Leonard Goldenstein1, Todd H Driver2, Linda F Fried3, Dena E Rifkin4, Kushang V Patel5, Robert H Yenchek6, Tamara B Harris7, Stephen B Kritchevsky8, Anne B Newman9, Mark J Sarnak10, Michael G Shlipak11, Joachim H Ix12. 1. Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA. 2. Department of Medicine, University of California, San Francisco, San Francisco, CA. 3. Nephrology Section, Veterans Affairs Hospital, Pittsburgh, PA; Division of Nephrology, Department of Medicine, Pittsburgh, PA; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA. 4. Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA; Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California San Diego, San Diego, CA. 5. Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA. 6. Division of Nephrology, Department of Medicine, University of Utah, Salt Lake City, UT. 7. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD. 8. Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC. 9. Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA. 10. Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA. 11. Department of Medicine, University of California, San Francisco, San Francisco, CA; General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA. 12. Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA; Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California San Diego, San Diego, CA. Electronic address: joeix@ucsd.edu.
Abstract
BACKGROUND: In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and CKD progression among community-living persons with predominantly preserved kidney function is unknown. STUDY DESIGN: Longitudinal observational cohort study. SETTING & PARTICIPANTS: Well-functioning community-living elders aged 70-79 years at inception. PREDICTOR: Serum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. OUTCOMES: Change in eGFR over 7 years, and new eGFR < 60 mL/min/1.73 m(2) with a rate of loss of at least 1 mL/min/1.73 m(2) per year. MEASUREMENTS: Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR < 60 mL/min/1.73 m(2). RESULTS: At baseline, mean eGFR was 84 ± 16 (SD)mL/min/1.73 m(2), and serum bicarbonate level was 25.2 ± 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n = 85 [8%]) lost eGFR0.55 (95% CI, 0.13-0.97) mL/min/1.73 m(2) per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFRs > 60 mL/min/1.73 m(2), 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m(2) at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFRs < 60 mL/min/1.73 m(2) (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations. LIMITATIONS: Only 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population. CONCLUSIONS: Lower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m(2) in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development. Published by Elsevier Inc.
BACKGROUND: In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and CKD progression among community-living persons with predominantly preserved kidney function is unknown. STUDY DESIGN: Longitudinal observational cohort study. SETTING & PARTICIPANTS: Well-functioning community-living elders aged 70-79 years at inception. PREDICTOR: Serum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. OUTCOMES: Change in eGFR over 7 years, and new eGFR < 60 mL/min/1.73 m(2) with a rate of loss of at least 1 mL/min/1.73 m(2) per year. MEASUREMENTS: Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR < 60 mL/min/1.73 m(2). RESULTS: At baseline, mean eGFR was 84 ± 16 (SD)mL/min/1.73 m(2), and serum bicarbonate level was 25.2 ± 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n = 85 [8%]) lost eGFR0.55 (95% CI, 0.13-0.97) mL/min/1.73 m(2) per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFRs > 60 mL/min/1.73 m(2), 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m(2) at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFRs < 60 mL/min/1.73 m(2) (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations. LIMITATIONS: Only 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population. CONCLUSIONS: Lower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m(2) in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development. Published by Elsevier Inc.
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