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

Abstract

Aims/hypothesis <div>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. </div><div><br /></div><div>Methods </div><div>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. </div><div><br /></div><div>Results </div><div>Plasma kallikrein activity was associated with diabetes duration (<i>p</i> < 0.001) and eGFR (<i>p </i>< 0.001), and plasma kallikrein activity was lower with more advanced diabetic nephropathy, being lowest in individuals on dialysis. The minor alleles of the <i>KNG1</i> rs5030062 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, <i>p</i> = 0.01; rs710446 beta = 0.03, <i>p</i> = 0.005) in the FinnDiane cohort of 4400 individuals with type 1 diabetes. </div><div><br /></div><div>Conclusions/interpretation </div><div>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.</div>