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 urinary excretion of retinol-binding protein (RBP) was studied in 101 insulin-dependent diabetic patients allocated to three groups according to 24-h urinary albumin excretion rate (UAE) (median of three urine collections): group 1 (n = 45), normal UAE less than 30 mg/24 h; group 2 (n = 27), microalbuminuria (UAE 30-300 mg/24 h); and group 3 (n = 29), clinical diabetic nephropathy (UAE greater than 300 mg/24 h). We used 23 healthy subjects as controls. Fractional clearance of RBP (FC-RBP) and its 24-h urinary excretion rate (URBP) were higher in each diabetic group than in healthy subjects, the highest values being found in group 3. Groups 1 and 2 did not differ in URBP and FC-RBP. There was a correlation between FC-RBP and haemoglobin A1c in both the total diabetic cohort (P less than 0.001) and in diabetic patients in groups 1 and 2 with a glomerular filtration rate of more than 90 ml/min (P less than 0.05). No correlation was found between FC-RBP and UAE and/or duration of diabetes in any of the diabetic groups. We conclude that the increased urinary excretion of RBP, indicating proximal tubular dysfunction, is already present in normoalbuminuric insulin-dependent diabetic patients and correlates with metabolic control. Further deterioration in proximal tubular function was not observed in microalbuminuric patients, but is a late event in clinical diabetic nephropathy.
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PMID:Urinary excretion of retinol-binding protein in type 1 (insulin-dependent) diabetic patients with microalbuminuria and clinical diabetic nephropathy. 157 56

A sensitive latex particle assay has been developed to study the occurrence of protein 1 in human urine. The coefficients of variation (CVs) of the method which is fully automated vary between 3 and 11.5%. The assayable concentration range is 0.3 to 40 micrograms/l. Protein 1 is clearly a sex-dependent protein. In contrast to urinary retinol-binding protein (RBP) which shows no variation with age or sex, protein 1 is excreted in greater amounts in males from the puberty. In adults, the mean concentration of protein 1 in urine of men is approximately 5 times that of women. In the urine from both sexes, protein 1 occurs as a single component with a Mr around 21,000 and an pI of about 4.8. Protein 1 is correlated with RBP in the urine from female or male patients with impaired proximal tubular function, which suggests that it is handled by the kidney in a similar manner as RBP. Diabetics, however, show elevations of urinary protein 1 which do not correlate with the RBP excretion but with the albuminuria. A competition between albumin and protein 1 for renal tubular uptake might explain this paradoxical behaviour of protein 1 in the course of diabetic nephropathy.
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PMID:Determination by latex immunoassay of protein 1 in normal and pathological urine. 175 96

The nature and origin of proteinuria in diabetes mellitus have been investigated by measuring the urinary excretion of seven specific proteins of low (beta 2-microglobin, retinol-binding protein) or high molecular weight (albumin, transferrin, hemopexin and IgG). Using the Alcian Blue binding test, we also measured negative charges on red blood cell (RBC) membrane which according to recent studies might mirror the glomerular polyanion charge. A group of 190 diabetics was examined, including 90 patients with type I diabetes, 23 type II diabetics treated with diet and/or hypoglycaemic agents and 77 longstanding type II diabetics requiring insulin therapy. With the exception of beta 2-microglobulin all proteins measured were excreted in the urine of diabetics in significantly higher amounts than in controls. The assay of transferrin proved the most sensitive (58% positive) followed by albumin (49%), IgG (34%), hemopexin (28%) and retinol-binding protein (26%). Practically the same ranking was obtained when only type I diabetics were considered. RBC membrane negative charges were diminished in diabetics and negatively correlated with the urinary excretion of albumin (r = -0.61, n = 190). RBC charges were also negatively correlated with other urinary proteins of high molecular mass (r between - 0.5 and - 0.2) but presented no relation with urinary beta 2-microglobulin or retinol-binding protein. The loss of RBC charges in diabetics most likely reflects the concomitant depletion of the glomerular polyanion responsible for the increased glomerular leakage of high molecular mass plasma proteins. The preferential increase in transferrin excretion together with the progressive rise in the urinary excretion of IgG lead us to postulate that the loss of glomerular polyanion in diabetes is accompanied, from the early stage, by a progressive decrease in the size-selectivity of the glomerular filter. The urinary excretion of retinol-binding protein was weakly correlated with albuminuria (r = 0.26, n = 186). Eight % of diabetics showed an elevation of urinary retinol-binding protein without evidence of microalbuminuria, which clearly demonstrates that a proximal tubular impairment can occur independently of the glomerular alterations in the course of diabetic nephropathy.
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PMID:Urinary proteins and red blood cell membrane negative charges in diabetes mellitus. 225 3

Urinary excretion of the retinol-binding protein (RBP) was studied in 36 insulin-dependent diabetics with serum creatinine concentrations within the normal range and no microalbuminuria. The excretion was significantly (p less than 0.05) higher in the diabetics as compared to a group of apparently healthy persons. The diabetes control indices HbA1 and serum fructosamine showed no correlation to the rate of urinary RBP excretion. The present data support the idea that tubular dysfunction may be an early symptom of diabetic nephropathy.
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PMID:Increased urinary excretion of the retinol-binding protein in insulin-dependent diabetes mellitus in the absence of microalbuminuria. 343 68

