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

Haemostatic activation was measured in patients with either non-diabetic chronic renal failure (CRF) or diabetic nephropathy. We have investigated the relationship between these haemostatic markers and the rate of progression of renal failure. When compared with age- and sex-matched healthy controls, both patient groups showed significantly elevated plasma concentrations of D dimer, von Willebrand factor antigen (vWFAg), and C-reactive protein (CRP) (all P less than 0.001), as well as an increase in spontaneous platelet aggregation (P less than 0.01). Plasma concentration of platelet factor 4 was slightly but not significantly increased. Serum thromboxane was subnormal (P less than 0.01). Multiple regression analysis showed that in non-diabetic CRF proteinuria and serum TxB2 were independently related to the rate of progression of renal failure; in diabetic nephropathy proteinuria and vWFAg were independently related to the rate of progression. In both groups the relationship was stronger with proteinuria (standardised regression coefficients 0.56 and 0.45 respectively) than with serum TxB2 (0.29) or with vWFAg (0.37). We have found haemostatic activation in both non-diabetic and diabetic progressive renal failure. Proteinuria, and also in this study serum TxB2 and vWFAg, appear to be determining factors in the progression of renal failure, and their measurement may have prognostic value.
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PMID:Haemostatic activation and proteinuria as factors in the progression of chronic renal failure. 205 12

Insulin-dependent diabetic patients with nephropathy have a high risk of cardiovascular disease. Chronic inflammation is a part of the pathogenesis of atherosclerosis, and presently we have studied the relation between the inflammatory state, measured as levels of interleukin-6 and C-reactive protein and fibrinogen in diabetic nephropathy. Thirty-three insulin-dependent diabetic patients with diabetic nephropathy (urinary albumin excretion rate (AER) > 300 mg/24-h) and 22 patients with incipient diabetic nephropathy (AER 30-300 mg/24-h) were compared with 14 non-diabetic controls and 17 diabetic patients with normal AER (<30 mg/24-h). Fibrinogen was significantly higher in diabetic nephropathy than in non-diabetic controls and diabetic patients with normal AER (median 8.1, range (5.4-15.6) mu mol/l vs. 6.6 (5.0-12.1) mu mol/l, p < 0.05, and 6.2 (5.0-9.0) mu mol/l, p < 0.005, respectively), while C-reactive protein did not deviate between groups. Interleukin-6 was significantly elevated in all insulin-dependent diabetic patients (diabetic nephropathy (3.2 (1.0-14.5) pg/ml, p < 0.005), incipient nephropathy (3.7 (1.0-22.9) pg/ml, p < 0.005) and diabetic patients with normal AER (2.7 (1.0-9.0) pg/ml, p < 0.05) compared with nondiabetic controls (1.2 (1.0-6.2) pg/ml)). When fibrinogen was adjusted for interleukin-6, C-reactive protein or both, the level of fibrinogen was still higher in patients with diabetic nephropathy than in patients without nephropathy (p < 0.05), which suggests that inflammation is not the only mechanism that increases fibrinogen levels in patients with diabetic nephropathy.
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PMID:Elevated fibrinogen and the relation to acute phase response in diabetic nephropathy. 890 98

Renal anaemia starts earlier in the progression of chronic kidney disease (CKD) than was previously thought and is often inadequately monitored and treated. Current treatment guidelines recommend giving recombinant erythropoietin (rHuEPO) as soon as haemoglobin (Hb) concentration falls below 11 g/dl and alternative causes of anaemia have been ruled out. Recent studies show that, in practice, few patients receive rHuEPO in the pre-dialysis period and Hb concentrations are often <9 g/dl at the start of haemodialysis. This is at odds with best practice since renal anaemia is a major risk factor for left ventricular hypertrophy. Many factors other than provision of rHuEPO therapy can affect the occurrence and severity of renal anaemia. Iron deficiency is the most common cause of resistance to rHuEPO and appropriate use of iron supplementation in patients with CKD is still being debated. The acute-phase immune response has a more significant role in renal anaemia and rHuEPO resistance than previously believed, as demonstrated by the need for higher rHuEPO doses in patients with raised levels of C-reactive protein. Women often need higher doses of rHuEPO than men, which may be related to differences in androgen levels between the sexes. Low erythropoietin concentrations are a major factor in diabetic nephropathy. Correction of anaemia with rHuEPO may slow progression of CKD by reducing oxidative stress. These and other factors need to be considered for the optimal treatment of patients with anaemia of CKD.
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PMID:Non-erythropoietin-based anaemia management in chronic kidney disease. 1238 56

