Advertisement
American Journal of Kidney Diseases

Plasma Soluble Tumor Necrosis Factor Receptor Concentrations and Clinical Events After Hospitalization: Findings From the ASSESS-AKI and ARID Studies

Published:September 12, 2022DOI:https://doi.org/10.1053/j.ajkd.2022.08.007

      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.

      Index Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Coca S.G.
        • Singanamala S.
        • Parikh C.R.
        Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis.
        Kidney Int. 2012; 81: 442-448https://doi.org/10.1038/ki.2011.379
        • Parr S.K.
        • Siew E.D.
        Delayed consequences of acute kidney injury.
        Adv Chronic Kidney Dis. 2016; 23: 186-194https://doi.org/10.1053/j.ackd.2016.01.014
        • Hansen M.K.
        • Gammelager H.
        • Jacobsen C.J.
        • et al.
        Acute kidney injury and long-term risk of cardiovascular events after cardiac surgery: a population-based cohort study.
        J Cardiothorac Vasc Anesth. 2015; 29: 617-625https://doi.org/10.1053/j.jvca.2014.08.020
        • Matsuura R.
        • Iwagami M.
        • Moriya H.
        • et al.
        The clinical course of acute kidney disease after cardiac surgery: a retrospective observational study.
        Sci Rep. 2020; 10: 6490https://doi.org/10.1038/s41598-020-62981-1
        • Saran R.
        • Li Y.
        • Robinson B.
        • et al.
        US Renal Data System 2015 Annual Data Report: epidemiology of kidney disease in the United States.
        Am J Kidney Dis. 2016; 67: S1-S305https://doi.org/10.1053/j.ajkd.2015.12.014
        • Silver S.A.
        • Siew E.D.
        Follow-up care in acute kidney injury: lost in transition.
        Adv Chronic Kidney Dis. 2017; 24: 46-252https://doi.org/10.1053/j.ackd.2017.05.008
        • Chawla L.S.
        • Eggers P.W.
        • Star R.A.
        • Kimmel P.L.
        Acute kidney injury and chronic kidney disease as interconnected syndromes.
        N Engl J Med. 2014; 371: 58-66https://doi.org/10.1056/NEJMra1214243
        • See E.J.
        • Jayasinghe K.
        • Glassford N.
        • et al.
        Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure.
        Kidney Int. 2019; 95: 160-172https://doi.org/10.1016/j.kint.2018.08.036
        • Pannu N.
        • James M.
        • Hemmelgarn B.R.
        • et al.
        Modification of outcomes after acute kidney injury by the presence of CKD.
        Am J Kidney Dis. 2011; 58: 206-213https://doi.org/10.1053/j.ajkd.2011.01.028
        • Ostermann M.
        • Zarbock A.
        • Goldstein S.
        • et al.
        Recommendations on acute kidney injury biomarkers from the Acute Disease Quality Initiative Consensus Conference: a consensus statement.
        JAMA Netw Open. 2020; 3e2019209https://doi.org/10.1001/jamanetworkopen.2020.19209
        • McBride W.T.
        • Kurth M.J.
        • McLean G.
        • et al.
        Stratifying risk of acute kidney injury in pre and post cardiac surgery patients using a novel biomarker-based algorithm and clinical risk score.
        Sci Rep. 2019; 916963https://doi.org/10.1038/s41598-019-53349-1
        • Kurth M.J.
        • McBride W.T.
        • McLean G.
        • et al.
        Acute kidney injury risk in orthopaedic trauma patients pre and post surgery using a biomarker algorithm and clinical risk score.
        Sci Rep. 2020; 1020005https://doi.org/10.1038/s41598-020-76929-y
        • Bhatraju P.K.
        • Zelnick L.R.
        • Shlipak M.
        • Katz R.
        • Kestenbaum B.
        Association of soluble TNFR-1 concentrations with long-term decline in kidney function: the Multi-Ethnic Study of Atherosclerosis.
        J Am Soc Nephrol. 2018; 29: 2713-2721https://doi.org/10.1681/ASN.2018070719
        • Ye X.
        • Luo T.
        • Wang K.
        • et al.
        Circulating TNF receptors 1 and 2 predict progression of diabetic kidney disease: a meta-analysis.
        Diabetes Metab Res Rev. 2019; 35e3195https://doi.org/10.1002/dmrr.3195
        • Salimi S.
        • Shardell M.D.
        • Seliger S.L.
        • et al.
