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

Abstract

Objective: Proton pump inhibitors are widely used as treatment of acid-related disorders. They are considered safe although their long-term use has been associated with some adverse effects including an increased propensity for urinary calculi formation. The aim of this study was to systematically review available data from studies evaluating the association of PPIs and nephrolithiasis. Materials and methods: We searched two electronic databases (PubMed and EMBASE) for cohort studies or case-control studies evaluating the relationship between treatment with proton pump inhibitors and the risk of stone formation published up to 31 October 2022. The overall association of PPIs and urinary calculi was analyzed using a random effects model (RevMan5). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Results: A total of 550 studies were retrieved; 7 were selected by title and abstract screening; after removal of duplicates, 4 records were evaluated by full-text examination. An additional study was retrieved by handsearching the references included in screened studies. In the unadjusted analysis, the odds of urinary calculi were greater in subjects taking PPIs compared to controls (unadjusted OR = 2.10, 95% CI 1.74-2.52, p < 0.00001). The pooled odds ratio of two case-control studies confirmed that use of PPIs increased the odds of urinary calculi compared with non-use (OR 2.44, 95% CI 2.29 to 2.61). Pooled analysis of three cohort studies evaluating incident nephrolithiasis showed an overall hazard ratio estimate of 1.34 (95% CI = 1.28-1.40). One study found lower urinary citrate and urinary magnesium levels in subjects exposed to PPIs. The Newcastle-Ottawa Quality Assessment Scale scores ranged between 6 and 8. Conclusions: PPIs showed an association with urinary calculi in patients included in the studies included in this review. If these data will be confirmed in adequately powered randomized trials, clinicians may consider limiting the long-term use of PPIs, to avoid unnecessary prolongation of treatment. Urinary magnesium and citrate should be evaluated in renal stone forming patients taking PPIs to supplement their intake when requested.

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)

“…PPIs are commonly prescribed for acid-related disorders, and patients with these conditions may be at higher risk of kidney stone formation 26. In this study, we employed the PSM analysis to minimise potential differences between PPI users and non-users, yet still identified a significant association between PPI use and the occurrence and recurrence of kidney stones.…”

“…PPIs are commonly prescribed for acid-related disorders, and patients with these conditions may be at higher risk of kidney stone formation. 26 In this study, we employed the PSM analysis to minimise potential differences between PPI users and non-users, yet still identified a significant association between PPI use and the occurrence and recurrence of kidney stones. Subgroup analyses further revealed that certain patient groups, including the elderly, females, non-Hispanic white and those with a BMI of 25 kg/m 2 or higher, exhibited a stronger positive association between PPI use and the prevalence of kidney stones, highlighting the importance of considering potential side effects of PPI use in these populations.…”

Behavior Of Rural Women Of Special Region Of Yogyakarta (Diy) In An Effort To Prevent Menopausal Complaints And Weight Gain

“…Isoflavones that have estrogenic effects include genistein, daidzein and glycosides which are found in legumes (Leguminosae) such as soy beans and red clover. In addition to phytoestrogens, calcium and vitamin D can also be hormone replacement therapy (Bapir et al, 2023).…”