Todd H Driver1, Michael G Shlipak2, Ronit Katz3, Leonard Goldenstein4, Mark J Sarnak5, Andrew N Hoofnagle3, David S Siscovick6, Bryan Kestenbaum3, Ian H de Boer3, Joachim H Ix7. 1. School of Medicine, University of California, San Francisco. 2. Department of Medicine, University of California, San Francisco; Department of Epidemiology and Biostatistics, University of California, San Francisco; Department of General Internal Medicine, San Francisco VA Medical Center, San Francisco, CA. 3. Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, WA. 4. Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, CA. 5. Division of Nephrology, Tufts Medical Center, Boston, MA. 6. Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, WA; Cardiovascular Health Research Unit, University of Washington, Seattle, WA; Department of Medicine, University of Washington, Seattle, WA; Department of Epidemiology, University of Washington, Seattle, WA. 7. Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, CA; Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA. Electronic address: joeix@ucsd.edu.
Abstract
BACKGROUND: Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation. PREDICTORS: Serum bicarbonate concentrations. OUTCOMES: Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). RESULTS: Average bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. LIMITATIONS: Cause of metabolic acidosis cannot be determined in this study. CONCLUSIONS: Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2).
BACKGROUND: Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation. PREDICTORS: Serum bicarbonate concentrations. OUTCOMES: Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). RESULTS: Average bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. LIMITATIONS: Cause of metabolic acidosis cannot be determined in this study. CONCLUSIONS: Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2).
Authors: Leonard Goldenstein; Todd H Driver; Linda F Fried; Dena E Rifkin; Kushang V Patel; Robert H Yenchek; Tamara B Harris; Stephen B Kritchevsky; Anne B Newman; Mark J Sarnak; Michael G Shlipak; Joachim H Ix Journal: Am J Kidney Dis Date: 2014-06-18 Impact factor: 8.860
Authors: E J Mayer-Davis; M Z Vitolins; S L Carmichael; S Hemphill; G Tsaroucha; J Rushing; S Levin Journal: Ann Epidemiol Date: 1999-07 Impact factor: 3.797
Authors: Diane E Bild; David A Bluemke; Gregory L Burke; Robert Detrano; Ana V Diez Roux; Aaron R Folsom; Philip Greenland; David R Jacob; Richard Kronmal; Kiang Liu; Jennifer Clark Nelson; Daniel O'Leary; Mohammed F Saad; Steven Shea; Moyses Szklo; Russell P Tracy Journal: Am J Epidemiol Date: 2002-11-01 Impact factor: 4.897
Authors: Leonard Goldenstein; Todd H Driver; Linda F Fried; Dena E Rifkin; Kushang V Patel; Robert H Yenchek; Tamara B Harris; Stephen B Kritchevsky; Anne B Newman; Mark J Sarnak; Michael G Shlipak; Joachim H Ix Journal: Am J Kidney Dis Date: 2014-06-18 Impact factor: 8.860
Authors: Wei Chen; Anne B Newman; Linda F Fried; Dena E Rifkin; Michael G Shlipak; Mark J Sarnak; Ronit Katz; Magdalena Madero; Kalani L Raphael; David A Bushinsky; Joachim H Ix Journal: Nephrol Dial Transplant Date: 2018-09-01 Impact factor: 5.992
Authors: Dominik Steubl; Petra Buzkova; Pranav S Garimella; Joachim H Ix; Prasad Devarajan; Michael R Bennett; Paolo H M Chaves; Michael G Shlipak; Nisha Bansal; Mark J Sarnak Journal: Am J Kidney Dis Date: 2019-05-22 Impact factor: 8.860
Authors: Jessica B Kendrick; Leila Zelnick; Michel B Chonchol; David Siscovick; Andrew N Hoofnagle; Joachim H Ix; Mark Sarnak; Michael G Shlipak; Bryan Kestenbaum; Ian H de Boer Journal: Am J Nephrol Date: 2016-12-10 Impact factor: 3.754