        Inflammation and trajectory of renal function in community-dwelling older adults.
        J Am Geriatr Soc. 2018; 66: 804-811https://doi.org/10.1111/jgs.15268
        • Wilson M.
        • Packington R.
        • Sewell H.
        • et al.
        Biomarkers during recovery from AKI and prediction of long-term reductions in estimated GFR.
        Am J Kidney Dis. 2022; 79: 646-656.e1https://doi.org/10.1053/j.ajkd.2021.08.017
        • Murugan R.
        • Wen X.
        • Keener C.
        • et al.
        Associations between intensity of RRT, inflammatory mediators, and outcomes.
        Clin J Am Soc Nephrol. 2015; 10: 926-933https://doi.org/10.2215/CJN.04560514
        • Kellum J.A.
        • Sileanu F.E.
        • Bihorac A.
        • Hoste E.A.
        • Chawla L.S.
        Recovery after acute kidney injury.
        Am J Respir Crit Care Med. 2017; 195: 784-791https://doi.org/10.1164/rccm.201604-0799OC
        • Bagshaw S.M.
        Epidemiology of renal recovery after acute renal failure.
        Curr Opin Crit Care. 2006; 12: 544-550https://doi.org/10.1097/01.ccx.0000247444.63758.0b
        • Amdur R.L.
        • Chawla L.S.
        • Amodeo S.
        • Kimmel P.L.
        • Palant C.E.
        Outcomes following diagnosis of acute renal failure in U.S. veterans: focus on acute tubular necrosis.
        Kidney Int. 2009; 76: 1089-1097https://doi.org/10.1038/ki.2009.332
        • Chawla L.S.
        • Amdur R.L.
        • Shaw A.D.
        • Faselis C.
        • Palant C.E.
        • Kimmel P.L.
        Association between AKI and long-term renal and cardiovascular outcomes in United States veterans.
        Clin J Am Soc Nephrol. 2014; 9: 448-456https://doi.org/10.2215/CJN.02440213
        • Heung M.
        • Steffick D.E.
        • Zivin K.
        • et al.
        Acute kidney injury recovery pattern and subsequent risk of CKD: an analysis of Veterans Health Administration data.
        Am J Kidney Dis. 2016; 67: 742-752https://doi.org/10.1053/j.ajkd.2015.10.019
        • McAdams M.
        • Ortiz-Soriano V.
        • Jordan M.
        • et al.
        Kidney recovery in patients discharged to an acute rehabilitation facility with acute kidney injury requiring hemodialysis.
        Clin Nephrol. 2019; 92: 15-24https://doi.org/10.5414/CN109743
        • Siew E.D.
        • Abdel-Kader K.
        • Perkins A.M.
        • et al.
        Timing of recovery from moderate to severe AKI and the risk for future loss of kidney function.
        Am J Kidney Dis. 2020; 75: 204-213https://doi.org/10.1053/j.ajkd.2019.05.031
        • Ishani A.
        • Xue J.L.
        • Himmelfarb J.
        • et al.
        Acute kidney injury increases risk of ESRD among elderly.
        J Am Soc Nephrol. 2009; 20: 223-228https://doi.org/10.1681/ASN.2007080837
        • Go A.S.
        • Parikh C.R.
        • Ikizler T.A.
        • et al.
        The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods.
        BMC Nephrol. 2010; 11: 22https://doi.org/10.1186/1471-2369-11-22
        • Horne K.L.
        • Packington R.
        • Monaghan J.
        • Reilly T.
        • Selby N.M.
        Three-year outcomes after acute kidney injury: results of a prospective parallel group cohort study.
        BMJ Open. 2017; 7e015316https://doi.org/10.1136/bmjopen-2016-015316
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612https://doi.org/10.7326/0003-4819-150-9-200905050-00006
        • Selby N.M.
        • Crowley L.
        • Fluck R.J.
        • et al.
        Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients.
        Clin J Am Soc Nephrol. 2012; 7: 533-540https://doi.org/10.2215/CJN.08970911
        • Horne K.L.
        • Shardlow A.
        • Taal M.W.
        • Selby N.M.
        Long term outcomes after acute kidney injury: lessons from the ARID study.
        Nephron. 2015; 131: 102-106https://doi.org/10.1159/000439066
        • Mahmood S.S.
        • Wang T.J.
        The epidemiology of congestive heart failure: the Framingham Heart Study perspective.