The annual statistical survey conducted at the end of 2000 by the Japanese Society for Dialysis Therapy collected responses from 3358 (99.94%) of 3360 institutions. Japan's total dialysis patient population at the end of the year 2000, as identified by this survey, was 206,134, an increase of 8921 (4.5%) over 1999. This translates to 1624.1 patients per million population. The annual crude mortality rate was 9.4% for the period starting at the end of the year 1999 and ending at the end of the year 2000. The mean patient age at the initiation of dialysis treatment was 63.8 (+/- 13.9; +/- SD) years; the mean age of the overall dialysis patient population was 61.2 years (+/- 13.3). Both these mean ages, which had been increasing since 1983, again continued to increase. Among the primary diagnosis, the prevalence of diabetic nephropathy had continued to increase again since 1999, to 36.6%, whereas that of chronic glomerulonephritis had continued to decline, down to 32.5%, during the same one-year period since the 1999 survey. The 2000 years-end survey incorporated the following additional variables for the first time: usage of oral antihypertensives, pre- and post-dialysis systolic and diastolic blood pressures, serum HDL cholesterol level, types and dosage of oral Vitamin D analogs administered, dosage of oral calcium carbonate administered, history of intervention for peripheral vascular disease (bypass surgery, synthetic graft replacement, stenting), history of coronary artery bypass grafting (CABG), history of percutaneous transluminal coronary angioplasty (PTCA), whether stenting had been previously performed for the treatment of ischemic heart disease, number of cigarettes smoked, the type of vascular access used at the initiation of dialysis, and the year and month the vascular access was created. The survey results indicate that 60.9% of the total dialysis patient population was using oral antihypertensives. The patients' mean serum HDL cholesterol level was 47.65 +/- 18.47 mg/dL, showing positive correlation with serum albumin level and reverse correlation with body mass index. 1.6% of all dialysis patients had previously undergone amputation, and 0.7% had a history of bypass surgery for peripheral vascular disorder. 4.5% of hemodialysis patients had a history of cardiac infarction, 1.6% had previously undergone CABG, and 2.8%, PTCA. At the time the survey was conducted, 2.0% of all dialysis patients were undergoing oral Vitamin D analog pulse therapy, and 6% were undergoing intravenous Vitamin D analog pulse therapy. A history of amputation, myocardial infarction, cerebral infarction, and cerebral bleeding were identified as high-risk factors of vital prognosis. Additionally, high mortality risk was associated with the following: glutamic-pyruvic transaminase levels exceeding 20 IU/L; positive HCV antibody status; comorbid conditions such as hepatic cell carcinoma and liver cirrhosis; platelet counts below 100,000/mL or equal to or greater than 200,000/mL; C-reactive protein levels of 0.2 mg/dL and higher, leukocyte counts of less than 3000/mL or equal to or greater than 8000/mL; and body mass index of below 22 kg/m2, as well as total serum cholesterol levels of below 160 mg/dL or equal to or greater than 260 mg/dL.
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PMID:The current state of chronic dialysis treatment in Japan (as of December 31, 2000). 1292 Nov 11

Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by 51Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P < 0.03 and P < 0.001, respectively). GBM width and Vv(mes/glom) increased from normoalbuminuric to proteinuric patients [P < 0.005 normoalbuminuric and microalbuminuric versus proteinuric for GBM, P < 0.01 normoalbuminuric versus proteinuric for Vv(mes/glom)]. In patients with increased GBM width (> 396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r = 0.33, P < 0.002) and IL-6 (r = 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy.
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PMID:Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. 1593 41

