Dataset Information

Longitudinal TNFR1 and TNFR2 and Kidney Outcomes: Results from AASK and VA NEPHRON-D.

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.

SUBMITTER: Chen TK

PROVIDER: S-EPMC9063900 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Longitudinal TNFR1 and TNFR2 and Kidney Outcomes: Results from AASK and VA NEPHRON-D.

Chen Teresa K TK Coca Steven G SG Estrella Michelle M MM Appel Lawrence J LJ Coresh Josef J Thiessen Philbrook Heather H Obeid Wassim W Fried Linda F LF Heerspink Hiddo J L HJL Ix Joachim H JH Shlipak Michael G MG Kimmel Paul L PL Parikh Chirag R CR Grams Morgan E ME

Journal of the American Society of Nephrology : JASN 20220321 5

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 35314457

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Project description:BackgroundAnemia is common in chronic kidney disease (CKD) and associated with poor outcomes. In cross-sectional studies, lower estimated glomerular filtration rate (eGFR) has been associated with increased risk for anemia. The aim of this study was to determine how hematocrit changes as eGFR declines and what factors impact this longitudinal association.MethodsWe followed 1094 African-Americans with hypertensive nephropathy who participated in the African-American Study of Kidney Disease and Hypertension. Mixed effects models were used to determine longitudinal change in hematocrit as a function of eGFR. Interaction terms were used to assess for differential effects of age, gender, baseline eGFR, baseline proteinuria, malnutrition and inflammation on eGFR-associated declines in hematocrit. In sensitivity analyses, models were run using iGFR (by renal clearance of I(125) iothalamate) in place of eGFR.ResultsAt baseline, mean hematocrit was 39% and 441 (40%) individuals had anemia. The longitudinal relationship between eGFR and hematocrit differed by baseline eGFR and was steeper when baseline eGFR was <45 mL/min/1.73 m(2). For example, the absolute decline in hematocrit per 10 mL/min/1.73 m(2) decline in longitudinal eGFR was -3.7, -1.3 and -0.5% for baseline eGFR values of 20, 40 and 60 mL/min/1.73 m(2), respectively (P < 0.001 comparing the longitudinal association between baseline eGFR = 40 or 60 versus baseline eGFR = 20 mL/min/1.73 m(2)). Similarly, male sex, younger age (<65 years) and higher baseline proteinuria (protein-to-creatinine ratio >0.22) were associated with greater hematocrit declines per unit decrease in longitudinal eGFR compared with female sex, older age and low baseline proteinuria, respectively (P-interaction <0.05 for each comparison). The longitudinal eGFR-hematocrit association did not differ by body mass index, serum albumin or C-reactive protein.ConclusionsMen, younger individuals and those with low baseline eGFR (<45 mL/min/1.73 m(2)) or baseline proteinuria are particularly at risk for eGFR-related declines in hematocrit.

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Dataset Information

Longitudinal TNFR1 and TNFR2 and Kidney Outcomes: Results from AASK and VA NEPHRON-D.

Background

Methods

Results

Conclusions

Publications

Longitudinal TNFR1 and TNFR2 and Kidney Outcomes: Results from AASK and VA NEPHRON-D.

Similar Datasets

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