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Publication Information
Affiliation
1Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;
2Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA;
3Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4Kidney Health Research Collaborative and Division of Nephrology, Department of Medicine, University of California, San Francisco, California, San Francisco, CA and San Francisco VA Health Care System
5Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;
6Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA;
7Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA;
8Departments of Medicine, Epidemiology, and Clinical and Translational Science, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;
9The George Institute for Global Health, Sydney, Australia;
10Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, and Veterans Affairs San Diego Healthcare System, San Diego, California, USA;
11National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
Authors
Appel LJ, Chen TK, Coca SG, Coresh J, Estrella MM, Fried LF, Grams ME, Heerspink HJL, Ix JH, Kimmel PL, Obeid W, Parikh CR, Philbrook HT
Studies
Abstract
Background: Higher baseline levels of soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2) have been associated with progressive CKD in patients with and without diabetes. Whether longitudinal changes in these two biomarkers of inflammation are also associated with worse kidney outcomes is unclear.
Methods: We evaluated associations of longitudinal sTNFR1 and sTNFR2 change with ESKD in the African American Study of Kidney Disease and Hypertension (AASK; 0% diabetes) and kidney function decline in the Veterans Affairs Nephropathy in Diabetes trial (VA NEPHRON-D; 100% diabetes) using Cox models. Biomarkers were measured from stored samples collected at the 0, 12, and 24-month visits of AASK (serum) and 0 and 12-month visits of VA NEPHRON-D (plasma). Biomarker slopes (AASK) were estimated using linear mixed-effects models. Covariates included biomarker level, sociodemographic and clinical factors, and kidney function at 0 months.
Results: There were 129 ESKD events over a median of 7.0 years in AASK (n=418) and 118 kidney function decline events over a median of 1.5 years in VA NEPHRON-D (n=754). In AASK, each 1 standard deviation (SD) increase in sTNFR1 and sTNFR2 slope was associated with 2.20 and 1.64-fold higher risks of ESKD, respectively. In VA NEPHRON-D, each 1 SD greater sTNFR1 and sTNFR2 change was associated with 3.20 and 1.43-fold higher risks of kidney function decline, respectively.
Conclusions: Among individuals with and without diabetes, longitudinal increases in sTNFR1 and sTNFR2 were associated with progressive CKD, independent of initial biomarker level or kidney function.