The high sensitivity C-reactive protein (hsCRP) is known to be a sensitive predictor of coronary heart disease and type 2 diabetes. This study evaluated the association between the serum hsCRP and the components of metabolic syndrome (MS) and microvascular complications in type 2 diabetes. Two hundred and sixty-nine patients with type 2 diabetes were enrolled. All the subjects underwent measurement of MS and carotid intima-media thickness (IMT). The serum hsCRP concentrations and the 24 h urine albumin excretion amounts were measured. Ophthalmoscope examinations and nerve conduction velocity tests were performed to evaluate microvascular complications. The hsCRP was significantly higher in the patients with MS than in those without (p=0.019). The serum hsCRP was significantly correlated with all the components of MS. There were no differences between the serum hsCRP levels of those with and without retinopathy and neuropathy. The serum hsCRP was correlated with the 24 h urine albumin excretion amount. Serum hsCRP level has a significant correlation with MS and might be used as the future criteria of MS. Among microvascular complications, only diabetic nephropathy is associated with the serum hsCRP level. It suggests that the inflammatory process plays a role in nephropathy in type 2 diabetes.
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PMID:Relationship of serum high sensitivity C-reactive protein to metabolic syndrome and microvascular complications in type 2 diabetes. 1600 64

Patients with diabetic nephropathy have a high rate of cardiovascular events and mortality. Nontraditional cardiovascular risk factors such as oxidative stress and inflammation are thought to be particularly important in mediating these events. Studies suggest that thiazolidinediones (TZDs) can reduce the level of nontraditional cardiovascular risk in people with or without diabetes mellitus. Whether this benefit occurs in patients with diabetic nephropathy is unknown. I hypothesized that the TZD pioglitazone will mitigate oxidative stress and inflammation compared with glipizide in patients with overt diabetic nephropathy. Markers of oxidative stress (plasma and urine albumin carbonyl and total protein carbonyls and malondialdehyde), inflammation [white blood cell (WBC) count, C-reactive protein (CRP), plasma IL-6, TNF-alpha], and plaque stability [matrix metalloproteinase 9 (MMP-9)] were measured in frozen samples obtained from patients with overt diabetic nephropathy participating in a randomized, open-label, blinded end-point, 16-wk trial with glipizide (n = 22) or pioglitazone (n = 22). Pioglitazone therapy in men with advanced diabetic nephropathy reduced WBC count by 1,125/mul (P < 0.001), CRP by 41% (P = 0.042), IL-6 by 38% (P = 0.009), and MMP-9 by 29% (P = 0.016). Specific differential reductions in WBC count of 1,251/mul (P = 0.009) and reduction in IL-6 of 58% with pioglitazone (P = 0.001) were seen compared with glipizide. There were no statistically significant changes observed with plasma TNF-alpha concentrations or markers of oxidative stress with either hypoglycemic agent. In conclusion, pioglitazone reduces proinflammatory markers in patients with overt diabetic nephropathy, which indicates potentially beneficial effects on overall cardiovascular risk. This surrogate end point needs to be confirmed in trials designed to demonstrate cardiovascular protection.
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PMID:Anti-inflammatory effects of short-term pioglitazone therapy in men with advanced diabetic nephropathy. 1615 95

Diabetic nephropathy is diagnosed either when persistent increase of urinary albumin excretion rate (UAER) above 30 mg/24h in a patient with diabetes was discovered (early or incipient nephropathy) or when UAER values are persistently elevated above 300 mg/24h (overt or clinical nephropathy). In both situations the additional criteria of presence of diabetic retinopathy and the absence of the evidence of other kidney or renal tract disease should be fulfilled. It was found that the excess of cardiovascular events and mortality occurs already in diabetic patients with persistent microalbuminuria, but is particularly evident in macroalbuminuric diabetic patients and results not only from end-stage renal failure (ESRF) but rather from cardiovascular disease (CVD), the latter mainly in type 2 diabetic patients. Several traditional risk factor for atherosclerosis has been identified in diabetic patients with micro- or macroalbuminuria including elevated blood pressure levels, dyslipidemia and procoagulatory state associated with endothelial dysfunction. Microalbuminuria is currently regarded as a marker of generalized endothelial damage, it reflects transvascular albumin leakage, now recognized as an early event in atherogenesis. Recently the association of microalbuminuria with the marker of chronic inflammation (C-reactive protein) and with increased production of vascular endothelial growth factor (VEGE) was described. Thus, multiple mechanisms are involved in the development and progression of cardiovascular complications both in micro- and macroalbuminuric diabetic patients and all these mechanisms should be regarded as the target for therapeutic intervention.
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PMID:Diabetic nephropathy and cardiovascular diseases. 1635 50

