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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Diabetic nephropathy is a serious microvascular complication in patients with insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30-45% of such patients. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and free-radical activity may be important factors. 2. Forty normotensive patients with insulin-dependent diabetes mellitus of between 10 and 20 years duration with persistent normoalbuminuria (albumin excretion < 30 mg/day) and normal renal function were investigated for markers of endothelial dysfunction (plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity), free oxygen radical generation (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. 3. Patients were divided into two groups. Group 1 comprised 21 patients with elevated markers of endothelial dysfunction, and group 2 comprised 19 patients with normal levels of plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty-eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and 2 were similar in age, sex, body weight, duration of diabetes mellitus and recent glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria were similar in the three groups. Group 1 patients had significantly increased oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients and control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus. 828 43

The levels of soluble thrombomodulin (TM) in serum samples were measured by one-step sandwich enzyme immunoassay. The aim of the present study was to determine if levels of soluble TM in sera might correlate with disease activity in patients with diabetic nephropathy. Three hundred and twenty patients with diabetic nephropathy were examined. Patients with diabetic retinopathy were excluded from the present study. This study showed an increase of soluble TM levels in sera from patients with diabetic nephropathy. The levels of soluble TM in sera from the macroalbuminuric stage with renal dysfunction were significantly increased compared with those from the normo-, micro-, or macroalbuminuric stage of diabetic nephropathy without renal dysfunction. The increase of soluble TM in sera paralleled levels of urinary albumin, blood urea nitrogen (BUN), s-creatinine (Cr), and duration of noninsulin-dependent diabetes mellitus (NIDDM). Furthermore, a decrease of TM staining in the glomerular capillary walls was observed in both microalbuminuric and macroalbuminuric stages by immunofluorescence. It appears that the measurement of soluble TM in sera is useful in evaluating the degree of glomerular endothelial injuries in patients with diabetic nephropathy.
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PMID:Measurement of soluble thrombomodulin in sera from various clinical stages of diabetic nephropathy. 873 97

Serum and urinary levels of soluble thrombomodulin (TM) were measured in 71 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 132 age-matched control subjects to elucidate the mechanisms involved in increased TM levels. We compared the TM level with urinary albumin excretion (UAE), creatinine (Cr) clearance, and indices of renal tubular damage such as urinary beta2-microglobulin. Serum TM was significantly higher in diabetic patients versus control subjects (P < .001) regardless of whether the patients had diabetic nephropathy. Urinary TM levels were also higher in diabetic patients than in control subjects (P < .001). Serum TM in diabetic patients was correlated positively with serum Cr and UAE and inversely with the Cr clearance rate (P < .001, respectively). The urinary level of TM in diabetic patients was significantly correlated with 24-hour glucose excretion and the serum level of 1,5-anhydroglucitol (1,5-AG) (P < .001). However, no correlations were found between urinary TM levels and renal function in diabetic patients. There was also no correlation between serum and urinary levels of TM in the patients. These results suggest that although the serum TM level is influenced by an impairment of the renal clearance of TM, this parameter may be a useful marker for vascular endothelial injury in diabetic patients. On the other hand, since the elevated urinary level of TM in the patients paralleled their urinary excretion of glucose, urinary TM levels do not correlate with vascular endothelial injury in diabetic patients.
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PMID:Mechanisms of elevation of serum and urinary concentrations of soluble thrombomodulin in diabetic patients: possible application as a marker for vascular endothelial injury. 950 May 78

Plasma thrombomodulin (PTM) may be a marker of vascular endothelial damage and is increased in active vasculitis. However, since PTM is a mixture of glycoproteins (MW between 28 to 105 kD), some may be variably excreted by the kidney. PTM level thus may be affected both renal impairment and proteinuria. This study examines patients with varied renal pathology and relates PTM levels to renal function and proteinuria. PTM levels were measured in eighty nine renal patients with varied renal pathology: 23 patients on hemodialysis (HD), 66 with variable renal function (from normal to severe renal impairment), and proteinuria from insignificant to nephrotic range. PTM levels rose as renal function declined and were highest in HD patients. PTM levels also seemed to rise with increasing proteinuria. Indeed, this relationship appeared to be exaggerated in patients with hypertensive and diabetic nephropathy compared to those with primary glomerulonephritis. Measurements of PTM are clearly affected both by renal function and proteinuria. Thus the confidence limits above which an abnormal level is recognised should be increased as renal function declines.
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PMID:Plasma thrombomodulin in renal disease: effects of renal function and proteinuria. 987 5

