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)

Adynamic bone disease and elevated serum levels of advanced glycation end products (AGEs) often are found in patients with renal failure caused by diabetic nephropathy. To clarify the role of AGEs in adynamic bone disease, we investigated the effect of these substances on cultured human osteoblasts and parathyroid cells. After 72 hours of incubation with AGEs-bovine serum albumin (BSA) (1,000 microgram/mL), there was significant inhibition of the synthesis of type I collagen and osteocalcin in response to stimulation with 10(-10) to 10(-8) M of 1,25-dihydroxycholecalciferol. In a human osteoblastic cell line (MG 63), AGEs-BSA did not affect human osteocalcin promoter activity. In human parathyroid cells, a receptor for AGEs was detected by reverse-transcriptase polymerase chain reaction. Incubation with AGEs-BSA for 48 hours significantly inhibited parathyroid hormone secretion in response to a low calcium concentration of 0.81 mM (P < 0.01). In HEK-293 cells, expressing calcium-sensing receptors, the same AGE concentration caused a significant potentiation of the extracellular Ca(2+) induced-intracellular calcium concentration after 24 and 48 hours of incubation (P < 0.05 and P < 0.01). These data suggest that AGEs are involved in the pathogenesis of adynamic bone disease by inhibiting osteoblastic activity and by inhibiting parathyroid hormone secretion in response to hypocalcemia.
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PMID:Role of advanced glycation end products in adynamic bone disease in patients with diabetic nephropathy. 1157 45

Advanced glycation end products (AGE) have been implicated in the pathogenesis of glomerulosclerosis in diabetes. However, their involvement in the development of the early phase of diabetic nephropathy has not been fully elucidated. We investigated the effects of AGE on growth and on vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) expression in human cultured mesangial cells. We prepared three immunochemically distinct AGE by incubating bovine serum albumin (BSA) with glucose, glyceraldehyde, or glycolaldehyde. When human mesangial cells were cultured with various types of AGE-BSA, viable cell numbers as well as DNA syntheses were significantly decreased. All of the AGE-BSA were found to significantly increase p53 and Bax protein accumulations and subsequently induce apoptotic cell death in mesangial cells. An antioxidant, N-acetylcysteine, significantly prevented the AGE-induced apoptotic cell death in mesangial cells. Human mesangial cells stimulated prostacyclin production by co-cultured glomerular endothelial cells. Furthermore, various types of AGE-BSA were found to up-regulate the levels of mRNAs for VEGF and stimulate the secretion of VEGF and MCP-1 proteins in mesangial cells. The results suggest that AGE disturbed glomerular homeostasis by inducing apoptotic cell death in mesangial cells and elicited hyperfiltration and microalbuminuria by stimulating the secretion of VEGF and MCP-1 proteins, thereby being involved in the pathogenesis of the early phase of diabetic nephropathy.
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PMID:Advanced glycation end product-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattractant protein-1 in human-cultured mesangial cells. 1191 19

Nephrotic syndrome is a condition commonly associated with end-stage renal disease secondary to diabetic nephropathy. It is usually associated with long-standing renal insufficiency, microalbuminuria, and overt proteinuria. We present a diabetic patient with acute oliguric renal failure and nephrotic syndrome. At presentation, he had a serum creatinine of 2.3 mg/dl, blood urea nitrogen (BUN) of 69 mg/dl, urinary protein excretion of 10.5 g/24 h, serum albumin of 1.3 g/dl, and a urine output < 400 cc/24 h. A renal biopsy was done and the renal pathology was compatible with early diabetic nephropathy. Despite intense diuretic therapy, the patient's renal condition did not improve, and peritoneal dialysis was started several months after diagnosis. After 8 months of dialysis therapy, the patient's renal parameters and urinary output spontaneously restored to normal limits (serum creatinine was 1.1 mg/dl, urinary albumin excretion was 411 mg/24 h, serum albumin was 4.3 g/dl, and normal urine output) and dialysis was discontinued. His renal function did not deteriorate after discontinuation of dialysis. We conclude that this patient's reversible acute renal failure and nephrotic syndrome were associated with minimal change disease and not due to diabetic nephropathy.
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PMID:Reversible acute renal failure and nephrotic syndrome in a Type 1 diabetic patient. 1201 96