In 70 nonobese inpatients with Type 2 diabetes [body mass index (BMI): 24.0+/-4.4 kg/m(2)], we examined circulating monocyte chemoattractant protein (MCP) -1 as a candidate marker of atherosclerosis by comparison with established markers: serum high-sensitivity C-reactive protein (hsCRP), plasma fibrinogen, and combined carotid artery intimal-medial thickness (IMT). In addition, an association was sought between circulating MCP-1 and urinary albumin excretion (UAE), reflecting diabetic renal microangiopathy. Serum MCP-1 was determined by enzyme-linked immunosorbent assay (ELISA). Patients were grouped by UAE: normoalbuminuria, below 30 mg/g of creatinine (Cr); microalbuminuria, 30 to 300 mg/g Cr; or macroalbuminuria, over 300 mg/g Cr. Serum MCP-1 for all participants, men, and women was 280.0+/-78.9, 269.0+/-68.8, and 294.9+/-87.9 pg/ml, respectively, showing no difference between genders. No correlation was noted between MCP-1 and hsCRP, fibrinogen, or carotid artery IMT. No correlation of MCP-1 was observed with age, duration of diabetes, fasting plasma glucose (FPG), hemoglobin (Hb) A(1C), BMI, diastolic blood pressure (DBP), or serum lipid concentrations, but significant correlations were found with systolic blood pressure (SBP; R=.2723, P=.0225) and with log(10)-transformed (log) UAE (R=.3343, P=.0047). Patients with macroalbuminuria had significant higher circulating MCP-1 than did those with normo- or microalbuminuria (P=.0063 and P=.0188, respectively). By stepwise regression analysis, only log UAE independently predicted serum MCP-1 (beta=.3700, P=.0020). Thus, in nonobese Type 2 diabetic patients, MCP-1 might not be a marker of atherosclerosis and might be influenced significantly by diabetic nephropathy.
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PMID:Association between circulating monocyte chemoattractant protein-1 and urinary albumin excretion in nonobese Type 2 diabetic patients. 1650 38

In this study we evaluated the effect of a dual blockade with enalapril and losartan on the reduction of overt macroproteinuria and its potential mechanism(s) in hypertensive patients with type 2 diabetes. Twenty-six hypertensive patients with type 2 diabetes at the baseline were administered 5 mg of enalapril once daily for 12 weeks. At the beginning of the study, the subjects were assigned to receive an add-on of 50 mg of losartan once daily or 5 mg of enalapril once daily for another 12 weeks. Blood samples were collected at the baseline, at the beginning, and at the end of the study for the measurement of laboratory parameters, and these data, including blood pressure, were compared between the two groups. Treatment with 5 mg of enalapril significantly decreased the systolic blood pressure level in both groups, and the addition of losartan and/or enalapril further decreased the levels. There was no difference in blood pressure between the two groups. However, the addition of losartan, but not enalapril, significantly decreased the urinary protein excretion level, plasma aldosterone, and hypersensitive-C-reactive protein at the end of the study. The results established that the dual blockade of angiotensin II with enalapril and losartan has a greater clinical benefit for high-risk patients with hypertension and advanced diabetic nephropathy.
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PMID:Dual blockade of angiotensin II with enalapril and losartan reduces proteinuria in hypertensive patients with type 2 diabetes. 1682 7


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