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)

1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity. 2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects. 3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean +/- SEM, 0.26 +/- 0.12 mmol of Li+ h-1 (l of cells)-1] was not significantly higher than in the uncomplicated diabetic patients [0.27 +/- 0.03 mmol of Li+ h-1 (l of cells)-1] or in the normal control subjects [0.25 +/- 0.02 mmol of Li+ h-1 (l of cells)-1]. 4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax. 5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes. 6. The characteristic kinetic changes in sodium-lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes.
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PMID:Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy. 131 15

Angiotensin-converting enzyme (ACE) inhibitors decrease albuminuria in patients with diabetic nephropathy. To study the change in albuminuria in relation to changes in systemic and renal hemodynamics, nine normotensive patients with type 1 (insulin-dependent) diabetes mellitus and persistent proteinuria were given a single oral dose of 25 mg of the ACE inhibitor captopril. Blood pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and albumin excretion rate (AER) were measured in two periods of 40 minutes before and in four periods of 40 minutes after administration of captopril. A constant water diuresis was maintained. Blood pressure did not decrease significantly (130/79 +/- 4/3 v 124/74 +/- 4/3 mm Hg; mean +/- SEM), median AER decreased from 403 (interquartile range [IQR], 812) micrograms/min to 333 (707) micrograms/min (P < 0.01). GFR did not change (123 +/- 13 v 117 +/- 14 mL/min), but ERPF increased significantly from 609 +/- 56 to 714 +/- 55 mL/min (P < 0.01). Consequently, the filtration fraction (FF; quotient of GFR and ERPF) decreased from 0.20 +/- 0.014 to 0.17 +/- 0.014 (P < 0.01). A strong correlation was found between the decrease of AER and the decrease of FF (rs = 0.75; P < 0.02). No correlation was found between the decrease in AER and changes in GFR or blood pressure. In the normotensive patient with diabetic nephropathy, captopril causes an acute reduction of AER, which is probably mediated by a lowering of the intraglomerular pressure.
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PMID:Captopril acutely lowers albuminuria in normotensive patients with diabetic nephropathy. 146 82

The objective was to study the natural history and the predictive value of glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c for diabetic nephropathy. A cohort of 75 type-1 diabetic adolescents with a diabetes duration of 8 years was studied. Thirty-one females, 33 males, mean age 16.9 +/- 0.3 (SEM) participated in the follow-up study. Glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c were measured every second year during 8 years to determine the predictive value of glomerular filtration rate for future nephropathy. Initial differences and patterns of changes in glomerular filtration rate, albumin excretion rate, and hemoglobin A1c were examined in patients who did (group 1) and did not (group 2) develop incipient or overt nephropathy. Five of 64 patients developed overt nephropathy. They had an initial glomerular filtration rate of greater than 125 ml/min/1.73 m2. Fifteen of 53 initially normoalbuminuric patients developed incipient and three of 53 overt nephropathy. Age, age at onset, diabetes duration, initial albumin excretion rate, initial blood pressure, and hemoglobin A1c were similar in groups 1 and 2. Glomerular filtration rate was initially higher in group 1 than in group 2 (P = 0.01). The positive predictive value for combined incipient and overt nephropathy of an initial glomerular filtration rate greater than 125 ml/min was 53%. The negative predictive value of glomerular filtration rate less than 125 ml/min was 95%. In initially normoalbuminuric patients multiple regression revealed initial glomerular filtration rate as the only significant independent predictor for nephropathy when also corrected for hemoglobin A1c (P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased glomerular filtration rate as a predictor of diabetic nephropathy--an 8-year prospective study. 151 4

The present study was conducted on 8 patients with advanced diabetic nephropathy who showed a significant reduction of proteinuria through ACE inhibition. Camostat mesilate, one of the most potent protease inhibitors developed for oral use, was administered to these patients at a daily dose of 600 mg starting after 4 weeks of ACE inhibitor administration. Laboratory data were obtained 1) just before the ACE inhibition, 2) after 4 weeks of the ACE inhibitor single treatment, and 3) after another 4 weeks of the additional treatment with camostat mesilate. The urinary protein excretion decreased from 1) 10.1 +/- 1.3 to 2) 7.3 +/- 1.1, and 3) 4.6 +/- 0.9 g/day [mean +/- SEM; significance of difference 1)-2), p less than 0.05; 2)-3), p less than 0.01], and the serum total protein values increased from 1) 5.0 +/- 0.3 to 2) 5.2 +/- 0.2, and 3) 5.4 +/- 0.3 g/dl [1)-3), p less than 0.05]. The plasma levels of fibrinogen, and of E fragment and D-dimer of FDP changed from 1) 476 +/- 43 to 2) 477 +/- 41, and 3) 374 +/- 33 mg/dl [2)-3), p less than 0.01], from 1) 125 +/- 19 to 2) 147 +/- 27, and 3) 104 +/- 30 ng/ml [2)-3), p less than 0.05], and from 1) 261 +/- 60 to 2) 272 +/- 86, and 3) 185 +/- 56 ng/ml [2)-3), p less than 0.05], respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-proteinuric and anti-coagulatory effects of camostat mesilate in azotemic diabetics. 163 86

