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

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dc.contributor.authorMartin, William P.-
dc.contributor.authorTuohy, Colm-
dc.contributor.authorDoody, Alison-
dc.contributor.authorJackson, Sabrina-
dc.contributor.authorCanavan, Ronan J.-
dc.contributor.authorSlattery, David-
dc.contributor.authorTwomey, Patrick J.-
dc.contributor.authorMcKenna, Malachi J.-
dc.contributor.authorle Roux, Carel W.-
dc.contributor.authorDocherty, Neil G.- the Authorsen_US
dc.identifier.citationScientific Reportsen_US
dc.description.abstractIdentification of people with diabetes and chronic kidney disease at high-risk of early mortality is a priority to guide intensification of therapy. We aimed to investigate the complementary prognostic value of baseline urine albumin-to-creatinine ratio (uACR) and plasma soluble tumour necrosis factor receptor-1 (sTNFR1) with respect to early mortality and renal functional decline in a population with type 2 diabetes and advanced chronic kidney disease. We measured plasma sTNFR1 in people with type 2 diabetes (HbA1c ≥ 48 mmol/mol) at 2 hospital sites in Dublin between October 15th, 2014 and July 17th, 2015. In a subgroup of patients with advanced chronic kidney disease at baseline (estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/BSA) (n = 118), we collected clinical and longitudinal laboratory data to investigate relationships between sTNFR1 and renal and mortality endpoints by multivariable linear mixed-effects models and Cox proportional hazards regression models. The cohort was 64% male and 97% Caucasian. Mean age was 74 years, with a median type 2 diabetes duration of 16 years. Mean CKD-EPI eGFR was 42 mL/min/BSA and median [IQR] uACR was 3 [11] mg/mmol. Twenty-three (39%) people in quartiles 3 and 4 for plasma sTNFR1 died over 4-year follow-up. After adjustment for clinical variables, annual CKD-EPI eGFR decreased by − 0.56 mL/min/BSA/year for each logarithm unit increase in baseline uACR, corresponding to an annual loss of renal function of 3% per year. Furthermore, elevated uACR, but not sTNFR1, increased the risk of ≥ 40% decline in CKD-EPI eGFR (HR 1.5, p = 0.001) and doubling of serum creatinine (HR 2.0, p < 0.001). Plasma sTNFR1 did not predict a more negative trajectory in eGFR slope. However, for those people in quartiles 3 and 4 for plasma sTNFR1, an increased risk of incident mortality was detected (HR 4.9, p = 0.02). No such association was detected for uACR. In this elderly cohort of patients with type 2 diabetes and chronic kidney disease, sTNFR1 predicted short-to-medium term mortality risk but not risk of progressive renal functional decline. In contrast, parallel assessment of uACR predicted renal functional decline but not mortality, highlighting the complementary prognostic information provided by both parameters.en_US
dc.description.sponsorshipHealth Research Boarden_US
dc.description.sponsorshipHealth Service Executiveen_US
dc.description.sponsorshipScience Foundation Irelanden_US
dc.description.sponsorshipUniversity College Dublinen_US
dc.description.sponsorshipWellcome Trusten_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
dc.subjectChronic kidney diseaseen_US
dc.subjectDiabetes complicationsen_US
dc.subjectPrognostic markersen_US
dc.titleParallel 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 deathen_US
dc.typeJournal Articleen_US
dc.statusPeer revieweden_US
dc.citation.otherArticle Number: 14852en_US
dc.neeo.contributorMartin|William P.|aut|-
dc.neeo.contributorCanavan|Ronan J.|aut|-
dc.neeo.contributorTwomey|Patrick J.|aut|-
dc.neeo.contributorMcKenna|Malachi J.|aut|-
dc.neeo.contributorle Roux|Carel W.|aut|-
dc.neeo.contributorDocherty|Neil G.|aut|-
dc.description.othersponsorshipSwedish Research Councilen_US
dc.identifier.grantidGRANT NUMBER: 203930/B/16/Z-
dc.identifier.grantidBI 2017_3-
item.fulltextWith Fulltext-
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