Increased oxidative stress and subsequent activation of the transcription factor NF-kappaB has been linked to the development of late diabetic complications. To determine whether oxidative stress dependent NF-kappaB activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine NF-kappaB activation in ex vivo isolated peripheral blood mononuclear cells. We examined 33 patients with diabetes mellitus (Type I and Type II). Patients with diabetic nephropathy showed higher NF-kappaB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kappaBp65 than patients without renal complications. NF-kappaB binding activity correlated with the degree of albuminuria (r = 0.316) and with thrombomodulin plasma concentrations (r = 0.33), indicative for albuminuria associated endothelial dysfunction. In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid (alpha-lipoic acid) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48% and NF-kappaB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38%. In conclusion, activation of the transcription factor NF-kappaB in ex vivo isolated peripheral blood mononuclear cells of patients with diabetes mellitus correlates with the degree of diabetic nephropathy. NF-kappaB activation is at least in part dependent on oxidative stress since thioctic acid (alpha-lipoic acid) reduced NF-kappaB binding activity.
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PMID:Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kappaB. 1006 3

To elucidate the hypothesis that albuminuria in diabetic subjects reflects widespread vascular damage, plasma markers for vascular endothelial damage was measured in diabetic subjects with various degrees of albuminuria and compared to results in patients with primary renal disease. The groups consisted of 31 non-diabetic patient controls with normoalbuminuria, 109 type 2 diabetic patients with normo- micro- and macro-albuminuria, and 16 proteinuric patients with primary renal disease. Endothelial markers, plasma von Willebrand factor (vWF) and thrombomodulin (TM), were measured by enzyme-linked immunosolvent assay and enzyme immunoassay (EIA) methods, respectively. Plasma vWF levels were similar in controls (119+/-7%, mean+/-S.E.M.) and diabetic patients with normoalbuminuria (139+/-6), but significantly elevated in diabetic patients with microalbuminuria (174+/-11) and macroalbuminuria (204+/-17), while the level was not increased in patients with primary renal disease (124+/-11). Because plasma TM level was strongly affected by kidney function, TM index (TM (FU/ml)/serum creatinine (mg %)) was used as an endothelial marker. The TM index was substantially increased in diabetic patients with overt nephropathy compared with controls (5.29+/-2.98 vs. 2.35+/-0.85), whereas this was not observed in patients with primary renal disease (3.25+/-0.29). Both vWF and TM index were significantly higher in diabetic patients with retinopathy than in the patients without retinopathy. These results suggest that generalized vascular endothelial damage occurs in diabetic nephropathy including the microalbuminuric stage, which is not attributed to kidney damage per se.
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PMID:Vascular endothelial markers, von Willebrand factor and thrombomodulin index, are specifically elevated in type 2 diabetic patients with nephropathy: comparison of primary renal disease. 1090 Feb 93

Serum thrombomodulin (TM) levels were determined in diabetic patients, and the effects of diabetic complications and renal function on TM were studied. Serum TM levels increased in diabetics, and patients with diabetic nephropathy tended to manifest higher levels of TM. There was a significant correlation between TM and serum creatinine levels. In addition, there was a significant elevation in serum TM levels in diabetics over time (1 year to 1 year 8 months), and the changes were particularly evident in patients who had a higher TM level from before the observation period. Furthermore, when patients were treated with an antiplatelet agent--beraprost (CAS 88475-69-8) or cilostazol (CAS 73963-72-1)--a significant reduction in TM levels was observed after 3 months. It is suggested that TM could be used as index to assess the development of clinical complications in diabetics and that anti-platelet agents have potential usefulness in delaying the aggravation of diabetic complications.
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PMID:Effects of beraprost and cilostazol and renal function on serum thrombomodulin levels in diabetic patients. 1091 46

