Decreased plasma kallikrein activity is associated with reduced kidney function in individuals with type 1 diabetes

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Finndiane Study Grp , Härma , M-A , Dahlström , E H , Sandholm , N , Forsblom , C , Groop , P-H & Lehto , M 2020 , ' Decreased plasma kallikrein activity is associated with reduced kidney function in individuals with type 1 diabetes ' , Diabetologia , vol. 63 , no. 7 , pp. 1349-1354 . https://doi.org/10.1007/s00125-020-05144-1

Title: Decreased plasma kallikrein activity is associated with reduced kidney function in individuals with type 1 diabetes
Author: Finndiane Study Grp; Härma, Mari-Anne; Dahlström, Emma H.; Sandholm, Niina; Forsblom, Carol; Groop, Per-Henrik; Lehto, Markku
Contributor: University of Helsinki, Nefrologian yksikkö
University of Helsinki, HUS Abdominal Center
University of Helsinki, Medicum
University of Helsinki, Research Programs Unit
University of Helsinki, HUS Abdominal Center
University of Helsinki, HUS Abdominal Center
Date: 2020-07
Language: eng
Number of pages: 6
Belongs to series: Diabetologia
ISSN: 0012-186X
URI: http://hdl.handle.net/10138/317711
Abstract: Aims/hypothesis Plasma kallikrein is the central mediator of the plasma kallikrein-kinin system, which is involved both in vascular control and thrombin formation cascades. The plasma kallikrein-kinin system has also been considered protective in pathological conditions, but the impact of plasma kallikreins on diabetic nephropathy remains unknown. The objective of this cross-sectional study was to explore the association of plasma kallikrein with diabetic nephropathy. Methods We measured plasma kallikrein activity in 295 individuals with type 1 diabetes at various stages of diabetic nephropathy, and we tested the genetic association between the plasma kallikrein-kinin system and kidney function in 4400 individuals with type 1 diabetes. Results Plasma kallikrein activity was associated with diabetes duration (p <0.001) and eGFR (p <0.001), and plasma kallikrein activity was lower with more advanced diabetic nephropathy, being lowest in individuals on dialysis. The minor alleles of theKNG1rs5030062 and rs710446 variants, which have previously been associated with increased plasma pre-kallikrein and/or factor XI (FXI) protein levels, were associated with higher eGFR (rs5030062 beta = 0.03,p = 0.01; rs710446 beta = 0.03,p = 0.005) in the FinnDiane cohort of 4400 individuals with type 1 diabetes. Conclusions/interpretation Plasma kallikrein activity and genetic variants known to increase the plasma kallikrein level are associated with higher eGFR in individuals with type 1 diabetes, suggesting that plasma kallikrein might have a protective effect in diabetic nephropathy.
Subject: Diabetic nephropathy
Kidney function
Plasma kallikrein
Plasma kallikrein-kinin system
Type 1 diabetes
MOLECULAR-WEIGHT KININOGEN
ENDOTHELIAL-CELLS
ACTIVATION
SYSTEM
PREKALLIKREIN
3121 General medicine, internal medicine and other clinical medicine
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