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

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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 . https://doi.org/10.1007/s00125-019-4883-4

Title: Soluble receptor for AGE in diabetic nephropathy and its progression in Finnish individuals with type 1 diabetes
Author: Finndiane Study Grp; Waden, Jenny M.; Dahlström, Emma H.; Elonen, Nina; Thorn, Lena M.; Waden, Johan; Sandholm, Niina; Forsblom, Carol; Groop, Per-Henrik
Other contributor: University of Helsinki, HUS Abdominal Center
University of Helsinki, Diabetes and Obesity Research Program
University of Helsinki, Nefrologian yksikkö
University of Helsinki, Nefrologian yksikkö
University of Helsinki, HUS Abdominal Center
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, HUS Abdominal Center







Date: 2019-07
Language: eng
Number of pages: 7
Belongs to series: Diabetologia
ISSN: 0012-186X
DOI: https://doi.org/10.1007/s00125-019-4883-4
URI: http://hdl.handle.net/10138/304537
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.
Subject: Diabetic nephropathy
End-stage renal disease
Soluble receptor for advanced glycation end-products
Type 1 diabetes
GLYCATION END-PRODUCTS
ALL-CAUSE MORTALITY
KIDNEY-DISEASE
RAGE
ATHEROSCLEROSIS
GLYCOSYLATION
ASSOCIATION
S100A12
SRAGE
3121 General medicine, internal medicine and other clinical medicine
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