (CKD) and CKD progression. Metabolic acidosis, as a consequence of CKD, results in a reduced urine pH which promotes the formation of some types of kidney stones and inhibits the formation of others. While metabolic acidosis is a risk factor for CKD progression, the association of serum bicarbonate with risk of incident kidney stones is not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used an Integrated Claims-Clinical dataset of US patients to generate a cohort of patients with non-dialysis-dependent CKD with two serum bicarbonate values of 12 to &amp;lt;22\u00a0mmol\/L (metabolic acidosis) or 22 to &amp;lt;30\u00a0mmol\/L (normal serum bicarbonate). Primary exposure variables were baseline serum bicarbonate and change in serum bicarbonate over time. Cox proportional hazards models evaluated time to first occurrence of kidney stones during a median 3.2-year follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 142\u2009884 patients qualified for the study cohort. Patients with metabolic acidosis experienced post\u2013index date kidney stones at greater frequency than patients with normal serum bicarbonate at the index date (12.0%\u00a0vs 9.5%, P\u00a0&amp;lt;\u00a0.0001). Both lower baseline serum bicarbonate [hazard ratio (HR) 1.047; 95% confidence interval (CI) 1.036\u20131.057] and decreasing serum bicarbonate over time (HR 1.034; 95% CI 1.026\u20131.043) were associated with increased risk of kidney stone development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Metabolic acidosis was associated with a higher incidence of kidney stones and shorter time to incident stone formation in patients with CKD. Future studies may investigate the role of correcting metabolic acidosis to prevent stone formation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ckj\/sfad034","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T17:17:48Z","timestamp":1678123068000},"page":"1113-1121","source":"Crossref","is-referenced-by-count":14,"title":["Association of serum bicarbonate with the development of kidney stones in patients with chronic kidney disease: a retrospective cohort study"],"prefix":"10.1093","volume":"16","author":[{"given":"Navdeep","family":"Tangri","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba ; Winnipeg, Manitoba , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3089-8205","authenticated-orcid":false,"given":"Vandana","family":"Mathur","sequence":"additional","affiliation":[{"name":"MathurConsulting LLC , Woodside, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L","family":"Reaven","sequence":"additional","affiliation":[{"name":"Strategic Health Resources , La Canada, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E","family":"Funk","sequence":"additional","affiliation":[{"name":"Strategic Health Resources , La Canada, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7046-0358","authenticated-orcid":false,"given":"Reid H","family":"Whitlock","sequence":"additional","affiliation":[{"name":"Seven Oaks Hospital Chronic Disease Innovation Centre ; Winnipeg, Manitoba , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald E","family":"Wesson","sequence":"additional","affiliation":[{"name":"Dell Medical School, The University of Texas , TX , USA"},{"name":"at Austin, Austin, TX, USA; Donald E Wesson Consulting, LLC , TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Bushinsky","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine , Rochester, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"2023063001083758300_bib1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41581-021-00513-4","article-title":"The genetics of kidney stone disease and nephrocalcinosis","volume":"18","author":"Singh","year":"2022","journal-title":"Nat Rev Nephrol"},{"key":"2023063001083758300_bib2","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.semnephrol.2022.04.012","article-title":"Sex differences and the risk of kidney stones","volume":"42","author":"Ferraro","year":"2022","journal-title":"Semin Nephrol"},{"key":"2023063001083758300_bib3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00240-020-01210-w","article-title":"Trends in the prevalence of kidney stones in the United States from 2007 to 2016","volume":"49","author":"Chewcharat","year":"2021","journal-title":"Urolithiasis"},{"key":"2023063001083758300_bib4","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1097\/01.ju.0000152082.14384.d7","article-title":"Urologic diseases in America project: urolithiasis","volume":"173","author":"Pearle","year":"2005","journal-title":"J Urol"},{"key":"2023063001083758300_bib5","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.mayocp.2015.07.016","article-title":"Stone composition among first-time symptomatic kidney stone formers in the community","volume":"90","author":"Singh","year":"2015","journal-title":"Mayo Clin Proc"},{"key":"2023063001083758300_bib6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1159\/000104439","article-title":"Stones and urinary tract infections","volume":"79 Suppl","author":"Miano","year":"2007","journal-title":"Urol Int"},{"key":"2023063001083758300_bib7","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.eururo.2012.03.052","article-title":"Urologic Diseases in America Project. Prevalence of kidney stones in the United States","volume":"62","author":"Scales","year":"2012","journal-title":"Eur Urol"},{"key":"2023063001083758300_bib8","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1136\/bmj.300.6734.1234","article-title":"Kidney stones and hypertension: population based study of an independent clinical association","volume":"300","author":"Cappuccio","year":"1990","journal-title":"BMJ"},{"key":"2023063001083758300_bib9","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s11892-007-0075-6","article-title":"Diabetes and nephrolithiasis","volume":"7","author":"Daudon","year":"2007","journal-title":"Curr Diab Rep"},{"key":"2023063001083758300_bib10","doi-asserted-by":"crossref","first-page":"c159","DOI":"10.1159\/000317196","article-title":"An update and practical guide to renal stone management","volume":"116","author":"Johri","year":"2010","journal-title":"Nephron Clin Pract"},{"key":"2023063001083758300_bib11","doi-asserted-by":"crossref","first-page":"804","DOI":"10.2215\/CJN.05811108","article-title":"Kidney stones and the risk for chronic kidney