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 angiotensin-converting-enzyme inhibitors (ACEIs) in the treatment of progressive renal disease is described. Researchers have evaluated the use of ACEIs in patients with two types of progressive kidney disease: diabetic nephropathy and renal insufficiency associated with connective-tissue disease. When introduced early in the course of diabetic nephropathy, ACEIs appear to produce greater reductions in urinary protein concentrations than do other antihypertensive agents, even when systemic blood pressure does not decrease. They also slow the rate of decline of renal plasma flow and glomerular filtration rate. Results are less impressive when ACEIs are initiated at a later stage of disease. Captopril has been shown to be associated with a decline in serum creatinine level in patients with systemic scleroderma, and with reductions in blood pressure and increases in the glomerular filtration rate in patients with systemic lupus erythematosus. Because these patients were receiving other agents that might have influenced study outcome, specific conclusions about the efficacy of ACEIs in connective-tissue disease cannot yet be drawn. They may, however, be recommended as adjunctive agents in treatment of this condition. The relative safety of the ACEIs, combined with their ability to arrest or slow the progression of renal failure, makes them primary options in the management of selected renal diseases.
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PMID:Use of angiotensin-converting-enzyme inhibitors in the management of renal disease. 199 85

Angiotensin carboxypeptidase (ACP) activity has been detected in urine samples from normal subjects and patients with hypertension and diabetes by determining the enzyme's ability to convert angiotensin I to des-Leu angiotensin I. Gel filtration chromatography of a concentrated urine sample indicated that about equal amounts of the enzyme exist as 100 kDa and 500 kDa molecular weight forms, respectively. This ACP activity co-eluted with activity that cleaved histidine from des-Leu angiotensin I to form angiotensin II and activity that cleaved tyrosine from benzyloxycarbonyl-glutamyl-tyrosine (ZGT). These results suggest that the urinary ACP activity is due to cathepsin A as we have reported previously for the porcine kidney enzyme. Analysis of sequential urine samples from a single individual over a 6-day period revealed as much as a 6-fold fluctuation in creatinine-normalized ACP activity. Of five male healthy adult subjects, the creatinine-normalized urinary ACP activity ranged from 1.7 to 3.7 mU/mL with a mean of 2.8 mU/mL. However, five male patients with renovascular hypertension had elevated levels of ACP activity with a mean of 11.6 mU/mL. Of five male patients with diabetic nephropathy, all had elevated ACP activity levels with a mean of 21.0 mU/mL. It is concluded that ACP activity in the urine is due to cathepsin A probably derived from kidney tissue, and that the release is increased in patients with kidney damage. We suggest that urinary ACP activity should be evaluated further for a possible relationship to renal hypertension and as a potentially early marker for diabetic nephropathy.
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PMID:Angiotensin carboxypeptidase activity in urine from normal subjects and patients with kidney damage. 201 86

Microalbuminuria, i.e. elevated urinary albumin excretion rate between 20 and 200 micrograms/min, is a strong predictor of subsequent overt diabetic nephropathy. Screening for microalbuminuria is essential, since it has been shown that development of overt nephropathy can be delayed or even prevented by therapeutic measures such as strict metabolic control, early aggressive antihypertensive treatment, or restriction of protein intake. Several urine collection methods for the measurement of microalbuminuria have been proposed. In a prospective study with 40 diabetic outpatients we have compared albumin excretion in urine collected over 24 h, during a timed overnight period, and in a spot urine sample collected at random while the patient attended the outpatient clinic. In addition, the reproducibility of the three urine collection methods was assessed. For this purpose, each patient underwent 3 consecutive collections at an interval of at least 4 weeks. Our data indicate that calculation of an albumin/creatinine quotient in a spot urine probe is a reliable screening test for microalbuminuria. If this quotient is increased (greater than 2), timed overnight collection should be performed.
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PMID:[The practical assessment of micro-albuminuria as a marker for beginning diabetic nephropathy in: which urine sampling method?]. 202 35

The serum concentration of laminin P1 fragment was determined in various histologically proven renal diseases by a competitive radioimmunoassay directed against the pepsin-resistant fragment P1. The serum laminin P1 fragment level of healthy subjects (n = 71) was 1.35 +/- 0.19 U/ml. Serum levels of laminin P1 fragment in patients with minimal change nephrosis in the remission phase and those with IgA nephropathy showed no significant difference when compared with healthy controls. However, patients with minimal change nephrosis in the nephrotic phase, membranous glomerulonephritis, diabetic nephropathy, lupus nephritis and renal cell carcinoma showed significantly higher levels (P less than 0.01) of serum laminin P1 fragment. No correlation was observed between serum laminin P1 fragment level and creatinine clearance. These results suggest that changes in serum laminin P1 fragment level could be used to indicate alterations in glomerular basement membrane metabolism in renal disease.
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PMID:Serum laminin P1 fragment concentration in renal diseases. 202 84

