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

The purpose of the case study was to define a degree of destructive changes in the connective tissue at different stages of diabetic nephropathy (DN) progression. One hundred and twenty eight DN patients with type 1 diabetes mellitus, disease duration-5 to 20 years (classification according C. Mogensen, 1983) were examined. Special biochemical tools were used to evaluate the connective-tissue condition. The parameters of metabolism of the connective-tissue biopolymers were investigated in blood, urea and saliva, i.e. general and sulphated glucosamine glycine (GAG), sialic acid (SA) and oxyproline fractions. The results showed an increasing value of total and sulphated GAG and SA with a worsening DN severity, which is indicative of a destruction degree of glycoprotein-complexes in the microvascular basal membranes. A high level of bound oxyproline fractions denotes the fibril-genesis processes, which start to activate yet at the preclinical DN stage. The changes detected previously in the parameters of metabolism of the connective-tissue biopolymers, as observed in DN patients, ensure a timely choice of a therapy and a proper monitoring of its efficiency.
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PMID:[Clinical significance of assessment of the metabolism of connective-tissue biopolymers in patients with type 1 diabetes mellitus and with diabetic nephropathy]. 1466 78

The rate of decline of renal function (RDRF) in the pre-end stage renal disease setting (pre-ESRD) is highly variable. Several factors have been involved as potential modifiers of renal failure progression. This retrospective study attempts to establish which were the main determinants of the RDRF in pre-ESRD patients followed in the predialysis consult. The study group consisted of 230 patients with pre-ESRD not yet on dialysis who were referred to the predialysis consult from January 1998 to July 2002. The mean follow-up time per patient was 356 days. RDRF was assessed as delta of the average of creatinine and urea clearances (CrCl-UCl). Data obtained at time of referral to the predialysis consult were analyzed as potential predictors of the subsequent RDRF. These independent variables included: demographics, comorbid conditions, main hematological and biochemical data, antihypertensive and statin treatment, mean blood pressure, and CrCl-UCl at time of referral. The predictors of delta CrCl-UCl were determined by multiple linear regression analysis. The determinants of the survival without dialysis were established by the Cox regression hazard model, adjusted to renal function at time of referral. Mean CrCl-UCl at time of referral was 10.98 +/- 2.58 ml/min/1.73 m2, and mean delta CrCl-UCl was -0.37 +/- 0.46 ml/min/1.73 m2/month. Patients with diabetic nephropathy and chronic glomerulonephritis had the fastest RDRF, while patients with ischemic nephropathy and chronic interstitial nephritis had the slowest RDRF. Seventy-five patients (46%) required EPO therapy. The best determinants of delta CrCl-UCl were: the 24-hour proteinuria (p < 0.0001), and the hematocrit at time of referral (p = 0.0024). The best determinants of the survival rate without dialysis during the study period were: the proteinuria (in g/24 hours) (R 1, 16; p < 0.0001), the hematocrit at time of referral (OR: 0.88; p < 0.0001), the treatment with EPO (OR: 0.59; p = 0.02), and the diagnosis of diabetes mellitus (OR: 1.59; p = 0.01). In conclusion, apart from the rate of proteinuria, which could represent the best marker of the RDRF in chronic renal diseases, the development of anemia was associated with faster decline in renal function.
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PMID:[Progression of renal insufficiency in the pre-end-stage renal disease setting]. 1500 86

The status of dialytic therapy in Korea at the end of 2001 was reported by the end-stage renal disease (ESRD) registry committee of Korean Society of Nephrology, where data were collected through an internet on-line registry program. The number of dialysis centres was 335 and the number of haemodialysis machines was 5529. The total number of patients with dialysis was 23,057 (haemodialysis 17,568, peritoneal dialysis 5489). Prevalence and incidence of dialysis patients were 477.5 and 96.4 patients per million population. The most common primary cause of end-stage renal diseases was diabetic nephropathy (41.5%), hypertensive nephrosclerosis (15.4%), and chronic glomerulonephritis (13.6%). Eighty-six percent of haemodialysis patients were on dialysis therapy three times a week, the mean urea reduction ratio was 66.7 +/- 8.68% and mean Kt/V was 1.250 +/- 0.292 in male patients; 1.526 +/- 0.361 in female patients. The technical survival of haemodialysis in 5 years was 30.2% and peritoneal dialysis was 13.8%. The common complication of haemodialysis patients was hypertension (43.3%), gastrointestinal disease other than peptic ulcer (8.0%), congestive heart failure (7.6%), and of peritoneal dialysis patients were also hypertension (28.8%), congestive heart failure (5.0%), and peritonitis (4.8%). The most common causes of death were cardiac diseases (26.9%), vascular diseases, including cerebrovascular accidents (22.7%), and infection (17.8%).
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PMID:Current status of dialytic therapy in Korea. 1501 84

