Teresa K Chen1,2, Steven G Coca3, Michelle M Estrella4, Lawrence J Appel2,5,6, Josef Coresh2,5,6, Heather Thiessen Philbrook7, Wassim Obeid7, Linda F Fried8,9, Hiddo J L Heerspink10, Joachim H Ix11, Michael G Shlipak4, Paul L Kimmel12, Chirag R Parikh7,2,6, Morgan E Grams. 1. Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland tchen39@jhmi.edu. 2. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland. 3. Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York. 4. Kidney Health Research Collaborative and Division of Nephrology, Department of Medicine, University of California and San Francisco VA Health Care System, San Francisco, California. 5. Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. 6. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 7. Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 8. Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. 9. Departments of Medicine, Epidemiology, and Clinical and Translational Science, University of Pittsburgh, Pittsburgh, Pennsylvania. 10. The George Institute for Global Health, Sydney, Australia. 11. Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, and Veterans Affairs San Diego Healthcare System, San Diego, California. 12. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Abstract
BACKGROUND: Higher baseline levels of soluble TNF receptors (TNFR1 and TNFR2) have been associated with progressive CKD. Whether longitudinal changes in these biomarkers of inflammation are also associated with worse kidney outcomes has been less studied. METHODS: We evaluated associations of longitudinal changes in TNFR1 and TNFR2 with ESKD in the African American Study of Kidney Disease and Hypertension (AASK; 38% female; 0% diabetes) and kidney function decline (first occurrence of ≥30 ml/min per 1.73 m2 or ≥50% eGFR decline if randomization eGFR ≥60 or <60 ml/min per 1.73 m2, respectively; ESKD) in the Veterans Affairs Nephropathy in Diabetes trial (VA NEPHRON-D; 99% male; 100% diabetes) using Cox models. Biomarkers were measured from samples collected at 0-, 12-, and 24-month visits for AASK (serum) and 0- and 12-month visits for VA NEPHRON-D (plasma). Biomarker slopes (AASK) were estimated using linear mixed-effects models. Covariates included sociodemographic/clinical factors, baseline biomarker level, and kidney function. 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 SD increase in TNFR1 and TNFR2 slope was associated with 2.98- and 1.87-fold higher risks of ESKD, respectively. In VA NEPHRON-D, each 1 SD increase in TNFR1 and TNFR2 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 TNFR1 and TNFR2 were each associated with progressive CKD, independent of initial biomarker level and kidney function.
BACKGROUND: Higher baseline levels of soluble TNF receptors (TNFR1 and TNFR2) have been associated with progressive CKD. Whether longitudinal changes in these biomarkers of inflammation are also associated with worse kidney outcomes has been less studied. METHODS: We evaluated associations of longitudinal changes in TNFR1 and TNFR2 with ESKD in the African American Study of Kidney Disease and Hypertension (AASK; 38% female; 0% diabetes) and kidney function decline (first occurrence of ≥30 ml/min per 1.73 m2 or ≥50% eGFR decline if randomization eGFR ≥60 or <60 ml/min per 1.73 m2, respectively; ESKD) in the Veterans Affairs Nephropathy in Diabetes trial (VA NEPHRON-D; 99% male; 100% diabetes) using Cox models. Biomarkers were measured from samples collected at 0-, 12-, and 24-month visits for AASK (serum) and 0- and 12-month visits for VA NEPHRON-D (plasma). Biomarker slopes (AASK) were estimated using linear mixed-effects models. Covariates included sociodemographic/clinical factors, baseline biomarker level, and kidney function. 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 SD increase in TNFR1 and TNFR2 slope was associated with 2.98- and 1.87-fold higher risks of ESKD, respectively. In VA NEPHRON-D, each 1 SD increase in TNFR1 and TNFR2 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 TNFR1 and TNFR2 were each associated with progressive CKD, independent of initial biomarker level and kidney function.
Keywords:
AASK (African American Study of Kidney Disease and Hypertension); chronic inflammation; chronic kidney disease; diabetes mellitus; end-stage kidney disease; renal function decline
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