TY - JOUR
T1 - Plasma Soluble Tumor Necrosis Factor Receptor Concentrations and Clinical Events After Hospitalization
T2 - Findings From the ASSESS-AKI and ARID Studies
AU - Coca, Steven G.
AU - Vasquez-Rios, George
AU - Mansour, Sherry G.
AU - Moledina, Dennis G.
AU - Thiessen-Philbrook, Heather
AU - Wurfel, Mark M.
AU - Bhatraju, Pavan
AU - Himmelfarb, Jonathan
AU - Siew, Eddie
AU - Garg, Amit X.
AU - Hsu, Chi yuan
AU - Liu, Kathleen D.
AU - Kimmel, Paul L.
AU - Chinchilli, Vernon M.
AU - Kaufman, James S.
AU - Wilson, Michelle
AU - Banks, Rosamonde E.
AU - Packington, Rebecca
AU - McCole, Eibhlin
AU - Kurth, Mary Jo
AU - Richardson, Ciaran
AU - Go, Alan S.
AU - Selby, Nicholas M.
AU - Parikh, Chirag R.
N1 - Funding Information:
Steven G. Coca, DO, MS, George Vasquez-Rios, MD, Sherry G. Mansour, MD, MS, Dennis G. Moledina, MD, PhD, Heather Thiessen-Philbrook, MMath, Mark M. Wurfel, MD, PhD, Pavan Bhatraju, MD, MSc, Jonathan Himmelfarb, MD, Eddie Siew, MD, Amit X. Garg, MD, Chi-yuan Hsu, MD, Kathleen D. Liu, MD, PhD, Paul L. Kimmel, MD, Vernon M. Chinchilli, PhD, James S. Kaufman, MD, Michelle Wilson, MSc, Rosamonde E. Banks, PhD, Rebecca Packington, BSc, Eibhlin McCole, MSc, Mary Jo Kurth, PhD, Ciaran Richardson, PhD, Alan S. Go, MD, Nicholas M. Selby, MD, and Chirag R. Parikh, MD, PhD. Conception and design of the study: all authors; acquisition or interpretation of the data: all authors; analyzed the data: SGC, GV-R, HT-P, CRP; designed the ARID study and oversaw its delivery: NMS; carried out ARID study data collection: RP; performed and oversaw ARID study biomarker analysis: REB, EM, CR; performed ARID study data analysis: MW; provided input on ARID study data analysis: NMS, REB, CR, MJK, EM; SGC and GV-R contributed equally to this work. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated, and resolved, including with documentation in the literature if appropriate. Dr Coca has salary support from NIH grants R01DK115562, UO1DK106962, R01HL085757, R01DK112258, R01DK126477, and UH3DK114920. Dr Moledina is supported by an NIH grant (K23DK117065) and by the Yale O'Brien Kidney Center (P30DK079310). Dr Mansour is supported by AHA (18CDA34110151), the Yale O'Brien Kidney Center, and the Patterson Trust Fund. CRP is supported by NIH grant K24DK090203 and the P30DK079310 O'Brien Kidney Center Grant. Drs McCole, Richardson, and Kurth are employees of Randox. ASSESS-AKI was supported by cooperative agreements from the NIDDK (U01DK082223, U01DK082185, U01DK082192, and U01DK082183). We also acknowledge funding support from NIH grants R01HL085757, R01DK098233, R01DK101507, R01DK114014, K23DK100468, R03DK111881, R01DK093771, K01DK120783, P30DK079310, and P30DK114809. The ARID study was funded by a grant from Kidney Research UK (RP13/2015). The funders did not have any role in study design, data collection, analysis, reporting, or the decision to submit for publication. Dr Coca reports personal income and equity and stock options from Renalytix and pulseData and personal income from Axon Therapeutics, Bayer, Boehringer-Ingelheim, CHF Solutions, ProKidney, Vifor, and Takeda. Dr Siew reports personal income from Akebia Therapeutics, DaVita, and UpToDate; he also serves as an associate editor for the Clinical Journal of the American Society of Nephrology. Dr Kimmel reports being an editor of the textbook Chronic Renal Disease and the monograph Psychosocial Aspects of Chronic Kidney Disease. Dr Parikh reports personal income and equity