Protein kinase C (PKC)-induced changes in glomerular mesangial cell (MC) phenotypic behavior has been implicated in diabetes. The activity of diacylglycerol-sensitive PKC isoforms in MCs is altered by ambient changes in glucose, but the regulation of PKC activity and subsequent intracellular signaling events are not yet clearly defined. Small GTP-binding proteins of the ADP-ribosylation factor (Arfs) family, may regulate protein kinase membrane recruitment and hence its activity in signaling events of non-polarized cells. Members of the ARF family may coordinate membrane dynamics and other cellular functions through their interaction with PKC. We studied the activation of Arf, PKC betaI and phospholipase D (PLD) in MCs cultured under normal or high glucose conditions. MCs cultured in high glucose medium exhibited predominantly cytosolic localization of PKC betaI, Arf3 and Arf6. However, phorbol ester (PMA) stimulation of cells cultured in high glucose significantly enhanced membrane association of PKC betaI and Arf6, but not Arf3. Using [3H]choline chloride to prelabel MCs and measuring [3H]choline-containing metabolite release as PLD activity, PMA stimulated a significant increase of PLD activity under high glucose condition. Our data suggest that Arf6 plays a specific role in activation of PKC betaI and PLD under high glucose condition, and may be a significant intracellular event in the change of the mesangial cell phenotype associated with diabetic nephropathy.
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PMID:High glucose-induced membrane translocation of PKC betaI is associated with Arf6 in glomerular mesangial cells. 1503 Jan 77

1. Diabetic nephropathy is an important microvascular complication and one of the main causes of end-stage renal disease. Many in vivo and in vitro studies have indicated that oxidative stress is one of the major pathophysiological mechanisms involved in the development of diabetic nephropathy. In the present study, we examined the effect of an anti-oxidant bioflavonoid quercetin on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. 2. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection of STZ (45 mg/kg). Four weeks after STZ injection, quercetin (10 mg/kg per day) was given orally for 4 weeks in both control and diabetic rats. Plasma glucose levels and bodyweights were measured at 4 and 8 weeks after the STZ injection. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The renal oxidative stress marker malonaldehyde, glutathione levels and the anti-oxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. 3. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in bodyweight compared with age-matched control rats. After 8 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Treatment with quercetin significantly attenuated renal dysfunction and oxidative stress in diabetic rats. 4. These results confirm the role of oxidative stress in the development of diabetic nephropathy and point to the possible anti-oxidative mechanism being responsible for the nephroprotective action of quercetin.
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PMID:Quercetin, an anti-oxidant bioflavonoid, attenuates diabetic nephropathy in rats. 1505 21

Three hundred fifteen (315) elderly (> or = 60 years) patients with clinical renal diseases were evaluated for the evidence of glomerular diseases between November 1998 to June 2002. Glomerular diseases (GN) were observed in 20.6% (65/315) of the elderly patients. The age of the patients (male 56; female 9) ranged between 60-90 (mean 64.17 +/- 3.83) years. The clinical presentation of GN included: nephrotic syndrome 40 (61.5%), acute nephritic syndrome 19 (29.2%), rapidly progressive GN 4 (6.15%) and asymptomatic urinary abnormality 2 (3.0%). Overall, primary and secondary glomerular disease were seen in 47 (72.3%) and 18 (27.6%) elderly patients respectively. Idiopathic membranous nephropathy was the most common GN responsible for nephrotic syndrome in 11 (27.5%) of elderly patients. Diabetic Nephropathy related to type 2 diabetes mellitus was the second common cause 9 (22.5%) of nephrotic syndrome. Amyloidosis was noted in 6 (15%) patients. Nephrotic syndrome was related to leprosy in one patient. Amyloidosis occurred in association with multiple myeloma in 5 and carcinoma colon in 1 patient. Thus, primary and secondary GN were responsible for nephrotic syndrome in 60% and 40% of cases respectively. Endocapillary proliferative GN of post infectious etiology was the most prevalent (82.6%) form of acute GN in our elderly patients. Hypertension occurred in 78.2% of cases and edema in 69.5%. Pulmonary congestion (52.2%) and ARF (73.9%) were the dominant presenting feature of acute GN and 39% of patients required dialytic support. Glomerular crescents were seen in 4 (17.4%) patients with acute glomerulonephritis. Pauci-immune crescentic GN which is the commonest type of acute GN in the elderly in western countries was not observed in this study. Renal biopsy revealed mesangiocapillary GN (1) and mesangioproliferative GN (1) in two patients with asymptomatic urinary abnormalities. Thus, overall spectrum of glomerular disease in the Indian elderly population is similar to that of developed countries except in two ways: (1) post infectious endocapillary proliferative-GN was the commonest type of acute GN (2) rarity or absence of pauci-immune crescentic glomerulonephritis.
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PMID:Glomerular diseases in the elderly in India. 1507 10

