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)

Muzolimine is a diuretic with chemical features different from all other known diuretics, and its use seem to be particularly interesting in patients with chronic renal failure. In fact, similarly to furosemide, muzolimine presents a strong action on Henle's loop but with a slower and more lasting effect, as experimentally demonstrated in both animals and man. We used high doses muzolimine (240, 480, 720 mg/die) in 16 patients with chronic renal failure (creatinine clearance less than 20 ml/min) and clinical pattern of important hydrosaline retention (6 primitive glomerulonephritis, 3 interstitial nephrites, 1 vascular nephropathy, 1 diabetic nephropathy, 1 lupus nephritis, 1 amyloidosis, 1 polycystic nephropathy and 2 nephropathies of unknown diagnosis). Muzolimine diuretic action was compared with furosemide 500 mg/die. The schedule employed was: furosemide 500 mg/die for 5 days followed by 6 days of muzolimine treatment at increasing doses (240 mg on 1st and 2nd day, 480 mg on 3rd and 4th, 720 mg on 5th and 6th). In all patients (undergoing a diet constant in water, sodium, potassium and protein content) body weight, blood pressure, heart rate, serum and urinary electrolyte concentration, serum and urinary uric acid, BUN, creatinine clearance, glycaemia, hematocrit and hemoglobin were daily controlled. A clinical and laboratory investigation of the possible side effects was also assessed; in particular liver enzymes, bilirubin and total serum proteins were considered. In our study muzolimine increased the renal excretion of water, sodium and chloride in all cases. This effect is more evident during the treatment with the highest dose (720 mg/die) but already appears with the 480 mg/die dose and is higher than that obtained with comparable doses of furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muzolimine in chronic renal failure: a study in 16 patients. 400 86

Genetically diabetic mice (C57 BLKsJ db/db) aged 5-6 weeks were given a diet containing 20% by weight of non-nutritive bulk and compared with age matched control diabetic mice on a normal diet (fibre content 4.5%) and non-diabetic mice. The duration of study was 12 weeks. No adverse effects were observed in animals given the high fibre diet. Total food consumption was greater in mice receiving the fibre enriched diet, but their absolute caloric intake was 6% less than control diabetic mice. Both groups exhibited similar rates of growth and development. Water intake in the experimental diabetic mice was reduced and similar to that of normal non-diabetic mice. Fasting blood glucose was significantly decreased in the experimental diabetic mice at 12 weeks. Renal pathological lesions in the control diabetic mice showed glomerular mesangial expansion and deposition of immunoglobulins within the mesangium. The experimental diabetic animals exhibited significantly less renal pathology, including light and immunofluorescent lesions. It is concluded that addition of non-absorbable fibre to the diet of genetically diabetic mice improves glycaemic control and retards the development of diabetic nephropathy.
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PMID:The effect of a high fibre diet on diabetic nephropathy in the db/db mouse. 628 77

To evaluate the glomerulo-tubular balance of sodium and water in the proximal tubules of diabetic patients with elevated glomerular filtration rate, the renal plasma clearance of lithium and the glomerular filtration rate (51Cr-EDTA plasma clearance) were determined simultaneously in 11 ambulatory Type 1 (insulin-dependent) diabetic patients (aged 25-35 years) with no evidence of diabetic nephropathy and in 10 age-matched healthy subjects. The renal plasma clearance of lithium, which is a measure of flow from the proximal tubule into the thin descending limb of the loop of Henle, did not differ between diabetic and control subjects (28.9 +/- 4.0 versus 28.3 +/- 5.1 ml/min per 1.73 m2 surface area, mean +/- SD), whereas the glomerular filtration rate in the diabetic patients was significantly higher than in the control subjects (136 +/- 10.2 versus 108 +/- 13.6 ml/min per 1.73 m2, p less than 0.001). The same held true for the fractional reabsorption rate in the proximal tubules (78.7 +/- 3.2 versus 73.6 +/- 4.9%, p less than 0.02). The results indicate that the elevation of the glomerular filtration rate in diabetic patients is associated with a parallel increase in the proximal reabsorption rate. This type of glomerulo-tubular balance implies that the flow of water and flux of sodium to the segments distal to the proximal tubule are kept constant during variations in the glomerular filtration rate.
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PMID:Proximal glomerulo-tubular balance in patients with type 1 (insulin-dependent) diabetes mellitus. 648 54

Diabetes in the C57BL/KsJ(db/db) mouse is initially expressed as hyperinsulinemia, followed by hyperphagia, progressive obesity, and widespread pathologic abnormalities. This study was designed to evaluate the effects of metabolic control on the natural history of the diabetic nephropathy. Beginning at 1 mo of age and continuing for 12 wk, diabetic mice were subjected to controlled dietary restriction, such that their weight was maintained similar to that of age-matched, nondiabetic heterozygotes. Diet-restricted diabetics were compared with diabetics fed ad libitum and heterozygote nondiabetics. Significant lowering of fasting blood glucose, water intake, and plasma insulin was achieved by diet restriction. The diet-restricted diabetes demonstrated enhanced metabolic efficiency, consuming approximately half as much food as the nondiabetics, while maintaining a similar weight. Diabetics fed ad libitum evidenced well-defined renal lesions that included 3 + to 4 + immunoglobulin deposition in the glomerular mesangium, and generalized mesangial matrix expansion. These lesions were completely prevented in diet-restricted diabetes whose glomeruli were normal light microscopy, and demonstrated trace to 1 + mesangial immunoglobulin deposition, features identical in all respects to the nondiabetics. These results indicate that diabetic control achieved by preventing of obesity in the db/db mouse prevents the development of diabetic nephropathy.
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PMID:Prevention of diabetic nephropathy by diet control in the db/db mouse. 700 65

We examined the effect of two endogenous antioxidant agents, taurine and vitamin E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival rate was similar (70-90%) in all groups except vitamin E-treated animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with normal or insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria and albuminuria by nearly 50%. This treatment also prevented glomerular hypertrophy, preserved immunohistochemical staining for type IV collagen in glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in diabetic animals. The changes in renal function and structure in taurine-treated diabetic rats were associated with normalization of renal cortical malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in skin collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylation end products (AGEs) in skin collagen. We conclude that administration of taurine, but not vitamin E, to rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and less accumulation of AGEs within the kidney.
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PMID:Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats. 757 92

Tempocapril is a novel angiotensin-converting enzyme (ACE) inhibitor which is preferentially eliminated via the biliary tract. To examine whether it has a protective effect in diabetic nephropathy like conventional ACE inhibitors which are eliminated via the kidney, a study was performed in streptozotocin-induced diabetic rats for 8 months. Male Wistar rats were divided into 4 groups (control rats, diabetic rats treated with temocapril at the doses of 5 mg/l or 15 mg/l of drinking water, and untreated diabetic rats). There was no significant difference in the blood glucose levels of the 3 diabetic groups. Administration of temocapril at both doses of 5 mg/l and 15 mg/l significantly reduced the blood pressure as well as the urinary excretion of albumin and N-acetyl-beta-D-glucosaminidase. However, significant suppression of glomerular basement membrane hypertrophy was only induced by treatment with temocapril at the dose of 15 mg/l. Elevated glomerular filtration rate and filtration fraction in diabetic rats were decreased by tempocapril at the dose of 15 mg/l, but not significantly. These results indicate that tempocapril has a protective effect on diabetic nephropathy like conventional ACE inhibitors.
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PMID:[The effect of temocapril, an angiotensin-converting enzyme inhibitor with preferential biliary excretion, on experimental diabetic nephropathy]. 781 41

We investigated both sodium-lithium countertransport (Na-Li CT) and ouabain-sensitive sodium transport (Na pump) of erythrocytes in healthy subjects (group A), patients with non-insulin-dependent diabetes (NIDDM) without nephropathy (group B), patients in the proteinuric stage (group C), and those in the renal insufficiency stage (group D). Erythrocytes from all four groups had a similar initial water and ionic content and were loaded with similar degrees of Li and Na for efflux studies. There were no significant differences in erythrocyte Na-Li CT or Na pump among the four groups. However, the maximal rate of Na-Li CT was significantly higher in a group of subjects with essential hypertension when compared with groups A, B and C, consistent with the view that there is a genetic marker for essential hypertension. Ouabain-insensitive Na efflux (Na leak) of erythrocytes was found to be significantly higher in group D than in groups A or B. Also, a significant positive correlation existed between Na leak and urine protein levels of the subjects studied. Our results thus indicate that in contrast with insulin-dependent diabetic patients (IDDM) where an elevated Na-Li CT is observed, with diabetic nephropathy, Na-Li CT in NIDDM is apparently not associated with nephropathy; rather the ouabain-insensitive Na efflux appears to be correlated with the stages of nephropathy in NIDDM. The association suggests that the rate of ouabain-insensitive Na efflux may provide an index for assessing the degree of nephropathy in NIDDM patients.
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PMID:Abnormalities of sodium transport in non-insulin-dependent diabetes: association with renal disease. 810 99

This study was designed to clarify the mechanisms by which the progression of diabetic nephropathy is inhibited by low-protein diet. Six control and twenty-five streptozotocin-induced diabetic rats were divided into 4 group: Group I consisted of non-diabetic control rats administered a 40% protein diet (n = 6); Group II, diabetic rats administered a 40% protein diet (n = 8); Group III, diabetic rats treated with a 10% protein diet (n = 8), and Group IV, diabetic rats treated together with a 10% protein diet and ad lib, drinking water containing 0.75 mg/l of angiotensin-converting enzyme inhibitor (ACEI) (n = 9). The follow-up period was 24 weeks. Urinary albumin excretion rate (AER), glomerular filtration rate (GFR) and morphometric measurement of renal biopsy specimens obtained at 12 and 24 weeks were evaluated. AER was significantly increased in the untreated diabetic Group II compared with the control Group I. However, AER was significantly decreased in the treated Group III and IV compared with the untreated diabetic Group II. There was no significant difference in AER between Group III and IV. Compared with Group II, the increase in GFR was significantly inhibited in Group IV but not in Group III. The increase in mesangial matrix and GBM thickening were both prominent in the untreated diabetic Group II, and significantly inhibited in the treated Group III and IV.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mechanisms of prevention of progression of diabetic nephropathy by dietary protein restriction]. 841 63

Diabetic nephropathy is a major cause of end-stage renal failure. While our understanding of the pathogenesis of nephropathy is incomplete, progressive glomerular injury appears to play a significant role in the decline of renal function. Proton NMR spectroscopy and imaging techniques were used to address changes in renal pathology associated with glomerular mesangial expansion in vivo in kidneys from spontaneously obese and lean (control) littermate Zucker rats. Fully functioning rat kidneys were surgically exposed and externalized for direct NMR signal detection via a coil placed around the organ. High-resolution (78 microns in plane) proton images were obtained at 4.7 T magnetic field strength revealing fine structure within the well-defined cortical and medullary regions. The obese rat kidney images were distinct in appearance from the lean kidney images and exhibited marked cortical expansion as well as increased overall kidney size. Enlargement of mean glomerular diameter was verified histologically in the obese kidneys as compared with the lean kidneys. Proton T1 and T2 relaxation times were determined from the entire kidney using standard spectroscopic techniques, and from specific regions within the kidney from multiple T1- and T-2 weighted images. Additionally, image contrast enhancement resulting from saturation transfer between protons in restricted-mobility environments and mobile water protons within the kidney was investigated in the lean and obese rat kidneys using magnetization-transfer imaging techniques. At the early stage of renal injury examined in this study, diseased and healthy kidneys could not be differentiated on the basis of relaxation times alone. The magnitude of saturation transfer obtained in cortical tissue in the lean and obese kidneys was also not statistically significantly different. However, the magnitude of saturation transfer achieved in the medullary tissue of obese kidneys was statistically significantly less than that achieved in lean kidneys.
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PMID:In vivo NMR imaging and spectroscopic investigation of renal pathology in lean and obese rat kidneys. 845 Jul 42

1. It has been suggested that tubular damage may precede glomerular damage at the onset of diabetic nephropathy. This may be reflected by increased urinary excretion of low-molecular-mass proteins, such as retinol-binding protein. 2. We have measured the urinary excretion rate of retinol-binding protein overnight, during orthostasis and during a hyperinsulinaemic euglycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 34 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 10 normal control subjects. Normal control subjects were not clamped. A further four normoalbuminuric insulin-dependent diabetic patients were rendered euglycaemic without a water load. 3. Overnight retinol-binding protein excretion rate was 58 (16-157) [median(range)] ng/min in patients with insulin-dependent diabetes and 32 (15-72) ng/min in control subjects (P < 0.01). The excretion rate did not change during orthostasis [patients with insulin-dependent diabetes, 67 (3-173) ng/min; control subjects, 23 (5-78) ng/min]. During the euglycaemic clamp retinol-binding protein excretion rate increased to 383 (78-4897) ng/min in patients with insulin-dependent diabetes (P < 0.01). An average increment in retinol-binding protein excretion rate of greater than 4000% was noted after acute euglycaemia in those patients with insulin-dependent diabetes who were not water-loaded. 4. In insulin-dependent diabetes, both overnight and orthostatic retinal-binding protein excretion was not correlated with fasting blood glucose concentration, HbA1, fructosamine or duration of diabetes. The absolute and incremental excretion rates of retinol-binding protein during the clamp were, however, correlated with both fasting blood glucose concentration and glucose excretion rate (rs = 0.41-0.48, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of posture and acute glycaemic control on the excretion of retinol-binding protein in normoalbuminuric insulin-dependent diabetic patients. 848 50


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