and stock options from Renaltyix, personal income from Genfit Biopharmaceutical Company and Akebia Therapeutics, and receipt of grant funding (NIH R01HL085757) for support of the TRIBE-AKI Consortium. Drs McCole, Richardson, and Kurth are employees of Randox but do not own shares in the company. The remaining authors declare that they have no relevant financial interests. The authors would like to thank all of the ASSESS-AKI study participants, research coordinators, and support staff for making this study possible. The ARID study would like to acknowledge the support provided by John Lamont and Peter FitzGerald from Randox Laboratories Ltd. The results opinions expressed in this paper do not necessarily reflect those of the National Institute of Diabetes Digestive and Kidney Diseases, the National Institutes of Health, the US Department of Health and Human Services, or the government of the United States. A preprint version of this Original Investigation was posted November 10, 2021, at medRxiv with doi 10.1101/2021.11.08.21266015. Received February 21, 2022. Evaluated by 4 external peer reviewers and a statistician, with editorial input from an Acting Editor-in-Chief (Editorial Board Member Jorge Cerda, MD). Accepted in revised form August 4, 2022. The involvement of an Acting Editor-in-Chief to handle the peer-review and decision-making processes was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Funding Information:
Dr Coca has salary support from NIH grants R01DK115562, UO1DK106962, R01HL085757, R01DK112258, R01DK126477, and UH3DK114920. Dr Moledina is supported by an NIH grant (K23DK117065) and by the Yale O’Brien Kidney Center (P30DK079310). Dr Mansour is supported by AHA (18CDA34110151), the Yale O’Brien Kidney Center, and the Patterson Trust Fund. CRP is supported by NIH grant K24DK090203 and the P30DK079310 O’Brien Kidney Center Grant. Drs McCole, Richardson, and Kurth are employees of Randox. ASSESS-AKI was supported by cooperative agreements from the NIDDK (U01DK082223, U01DK082185, U01DK082192, and U01DK082183). We also acknowledge funding support from NIH grants R01HL085757, R01DK098233, R01DK101507, R01DK114014, K23DK100468, R03DK111881, R01DK093771, K01DK120783, P30DK079310, and P30DK114809. The ARID study was funded by a grant from Kidney Research UK (RP13/2015). The funders did not have any role in study design, data collection, analysis, reporting, or the decision to submit for publication.
Funding Information:
Dr Coca reports personal income and equity and stock options from Renalytix and pulseData and personal income from Axon Therapeutics, Bayer, Boehringer-Ingelheim, CHF Solutions, ProKidney, Vifor, and Takeda. Dr Siew reports personal income from Akebia Therapeutics, DaVita, and UpToDate; he also serves as an associate editor for the Clinical Journal of the American Society of Nephrology. Dr Kimmel reports being an editor of the textbook Chronic Renal Disease and the monograph Psychosocial Aspects of Chronic Kidney Disease. Dr Parikh reports personal income and equity and stock options from Renaltyix, personal income from Genfit Biopharmaceutical Company and Akebia Therapeutics, and receipt of grant funding (NIH R01HL085757) for support of the TRIBE-AKI Consortium. Drs McCole, Richardson, and Kurth are employees of Randox but do not own shares in the company. The remaining authors declare that they have no relevant financial interests.
Publisher Copyright:
© 2022 National Kidney Foundation, Inc.