For the early diagnosis of diabetic nephropathy, it is best to use the albumin excretion rate (AER). However, it is a complicated test to perform in the outpatient setting, and it is sometimes affected by inaccurate urine collection. Therefore, we have used the albumin/creatinine ratio, which is measured simply with randomly collected urine, for evaluation of microalbuminuria and found it to be of equal diagnostic value to the AER. The AER, albumin/creatinine ratio, and creatinine excretion rate were measured in 86 patients with NIDDN who were negative for proteinuria. Urine was obtained after bed rest and in the outpatients department (without rest). 1) The reproducibility of time-restricted urine sampling was investigated using the rate of creatinine excretion. The mean coefficient of variation was found to be 42%, and inaccurate urine sampling appeared to cause variation in the AER. 2) The AER and albumin/creatinine ratio obtained in the outpatient setting were higher than those after bed rest, and urine collection at the time of outpatient examination was considered to be more useful than that after bed rest. To check variations in urine collection at the time of outpatient examination, the albumin/creatinine ratio in random urine samples was superior on the basis of the correlation coefficients to urine obtained after bed rest. 3) The urinary creatinine excretion rate showed a significant sex difference (males: 0.823 +/- 0.152 mg/g. creat., females: 0.577 +/- 0.194 mg/g. creat) (p less than 0.001), but there was no significant difference for BMI and age. The relationship between each level of microalbuminuria and the creatinine excretion rate did not change significantly. 4) The following formula was used to calculate the albumin/creatinine ratio corresponding to the AER. Albumin/creatinine ratio formula; (see text) An AER of 30 micrograms/min thus corresponds to an albumin/creatinine ratio of 36 mg/g. creat. for males and 51 mg/g. creat. for females. 5) The percentage of positive results for microalbuminuria in patients with NIDDM showed that the albumin/creatinine ratio and the AER were equal as diagnostic criteria, when the sex difference was taken into consideration. Thus, the albumin/creatinine ratio is equal to the AER for evaluation of microalbuminuria, and it is a simple and convenient test to use in daily clinical practice.
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PMID:[Clinical evaluation of the albumin/creatinine ratio in outpatients with diabetes]. 206 14

Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin excretion in relation to urinary prostaglandins (PGs) excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Captopril (37.5 mg/day) was orally administered to 13 diabetic patients for an eight-week period. A single administration of captopril (12.5 mg) was performed in the same patients. The spot urine samples were collected in the early morning and 2 hr after the single administration of captopril. The albumin index (mg/gram-creatinine) was markedly decreased in eight patients (Group A) within four weeks, but no decrease was found in five patients (Group B). Furthermore, in Group A, by the single administration of captopril urinary excretions of 6-keto-PCF1 alpha (a stable metabolite of PGI2) and PGE2 were significantly (p less than 0.05) increased while urinary TXB2 (a stable metabolite of TXA2) excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio, which is significantly (p less than 0.05) low in diabetic patients was significantly (p less than 0.01) increased up to the normal value in Group A. In Group B, however, there were no significant changes in urinary PGs excretion. These results suggest that captopril enhances the production of intrarenal vasodilatory PGs such as PGI2 and PGE2, which may be deeply involved in the reduction of intraglomerular capillary pressure and urinary protein excretion in diabetic patients.
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PMID:Effects of captopril on urinary excretion of albumin and prostaglandins in patients with diabetic nephropathy. 209 82

Pravastatin, a novel inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, was administered to nine hypercholesterolemic patients with diabetes mellitus to examine its effects on diabetic nephropathy. Pravastatin treatment resulted in lowering serum total cholesterol by 22.1% on the average (p less than 0.001), and led to a significant reduction in urinary excretion of albumin and beta 2-microglobulin in patients with an elevated urinary protein excretion rate at the baseline period. But glycemic control, blood pressure, urinary excretion of creatinine and that of N-acetyl-beta-D-glucosaminidase showed no significant change during the study. These results suggest that reduction of atherogenic lipids and lipoproteins with pravastatin could alleviate diabetic glomerular injury.
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PMID:Amelioration of proteinuria with pravastatin in hypercholesterolemic patients with diabetes mellitus. 212 49

