TY - JOUR
T1 - Longitudinal TNFR1 and TNFR2 and Kidney Outcomes
T2 - Results from AASK and VA NEPHRON-D
AU - Chen, Teresa K.
AU - Coca, Steven G.
AU - Estrella, Michelle M.
AU - Appel, Lawrence J.
AU - Coresh, Josef
AU - Philbrook, Heather Thiessen
AU - Obeid, Wassim
AU - Fried, Linda F.
AU - Heerspink, Hiddo J.L.
AU - Ix, Joachim H.
AU - Shlipak, Michael G.
AU - Kimmel, Paul L.
AU - Parikh, Chirag R.
AU - Grams, Morgan E.
N1 - Publisher Copyright:
© 2022 by the American Society of Nephrology.
PY - 2022/5
Y1 - 2022/5
N2 - 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 (n5418) and 118 kidney function decline events over a median of 1.5 years in VA NEPHRON-D (n5754). 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.
AB - 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 (n5418) and 118 kidney function decline events over a median of 1.5 years in VA NEPHRON-D (n5754). 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.
UR - http://www.scopus.com/inward/record.url?scp=85129780827&partnerID=8YFLogxK
U2 - 10.1681/ASN.2021060735
DO - 10.1681/ASN.2021060735
M3 - Article
C2 - 35314457
AN - SCOPUS:85129780827
SN - 1046-6673
VL - 33
SP - 996
EP - 1010
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 5
ER -