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Prevalence of Metformin Use and the Associated Risk of Metabolic Acidosis in US Diabetic Adults With CKD: A National Cross-Sectional Study.

ABSTRACT: The use of metformin in chronic kidney disease (CKD) population has been intensely debated with conflicting evidence. Large population studies are needed to inform risk assessment and therapeutic decision-making. We evaluated the associations among metformin, metabolic acidosis, and CKD in a 10-year nationally representative noninstitutionalized civilian population in the United States.In this cross-sectional study, a total of 2279 diabetic adults aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2012 were included and had measurements of serum bicarbonate, sodium, potassium, and chloride. The exposure was metformin use. The outcome was subclinical and severe metabolic acidosis defined by serum bicarbonate <23 mEq/L and anion gap > 16mEq/L and by serum bicarbonate < 20 mEq/L, respectively.The prevalence of metformin use decreased from 67.2% among CKD-1 and -2, 40.6% among CKD-3, to 1.3% among advanced CKD-4 and -5. Across CKD stages up to CKD-3b, we observed a tendency of lower levels of serum bicarbonate that was significant in metformin users with CKD-2 and CKD-3a and marginally significant with CKD-3b compared to nonmetformin users. The corresponding tendency of higher anion gap in metformin users with the estimated glomerular filtration rate >60 mL/min/1.73 m was also observed. In multiple linear regression analysis, metformin was significantly associated with decreased serum bicarbonate levels (β = -0.45, 95% CI: -0.73, -0.17) and increased serum anion gap levels (β = 0.40, 95% CI: 0.19, 0.61). The adjusted odds ratio of subclinical high anion gap and severe metabolic acidosis for metformin users was 1.68 (95% CI: 1.11, 2.55) and 1.31 (0.49, 3.47), respectively. The association between metformin and serum bicarbonate was significantly modified by CKD status. No interaction was found between metformin and CKD stages for serum anion gap and acidosis.Metformin is associated with subclinical metabolic acidosis but not with severe metabolic acidosis. The propensity of serum bicarbonate-lowering effect was intensified in advanced CKD; however, such tendency was not associated with the risk of clinically defined acidosis. Our findings highlight a potential of cautious expansion of metformin use among CKD-3b patients with diabetes meriting further investigations.

SUBMITTER: Kuo CC

PROVIDER: S-EPMC4697969 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesTo assess the association between self-reported sleep duration and quality and odds of having CKD in Chinese adults on the basis of a community study.Design, setting, participants, & measurementsIn this cross-sectional study, we included 11,040 Chinese adults who participated in an ongoing prospective study, the Kailuan cohort. Survey questionnaire items addressed insomnia, daytime sleepiness, snoring, and sleep duration during their 2012 interview. Overall sleep quality was evaluated by summarizing these four sleep parameters. Fasting blood samples and single random midstream morning urine samples were collected in 2012 and analyzed for serum creatinine and proteinuria. CKD was defined by eGFR<60 ml/min per 1.73 m2 or proteinuria >300 mg/dl. We also examined those at high or very high risk of having CKD, on the basis of the Kidney Disease Improving Global Outcomes recommendations. The association between sleep quality and CKD was assessed using logistic regression model.ResultsWorse overall sleep quality was associated with higher likelihood of being high or very high risk for CKD (multiadjusted odds ratio, 2.69; 95% confidence interval, 1.30 to 5.59 comparing two extreme categories; P trend <0.01), but not overall CKD (multiadjusted odds ratio, 1.58; 95% confidence interval, 0.89 to 2.80 comparing two extreme categories; P trend =0.46), after adjusting for potential confounders. Specifically, individuals with worse sleep quality were more likely to have proteinuria (multiadjusted odds ratio, 1.95; 95% confidence interval, 1.03 to 3.67 comparing two extreme categories; P trend =0.02), rather than lower eGFR level (multiadjusted mean eGFR levels were 96.4 and 93.6 ml/min per 1.73 m2 in the two extreme sleep categories, respectively; P trend =0.13). However, there was no statistically significant association between individual sleep parameters and CKD status.ConclusionsWorse overall sleep quality was associated with higher odds of being high or very high risk for CKD and proteinuria in Chinese adults.

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Prevalence of Metformin Use and the Associated Risk of Metabolic Acidosis in US Diabetic Adults With CKD: A National Cross-Sectional Study.

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