To determine correlations among the levels of urinary MMP-9 and type-IV collagen, hyperglycemia, urinary protein excretion, and renal injuries in patients with type 2 diabetic nephropathy, we measured levels of urinary MMP-9 and protein, blood urea nitrogen (BUN), serum creatinine (s-Cr), fasting plasma glucose (FPG), and glycohemoglobin A1c (HbA1c) in 47 diabetic patients and 14 healthy adults. Urinary type-IV collagen was also measured in 28 diabetic patients and seven healthy adults. Patients with diabetic nephropathy were divided into two groups: 1). patients with normoalbuminuria or microalbuminuria (0-299 mg/g.Cr; n=27), and 2). patients with macroalbuminuria (>300 mg/g.Cr; n=20). The mean level of urinary MMP-9 in group 2 was significantly higher than those in healthy adults (P<0.05), and the levels of urinary MMP-9 in patients with diabetic nephropathy increased in accordance with the clinical stage of the disease. The levels of urinary MMP-9 tended to be correlated with HbA1c in these patients, but the correlation was not statistically significant. The mean level of urinary type-IV collagen in group 2 of patients with diabetic nephropathy was significantly higher than that in group 1 and healthy adults. Levels of urinary type-IV collagen in patients with diabetic nephropathy also increased in accordance with the clinical stage of the disease. The results suggest that measurements of urinary MMP-9, as well as urinary type-IV collagen, may be useful for evaluating the degree of renal injuries in patients with type 2 diabetic nephropathy, especially in the early stage.
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PMID:Levels of urinary matrix metalloproteinase-9 (MMP-9) and renal injuries in patients with type 2 diabetic nephropathy. 1510 87

Large-scale clinical trials have shown that the oral adsorbent AST-120 improves renal function and delays the initiation of dialysis in chronic renal failure (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via common mechanisms, then the same effects can be expected in diabetic nephropathy. However, no study on diabetic nephropathy has been reported. Thus, we enrolled patients with statistically significant progression of CRF secondary to diabetic nephropathy, and analyzed the changes in renal function after AST-120 therapy, and the clinical factors associated with response to therapy. We enrolled 276 patients with diabetic nephropathy, whose serum creatinine (Scr) had increased from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical data were analyzed by dividing the patients into three groups based on the changes in Scr after AST-120 therapy, with responders showing a decrease (N = 82), partial responders showing <1.5-fold increase (N = 144), and non-responders showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of 1/Scr-time line, suggesting that AST-120 suppressed the progression of renal impairment. No responders required dialysis, whereas 24.3% of the partial responders and 36.0% of the non-responders started dialysis therapy. In responders, the 1/Scr-time slope showed a negative-to-positive shift and serum urea nitrogen decreased significantly, whereas the improvement was moderate in partial responders and minimal in non-responders. Among responders, AST-120 therapy significantly improved renal function despite the presence of hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The beneficial effect of AST-120 was significantly more marked in patients with blood pressure controlled within the normal ranges and hematocrit maintained at 30% or above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis therapy in patients with progressive aggravation of CRF secondary to diabetic nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and hypertension. Active use of AST-120 may be recommended in patients with good control of blood pressure and hematocrit above 30%.
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PMID:Protective effect of an oral adsorbent on renal function in chronic renal failure: determinants of its efficacy in diabetic nephropathy. 1515 77

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

Recent evidences indicate a pivotal role of reactive oxygen species in etiology of diabetic nephropathy, an important microvascular complication of diabetes mellitus. Moreover, oxidative stress leads to an increased production of lipoxygenase derivatives which also play a role in diabetic nephropathy. The present study was thus designed to examine the effect of an antioxidant and a lipoxygenase inhibitor, nordihydroguairetic acid (NDGA), on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) in rats. After the 4th week of STZ injection, NDGA (5 and 10 mg/kg) was given subcutaneously (s.c.) for another 4 weeks to both control and diabetic rats. At the end of the 8th week, diabetic rats exhibited renal dysfunction as evidenced by reduced creatinine and urea clearance along with enhanced albumin excretion rate as compared with control rats. Biochemical analysis of kidneys revealed a marked increase in oxidative stress demonstrated by increased lipid peroxidation and decreased activities of key antioxidant enzymes, glutathione (GSH), superoxide dismutase (SOD) and catalase in diabetic rats. Chronic treatment with NDGA in diabetic rats significantly prevented both renal dysfunction and oxidative stress as compared with vehicle-treated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening and moderate interstitial fibrosis and arteriolopathy, whereas NDGA administration in diabetic rats markedly prevented renal morphological alterations. These results emphasize the role of oxidative stress in the pathophysiology of diabetic nephropathy and point towards the potential of NDGA as a complementary therapy for the prevention/treatment of diabetic nephropathy.
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PMID:Nordihydroguairetic acid, a lignin, prevents oxidative stress and the development of diabetic nephropathy in rats. 1529 54


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