Serum concentration of soluble thrombomodulin (TM) is thought to be a marker for endothelial damage. Although several studies have reported that serum TM concentrations are increased in patients with diabetes mellitus, there is little information on the physiological function of soluble TM in human plasma. To evaluate the relationship of soluble TM in plasma between coagulation and/or fibrinolysis system in patients with diabetes, we measured plasma soluble TM, protein C activity (a natural anticoagulant induced by thrombin-TM complex), prothrombin F1+2 (a direct marker of thrombin generation), and plasmin-alpha 2-antiplasmin complex (PAP) and D dimer (measures of fibrinolytic activity) in 55 patients with type 2 diabetes mellitus. The plasma concentrations of soluble TM (P<0.01), protein C activity (P<0.01), prothrombin F1+2 (P<0.05), PAP (P<0.001) and D dimer (P<0.001) were significantly higher in the diabetic patients than the 48 age-matched control subjects. The plasma concentrations of TM and PAP were obviously increased in patients with diabetic nephropathy. In the diabetic patients, the plasma concentrations of soluble TM were inversely correlated with the protein C activity (r=-0.43, P<0.005), and were positively correlated with the plasma concentrations of prothrombin F1+2 (r=0.63, P<0.0001) and the plasma PAP concentrations (r=0.30, P<0.05). The present study demonstrated that both coagulation and fibrinolysis are enhanced concomitantly in patients with type 2 diabetes mellitus, and that an increase in plasma concentration of soluble TM is associated not only with hypercoagulability but also with enhanced fibrinolysis in diabetic patients.
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PMID:Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes. 1102 Apr 68

Oxidative stress plays a central role in the pathogenesis and progression of late microangiopathic complications (diabetic nephropathy) in diabetes mellitus. Previous studies suggested that treatment of diabetic patients with the antioxidant alpha-lipoic acid reduce oxidative stress and urinary albumin excretion. In this prospective, open and non-randomized study, the effect of alpha-lipoic acid on the progression of endothelial cell damage and the course of diabetic nephropathy, as assessed by measurement of plasma thrombomodulin and urinary albumin concentration (UAC), was evaluated in 84 patients with diabetes mellitus over 18 months. Forty-nine patients (34 with Type 1 diabetes, 15 with Type 2 diabetes) had no antioxidant treatment and served as a control group. Thirty-five patients (20 with Type 1 diabetes, 15 with Type 2 diabetes) were treated with 600 mg alpha-lipoic acid per day. Only patients with an urinary albumin concentration <200 mg/l were included into the study. After 18 months of follow up, the plasma thrombomodulin level increased from 35.9+/-9.5 to 39.7+/-9.9 ng/ml (P<0.05) in the control group. In the alpha-lipoic acid treated group the plasma thrombomodulin level decreased from 37.5+/-16.2 to 30.9+/-14.5 ng/ml (P<0.01). The UAC increased in patients without alpha-lipoic acid treatment from 21.2+/-29.5 to 36.9+/-60.6 ng/l (P<0.05), but was unchanged with alpha-lipoic acid. It is postulated that the significant decrease in plasma thrombomodulin and failure of UAC to increase observed in the alpha-lipoic acid treated group is due to antioxidative effects of alpha-lipoic acid, and if so that oxidative stress plays a central role in the pathogenesis of diabetic nephropathy. Furthermore, progression of the disease might be inhibited by antioxidant drugs. A placebo-controlled study is needed.
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PMID:Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study. 1132 87

KK mice and KK-Ay mice were examined for age related changes in blood and urinary biophysiological parameters. Blood hemoglobin A1c levels were significantly higher in KK-Ay and KK mice as compared to non-diabetic ddY mice. In both diabetic mice, especially KK-Ay mice, plasma insulin levels markedly increased at 2 to 4 months of age, and the urinary glucose and microalbumin levels and albumin-to-creatinine ratios increased dependent on age. Plasma thrombomodulin levels significantly increased at 2 to 4 months of age in both KK and KK-Ay mice. Mild enlargement of mesangial matrix and segmental proliferative glomerular nephritis were revealed in KK and KK-Ay mice, respectively, at 4 months of age. KK-Ay mice with insulin resistance and high urine mAlb level might be useful as models for the early stage of diabetic nephropathy.
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PMID:Diabetic nephropathy in KK and KK-Ay mice. 1201 32


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