Dataset Information

Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.

ABSTRACT: The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H₂-receptor antagonists (H₂ blockers; n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H₂ blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m² and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31-90, 91-180, 181-360, and 361-720 days compared with those exposed for ?30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H₂ blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.

SUBMITTER: Xie Y

PROVIDER: S-EPMC5042677 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.

Xie Yan Y Bowe Benjamin B Li Tingting T Xian Hong H Balasubramanian Sumitra S Al-Aly Ziyad Z

Journal of the American Society of Nephrology : JASN 20160414 10

The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H<sub>2</sub>-receptor antagonists (H<sub>2</sub> blockers; n=20,270) and followed these patients over 5 years to ascertain renal outcome ...[more]

PMID: 27080976

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Project description:Background and objectivesExperimental evidence suggests a role for monocytes in the biology of kidney disease progression; however, whether monocyte count is associated with risk of incident CKD, CKD progression, and ESRD has not been examined in large epidemiologic studies.Design, settings, participants, & measurementsWe built a longitudinal observational cohort of 1,594,700 United States veterans with at least one eGFR during fiscal year 2004 (date of last eGFR during this period designated time zero) and no prior history of ESRD, dialysis, or kidney transplant. Cohort participants were followed until September 30, 2013 or death. Monocyte count closest to and before time zero was categorized in quartiles: quartile 1, >0.00 to ≤0.40 thousand cells per cubic millimeter (k/cmm); quartile 2, >0.40 to ≤0.55 k/cmm; quartile 3, >0.55 to ≤0.70 k/cmm; and quartile 4, >0.70 k/cmm. Survival models were built to examine the association between monocyte count and risk of incident eGFR<60 ml/min per 1.73 m2, risk of incident CKD, and risk of CKD progression defined as doubling of serum creatinine, eGFR decline ≥30%, or the composite outcome of ESRD, dialysis, or renal transplantation.ResultsOver a median follow-up of 9.2 years (interquartile range, 8.3-9.4); in adjusted survival models, there was a graded association between monocyte counts and risk of renal outcomes. Compared with quartile 1, quartile 4 was associated with higher risk of incident eGFR<60 ml/min per 1.73 m2 (hazard ratio, 1.13; 95% confidence interval, 1.12 to 1.14) and risk of incident CKD (hazard ratio, 1.15; 95% confidence interval, 1.13 to 1.16). Quartile 4 was associated with higher risk of doubling of serum creatinine (hazard ratio, 1.22; 95% confidence interval, 1.20 to 1.24), ≥30% eGFR decline (hazard ratio, 1.18; 95% confidence interval, 1.17 to 1.19), and the composite renal end point (hazard ratio, 1.19; 95% confidence interval, 1.16 to 1.22). Cubic spline analyses of the relationship between monocyte count levels and renal outcomes showed a linear relationship, in which risk was higher with higher monocyte count. Results were robust to changes in sensitivity analyses.ConclusionsOur results show a significant association between higher monocyte count and risks of incident CKD and CKD progression to ESRD.

Project description:Nutrition is linked strongly with health outcomes in chronic kidney disease (CKD). However, few studies have examined relationships between dietary patterns and health outcomes in persons with CKD.Observational cohort study.3,972 participants with CKD (defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 or albumin-creatinine ratio ? 30 mg/g at baseline) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a prospective cohort study of 30,239 black and white adults at least 45 years of age.5 empirically derived dietary patterns identified by factor analysis: "convenience" (Chinese and Mexican foods, pizza, and other mixed dishes), "plant-based" (fruits and vegetables), "sweets/fats" (sugary foods), "Southern" (fried foods, organ meats, and sweetened beverages), and "alcohol/salads" (alcohol, green-leafy vegetables, and salad dressing).All-cause mortality and end-stage renal disease (ESRD).816 deaths and 141 ESRD events were observed over approximately 6 years of follow-up. There were no statistically significant associations of convenience, sweets/fats, or alcohol/salads pattern scores with all-cause mortality after multivariable adjustment. In Cox regression models adjusted for sociodemographic factors, energy intake, comorbid conditions, and baseline kidney function, higher plant-based pattern scores (indicating greater consistency with the pattern) were associated with lower risk of mortality (HR comparing fourth to first quartile, 0.77; 95% CI, 0.61-0.97), whereas higher Southern pattern scores were associated with greater risk of mortality (HR comparing fourth to first quartile, 1.51; 95% CI, 1.19-1.92). There were no associations of dietary patterns with incident ESRD in multivariable-adjusted models.Missing dietary pattern data, potential residual confounding from lifestyle factors.A Southern dietary pattern rich in processed and fried foods was associated independently with mortality in persons with CKD. In contrast, a diet rich in fruits and vegetables appeared to be protective.

Dataset Information

Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.

Publications

Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.

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