From the results of the Modification of Diet in Renal Disease (MDRD) study, a prediction equation for a more accurate estimate of glomerular filtration rate (GFR), was developed. The present study ais to compare the GFR estimated by MDRD formula and that calculated by the average of creatinine and urea clearances in unselected patients with advanced renal failure. The study group consisted of 320 (163 males) with advanced renal failure not yet on dialysis. Their mean age was 63 +/- 14 years. Diabetic nephropathy was the most common etiology of renal failure (25%). Significant comorbidity was observed in 115 patients. Serum creatinine (Cr), urea and albumin were determined in all patients. Creatinine (Ccr) and urea clearance (Cu) were calculated on a 24-hour urine collection. The GFR was estimated by summing Ccr and Cu, and dividing by two (Ccr-Cu). THe clearances were corrected for a body surface area of 1.73 m2. The MDRD formula for the estimation of GFR included the following parameters: serum Cr, BUN, age, gender and serum albumin. Linear regression analysis and Bland-Altmann plot were utilized to establish the degree of correlation and agreement between both estimations of GFR. The percent differences between the two estimations of GFR was especially analyzed in those subgroups of patients which were not included in the MDRD study (patients older than 70 years, diabetics and those with comorbid conditions). The mean GFR estimated by Ccr-Cu and by MDRD formula were 10.04 +/- 3.10 ml/min and 10.55 +/- 3.60 ml/min, respectively (p < 0.0001). The two parameters correlated significantly (R = 0.76, p < 0.0001). GFR by the MDRD formula tended to overestimate the highest values of Ccr-Cu. The mean percent difference between both methods was 6.5 +/- 23.6. MDRD predictive equation overestimated significantly Ccr-Cu in patients older than 70 years (mean overestimation of 15%), males (10%), diabetics (10%), and mainly in patients with comorbidity (17%). In conclusion, the GFR estimated by MDRD formula is very similar to Ccr-Cu in young uremic patients without comorbidity. However, major discrepancies between these two methods could be observed in older patients, and mainly in those with comorbidity.
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PMID:[Differences between the glomerular filtration rate estimated by the MDRD equation and the measurement of creatinine and urea clearance in unselected patients with terminal renal insufficiency]. 1249 44

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

We investigated the relationship between the levels of serum albumin (ALB), serum transthyretin (TTR) or retinol binding protein (RBP) and those of serum cystatin C or clinical gradings in patients with diabetic nephropathy. Serum samples were obtained from 85 patients with type 2 diabetic nephropathy in our hospital. The levels of serum ALB, TTR, RBP and cystatin C were measured by the Dade Behring assay system using the automated Dade Behring Nephelometer II (BN II). The grades of diabetic nephropathy were classified into five groups according to Report of the Ministry of Health and Welfare, Japan. The serum levels of RBP showed a significant correlation between the serum levels of cystatin C and the grades of diabetic nephropathy. However, the serum levels of TTR were not significantly correlated with those of serum cystatin C or the grades of diabetic nephropathy. In this study, the serum levels of TTR were not influenced by renal function although those of RBP and ALB were influenced by renal function. In spite of clinical usefulness in the nutritional assessment of healthy controls and hemodialysis patients, RBP and ALB are not suitable nutrition marker in patients with chronic renal failure. However, TTR is suitable marker in patients with chronic renal failure.
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PMID:[Effective usage of nutrition assessment proteins in patients with diabetic nephropathy]. 1505 7

Amadori-modified glycated albumin stimulates extracellular matrix and transforming growth factor-beta (TGF-beta) expression in cultured mesangial cells. Smad proteins transduce the TGF-beta-mediated signal, and Smad-binding CAGA sequences are present in the plasminogen activator inhibitor-1 (PAI-1) promoter. This study examined whether glycated albumin induces PAI-1 transcription in human mesangial cells (HMC) through Smad-binding sites in the PAI-1 promoter. Quiescent HMC were exposed to 200 microg/ml bovine serum albumin (BSA) or glycated BSA (Gly-BSA) for 12-72 h. At 24 h, Gly-BSA stimulated TGF-beta1 and PAI-1 mRNA expression in HMC to 1.8 and 3.2 times that in the BSA-treated control cells. Gly-BSA also activated the PAI-1 promoter luciferase activity 2.3-fold. Gly-BSA-treated cells enhanced Smad2 and Smad3 protein levels 2.5 times the control levels in the nuclei. An electrophoretic mobility shift assay performed using CAGA sequences as a probe showed that Gly-BSA increased DNA/protein complexes. When nuclear extracts were preincubated with 100-fold molar excess of unlabeled CAGA oligonucleotide, the formation of complex was prevented. The DNA-binding protein was shown to be Smad3 by antibody supershift. Transfection of phosphorothioate CAGA oligonucleotide, a CAGA antisense analog, inhibited Gly-BSA-induced PAI-1 mRNA expression. Cotransfection of phosphorothioate CAGA oligonucleotides with PAI-1 reporter vector also blocked Gly-BSA-induced PAI-1 promoter luciferase activity. These results indicate that Gly-BSA increases DNA binding activity of Smad3 and that it stimulates PAI-1 transcription through Smad-binding CAGA sequences in the PAI-1 promoter in HMC. Thus progression of diabetic nephropathy may be promoted by PAI-1 upregulation mediated by the glycated albumin-induced Smad/DNA interactions.
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PMID:Glycated albumin activates PAI-1 transcription through Smad DNA binding sites in mesangial cells. 1519 28