        Glob Heart. 2013; 8: 77-82https://doi.org/10.1016/j.gheart.2012.12.006
        • Heagerty P.J.
        • Lumley T.
        • Pepe M.S.
        Time-dependent ROC curves for censored survival data and a diagnostic marker.
        Biometrics. 2000; 56: 337-344https://doi.org/10.1111/j.0006-341x.2000.00337.x
        • Pencina M.J.
        • D’Agostino Sr., R.B.
        • Steyerberg E.W.
        Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers.
        Stat Med. 2011; 30: 11-21https://doi.org/10.1002/sim.4085
        • Mehta S.
        • Chauhan K.
        • Patel A.
        • et al.
        The prognostic importance of duration of AKI: a systematic review and meta-analysis.
        BMC Nephrol. 2018; 19: 91https://doi.org/10.1186/s12882-018-0876-7
        • Coca S.G.
        • King Jr., J.T.
        • Rosenthal R.A.
        • Perkal M.F.
        • Parikh C.R.
        The duration of postoperative acute kidney injury is an additional parameter predicting long-term survival in diabetic veterans.
        Kidney Int. 2010; 78: 926-933https://doi.org/10.1038/ki.2010.259
        • Basile D.P.
        • Bonventre J.V.
        • Mehta R.
        • et al.
        Progression after AKI: understanding maladaptive repair processes to predict and identify therapeutic treatments.
        J Am Soc Nephrol. 2016; 27: 687-697https://doi.org/10.1681/ASN.2015030309
        • Legrand M.
        • Rossignol P.
        Cardiovascular consequences of acute kidney injury.
        N Engl J Med. 2020; 382: 2238-2247https://doi.org/10.1056/NEJMra1916393
        • Schulz R.
        • Heusch G.
        Tumor necrosis factor-alpha and its receptors 1 and 2: yin and yang in myocardial infarction?.
        Circulation. 2009; 119: 1355-1357https://doi.org/10.1161/CIRCULATIONAHA.108.846105
        • Carlsson A.C.
        • Ruge T.
        • Kjøller E.
        • et al.
        10-year associations between tumor necrosis factor receptors 1 and 2 and cardiovascular events in patients with stable coronary heart disease: a CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) trial substudy.
        J Am Heart Assoc. 2018; 7e008299https://doi.org/10.1161/JAHA.117.008299
        • Nilsson L.
        • Szymanowski A.
        • Swahn E.
        • Jonasson L.
        Soluble TNF receptors are associated with infarct size and ventricular dysfunction in ST-elevation myocardial infarction.
        PLoS One. 2013; 8e55477https://doi.org/10.1371/journal.pone.0055477
        • Bae E.
        • Cha R.
        • Kim Y.C.
        • et al.
        Circulating TNF receptors predict cardiovascular disease in patients with chronic kidney disease.
        Medicine (Baltimore). 2017; 96e6666https://doi.org/10.1097/MD.0000000000006666
        • Martin W.P.
        • Tuohy C.
        • Doody A.
        • et al.
        Parallel assessment of albuminuria and plasma sTNFR1 in people with type 2 diabetes and advanced chronic kidney disease provides accurate prognostication of the risks of renal decline and death.
        Sci Rep. 2020; 1014852https://doi.org/10.1038/s41598-020-71684-6
        • Neirynck N.
        • Glorieux G.
        • Schepers E.
        • Verbeke F.
        • Vanholder R.
        Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease: a prospective cohort study.
        PLoS One. 2015; 10e0122073https://doi.org/10.1371/journal.pone.0122073
        • Prowle J.R.
        • Kolic I.
        • Purdell-Lewis J.
        • Taylor R.
        • Pearse R.M.
        • Kirwan C.J.
        Serum creatinine changes associated with critical illness and detection of persistent renal dysfunction after AKI.
        Clin J Am Soc Nephrol. 2014; 9: 1015-1023https://doi.org/10.2215/CJN.11141113
        • Sunder S.
        • Jayaraman R.
        • Mahapatra H.S.
        • et al.
        Estimation of renal function in the intensive care unit: the covert concepts brought to light.
        J Intensive Care. 2014; 2: 31https://doi.org/10.1186/2052-0492-2-31
        • Wetmore J.B.
        • Liu J.
        • Li S.
        • et al.
        The Healthy People 2020 objectives for kidney disease: how far have we come, and where do we need to go?.
        Clin J Am Soc Nephrol. 2017; 12: 200-209https://doi.org/10.2215/CJN.04210416