Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypofibrinolysis is a common finding in patients with diabetes mellitus and a risk factor for diabetic nephropathy. Recently, a new potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor (TAFI), has been isolated from human plasma. The possibility that TAFI also participates in the mechanism of hypofibrinolysis has not been appraised in diabetic patients with microalbuminuria. In the present study, we investigated the plasma levels of TAFI and its relation to urinary albumin excretion in normotensive diabetic patients with normo- and microalbuminuria. Thirty-nine normotensive nonobese type 2 diabetic patients (27 with normoalbuminuria, 12 with microalbuminuria) and 20 age-matched normal subjects were enrolled in this study. The plasma level of thrombin-antithrombin complex was significantly increased (22.1 +/- 2.6 vs. 8.3 +/- 1.0 nmol/liter; P < 0.05), whereas the D-dimer/thrombin-antithrombin complex ratio was significantly decreased (15.7 +/- 1.4 vs. 26.5 +/- 2.2; P < 0.05), showing the occurrence of hypercoagulability and hypofibrinolysis in diabetic patients. The plasma level of TAFI in diabetic patients was significantly elevated, compared with normal subjects (147.4 +/- 11.6 vs. 99.5 +/- 4.9%; P < 0.05). The plasma level of TAFI in diabetic patients with microalbuminuria was significantly higher than the level in diabetic patients with normoalbuminuria (194.1 +/- 24.5 vs. 128.8 +/- 12.3%; P < 0.02) or normal subjects (194.1 +/- 24.5 vs. 99.5 +/- 4.9%; P < 0.005). Univariate analysis showed that the plasma TAFI levels are significantly and proportionally correlated with urinary albumin excretion rate (r = 0.58; P < 0.005) and with plasma soluble thrombomodulin level, a marker of endothelial cell damage, in all diabetic patients (r = 0.42; P < 0.01). These data suggest that increased plasma level of TAFI may be involved in the mechanism of vascular endothelial damage in patients with type 2 diabetes mellitus.
 ...
PMID:Increased plasma thrombin-activatable fibrinolysis inhibitor levels in normotensive type 2 diabetic patients with microalbuminuria. 1257 7

Adiponectin has antiatherogenic properties and attenuates endothelial inflammatory responses. CD146 is a novel cell adhesion molecule localized at the endothelial junction. In renal failure, endothelial dysfunction and atherosclerosis are almost universal. We studied possible correlations between adiponectin, CD146, and other markers of endothelial cell injury in patients with chronic renal failure (CRF) on conservative treatment and patients with and without diabetic nephropathy maintained on chronic ambulatory peritoneal dialysis (CAPD). We assessed adiponectin, tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor (PAI-1), thrombin-activatable fibrinolysis inhibitor, and endothelial function/injury markers: von Willebrand factor, thrombomodulin, vascular cell adhesion molecule (VCAM), intercellular adhesion molecule, and CD146. Adiponectin was elevated in patients with CRF and on CAPD. It correlated significantly, with PAI-1, thrombin-activatable fibrinolysis inhibitor, intercellular adhesion molecule, VCAM, and CD146 in nondiabetics on CAPD. In diabetics, CAPD adiponectin correlated positively with C146 and VCAM and negatively with PAI and TFPI. In multivariate regression analysis, only CD146 remained a positive predictor of adiponectin in all CAPD patients. In CRF, adiponectin correlated with CD146. In healthy volunteers, adiponectin correlated with TFPI and CD146. Elevated adiponectin related to CD146 may be the expression of a counterregulatory response aimed at mitigating the consequences in endothelial damage and increased cardiovascular risk in renal failure.
 ...
PMID:Adiponectin is related to CD146, a novel marker of endothelial cell activation/injury in chronic renal failure and peritoneally dialyzed patients. 1535 72

Diabetic nephropathy is a kidney disease or damage that results as a complication of diabetes, especially Type 2 diabetes, while albuminuria is an early marker for diabetic nephropathy as it can predict cardiovascular events and mortality in diabetic patients. A potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor (TAFI) has been isolated and characterized from human plasma. We investigated the associations of the activity-related variants in the TAFI coding gene (505A/G,1040C/T) with the risk of diabetic nephropathy by examining 297samples including 140 health controls and 157 confirmed diabetic nephropathy patients. Diabetic nephropathy grades were further categorized by the urine albumin excretion (UAE)-to-creatinine ratios (ACR). We found little difference that was statistically significant in terms of 505A/G among patients and controls. While at 1040C/T, the detected frequency for the T allele in the group of diabetic nephropathy patients was significantly smaller than that of the control group (15.6% vs 25.7%, respectively; p<0.05). This was due to the relative decrease of T/T homozygotes in the patients (p<0.05, 95% odds ratio 0.28, confidence interval 0.11-0.70). Surprisingly, the difference was only observed with initial diabetic nephropathy stages. This study clearly indicates that, at 1040C/T, the frequency for the T allele is strongly associated with increased risk for diabetic nephropathy in a subset of the general population, implying that the T allele confers protection against the onset of diabetic nephropathy only in homozygosity and may function as a recessive trait.
 ...
PMID:Genetic variation in thrombin-activatable fibrinolysis inhibitor is associated with the risk of diabetic nephropathy. 2293 73