Although angiotensin-converting enzyme (ACE) inhibitors may lower urinary protein excretion, it is not known whether these agents can completely eliminate microalbuminuria. This study examined whether the ACE inhibitor, enalapril, can abolish low levels of microalbuminuria in diabetic patients. Six men with adult-onset, insulin-dependent diabetes mellitus, most of whom had low levels of microalbuminuria, were studied in a clinical research center, where they ate a controlled diet and performed regulated exercises daily. After 2 weeks of baseline measurements, the patients received 5-15 mg/day of enalapril for 4 weeks. They were then monitored for 2 more weeks without enalapril. Urinary albumin excretion (UAE) fell in each patient with enalapril treatment and was within the normal range at some time during enalapril treatment in 5 of 6 patients. After stopping enalapril, UAE rose. UAE was 53.6 +/- 20.7 (SEM), 31.5 +/- 8.9 and 39.4 +/- 8.0 mg/24 h during the baseline, enalapril and postenalapril periods, respectively (baseline vs. enalapril, p less than 0.02; postenalapril vs. enalapril, p less than 0.01). The magnitude of fall in UAE correlated with the baseline UAE (r = 0.90). During enalapril treatment, renal plasma flow and GFR did not change, although blood pressure fell slightly. These data suggest that enalapril can reduce or abolish UAE in diabetic patients with microalbuminuria. Whether long-term treatment with enalapril will continue to suppress microalbuminuria and prevent progressive diabetic nephropathy remains to be determined.
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PMID:Enalapril reduces albumin excretion in diabetic patients with low levels of microalbuminuria. 207 3

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

We studied the effects of perindopril, an angiotensin converting enzyme (ACE) inhibitor administered during 12 months, on creatinine clearance, albuminuria and glycaemic control in diabetic subjects with mild to moderate hypertension. After 1 month placebo, 40 insulin-treated patients were divided into 3 groups based upon their urinary albumin excretion rate. Group 1 had a normoalbuminuria (less than 15 mg/24 h), group II had a microalbuminuria (15-150 mg/24 h) and group III had a macroproteinuria (greater than 150 mg/24 h and Albustix +). They were given perindopril 4 to 8 mg orally once daily, and received a stable diet. Diastolic blood pressure was normalized within the first 3 months in 80% of the patients. From these, 28 (14.7 and 7 from groups I, II and III respectively) were followed during a total active treatment period of 12 months. They were matched for age, duration of diabetes and hypertension, systolic and diastolic blood pressures, daily insulin dose, postprandial plasma C-peptide and quality of glycaemic control. Mean supine diastolic blood pressure was decreased by 15 and 18% at 1 and 12 months respectively. Heart rate was not significantly modified. At 3 months, plasma ACE activity was nearly totally inhibited while plasma renin activity was markedly increased. In patients of group II, microalbuminuria was reduced from 66 +/- 13 (mean +/- SEM after placebo) to 39 +/- 6 mg/24 h after 1 month perindopril and this effect was maintained at 12 months. In group I, albuminuria remained within the normal range. In group III, macroproteinuria was not consistently modified by perindopril. Creatinine clearance did not change and glycaemic control remained stable throughout the study in the 3 groups. No major side effects were observed. We conclude that perindopril normalizes blood pressure in a large majority of hypertensive diabetic patients without affecting the quality of diabetes control. It also induces a marked and sustained reduction of microalbuminuria in patients at risk of developing diabetic nephropathy.
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PMID:[Long-term decrease of microalbuminuria after one year of treatment with perindopril in hypertensive diabetic patients]. 228 20

