Proton-pump inhibitors associated with decreased urinary citrate excretion

Patel, Parth M.; Kandabarow, Alexander M.; Aiwerioghene, Eseosa; Blanco-Martinez, Enrique; Hart, Spencer; Leehey, David J.; Farooq, Ahmer; Baldea, Kristin G.; Türk, Thomas

doi:10.1007/s11255-020-02719-0

Cited by 5 publications

(7 citation statements)

References 26 publications

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“…A meta-analysis estimated that the pooled adjusted odds ratio of PPI use for hypomagnesemia was 1.71 (95% CI = 1.33–2.19) [ 18 ]. In addition, patients with PPI use demonstrated a 12% lower urinary citrate excretion [ 19 ]. Citrate inhibits the formation of urolithiasis by binding with calcium and is excreted as a soluble calcium citrate complex [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…It was also reported that patients with PPI use had lower urinary citrate and magnesium concentrations in 24-h urine data (both p < 0.05) [ 10 ]. On the other hand, the urinary oxalate concentration was not significantly different between PPI users and PPI non-users [ 10 , 19 ]. Thus, the lower urinary citrate and magnesium levels in patients with PPI use can mediate an increased risk of urolithiasis.…”

Section: Discussionmentioning

confidence: 99%

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

Kim

Yoo

Bang

et al. 2022

JCM

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Kim

Yoo

Bang

et al. 2022

JCM

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“…The reduction of urinary excretion of both calcium and magnesium during PPI treatment may have conflicting effects on the overall risk of kidney stone formation, because the reduced urinary calcium excretion decreases urinary saturation with respect to calcium oxalate and calcium phosphate, but the reduced magnesium excretion increases the risk of stone formation due to the decrease of urinary inhibitory activity of crystallization. Studies focused on the effect of PPIs on the urinary excretion of citrates, which are potent crystallization inhibitors, whose decline in the urine can increase the risk of kidney stone formation (28)(29)(30). The urinary levels of citrate are reduced in conditions of acidosis, which induces an increase in the metabolism of citrate in the renal proximal tubule cells with a consequent decreased excretion of citrate in the urine (31).…”

Section: Discussionmentioning

confidence: 99%

“…renal stone patients receiving PPIs showed that patients tended to show decreased citrate levels (28). This finding was explained by the net gastric acid loss due to reduced gastric acid production by proton pump inhibition, resulting in reduced bicarbonate generation and decreased renal excretion of citrate.…”

Section: Pooled Hazard Ratios Of Incident Nephrolithiasis In Patients...mentioning

confidence: 99%

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

Bapir¹,

Bhatti

Eliwa

et al. 2022

Arch Ital Urol Androl

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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.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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)

Liu,

Wang,

Wang

et al. 2023

BMJ Open

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ObjectiveSeveral studies have suggested a potential link between use of proton pump inhibitors (PPIs) and the risk of kidney stones, attributed to alterations in urine mineral levels. Our study aimed to investigate the association between PPI use and kidney stones in US adults.DesignCross-sectional study.SettingNational Health and Nutrition Examination Survey (2007–2018).Participants27 075 individuals with complete information on PPI use and history of kidney stones were included in this study.Outcomes and analysesNon-linear analysis, logistic regression analysis and subgroup analysis were conducted to estimate the relationship between PPI use and the occurrence and recurrence of kidney stones, after adjusting for potential confounding factors.ResultsMultivariable logistic regression analysis revealed a significant association between PPI use and kidney stones (OR 1.31, 95% CI 1.07 to 1.60), with a 4% increase in the prevalence of kidney stones for each additional year of PPI use (p<0.001). Similarly, PPI use was significantly associated with recurrent kidney stones (OR 1.49, 95% CI 1.04 to 2.13), with a 7% increase in the recurrence of kidney stones for each additional year of PPI use (p<0.001). Furthermore, these associations remained significant even after conducting propensity score matching analysis on a subset of PPI users and non-users (all p≤0.001). Subgroup analyses showed that the effects of PPI use on kidney stones differed by age, sex, race and body mass index.ConclusionsThis study indicated that long-term use of PPI was associated with a higher risk of both the presence and recurrence of kidney stones.

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Proton-pump inhibitors associated with decreased urinary citrate excretion

Cited by 5 publications

References 26 publications

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

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

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

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)

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