Association between Urolithiasis and History Proton Pump Inhibitor Medication: A Nested Case-Control Study

Abstract

A few retrospective studies have suggested the risk of urolithiasis associated with the use of proton pump inhibitors (PPIs). The current research intended to estimate the risk of urolithiasis according to previous PPI use. A nested case-control study was conducted using the National Health Insurance Service-National Health Screening Cohort in Korea. A total of 28,962 patients with urolithiasis and 115,848 control participants were selected. The previous prescription history of PPI with days of PPI prescription was collected. To calculate the odds ratios (OR) of past, current, and days of PPI use for urolithiasis, logistic regression models were used. Subgroup analyses were conducted. The urolithiasis group demonstrated a higher rate of current PPI users than the control group (60.9% vs. 43.7%). The current PPI users indicated 2.49 times higher odds for urolithiasis than no PPI users (95% confidence intervals [CI] = 2.33–2.66). A longer duration of PPI use was associated with greater odds for urolithiasis (adjusted OR = 1.65 (95% CI = 1.54–1.77) < 1.97 (95% CI = 1.84–2.11) < 2.32 (95% CI = 2.14–2.49) for 1–19 days, 30–364 days, and 365 or more days of PPI prescription). All subgroup analyses described a consistently positive association of previous PPI use with urolithiasis. Prior PPI use was related to a higher risk of urolithiasis. The relationship between previous PPI use and urolithiasis demonstrated a dose-response association.

Risk of urinary stone formation associated to proton pump inhibitors: A systematic review and metanalysis

“…The latter adjusted their multivariate analysis for male gender, middle to old age, white ethnicity, obesity, diabetes, and elevated creatinine levels. Similarly, Kim et al (14) adjusted their multivariable logistic regression analysis for age, sex, income, region of residence, total cholesterol, SBP, DBP, fasting blood glucose, CCI score, prescription dates within 1 year of each H2 blocker and NSAID, and number of GERD treatments, and performed subgroup analyses according to age, sex, income, region of residence, obesity, smoking, alcohol consumption, total cholesterol, systolic blood pressure, and fasting blood glucose. Simonov et al (15) used a time-varying Cox proportional hazards model adjusted for baseline covariates including sex, race/ethnicity, age, creatinine, medications (H2RAs, thiazide diuretics, loop diuretics, gout medications), medical history (gastroesophageal reflux disease, peptic ulcer disease, Barrett's disease, gastrointestinal bleed, gastritis, functional dyspepsia, gastrointestinal surgical history, diabetes, gout) and total number of inpatient/outpatient encounters in the previous year.…”

“…Results concerning the effect of the duration of PPI treatment on the risk of stone formation are controversial. Kim et al (14) found higher odds for urolithiasis when treatment with PPI was extended to 365 days or longer (OR 2.32) compared to shorter periods (30-364 days: OR 1.97, 1-19 days: OR 1.65). This confirms the finding of Kwak et al (13) who reported higher rates of urinary calculi in subjects taking PPIs for more than 5 years.…”

“…Two studies, presented as congress communications but never published as full-text reports, demonstrated that the use of PPIs and H2 blockers was associated with an increased risk of kidney stones (12,13). More recently, three articles were published, evaluating in three different large population from the United States (N = 2) and Korea (N = 1) the risk of stone formation in patients taking PPIs (14)(15)(16). The aim of this study was to systematically review the data from studies evaluating the association of PPIs and nephrolithiasis and, where possible, to perform a pooled analysis of the prevalence of urinary stone disease in patients taking PPIs.…”

Association of proton pump inhibitor use with risk of kidney stones: an analysis of cross-sectional data from the US National Health and Nutrition Examination Survey (2007–2018)

“…Several studies have shown that PPI use could increase the risk of kidney stones, with a dose–response relationship 10–12. A retrospective study conducted on the Women’s Veterans Cohort, which included 465 891 individuals, revealed that PPI use was linked to a 1.25-fold higher risk of kidney stones (95% CI=1.19 to 1.33) 10.…”

“…Long-term PPI intake is associated with a reduction in intestinal absorption of essential vitamins and minerals and increased susceptibility to infections, chronic kidney disease and dementia 7. Given that PPI can inhibit gastric acid secretion, thereby affecting the intestinal absorption of essential minerals and altering the levels of calcium, magnesium and citrate,8 9 several studies have investigated the impact of PPI use on the risk of kidney stones 10–12. For instance, Sui et al found that PPI use might elevate the risk of kidney stones by lowering the levels of urinary citrate and magnesium, which could compromise their inhibitory effect on kidney stone formation 11.…”