Camostat mesilate is a developed derivative of gabexate mesilate for oral administration and is known to be one of the most potent protease inhibitors. We administered this drug to 15 patients with advanced diabetic nephropathy at a daily dose of 600 mg for 4 to 6 weeks. All patients had been treated with conventional therapy including angiotensin-converting enzyme inhibitors, and their diseases had stabilized for at least 2 weeks before the camostat mesilate therapy. Urinary protein excretion decreased promptly from 4.8 +/- 0.6 to 2.9 +/- 0.4 gm/day (mean +/- SEM, p less than 0.01) and serum albumin level increased from 2.7 +/- 0.2 gm/dl to 2.9 +/- 0.2 gm/dl (mean +/- SEM, p less than 0.05) within 4 to 6 weeks. The amount of plasma fibrinogen significantly decreased from 419.7 +/- 42.3 mg/dl to 306.6 +/- 28.3 mg/dl (mean +/- SEM, p less than 0.01), and urinary total fibrinogen degradation product excretion over 24 hours also decreased from 26,118 +/- 9,696 to 18,072 +/- 7,107 micrograms/day (mean +/- SEM, p less than 0.05). The value for serum creatinine level did not change during this intervention. We suggest that camostat mesilate suppresses the hypercoagulable state originating from diabetes mellitus, and changes the permselectivity of the glomerular capillary wall. These effects of camostat mesilate may improve the prognosis of diabetic nephropathy.
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PMID:Effect of camostat mesilate for the treatment of advanced diabetic nephropathy. 239 38

In a study of the effect of a low-protein diet on the progression of renal disease 19 insulin-dependent diabetic patients with persistent clinical proteinuria were observed for 12-39 (mean 29) months while they were on a normal-protein diet (1.13 [0.06] g/kg per day), then for 12-49 (mean 33) months on a low-protein diet (0.67 [0.03] g/kg per day). The low-protein diet had no adverse effect on nutrition or glycosylated haemoglobin concentration. Mean supine blood pressure (BP) fell slightly on the low-protein diet and was probably due to the start or modification of antihypertensive medication in 9 patients. The mean rate of decline in glomerular filtration rate fell from 0.61 (SEM 0.14) ml/min per month with the normal-protein diet to 0.14 (0.08) with the low-protein diet, and this effect remained highly significant after adjustment for blood pressure, energy intake, and glycosylated haemoglobin. The rise in the fractional clearance of albumin during a normal-protein diet stopped with the low-protein diet, and there was a significant fall in albumin excretion from 467 (95% CI 234-895) micrograms/24 h on the normal-protein to 340 (138-719) on the low-protein diet. Thus, a low-protein diet, with its reduction in protein and possibly other dietary components such as phosphate or fat, seems to retard the rate of decline of glomerular filtration rate in diabetic nephropathy independently of blood pressure changes and glycaemic control.
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PMID:Restriction of dietary protein and progression of renal failure in diabetic nephropathy. 196 36

In a double-blind, randomized, cross-over study in 23 diabetic patients, insulin treated (N = 11) or noninsulin treated (N = 12), with mild to moderate hypertension, the hypotensive effects of captopril and atenolol were compared. Five patients had overt diabetic nephropathy. All patients received 50 mg twice daily of either drug. Treatment periods lasted 6 weeks and were preceded and separated by a placebo period. Two patients dropped out, one because of intermittent claudication during atenolol, one with cardiac arrhythmia during placebo. Blood pressure was reduced from 165 +/- 5/96 +/- 1 to 154 +/- 5/89 +/- 2 mmHg (mean +/- SEM: P less than 0.01) during captopril and from 171 +/- 5/98 +/- 1 to 159 +/- 6/89 +/- 2 mmHg (P less than 0.01) during atenolol. These antihypertensive effects are not significantly different. There was a wide inter- and intraindividual variation in hypotensive response to both drugs, which may have important consequences for treatment strategies. No consistent differences between insulin and noninsulin treated patients were seen. Parameters of glycemic control did not change during any therapy, neither in insulin treated nor in non-insulin treated patients. Albuminuria and renal function did not change. During captopril treatment one patient complained of a non-productive cough. Two patients experienced a severe hypoglycemic reaction during atenolol. No other major side-effects were seen. In conclusion, this study showed equal hypotensive effectivity of 100 mg captopril and 100 mg atenolol daily in hypertensive diabetics, without evident effect on glycemic control.
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PMID:A comparison of the hypotensive effects of captopril and atenolol in the treatment of hypertension in diabetic patients. 265 75


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