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)

Diabetic nephropathy is related to glomerular extracellular matrix (ECM) accumulation that leads to glomerulosclerosis. Fluvastatin as a lipid-lowering medicine significantly prevents diabetic nephropathy, probably not only through its lipid-lowering action, but also mainly through its direct suppression of glomerular ECM accumulation. To test this hypothesis, in the present study, a five-sixths nephrectomized (5/6Nx) rat model to induce a renal ECM accumulation without coexistence of hyperlipidemia was used to investigate the effect of fluvastatin on renal function, glomerular ECM accumulation and expression of connective tissue growth factor (CTGF). 5/6Nx induced a significant nephropathy in rats at 13 weeks, indicated by renal dysfunction including increases in blood urine nitrogen, creatinine and urinary protein excretion, and renal histopathological changes. Administration of fluvastatin significantly prevented the renal dysfunction and histological abnormalities in the 5/6Nx rats. Furthermore, both significant suppression of matrix metalloproteinases (MMPs) activity such as MMP-2 and significant activation of tissue inhibitors of MMP (TIMPs) such as TIMP-2 observed in the 5/6Nx rats were almost completely prevented by fluvastatin, resulting in a significant prevention of glomerular ECM accumulation. For upstream mediator of ECM accumulation, 5/6Nx significantly up-regulated CTGF mRNA expression, but fluvastatin treatment prevented CTGF up-regulation. These results suggest that fluvastatin, as one of well-known lipid-lowering agents, plays an important role in the prevention of nephropathy, likely through suppression of CTGF-mediated ECM accumulation. Therefore, fluvastatin may be a potential candidate for developing a pharmaceutical approach to the prevention of diabetic nephropathy due to its both lipid-lowering and direct anti-renal ECM accumulation actions.
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PMID:Fluvastatin prevents nephropathy likely through suppression of connective tissue growth factor-mediated extracellular matrix accumulation. 1473 71

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

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

A 29-year-old man developed diabetes mellitus in 1983 and diabetic nephropathy which gradually worsened from 1998. He was admitted to our hospital for initiation of peritoneal dialysis in May 2002. However, the efficiency of dialysis was not sufficient to improve elevated levels of blood urea nitrogen and serum creatinine. His body weight and cardiothoracic index by chest roentgenography gradually increased starting 9 days after admission. To improve the efficiency of dialysis, we tried to increase the dialysis fluid. Nevertheless, the efficiency of peritoneal dialysis remained low, and the patient complained of nausea 14 days after admission. Hypotension suddenly occurred 16 days after admission. Echocardiography showed massive pericardial effusion and collapse of the right ventricle. The diagnosis was cardiac tamponade. We performed cardiac centesis and pericardial drainage which revealed bloody pericardial effusion. Urgent hemodialysis was performed. The differential diagnosis of cardiac tamponade was established. After hemodialysis, the amount of pericardial effusion decreased, the gastro-intestinal symptoms disappeared, and the blood urea nitrogen and serum creatinine levels decreased. We speculated that the cause of cardiac tamponade was uremic pericarditis after ruling out infectious disease, collagen disease, malignant disease, and aortic dissection. Cardiac tamponade due to uremic pericarditis has become very rare since hemodialysis was developed.
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PMID:[Uremic pericarditis complicating cardiac tamponade: a case report]. 1563 26

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

The effects of dried Rehmanniae Radix (Di Huang) extract were investigated using a diabetic nephropathy model: rats given streptozotocin after nephrectomy. The results showed that this crude drug reduced the magnitudes of the increases in glucose, urea nitrogen, 5-hydroxymethylfurfural and thiobarbituric acid (TBA)-reactive substance levels, with the effects being most marked in the high blood glucose group. The renal histopathological lesions, which were conspicuous in rats not given dried Rehmanniae Radix extract, were ameliorated considerably in the high blood glucose group given this extract. It appears that dried Rehmanniae Radix extract may be useful as a therapeutic agent for inhibiting the progression of diabetic nephropathy. On the basis of these results, the possible mechanisms of action of this crude drug are discussed.
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PMID:Amelioration of diabetic nephropathy by dried Rehmanniae Radix (Di Huang) extract. 1567 89

Diabetic nephropathy is the main cause of end stage renal damage. Oxidative stress is involved in the etiology of diabetic nephropathy and intracellular calcium is reported to play a considerable role in the development of renal damage in the diabetic kidney. Calcium antagonism can slow the progression of renal impairment in diabetes. The present study was thus designed to examine the effect of a nondihydropyridine calcium channel blocker, diltiazem, on renal function, oxidative stress, and nitric oxide (NO) release in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, the rats were divided in to four groups: control rats, diabetic rats treated with saline, and two groups of diabetic rats treated with diltiazem (5 and 10 mg/kg, i.p, respectively) for 8 weeks starting from 4 weeks after STZ injection. Renal function was assessed by creatinine, blood urea nitrogen, creatinine clearance, and urea clearance. Oxidative stress was measured by renal malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase. We also measured renal nitrite levels. At the end of the 8 weeks, 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, GSH, SOD, and catalase in diabetic rats. Release of NO also significantly higher in diabetic rats than controls. Chronic treatment with diltiazem in diabetic rats significantly attenuated both renal dysfunction and oxidative stress along with increased NO levels as compared with untreated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening, and moderate interstitial fibrosis and arteriolopathy, whereas diltiazem administration markedly prevented diabetic-induced renal morphological alterations. The present study suggests that oxidative stress/nitrosative stress is increased in the diabetic kidney and calcium channel blockage can prevent these changes. The results also suggest that in STZ-induced diabetic rats, the protective action of diltiazem might be mediated, at least in part, by its effect on tissue oxidant/antioxidant status.
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PMID:Diltiazem attenuates oxidative stress in diabetic rats. 1595 52

In this study we examined the effect of green tea polyphenols (GTP) and partially hydrolysed guar gum (PHGG) as dietary fibre on diabetic nephropathy, using rats that had been subjected to subtotal nephrectomy and injection of streptozotocin. The subtotally nephrectomized rats were subjected to resection of three-quarters of the kidney. Rats with diabetic nephropathy were divided into four groups: untreated controls, and animals that received GTP (100 mg kg-1 body weight day-1), PHGG (100 mg kg-1 body weight day-1) and GTP plus PHGG (50 mg kg-1 body weight day-1 plus 50 mg kg-1 body weight day-1). After 50 days of administration, attenuation of urinary protein excretion and the morphological changes peculiar to diabetic nephropathy were observed in all three treated groups. Furthermore, the group treated with GTP plus PHGG showed an improvement of kidney weight and serum levels of urea nitrogen, creatinine and creatinine clearance. Hyperglycaemia, as assessed in terms of blood glucose and glycosylated protein levels, was also improved by administration of GTP plus PHGG. On the other hand, GTP administration increased the activity of superoxide dismutase in the kidney to a significant extent. A significant reduction in the total cholesterol concentration was also observed in the PHGG-treated group. These results suggest that GTP and PHGG could be beneficial as additional therapy in the management of diabetic nephropathy.
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PMID:Green tea polyphenols and dietary fibre protect against kidney damage in rats with diabetic nephropathy. 1596 33


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