Carl P Walther1, Joachim H Ix2, Mary L Biggs3, Jorge R Kizer4, Sankar D Navaneethan5, Luc Djoussé6, Kenneth J Mukamal7. 1. Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX. Electronic address: carl.walther@bcm.edu. 2. Nephrology Section, Veterans Affairs San Diego Healthcare System, and Division of Nephrology-Hypertension, University of California-San Diego, La Jolla, CA. 3. Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA. 4. Cardiology Section, San Francisco Veterans Affairs Healthcare System, and Departments of Medicine, Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA. 5. Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX; Section of Nephrology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX. 6. Division of Aging, Department of Medicine, Brigham and Women's Hospital, and Boston Veterans Affairs Healthcare System, Boston, MA. 7. Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
Abstract
RATIONALE & OBJECTIVE: Circulating nonesterified fatty acids (NEFAs) make up a small portion of circulating lipids but are a metabolically important energy source. Excessive circulating NEFAs may contribute to lipotoxicity in many tissues, including the kidneys. We investigated the relationship between total circulating NEFA concentration and kidney outcomes in older, community-dwelling adults. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 4,698 participants≥65 years of age in the Cardiovascular Health Study who underwent total fasting serum NEFA concentration measurements in 1992-1993. EXPOSURE: Fasting serum NEFA concentration at one time point. OUTCOME: Three primary outcomes: estimated glomerular filtration rate (eGFR) decline of≥30%, the composite of eGFR decline≥30% or kidney failure with replacement therapy, and change in eGFR. These outcomes were assessed over 4- and 13-year periods. ANALYTICAL APPROACH: Logistic regression for the dichotomous outcomes and mixed effects models for the continuous outcome, with sequential adjustment for baseline covariates. Inverse probability of attrition weighting was implemented to account for informative attrition during the follow-up periods. RESULTS: Serum NEFA concentrations were not independently associated with kidney outcomes. In unadjusted and partially adjusted analyses, the highest quartile of serum NEFA concentration (compared with lowest) was associated with a higher risk of≥30% eGFR decline at 4 years and faster rate of decline of eGFR. No associations were evident after adjustment for comorbidities, lipid levels, insulin sensitivity, medications, and vital signs: the odds ratio for the eGFR decline outcome was 1.33 (95% CI, 0.83-2.13), and the difference in eGFR slope in the highest versus lowest quartile of serum NEFA concentration was-0.15 (95% CI, -0.36 to 0.06) mL/min/1.73m2 per year. LIMITATIONS: Single NEFA measurements, no measurements of post-glucose load NEFA concentrations or individual NEFA species, no measurement of baseline urine albumin. CONCLUSIONS: A single fasting serum NEFA concentration was not independently associated with long-term adverse kidney outcomes in a cohort of older community-living adults.
RATIONALE & OBJECTIVE: Circulating nonesterified fatty acids (NEFAs) make up a small portion of circulating lipids but are a metabolically important energy source. Excessive circulating NEFAs may contribute to lipotoxicity in many tissues, including the kidneys. We investigated the relationship between total circulating NEFA concentration and kidney outcomes in older, community-dwelling adults. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 4,698 participants≥65 years of age in the Cardiovascular Health Study who underwent total fasting serum NEFA concentration measurements in 1992-1993. EXPOSURE: Fasting serum NEFA concentration at one time point. OUTCOME: Three primary outcomes: estimated glomerular filtration rate (eGFR) decline of≥30%, the composite of eGFR decline≥30% or kidney failure with replacement therapy, and change in eGFR. These outcomes were assessed over 4- and 13-year periods. ANALYTICAL APPROACH: Logistic regression for the dichotomous outcomes and mixed effects models for the continuous outcome, with sequential adjustment for baseline covariates. Inverse probability of attrition weighting was implemented to account for informative attrition during the follow-up periods. RESULTS: Serum NEFA concentrations were not independently associated with kidney outcomes. In unadjusted and partially adjusted analyses, the highest quartile of serum NEFA concentration (compared with lowest) was associated with a higher risk of≥30% eGFR decline at 4 years and faster rate of decline of eGFR. No associations were evident after adjustment for comorbidities, lipid levels, insulin sensitivity, medications, and vital signs: the odds ratio for the eGFR decline outcome was 1.33 (95% CI, 0.83-2.13), and the difference in eGFR slope in the highest versus lowest quartile of serum NEFA concentration was-0.15 (95% CI, -0.36 to 0.06) mL/min/1.73m2 per year. LIMITATIONS: Single NEFA measurements, no measurements of post-glucose load NEFA concentrations or individual NEFA species, no measurement of baseline urine albumin. CONCLUSIONS: A single fasting serum NEFA concentration was not independently associated with long-term adverse kidney outcomes in a cohort of older community-living adults.
Authors: H O Steinberg; M Tarshoby; R Monestel; G Hook; J Cronin; A Johnson; B Bayazeed; A D Baron Journal: J Clin Invest Date: 1997-09-01 Impact factor: 14.808
Authors: Haochang Shou; Jesse Y Hsu; Dawei Xie; Wei Yang; Jason Roy; Amanda H Anderson; J Richard Landis; Harold I Feldman; Afshin Parsa; Christopher Jepson Journal: Clin J Am Soc Nephrol Date: 2017-07-27 Impact factor: 8.237
Authors: G Paolisso; P Gualdiero; D Manzella; M R Rizzo; M R Tagliamonte; A Gambardella; M Verza; S Gentile; M Varricchio; F D'Onofrio Journal: Am J Cardiol Date: 1997-10-01 Impact factor: 2.778
Authors: D E Kelley; K V Williams; J C Price; T M McKolanis; B H Goodpaster; F L Thaete Journal: J Clin Endocrinol Metab Date: 2001-11 Impact factor: 5.958
Authors: Jonas Sieber; Maja Tamara Lindenmeyer; Kapil Kampe; Kirk Nicholas Campbell; Clemens David Cohen; Helmut Hopfer; Peter Mundel; Andreas Werner Jehle Journal: Am J Physiol Renal Physiol Date: 2010-07-28
Authors: Stefano Turolo; Alberto Edefonti; Marie Louise Syren; Franca Marangoni; William Morello; Carlo Agostoni; Giovanni Montini Journal: J Ren Nutr Date: 2017-11-16 Impact factor: 3.655
Authors: Jun-Jae Chung; Tobias B Huber; Markus Gödel; George Jarad; Björn Hartleben; Christopher Kwoh; Alexander Keil; Aleksey Karpitskiy; Jiancheng Hu; Christine J Huh; Marina Cella; Richard W Gross; Jeffrey H Miner; Andrey S Shaw Journal: J Clin Invest Date: 2015-04-27 Impact factor: 14.808