Soluble receptor for AGE in diabetic nephropathy and its progression in Finnish individuals with type 1 diabetes

Show simple item record FinnDiane Study Grp Waden, Jenny M. Dahlström, Emma H. Elonen, Nina Thorn, Lena M. Waden, Johan Sandholm, Niina Forsblom, Carol Groop, Per-Henrik 2019-08-13T08:31:01Z 2019-08-13T08:31:01Z 2019-07
dc.identifier.citation FinnDiane Study Grp , Waden , J M , Dahlström , E H , Elonen , N , Thorn , L M , Waden , J , Sandholm , N , Forsblom , C & Groop , P-H 2019 , ' Soluble receptor for AGE in diabetic nephropathy and its progression in Finnish individuals with type 1 diabetes ' , Diabetologia , vol. 62 , no. 7 , pp. 1268-1274 .
dc.identifier.other PURE: 126097834
dc.identifier.other PURE UUID: 056e7f78-d837-4480-ac8e-6168eccfe9bf
dc.identifier.other WOS: 000471176200017
dc.identifier.other ORCID: /0000-0003-3999-0390/work/60612542
dc.identifier.other ORCID: /0000-0003-4322-6942/work/60612874
dc.identifier.other ORCID: /0000-0003-1271-8696/work/60613478
dc.description.abstract Aims/hypothesis Activation of the receptor for AGE (RAGE) has been shown to be associated with diabetic nephropathy. The soluble isoform of RAGE (sRAGE) is considered to function as a decoy receptor for RAGE ligands and thereby protects against diabetic complications. A possible association between sRAGE and diabetic nephropathy is still, however, controversial and a more comprehensive analysis of sRAGE with respect to diabetic nephropathy in type 1 diabetes is therefore warranted. Methods sRAGE was measured in baseline serum samples from 3647 participants with type 1 diabetes from the nationwide multicentre Finnish Diabetic Nephropathy (FinnDiane) Study. Associations between sRAGE and diabetic nephropathy, as well as sRAGE and diabetic nephropathy progression, were evaluated by regression, competing risks and receiver operating characteristic curve analyses. The non-synonymous SNP rs2070600 (G82S) was used to test causality in the Mendelian randomisation analysis. Results Baseline sRAGE concentrations were highest in participants with diabetic nephropathy, compared with participants with a normal AER or those with microalbuminuria. Baseline sRAGE was associated with progression from macroalbuminuria to end-stage renal disease (ESRD) in the competing risks analyses, but this association disappeared when eGFR was entered into the model. The SNP rs2070600 was strongly associated with sRAGE concentrations and with progression from macroalbuminuria to ESRD. However, Mendelian randomisation analysis did not support a causal role for sRAGE in progression to ESRD. Conclusions/interpretations RAGE is associated with progression from macroalbuminuria to ESRD, but does not add predictive value on top of conventional risk factors. Although sRAGE is a biomarker of diabetic nephropathy, in light of the Mendelian randomisation analysis it does not seem to be causally related to progression from macroalbuminuria to ESRD. en
dc.format.extent 7
dc.language.iso eng
dc.relation.ispartof Diabetologia
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Diabetic nephropathy
dc.subject End-stage renal disease
dc.subject Soluble receptor for advanced glycation end-products
dc.subject Type 1 diabetes
dc.subject RAGE
dc.subject ASSOCIATION
dc.subject S100A12
dc.subject SRAGE
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title Soluble receptor for AGE in diabetic nephropathy and its progression in Finnish individuals with type 1 diabetes en
dc.type Article
dc.contributor.organization HUS Abdominal Center
dc.contributor.organization Nefrologian yksikkö
dc.contributor.organization University of Helsinki
dc.contributor.organization Research Programs Unit
dc.contributor.organization Diabetes and Obesity Research Program
dc.contributor.organization Clinicum
dc.contributor.organization Department of Medicine
dc.contributor.organization Per Henrik Groop / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.issn 0012-186X
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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