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 role of hypertension for the combined occurrence of incipient diabetic nephropathy and diabetic retinopathy (RP) was evaluated in 155 insulin-dependent diabetic patients (74 male/81 female); mean age 32.4 +/- 12.2 STD years; means diabetes duration 12.8 +/- 10 STD years). Albumin excretion rate (AER) was measured in 24 hours urine samples by RIA, retinal status was determined by both, fundoscopy and fluorescein angiography. Analysis of the data revealed a statistically significant correlation between the duration of disease and elevated AER (p less than 0.012), and the occurrence of retinopathy (p less than 0.0001). Although there was a close correlation between retinopathy and elevated AER (p less than 0.0001), it is remarkable that 31% of the patients with normal AER (less than 15 micrograms/min) showed signs of non proliferative RP. On the other hand 30% of patients without retinal changes showed an elevated AER (less than 15 micrograms/min). In the group of microalbuminuric patients (greater than 15 micrograms/min) systolic (p less than 0.004) and diastolic (p less than 0.04) blood pressures were significantly higher than in normoalbuminuric patients (less than 15 micrograms/min). Patients with proliferative retinopathy showed significantly higher systolic and diastolic (p less than 0.015) blood pressures compared to patients without retinal changes, though albumin excretion rates were not different in both groups of patients. In conclusion, our results show that diabetic nephropathy and diabetic retinopathy do not develop simultaneously in a representative number of insulin-dependent diabetic patients, but hypertension may be a major risk factor for the development of both microangiopathic complications.
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PMID:[Significance of arterial blood pressure for the development of microalbuminuria and retinopathy in type I diabetes mellitus]. 323 57

Protein intake has been suggested to influence progression of renal disease by affecting intraglomerular pressures and flows. The renal disease of the diabetic mouse (C57BL/Ks/db/db) has been proposed as a suitable model of human diabetic nephropathy. Ten diabetic mice and ten non-diabetic controls were placed on 1 of 3 protein intakes, 4%, 27% and 50%, and serial functional measurements were made at 2 to 3 week intervals until week 20. All diabetic animals showed similar degrees of hyperglycemia. The creatinine clearances were generally higher in the diabetic mice than the controls, except the 4% protein intake diabetic group, until week 20 when the 27% db/db mice showed a significant decline (p less than 0.05) compared to the control mice. Albumin excretion was significantly higher in the 27% and 50% protein intake db/db mice than the controls. Again the 4% group showed albuminuria not different from the control animals. Histologic studies at 20 weeks showed minimal abnormalities in the normal and 4% protein intake diabetic group. The 27% and 50% intake diabetic mice showed a progressive increase in severity of mesangial matrix expansion with segmental sclerosis. Electron microscopy confirmed these findings. Immunofluorescence microscopy showed a marked increase in mesangial immunoglobulin G and M. With similar degree of hyperglycemia, higher protein intake was associated with more severe histologic changes, greater albuminuria and early decline in GFR. Thus protein intake can markedly affect the progression of renal disease in the diabetic mouse.
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PMID:Effect of varied protein intake on the nephropathy of the diabetic mouse (C57BL/s J db/db). 330 29

Albumin excretion rate was determined by radioimmunoassay in overnight urine from 102 normotensive patients with insulin-dependent diabetes mellitus of more than 10 year's duration. Based on two samples, 16 patients (16%) exhibited microalbuminuria, defined as a mean excretion rate greater than 20 micrograms/min. Microalbuminuric patients were significantly younger at onset of diabetes but did not differ from normoalbuminuric patients concerning age or duration of diabetes. Nonetheless, diastolic and mean arterial blood pressures were significantly higher in the microalbuminuric group. The existing glycemic control, assessed by glycosylated hemoglobin (HbA1c) was better in normoalbuminurics, but not significantly so. The albumin excretion rate in microalbuminuric patients correlated significantly (p less than 0.01) to diastolic (r = 0.69) and to mean arterial blood pressure (r = 0.69), but did not correlate to HbA1c. Thus, it is concluded that even normotensive patients with signs of early diabetic nephropathy, i.e. microalbuminuria, exhibit small, but significant increases in blood pressure.
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PMID:Microalbuminuria in long-term insulin-dependent diabetes mellitus. Prevalence and clinical characteristics in a normotensive population. 342 86

The aim of the study was to clarify whether antihypertensive treatment with a selective beta blocker would have an effect on the progression rate of kidney disease in patients with incipient diabetic nephropathy. Six male patients with juvenile-onset diabetes with incipient nephropathy (urinary albumin excretion above 15 micrograms/min and total protein excretion below 0.5 g/24 hr) were treated with metoprolol (200 mg daily). At the start of the antihypertensive treatment the mean age was 32 years +/- 4.2 (SD). The patients were followed a mean 5.4 years +/- 3.1 (SD) with repeated measurements of urinary albumin excretion before and during 2.6 years +/- 1.0 (SD) of treatment. The blood pressure was depressed by the treatment (systolic blood pressure from 135 mm Hg +/- 8.6 to 124 mm Hg +/- 6.2, NS; mean blood pressure from 107 mm Hg +/- 7.6 to 97 mm Hg +/- 3.4, 2p less than 0.05; diastolic blood pressure from 93 mm Hg +/- 9.1 to 84 mm Hg +/- 3.6, 2p less than 0.05. Albumin excretion decreased (131.0 micrograms/min X/divided by 2.9 [geometric mean X/divided by tolerance factor] to 56.1 micrograms/min X/divided by 3.7, 2p less than 0.02). The mean yearly increase in urinary albumin excretion before treatment was 18 +/- 17 (mean +/- SD). Albumin excretion decreased during treatment: 17% +/- 15 per year (mean +/- SD, 2p less than 0.02). No changes were seen in glomerular filtration rate or renal plasma flow (149 ml/min +/- 5.8 vs 144 ml/min +/- 11.1, and 516 ml/min +/- 31.0 vs 541 ml/min +/- 68.5 respectively [n = 5]).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of antihypertensive treatment on progression of incipient diabetic nephropathy. 390 17

Urinary N-acetyl-beta-D-glucosaminidase (NAG), a proximal tubule lysosomal enzyme, has been used as an indicator of subtle renal injury. Since it has been positively and significantly correlated with hemoglobin A1c and microalbuminuria, it has been suggested that this enzyme may also reflect metabolic control. Albumin excretion is exacerbated in adult diabetic individuals during exercise; such exercise-induced albuminuria may be a forerunner of diabetic nephropathy. Metabolic control, degree of exertion, and duration of diabetes have been suggested to influence this increase in albuminuria during exercise. Studies of children are few and have produced inconsistent results. Thus we studied 28 insulin-dependent diabetic children ranging in age from 5 yr to 16 yr and 27 age-matched controls using treadmill exercise; two exercise periods consisting of (1) graded increases in speed and grade at 3-min intervals until exhaustion and (2) a constant speed and grade necessary to produce 2/3-3/4 maximal heart rate for 30 min were performed. Capillary blood glucose, urinary NAG/creatinine (cr) ratios (UNAG/Ucr) and urinary albumin/creatinine ratio (Ualb/Ucr) were measured before and after each exercise period; hemoglobin A1c was also measured. The latter averaged 11.8 +/- 0.6% (mean +/- SEM); contrary to previous studies, this was not correlated with pre- or postexercise UNAG/Ucr. During both exercise periods, blood glucose dropped 271 +/- 19 mg/dl to 213 +/- 21 mg/dl (period 1) and 230 +/- 22 mg/dl to 157 +/- 21 mg/dl (period 2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of exercise on urinary N-acetyl-beta-D-glucosaminidase activity and albumin excretion in children with type I diabetes mellitus. 405 33

The reactive vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in diabetic patients with clinical signs of nephropathy. In this study, plasma homocysteine was measured in type 1 diabetic patients with normoalbuminuria (n = 22), microalbuminuria (n = 40) and proteinuria (n = 14) in order to investigate whether plasma homocysteine levels are increased already at the stage of incipient nephropathy, i.e. microalbuminuria. Furthermore, patients were characterized according to the degree of retinopathy. Plasma homocysteine in the whole population (n = 76) was related to B-Folate (r = 0.38, p < 0.01), S-Creatinine (r = 0.55, p < 0.001), S-Urea (r = 0.37, p < 0.01), U-Albumin (r = 0.46, p < 0.001), urinary N-acetyl-beta- glucosaminidase (r = 0.40, p < 0.001), systolic blood pressure (r = 0.36, p < 0.01) and diabetes duration (r = 0.44, p < 0.001). There were no differences in plasma homocysteine levels between patients with normoalbuminuria (8.0 +/- 1.7 mumol l-1; mean +/- SD) and those with microalbuminuria (9.1 +/- 3.4 mumol l-1). However, patients with clinical signs of nephropathy had higher plasma homocysteine levels (12.9 +/- 5.7 mumol l-1, p < 0.01) compared to the other two groups. There was no association between plasma homocysteine levels and different degrees of retinopathy. Thus, the present study does not show any relation between plasma homocysteine levels and early stages of diabetic nephropathy or retinopathy indicating that elevated concentrations of plasma homocysteine does not explain the increased risk for atherosclerosis observed in patients with microalbuminuria.
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PMID:Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus. 770 67

Microalbuminuria was determined in the urine of 6 diabetics who had been treated with Insulin for over 30 years an had a normal kidney function. The values gained by the radial immunodiffusion method (VLC--Partigen Albumin) range from 0.001 gr/l to 0.008 gr/l of albumins in the urine. These values are much below the risky ones (over 0.020 gr/l), which signalize the evolution to the macroproteinuria and the development of the diabetic nephropathy. Over 30 years duration of the insulin-dependent diabetes, with no macroproteinuria pretors on the expression of diabetic nephropathy. 5 locus which is known to have the influence on the intensity of the immunological response.
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PMID:[Microalbuminuria in diabetics treated with insulin for more than 30 years]. 786 28

Slightly elevated urinary albumin excretion rate (microalbuminuria) is a marker of early diabetic nephropathy, but it is unclear if the established definition of microalbuminuria (20-200 micrograms/min) is correct for children and adolescents. We investigated the albumin excretion rate, albumin/creatinine ratio and urinary albumin concentration in 150 healthy schoolchildren and adolescents to (a) obtain a reference value for albumin excretion rate, (b) relate albumin excretion to pubertal stages and (c) evaluate albumin/creatinine ratio and morning albumin concentration as screening methods for elevated albumin excretion rate. Albumin concentration was measured by immunoturbidimetry in timed overnight urine samples. The albumin excretion showed a skewed distribution (geometric mean 3.2 micrograms/min, 95 percentile 15.1 micrograms/min). In girls, a peak in the albumin excretion rate was found at the pubertal stage 4 (Tanner) and in boys at stage 5. Albumin/creatinine ratio of 2.5 mg/mmol as a screening level for elevated albumin excretion (15 micrograms/min) showed a high positive (0.88) and negative (0.99) predictive value.
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PMID:Urinary albumin excretion rate and puberty in non-diabetic children and adolescents. 824 47

The direct relationship between elevated glucose concentrations and accelerated protein glycation has implicated increased glycation as a potential mechanistic link between hyperglycemia and the pathogenesis of diabetic nephropathy. Albumin modified by Amadori glucose adducts has been shown to stimulate collagen secretion by mesangial cells in vitro, and to contribute to the overproduction of glomerular mesangial matrix in vivo. To delineate mechanisms responsible for these effects, we examined the influence of glycated albumin on transcriptional activation of the alpha 1 (IV) collagen gene in renal glomerular mesangial cells. These experiments used a stably transfected reporter mesangial cell line that exhibits responses to media manipulations that are directionally parallel with those of non-transformed mesangial cells, and that expresses luciferase driven by 5'-flanking and first intron regions of the alpha 1 (IV) collagen gene. In these cells, purified glycated albumin stimulated collagen IV gene transcription, whereas glucose-free albumin did not. Further, glycated albumin induced a significant increase in mesangial cell collagen IV mRNA, assessed by Northern blot analysis and quantified by calculation of the ratio of collagen IV mRNA to 18S ribosomal RNA after densitometric scanning. The stimulation of collagen gene transcription and mRNA expression were both prevented by monoclonal antibodies known to specifically recognize Amadori-modified albumin. The findings indicate that glycated albumin promotes mesangial cell transcriptional activation and mRNA expression of the alpha 1 (IV) collagen gene and further implicate increased glycated albumin in diabetes in the pathogenesis of diabetic nephropathy.
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PMID:Albumin modified by Amadori glucose adducts activates mesangial cell type IV collagen gene transcription. 858 15

Familial clustering of diabetic nephropathy points to genetic susceptibility. The observation that in non-diabetic subjects microalbuminuria occurs more frequently in the presence of a parental history of diabetes supports this hypothesis. However, the role of inherited factors in poorly understood in non-insulin dependent diabetes mellitus (NIDDM). This study investigated the albumin excretion rate in non-diabetic offspring of NIDDM patients with increased albumin excretion rate (> 20 micrograms/min) or normal albumin excretion rate (< 20 micrograms/min). We recruited 20 offspring of NIDDM patients with increased albumin excretion rate (A-off) and 20 offspring rate (N-off), matched for age, sex, body mass index, blood pressure and estimated protein intake. All offspring were normotensive, had normal creatinine clearance, normal glucose tolerance and sterile urine collection. Albumin excretion rate was measured on three sterile overnight urine collections and median values were used for calculations. Albumin excretion rate was significantly higher in A-off than in N-off (7.7 +/- 1.2 vs 3.4 +/- 0.6 micrograms/min p<0.01) and significantly related to parents' albumin excretion rate (p<0.01, r=0.53). These results suggest that an increased glomerular permeability is present in non-diabetic offspring of NIDDM patients with increased albumin excretion rate.
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PMID:Albumin excretion rate levels in non-diabetic offspring of NIDDM patients with and without nephropathy. 869 Jan 75


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