ecallantide and Diabetic-Nephropathies

Angiotensin II (Ang II) regulates a number of genes associated with progression of renal disease. The regulation of gene expression by Ang II occurs through specific receptors that are linked to changes in the activity of transcription factors within the nucleus of target cells. In particular, members of the nuclear factor-kappaB family of transcription factors are activated, which in turn fuels at least two autocrine reinforcing loops that amplify Ang II and tumor necrosis factor-alpha formation. Angiotensin converting enzymes (ACE) inhibitors and angiotensin antagonists (AIIAs) differ both pharmacokinetically and pharmacodynamically in patients with end-stage renal disease (ESRD). Several ACE inhibitors (such as captopril, enalapril and lisinopril) are dialyzable, whereas all of the AIIAs studied are not. Dose titration may be necessary when administering ACE inhibitors to patients with renal failure (ESRD), but is rarely a consideration when AIIAs are used.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Diabetic Nephropathies; Disease Progression; Humans; Kidney Failure, Chronic; Nephritis, Interstitial; Plasma Kallikrein; Renin-Angiotensin System

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.. 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.. 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 the KNG1 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 β = 0.03, p = 0.01; rs710446 β = 0.03, p = 0.005) in the FinnDiane cohort of 4400 individuals with type 1 diabetes.. 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.

Topics: Adult; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Factor XI; Female; Genotyping Techniques; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Plasma Kallikrein; Polymorphism, Single Nucleotide; Quality Control