Early diabetes mellitus is characterized by an increase in glomerular filtration rate and effective renal plasma flow which may initiate and potentiate glomerular injury which ultimately results in diabetic nephropathy. To investigate the role of hyperglycemia per se in mediating these hemodynamic changes, eight healthy adults had inulin clearance, creatinine clearance, and para-aminohippurate (PAH) clearance after steady state conditions of hyperglycemia were achieved (549 +/- 86). Clearances were repeated during equivalent osmotic diuresis with Mannitol. Euvolemia was maintained by quantitative fluid and electrolyte replacement of urinary losses. Mean inulin clearances were 87 +/- 6, 87 +/- 5, and 81 +/- 4 ml/min during control, glucose, and mannitol periods (p = ns). Creatinine clearance overestimated inulin clearance by 15-32% but there were no differences between control glucose and mannitol periods. PAH clearance fell from control values of 595 +/- 29 to 340 +/- 22 ml/min during hyperglycemia (p less than .05). During osmotic diuresis with mannitol PAH, clearance rose to control values. In vitro studies excluded the possibility that conjugation between glucose and PAH can explain the clearance results. These results in normal subjects documenting renal vasoconstriction with hyperglycemia are of particular interest in view of recent experimental data suggesting that failure to vasoconstrict characterizes the hemodynamics of early diabetes.
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PMID:Effects of hyperglycemia and mannitol infusions on renal hemodynamics in normal subjects. 212 74

The effects of atrial natriuretic peptide (ANP) on urinary protein excretion were examined in patients with renal parenchymal diseases (RPD, n = 18) and those with diabetes mellitus (DM, n = 12). Before and 30 min after intravenous injection of ANP (50 micrograms), urine samples were collected. ANP injection increased urinary volume and urinary sodium excretion in both groups. In RPD, urinary protein excretion (UprV) increased by 87% (1.5 +/- 0.7 [SEM] to 2.8 +/- 1.1 mg/min, p less than 0.05). ANP also increased UprV in patients with diabetic nephropathy [N(+); 1.7 +/- 0.8 to 5.0 +/- 2.5 mg/min, p less than 0.05] and those without nephropathy [N(-); 0.10 +/- 0.02 to 0.22 +/- 0.07 mg/min, p less than 0.05]. Since ANP increased creatinin clearance in both groups (+9.4 +/- 2.5 ml/min in RPD and +24.1 +/- 3.5 ml/min in DM, p less than 0.01 for both), urinary protein to creatinine excretion ratios (UprV/UcrV) were determined, which should be a parameter of glomerular protein permeability. The UprV/UcrV ratio increased by 48% (p less than 0.01) and 24% (p less than 0.05) in RPD and in DM, respectively. ANP did not change urinary composition of albumin and globulin. In RPD, increases in UprV by ANP were positively related to the basal serum creatinin levels (r = 0.57, p less than 0.01). In DM group, ANP-induced increases in the UprV/UcrV ratio were higher in the N(+) subgroup than in the N(-) subgroup (+0.8 +/- 0.4 vs +0.09 +/- 0.04, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effects of atrial natriuretic peptide on urinary protein excretion in patients with renal parenchymal disease and those with diabetic mellitus]. 214 Oct 91

The prevalence of microalbuminuria and persistent proteinuria was studied in a population of 801 diabetic patients (535 with type II and 266 with type I diabetes). Urinary albumin excretion rate (AER) was measured on morning samples by laser nephelometry. Normoalbuminuria, as defined, in the absence of contaminated urine, by an albumin: creatinine (A/C) ratio below 2, was found in 551 patients, microalbuminuria (NC greater than or equal to 2 with AER below 200 mg/l) in 190 patients and persistent proteinuria (AER greater than or equal to 200 mg/l) in 60 patients. Microalbuminuria was present in 48 (18 p. 100) IDDM patients and 142 NIDDM patients. In IDDM patients, AER increased with the duration of the disease with no apparent influence of age at the onset. The prevalence of hypertension was 25 p. 100 and 61 p. 100 in IDDM patients with microalbuminuria and macroproteinuria respectively versus 10 p. 100 in patients with normoalbuminuria. This prevalence increased in NIDDM patients from 39.3 p. 100 with normoalbuminuria to 40.8 p. 100 and 76.2 p. 100 with microalbuminuria or macroproteinuria respectively. Proliferative retinopathy in type I and type II patients with normal AER was 7.4 p. 100 and 1.2 p. 100 respectively increasing to 15.2 p. 100 and 8.9 p. 100 with microalbuminuria and 27.8 p. 100 and 23.1 p. 100 with macroproteinuria. The prevalence of coronary disease increased from 4 to 10.4 p. 100 in patients with type I diabetes and microalbuminuria. The prevalence of cardiac failure increased from 1.5 to 2.1 p. 100 in type I diabetics and from 3.2 to 7.8 p. 100 in type II diabetics in the presence of microalbuminuria. Patients with microalbuminuria had increased levels of glycosylated hemoglobin A 1C but statistical difference was only obtained for patients with type II diabetes. Routine analysis of AER in diabetics allows early detection of diabetic nephropathy and emphasizes the need for tight metabolic and blood pressure control. Hypertension can be detrimental to nephropathy but might also initiate renal lesions in NIDDM patients.
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PMID:[Microalbuminuria and diabetic nephropathy. Detection and correlation with other degenerative complications]. 214 8


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