PY - 2023/2
Y1 - 2023/2
N2 - Rationale & Objective: The role of plasma soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 in the prognosis of clinical events after hospitalization with or without acute kidney injury (AKI) is unknown. Study Design: Prospective cohort. Setting & Participants: Hospital survivors from the ASSESS-AKI (Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury) and ARID (AKI Risk in Derby) studies with and without AKI during the index hospitalization who had baseline serum samples for biomarker measurements. Predictors: We measured sTNFR1 and sTNFR2 from plasma samples obtained 3 months after discharge. Outcomes: The associations of biomarkers with longitudinal kidney disease incidence and progression, heart failure, and death were evaluated. Analytical Approach: Cox proportional hazard models. Results: Among 1,474 participants with plasma biomarker measurements, 19% had kidney disease progression, 14% had later heart failure, and 21% died during a median follow-up of 4.4 years. For the kidney outcome, the adjusted HRs (AHRs) per doubling in concentration were 2.9 (95% CI, 2.2-3.9) for sTNFR1 and 1.9 (95% CI, 1.5-2.5) for sTNFR2. AKI during the index hospitalization did not modify the association between biomarkers and kidney events. For heart failure, the AHRs per doubling in concentration were 1.9 (95% CI, 1.4-2.5) for sTNFR1 and 1.5 (95% CI, 1.2-2.0) for sTNFR2. For mortality, the AHRs were 3.3 (95% CI, 2.5-4.3) for sTNFR1 and 2.5 (95% CI, 2.0-3.1) for sTNFR2. The findings in ARID were qualitatively similar in terms of the magnitude of association between biomarkers and outcomes. Limitations: Different biomarker platforms and AKI definitions; limited generalizability to other ethnic groups. Conclusions: Plasma sTNFR1 and sTNFR2 measured 3 months after hospital discharge were independently associated with clinical events regardless of AKI status during the index admission. sTNFR1 and sTNFR2 may assist with the risk stratification of patients during follow-up.
AB - Rationale & Objective: The role of plasma soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 in the prognosis of clinical events after hospitalization with or without acute kidney injury (AKI) is unknown. Study Design: Prospective cohort. Setting & Participants: Hospital survivors from the ASSESS-AKI (Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury) and ARID (AKI Risk in Derby) studies with and without AKI during the index hospitalization who had baseline serum samples for biomarker measurements. Predictors: We measured sTNFR1 and sTNFR2 from plasma samples obtained 3 months after discharge. Outcomes: The associations of biomarkers with longitudinal kidney disease incidence and progression, heart failure, and death were evaluated. Analytical Approach: Cox proportional hazard models. Results: Among 1,474 participants with plasma biomarker measurements, 19% had kidney disease progression, 14% had later heart failure, and 21% died during a median follow-up of 4.4 years. For the kidney outcome, the adjusted HRs (AHRs) per doubling in concentration were 2.9 (95% CI, 2.2-3.9) for sTNFR1 and 1.9 (95% CI, 1.5-2.5) for sTNFR2. AKI during the index hospitalization did not modify the association between biomarkers and kidney events. For heart failure, the AHRs per doubling in concentration were 1.9 (95% CI, 1.4-2.5) for sTNFR1 and 1.5 (95% CI, 1.2-2.0) for sTNFR2. For mortality, the AHRs were 3.3 (95% CI, 2.5-4.3) for sTNFR1 and 2.5 (95% CI, 2.0-3.1) for sTNFR2. The findings in ARID were qualitatively similar in terms of the magnitude of association between biomarkers and outcomes. Limitations: Different biomarker platforms and AKI definitions; limited generalizability to other ethnic groups. Conclusions: Plasma sTNFR1 and sTNFR2 measured 3 months after hospital discharge were independently associated with clinical events regardless of AKI status during the index admission. sTNFR1 and sTNFR2 may assist with the risk stratification of patients during follow-up.
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U2 - 10.1053/j.ajkd.2022.08.007
DO - 10.1053/j.ajkd.2022.08.007
M3 - Article
C2 - 36108888
AN - SCOPUS:85142797189
SN - 0272-6386
VL - 81
SP - 190
EP - 200
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -