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)

The mortality among end-stage renal failure (ESRF) patients undergoing renal replacement therapy (RRT) remains high. An important proportion of these patients die shortly after the initiation of RRT. The present study aims to determine the best predictors for the early mortality in a group of 140 ESRF patients who initiated RRT between october 96 and december 99. The mean age of the study group was 61 +/- 13 years, and the mean follow-up time was 20 +/- 12 months. Diabetic nephropathy was the most prevalent etiology of renal failure (30%). The following data, collected immediately before the initiation of RRT, were included as independent variables: demographic and clinical characteristics, including the nutritional status established by the Subjective Global Assessment (SGA), follow-up time in the predialysis clinic (less or longer than 3 months), EPO therapy, vascular access, renal function (creatinine and urea clearances, and Kt/V urea), hematological and biochemical data including serum albumin, bicarbonate, transferrin, PTH and C-Reactive protein, as well as the protein catabolic rate and the percent of lean body mass normalized for ideal body weight, calculated from the 24 h total urine excretion of nitrogen and creatinine. The Cox proportional hazard regression model, stratified for an age over or less than 65 year, was utilized to determine the best predictors for the mortality during the study period. Sixty percent of patients had at least one comorbid condition, and 35% had cardiovascular diseases. Mild-moderate or severe malnutrition was observed in 48% of patients. The creatinine clearance and Kt/V urea before the initiation of RRT were: 9.50 +/- 2.64 ml/min/1.73 m2 and 1.47 +/- 0.44, respectively. Forty-one patients died during the study period (annual death rate: 17%). The best predictor of mortality was the nutritional status assessed by the SGA (OR: 2.32, IC 95% 1.54-3.48, p < 0.0001). In a second analysis in which the SGA was removed from the model, the previous history of cardiovascular diseases (OR: 2.07, CI 95%: 1.06-4.06, p = 0.032), and the percent of lean body mass/ideal weight (OR: 0.96; IC 95%: 0.93-0.99; p = 0.042), proved to be the best predictor of mortality. In conclusion, nutritional indices prior to the initiation of RRT, and the previous history of cardiovascular diseases were the best predictors of the early mortality in this unselected population on dialysis. Because nutritional status appeared to be a marker of the severity of the comorbid conditions, a better control of the number and severity of these comorbid conditions may be the best way for reducing the mortality in patients on RRT.
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PMID:[Predictors of early death during dialysis]. 1147 8

Angiotensin converting enzyme (ACE) inhibitors produce a number of beneficial effects in a condition where diabetes - mellitus and hypertension co-exist. The present investigation was undertaken to study the effect of chronic treatment with losartan (2mg/kg, p.o.) on streptozotocin (STZ)-induced (45mg/kg, single dose, tail vein) diabetic nephropathy in rats. Treatment of rats with STZ produced a significant loss of body weight, polyuria. polydipsia, hypoinsulinemia, hyperglycemia and increase in blood pressure. There was a significant increase in blood glucose levels in STZ-diabetic rats. Serum cholesterol, creatinine, urea and blood urea nitrogen (BUN) levels were found to be increased significantly in the STZ group diabetic rats. Treatment with losartan significantly prevented the raise in cholesterol, creatinine, urea and blood urea nitrogen levels. Creatinine clearance was significantly less in STZ-diabetic rats as compared to control animals and treatment with losartan significantly increased creatinine clearence. Our data suggest a beneficial effect of losartan in STZ-induced nephropathy in rats.
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PMID:Effect of chronic treatment with losartan on streptozotocin induced diabetic nephropathy. 1171 Jul 53

Nitric oxide (NO) is a multifunctional mediator that has been implicated in the short-term hemodynamic alterations that occur in acute streptozocin (STZ)-induced diabetes. We investigated the role of NO produced by inducible nitric oxide synthase (iNOS) in chronic STZ diabetic nephropathy. Diabetes was induced in C57BL/6 and iNOS knockout (KO) mice with two intraperitoneal injections of STZ, 100 mg/kg. Animals were maintained without insulin treatment for 40 weeks. There were no significant differences between the strains in blood urea nitrogen (BUN), serum creatinine or glucose concentration, or urinary protein excretion during the entire observation period. Urinary nitrite + nitrate excretion was significantly lower in iNOS KO mice compared to control animals at all time points; in C57 mice, urinary nitrite declined progressively with more prolonged duration of diabetes. Renal hypertrophy (kidney weight/body weight) was noted in both strains of mice. However, histopathological assessment of renal tissue specimens at 16 and 40 weeks demonstrated increased mesangial hypercellularity and expansion as well as more prominent tubulointerstitial fibrosis in iNOS KO versus C57 mice. These changes were accompanied by increased interstitial deposition of type I collagen at 16 and 40 weeks in iNOS KO mice. Glomerular basement membrane staining for type IV collagen was also increased at 40 weeks in diabetic iNOS KO mice. While iNOS protein was undetectable in any of the kidney specimens obtained from either strain, eNOS was present throughout the course of chronic STZ diabetes. Moreover, eNOS expression was significantly increased by approximately 40% at 16 and 40 weeks of observation in iNOS KO versus C57 mice. There was no difference in renal cortical malondialdehyde content between the strains early or late in the disease course. In time control animals, there was no evidence of renal histopathological damage in iNOS KO or C57 mice after 40 weeks. We conclude that iNOS-derived NO modulates glomerulosclerosis and tubulointerstitial fibrosis in chronic STZ nephropathy. This action is probably a result of the direct actions of NO on the synthesis and degradation of extracellular matrix proteins.
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PMID:Chronic diabetic nephropathy: role of inducible nitric oxide synthase. 1179 30

We examined the correlation among the levels of urinary monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), hyperglycemia, and renal injuries in patients with type 2 diabetic nephropathy. The levels of urinary MCP-1, IL-8, protein excretion, blood urea nitrogen (BUN), serum creatinine (s-Cr), glycohemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) were measured in 24 patients with type 2 diabetic nephropathy and 14 healthy adults as controls. Diabetic nephropathy was classified into three stages: stage 1 = normoalbuminuric, stage 2 = microalbuminuric, and stage 3 = macroalbuminuric. All of the patients showed normal ranges in renal function tests. Levels of urinary MCP-1 in all patients with diabetic nephropathy were significantly higher than those in healthy adults (P < 0.05). The levels of urinary MCP-1 in patients with diabetic nephropathy increased gradually according to the clinical stage of this disease. In contrast, the levels of urinary IL-8 in patients with diabetic nephropathy increased in stages 2 and 3. There was a significant correlation between the levels of urinary IL-8 and those of HbA1c. High glucose may stimulate MCP-1 and/or IL-8 production and their excretion into the urine independently of the phases or pathological lesions of this disease. It appears that IL-8 increased in the early stage of diabetic nephropathy, and MCP-1 increased in the advanced stage of this disease. It was concluded that measurement of urinary MCP-1 and IL-8 may be useful for evaluating the degree of renal injuries in patients with type 2 diabetic nephropathy.
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PMID:Urinary levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), and renal injuries in patients with type 2 diabetic nephropathy. 1183 23

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

The plasma pentosidine levels in patients with renal disease were measured by a simple method which was established for plasma and urinary pentosidine determinations. The method, which can be completed within a few hours, involves pretreating plasma with proteolytic enzyme (pronase) and measuring the concentration of pentosidine in the sample by ELISA using antipentosidine antibodies. The prepared antibodies showed no cross-reaction with the raw materials for pentosidine synthesis or with compounds having similar structures. SDS-PAGE indicated that the antibodies had a high purity. The reaction of the antibodies and keyhole limpet hemocyanin-pentosidine in the competitive ELISA system was inhibited by free pentosidine. Excellent standard curves for pentosidine determination were obtained. In actual measurements of clinical samples from patients, a good correlation (r = 0.9356) was obtained between the values measured by ELISA and HPLC. The plasma pentosidine level in patients with renal disease correlated significantly with plasma creatinine, urea nitrogen, beta2-microglobulin, and creatinine clearance, indicating its usefulness in evaluating the severity of renal disease. A significant elevation in plasma pentosidine levels was observed in mild renal dysfunction, whereas no significant increases in creatinine and urea nitrogen levels were detected, suggesting that the plasma pentosidine level is useful in the early diagnosis of beginning renal failure. In patients with chronic renal failure, no difference in plasma pentosidine levels was observed between diabetic nephropathy and chronic glomerulonephritis, while a significant correlation was observed with phosphatidylcholine hydroperoxide, suggesting the possibility that the plasma pentosidine level reflects injury due to oxidation. From these results, the quantitative measurement method developed by us is judged to be a superior innovation for measuring pentosidine in body fluids. The plasma pentosidine level may be useful for the early diagnosis of mild renal failure and to estimate the degree of the severity of renal diseases.
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PMID:Plasma pentosidine levels measured by a newly developed method using ELISA in patients with chronic renal failure. 1202 21