To investigate the effects of Hachimi-jio-gan on diabetic nephropathy, we employed an animal model, rats subjected to sub-total nephrectomy followed by streptozotocin injection, and administered Hachimi-jio-gan orally at a dose of 50, 100 or 200 mg/kg body weight/day for 15 weeks. The administration of Hachimi-jio-gan reduced dose-dependently the elevated blood glucose and urinary protein excretion levels in rats with diabetic nephropathy over the experimental period, whereas it increased creatinine clearance significantly, suggesting that Hachimi-jio-gan would prevent or delay the progression of diabetic nephropathy. In addition, the serum glycosylated protein and urea nitrogen levels were markedly elevated in rats with diabetic nephropathy compared with normal rats, and were significantly reduced by the administration of Hachimi-jio-gan, whereas Hachimi-jio-gan reversed the decrease in the serum albumin level. The serum triglyceride and total cholesterol concentrations were reduced by Hachimi-jio-gan, implying that Hachimi-jio-gan would improve the metabolic disorder of lipids caused by diabetic nephropathy. Moreover, Hachimi-jio-gan inhibited lipid peroxidation in the serum and kidney, which suggests that Hachimi-jio-gan would ameliorate oxidative stress associated with diabetic nephropathy. Furthermore, the disorders of the glucose-dependent metabolic pathway due to this pathological condition were also normalized by the administration of Hachimi-jio-gan through decreases in advanced glycation end-product formation and sorbitol levels in the kidney. Hachimi-jio-gan protected against the development of renal lesions, glomerular sclerosis, tubulointerstitial lesions, mesangial matrix expansion and arteriolar sclerosis, estimated by histopathological evaluation and scoring. This study suggests that Hachimi-jio-gan may be a novel therapeutic approach to improving diabetic nephropathy.
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PMID:A study on the effects to diabetic nephropathy of Hachimi-jio-gan in rats. 1521 22

Individuals with type 2 diabetes and nephropathy represent a particularly high-risk group for both adverse cardiac as well as renal events. Using the Irbesartan in Diabetic Nephropathy Trial (IDNT) cohort, our objective was to determine baseline characteristics of individuals with type 2 diabetic nephropathy and hypertension predictive for cardiac events. IDNT identified 1715 individuals with type 2 diabetic nephropathy and hypertension having serum creatinine of 1.0 to 3.0 mg/dL and urinary albumin excretion rates > or = 900 mg/day. A cardiovascular (CV) composite was used consisting of CV death, nonfatal MI, hospitalization for heart failure, stroke, amputation, and coronary and peripheral revascularization. Using multivariable Cox regression analysis, 41 baseline characteristics determined a priori were analyzed for their potential relationship to risk of experiencing a CV event. Of the 1715 individuals, 518 (30.2%) had at least one of the CV composite end points. Older age, male gender, longer duration of diabetes, history of cardiovascular disease, history of CHF, high urinary albumin:creatinine ratio, and low serum albumin were strong predictors for CV events; of these, prior history of CVD (RR 2.00, 95% CI 1.63-2.45; P < 0.0001) and high urinary albumin:creatinine ratio (RR 1.29 per natural log unit, 95% CI 1.13-1.48; P = 0.0002) at baseline were highly predictive for cardiovascular events. In conclusion, among individuals with hypertension and diabetic nephropathy, both the degree of albuminuria and lower serum albumin levels provide additional prognostic information concerning cardiovascular risk, in addition to traditional coronary risk factors.
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PMID:Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria. 1548 18

Thirty-three patients with type 2 diabetes mellitus (16 men, 17 women) were divided into 3 groups based on urinary excretion of albumin (U-Alb)--group A: U-Alb < 30 mg/d; group B: 30 mg/d < or = U-Alb < or = 300 mg/d; and group C: 300 mg/d < U-Alb. Serum creatinine levels were lower than 2.0 mg/dL in all the subjects. There was no difference in age, sex, therapy, body weight, body mass index (BMI), lean body mass (LBM), or hemoglobin A(1c) (HbA(1c)) levels among the 3 groups. Resting metabolic rate (RMR) (kJ/h/m(2)) and adjusted RMR for lean body mass (kJ/h/m(2)) were significantly increased in group C compared with groups A and B. Hb concentrations, serum albumin levels, and creatinine clearance were much lower in group C than in groups A and B (P < .001). There were no difference in serum urea nitrogen, total cholesterol, cholinesterase and free thyroxine, or plasma insulin-like growth factor I (IGF-I) levels among the 3 groups. Linear regression analysis revealed an inverse correlation between RMR and serum albumin levels, correlation between RMR and U-Alb, and inverse correlation between RMR and Hb concentrations, respectively, in these patients. In conclusion, RMR in diabetic patients correlated directly with U-Alb and inversely with serum albumin and Hb concentration. These findings suggest that RMR is related with urinary albumin loss and anemia in patients with type 2 diabetes mellitus accompanied by diabetic nephropathy.
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PMID:Increased resting metabolic rate in patients with type 2 diabetes mellitus accompanied by advanced diabetic nephropathy. 1553 91


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