A radioimmunoassay has been developed for the measurement in urine of retinol-binding protein (alpha 2-microglobulin) and used as an index of renal tubular function in adult Type 1 (insulin-dependent) diabetics and to define reference ranges in non-diabetic controls. There was a significantly greater excretion (P less than 0.001) of retinol-binding protein in the diabetic group compared to the controls in both overnight and daytime samples. There was a weak positive correlation with albumin excretion (r = 0.33; P less than 0.01) but no correlation with HbA1, duration of diabetes or arterial blood pressure. The results indicate that retinol-binding protein excretion may be increased in diabetic subjects without increased albumin excretion. The possibility therefore exists that renal tubular damage may occur early in diabetic nephropathy without apparent glomerular dysfunction.
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PMID:Retinol binding protein as a small molecular weight marker of renal tubular function in diabetes mellitus. 366 97

Although the protein leak of early diabetic nephropathy is said to be purely a glomerular lesion, there is still controversy as to the existence of a tubular component. We have, therefore, assessed the urine of insulin-dependent diabetics for tubular proteinuria as a feature of early diabetic nephropathy. The urine of 25 patients with increased albumin excretion rate was analyzed by sodium dodecyl polyacrylamide gel electrophoresis. One patient showed high molecular weight proteinuria, 2 showed low molecular weight proteinuria and 2 patients showed both low and high molecular weight proteinuria. The urine was also analyzed for 3 tubular proteins by single radial immunodiffusion. No patient showed elevated beta-2-microglobulin, but alpha-1-microglobulin (A1M) (corrected for creatinine excretion) was elevated in 3 out of 25 patients including 2 of the 4 patients with a low molecular weight pattern. One of the patients with raised A1M also had raised retinol-binding protein concentration. We conclude that, in early diabetic nephropathy, proteinuria can have a proximal tubular, as well as a glomerular, component.
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PMID:Low molecular weight proteinuria in insulin-dependent diabetes. 374 42

Two groups of patients with insulin-dependent diabetes mellitus of > 10 years duration and either persistent normoalbuminuria (group 1, n = 49; albumin excretion < 30 mg/day) or microalbuminuria (group 2, n = 33; albumin excretion 30-300 mg/day) were investigated for evidence of free oxygen radical activity (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl-glucosaminidase and leucine aminopeptidase) were also measured. Healthy controls (n = 38) were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum cholesterol and creatinine were similar in all three groups. Free-radical activity and oxidant injury were significantly higher in groups 1 and 2 than in controls (p < 0.001). Glomerular proteinuria, tubular proteinuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p < 0.01). Group 1 had significantly higher transferrinuria, tubular enzymuria and tubular proteinuria than controls. However, groups 1 and 2 were similar in degree of free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damage accompany and may even precede microalbuminuria. The presence of these abnormalities in the absence of glomerular proteinuria favours the hypothesis that alterations first occur in the peritubular microcirculation, which by causing oxidant injury and tubular damage, may initiate diabetic nephropathy.
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PMID:Evidence of oxidant injury and tubular damage in early diabetic nephropathy. 798 55

1. Diabetic nephropathy is a serious microvascular complication in patients with insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30-45% of such patients. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and free-radical activity may be important factors. 2. Forty normotensive patients with insulin-dependent diabetes mellitus of between 10 and 20 years duration with persistent normoalbuminuria (albumin excretion < 30 mg/day) and normal renal function were investigated for markers of endothelial dysfunction (plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity), free oxygen radical generation (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. 3. Patients were divided into two groups. Group 1 comprised 21 patients with elevated markers of endothelial dysfunction, and group 2 comprised 19 patients with normal levels of plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty-eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and 2 were similar in age, sex, body weight, duration of diabetes mellitus and recent glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria were similar in the three groups. Group 1 patients had significantly increased oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients and control subjects (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus. 828 43

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

We studied 24-h ambulatory blood pressure (SBP, DBP), actual glycemic control assessed from seven blood glucose measurements, 16-h daytime and 8-h nighttime urinary excretion of albumin (UAE) and retinol-binding protein (URBP) in 20 normoalbuminuric (group A, nighttime UAE < 20 micrograms/min) and 20 microalbuminuric and low-proteinuric type I diabetic patients (group B, nighttime UAE 20-500 micrograms/min) matched for age and diabetes duration. Glycemic control was similar in the two groups. Daytime and nighttime SBP and DBP were higher in group B compared to group A (p < 0.01). Nighttime decrease in SBP and DBP correlated with nighttime decrease in UAE in group B (p < 0.05, p < 0.001), but not in group A. There was no correlation between BP and actual glycemic control in either group. We found higher daytime and nighttime URBP in group B compared to group A (p < 0.05). We conclude that, in microalbuminuric and low-proteinuric patients, daytime and nighttime BP was elevated but still in the normal or borderline range, and nighttime decrease in BP correlated with nighttime decrease in UAE but not with actual glycemic control. Increased URBP in these patients suggests slightly impaired proximal tubular function in early stages of diabetic nephropathy.
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PMID:24-h ambulatory blood pressure, daytime and nighttime urinary albumin and retinol-binding protein excretion in type I diabetic patients. 857 35


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