Although it has been said that Syrian hamsters of the APA strain (APA hamsters) spontaneously develop glomerulosclerosis with age, more prominent and severe glomerulosclerosis with proteinuria as well as arteriosclerosis is induced in diabetic APA hamsters. In this study, in order to supply new information on APA hamsters, tests on renal function and histology were done on non-diabetic and streptozotocin (SZ)-induced diabetic APA hamsters (APA-N and APA-D, respectively), and the data were compared with those of normal Syrian (golden) hamsters (GOL). At 4, 8, 12, 20, and 32 weeks of age, the markers indicating renal function, serum urea nitrogen and creatinine levels and the urinary total protein level were measured and thereafter histological studies were done. Although there were no remarkable differences between APA-N and GOL in serum urea nitrogen and creatinine levels, APA-N excreted more urinary total protein from the early weeks of age. In APA-D, an apparent worsening in these markers indicating renal function was detected and diabetic nephropathy in this model was confirmed also in terms of renal function. In the histological studies, the major lesion observed in APA-D was diffuse glomerulosclerosis. This may mean that renal dysfunction in APA-D was mainly caused by the glomerular change and that it is similar to other experimental diabetic animals and human diabetic patients. These data show that the diabetic APA hamster is a desirable model of human diabetic nephropathy.
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PMID:Renal function tests on diabetes-induced and non-induced APA hamsters. 1245 4

Keishi-bukuryo-gan is a traditional herbal medicine, which is used clinically as a vascular system disorder-eliminating drug. In this study, its effect on the progression of diabetic nephropathy in experimental rats was investigated. The diabetic nephropathy model used in this study shows functional and morphological changes of the kidney resembling those seen in patients with diabetic nephropathy. Increased proteinuria and serum urea nitrogen and creatinine levels and decreased creatinine clearance, which are important parameters of renal function, were observed in rats with diabetic nephropathy. Pathological examination of the kidney revealed diffuse, nodular and exudative lesions and arteriolar hyalinosis. The deterioration of renal function was ameliorated in rats treated with Keishi-bukuryo-gan for 15 weeks and these results agreed with the renal histological findings. In addition, metabolic abnormalities mediated by persistent hyperglycaemia (the glycation reaction, excessive polyol pathway activity, oxidative stress and lipid metabolic abnormalities) were also observed. However, Keishi-bukuryo-gan reduced accumulation of advanced glycation end products, determined by measuring fluorescence, and serum lipid peroxidation, triglyceride and total cholesterol levels dose-dependently. Thus, this study indicates the potential therapeutic usefulness of Keishi-bukuryo-gan for retarding the progression of renal damage and suggests that its beneficial effects were due to its ability to improve metabolic abnormalities associated with diabetes.
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PMID:Therapeutic usefulness of Keishi-bukuryo-gan for diabetic nephropathy. 1263 15

The nonobese diabetic mouse is a model of spontaneous insulin-dependent diabetes mellitus. The present study made longitudinal observations of renal lesions in the acute-progressive phase of diabetic mice 0, 10, 20, 30, and 40 days after onset of diabetes without insulin therapy. Plasma creatinine and blood urea nitrogen concentrations gradually increased after onset of diabetes. Kidney weight increased and plateaued at day 20. Under electron microscopy the glomeruli demonstrated only mild changes on day 40. In the proximal tubules proliferating cell nuclear antigen-positive nuclei and nuclear divisions were increased on days 10 and 20. On day 40 of diabetes, increased periodic acid-Schiff-positive granules, confirmed as lysosomal dense bodies, increased neuronal nitric oxide synthase (nNOS) positive reaction, and decreased periodic acid-Schiff staining in the brush border were observed in the proximal straight tubules. In the juxtaglomerular apparatus stratified macula densa were decreased with time in diabetes compared with the findings on day 0, and this macula densa positively reacted with nNOS. No changes in renin levels were observed. In addition, apoptotic cells were not detected. In conclusion, this research represents the first thorough characterization of acute changes in nonobese diabetic mouse kidneys. The results demonstrated renal hypertrophy and slight glomerular injury in early stages and structural alteration of the proximal straight tubules at later stages during the acute phase of diabetes. Furthermore, increased nNOS may represent one of the pathogenic factors of diabetic nephropathy.
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PMID:Renal lesions in spontaneous insulin-dependent diabetes mellitus in the nonobese diabetic mouse: acute phase of diabetes. 1263 59

The biochemistry of protein modifications in human disease teaches us a number of lessons as it reveals factors and pathways implicated in the genesis of human pathology. For instance, diabetic renal damage is associated with a variety of stresses, e.g., glycemic stress resulting from hyperglycemia, oxidative stress from reactive oxygen species, carbonyl stress from reactive carbonyl compounds, and nitrosative stress from reactive nitrogen species. Proteins are particularly attractive targets for product analysis. Protein modifications are much more specific and stable biomarkers of the disease than lipids and other metabolites, and thus serve as footprints of biochemical processes. Their quantitative analysis not only facilitates better understanding of the physiopathology but also offers new therapeutic insight. In this review, we delineate oxidative protein modifications existing in diabetic nephropathy and discuss therapeutic perspectives towards the development of new classes of renoprotective agents.
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PMID:A detective story for biomedical footprints towards new therapeutic interventions in diabetic nephropathy. 1471 52


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