disease","volume":"4","author":"Rule","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"2023063001083758300_bib12","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1111\/j.1523-1755.2005.67128.x","article-title":"Decreased renal function among adults with a history of nephrolithiasis: a study of NHANES III","volume":"67","author":"Gillen","year":"2005","journal-title":"Kidney Int"},{"key":"2023063001083758300_bib13","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1681\/ASN.2019070677","article-title":"Mechanisms of metabolic acidosis-induced kidney injury in chronic kidney disease","volume":"31","author":"Wesson","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"2023063001083758300_bib14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.5049\/EBP.2011.9.2.45","article-title":"Mechanisms of the effects of acidosis and hypokalemia on renal ammonia metabolism","volume":"9","author":"Han","year":"2011","journal-title":"Electrolyte Blood Press"},{"key":"2023063001083758300_bib15","first-page":"S165","article-title":"Urinary pH and stone formation","volume":"23 Suppl","author":"Wagner","year":"2010","journal-title":"J Nephrol"},{"key":"2023063001083758300_bib16","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.semnephrol.2020.12.003","article-title":"Uric acid and urate in urolithiasis: the innocent bystander, instigator, and perpetrator","volume":"40","author":"Adomako","year":"2020","journal-title":"Semin Nephrol"},{"key":"2023063001083758300_bib17","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.kint.2022.02.032","article-title":"Effects of acid on bone","volume":"101","author":"Bushinsky","year":"2022","journal-title":"Kidney Int"},{"key":"2023063001083758300_bib18","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.1681\/ASN.2016030305","article-title":"Acidosis and urinary calcium excretion: insights from genetic disorders","volume":"27","author":"Alexander","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"2023063001083758300_bib19","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/B978-1-4160-6193-9.10039-9","article-title":"Nephrolithiasis","volume-title":"Brenner BM (ed.), The Kidney","author":"Bushinsky","year":"2012"},{"key":"2023063001083758300_bib20","doi-asserted-by":"crossref","first-page":"e5287","DOI":"10.1136\/bmj.e5287","article-title":"Kidney stones and kidney function loss: a cohort study","volume":"345","author":"Alexander","year":"2012","journal-title":"BMJ"},{"key":"2023063001083758300_bib21","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00240-011-0397-3","article-title":"Prevalence and densitometric characteristics of incomplete distal renal tubular acidosis in men with recurrent calcium nephrolithiasis","volume":"40","author":"Arampatzis","year":"2012","journal-title":"Urol Res"},{"key":"2023063001083758300_bib22","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/00005792-198803000-00002","article-title":"The syndrome of distal (type 1) renal tubular acidosis. Clinical and laboratory findings in 58 cases","volume":"67","author":"Caruana","year":"1988","journal-title":"Medicine (Baltimore)"},{"key":"2023063001083758300_bib23","first-page":"S46","article-title":"Renal tubular acidosis","volume":"19","author":"Laing","year":"2006","journal-title":"J Nephrol"},{"key":"2023063001083758300_bib24","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1046\/j.1523-1755.2002.00508.x","article-title":"Pathophysiologic basis for normouricosuric uric acid nephrolithiasis","volume":"62","author":"Sakhaee","year":"2002","journal-title":"Kidney Int"},{"key":"2023063001083758300_bib25","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1046\/j.1440-1754.2003.00159.x","article-title":"Carbohydrate intolerance and kidney stones in children in the Goldfields","volume":"39","author":"Baldwin","year":"2003","journal-title":"J Paediatr Child Health"},{"key":"2023063001083758300_bib26","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S0002-8223(95)00219-7","article-title":"Potential renal acid load of foods and its influence on urine pH","volume":"95","author":"Remer","year":"1995","journal-title":"J Am Diet Assoc"},{"key":"2023063001083758300_bib27","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1136\/bmj.328.7453.1420","article-title":"Kidney stones","volume":"328","author":"Parmar","year":"2004","journal-title":"BMJ"},{"key":"2023063001083758300_bib28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0022-5347(05)65405-5","article-title":"Estrogen replacement increased the citrate and calcium excretion rates in postmenopausal women with recurrent urolithiasis","volume":"167","author":"Dey","year":"2002","journal-title":"J Urol"},{"key":"2023063001083758300_bib29","doi-asserted-by":"crossref","first-page":"535","DOI":"10.7326\/0003-4819-158-7-201304020-00005","article-title":"Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline","volume":"158","author":"Fink","year":"2013","journal-title":"Ann Intern Med"},{"key":"2023063001083758300_bib30","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.eururo.2014.10.029","article-title":"Metabolic evaluation and recurrence prevention for urinary stone patients: EAU guidelines","volume":"67","author":"Skolarikos","year":"2015","journal-title":"Eur Urol"},{"key":"2023063001083758300_bib31","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1111\/j.1523-1755.2004.66029.x","article-title":"The effect of fruits and vegetables on urinary stone risk factors","volume":"66","author":"Meschi","year":"2004","journal-title":"Kidney Int"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfad034\/50212961\/sfad034.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/16\/7\/1113\/50704200\/sfad034.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/16\/7\/1113\/50704200\/sfad034.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T21:09:04Z","timestamp":1688072944000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/16\/7\/1113\/7077562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,14]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,3,14]]},"published-print":{"date-parts":[[2023,6,30]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfad034","relation":{},"ISSN":["2048-8505","2048-8513"],"issn-type":[{"value":"2048-8505","type":"print"},{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,7]]},"published":{"date-parts":[[2023,3,14]]}}}