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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In light of the growing understanding of the toxic effects of glycated albumin and of the preferential excretion of this substance, the excretion of glycated albumin could be considered a physiologic function of the kidney. Furthermore, if the increased load of glycated albumin in diabetic patients results in glycated albumin excretion rates in the range of 20 to 200 microg/min, might this not be considered "physiologic microalbuminuria"? The hypothesis is presented that microalbuminuria composed of glycated albumin is a homeostatic renal function. Although some proteins are glycosylated for their normal physiologic function, many proteins are glycated nonenzymatically according to ambient blood glucose. Albumin is subject to nonenzymatic glycation in all humans, but at increased rates in diabetic patients. Glycated albumin induces changes in the microvasculature and glomerulus that may lead to endothelial dysfunction and diabetic nephropathy, respectively. Renal excretion of glycated albumin is enhanced compared with native albumin. To explore this potential homeostatic function of the kidney, patients with impaired renal function were studied to determine whether glycated albumin accumulates. Plasma levels of glycated albumin were determined in diabetic and nondiabetic patients on hemodialysis. Hemoglobin A1c was used as an index of the rate of nonenzymatic glycation of proteins. Hemoglobin A1c was increased in the diabetic subjects but was normal in the nondiabetic group (7.9% +/- 0.5% v 6.2% +/- 0.2%, respectively; P < 0.01). On the other hand, the glycated albumin was elevated in both groups and was not significantly different between them (1.95% +/- 0.15% in the diabetic patients v 1.75% +/- 0.14% in the nondiabetic patients; P = NS). The results of this study provide the first clinical evidence supporting the hypothesis that the excretion of glycated albumin is a homeostatic renal function.
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PMID:Accumulation of glycated albumin in end-stage renal failure: evidence for the principle of "physiological microalbuminuria". 871 23

Based on animal experiments it has been proposed that antihypertensive agents may differentially influence albuminuria through their divergent effects on glomerular haemodynamics or glomerular sieving properties and may beneficially influence the progression of diabetic nephropathy even without an effect on blood pressure. However, to date this hypothesis has not been tested in normotensive patients with diabetic nephropathy. The main aim of this study was therefore to investigate the effects of the administration of two antihypertensive agents on albuminuria during rest and exercise. The study consisted of 3 x 3 randomised, cross-over periods with five days double blind administration of enalapril (E: 2.5 mg bid), nitrendipine (N: 5 mg bid) and placebo (P) on 18 Type 1 normotensive (blood pressure < 140/90 mmHg) diabetic patients with incipient diabetic nephropathy (albuminuria 30-300 mg/24 h, normal glomerular filtration rate, diabetes duration > 6 years and presence of diabetic reinopathy. The aim of this study was to investigate the effect of enalapril and nitrendipine on blood pressure values and albuminuria during exercise challenge (bicycle ergometry: 20 min at 75 W and 20 min at 100 W) in comparison to the placebo. Albumin excretion rates during pre-exercise rest (mean +/- SD; E: 6.2 +/- 6.0; N: 7.1 +/- 8.0; P: 7.7 +/- 7.0 mg/mmol creatinine) and during exercise (E: 8.7 +/- 9.4; N: 8.2 +/- 8.2; P: 11.1 +/- 11.4 mg/mmol creatinine) were comparable between the drugs and not significantly different after administration of placebo. Blood pressure values were significantly different between the medications (systolic blood pressure: p = 0.0269; diastolic blood pressure: p = 0.0021, ANOVA for repeated measurements). There were no significant correlations between blood pressure values and albuminuria at any time. In normotensive patients with incipient diabetic nephropathy low-dose administration of enalapril, nitrendipine and placebo does not result in clear cut differences in albuminuria.
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PMID:Effects of enalapril and nitrendipine on exercise albuminuria in normotensive type I diabetic patients with incipient nephropathy. 893 14

Albumin modified by Amadori glucose adducts, formed in increased amounts in diabetes, stimulates the synthesis of matrix by renal glomerular mesangial cells and has been causally linked to the pathogenesis of diabetic nephropathy. However, the effect of glycated albumin on the biology of glomerular endothelial cells, which elaborate a basement membrane that undergoes thickening in diabetes, has not been investigated. We used well-characterized rat glomerular endothelial cells to examine the influence of glycated albumin on the synthesis of extracellular matrix proteins by these cells in culture. Concentrations of glycated albumin that are present in clinical specimens stimulate fibronectin and collagen IV production by glomerular endothelial cells, and this effect is operative under normoglycemic conditions. These results support the hypothesis that increased glycated albumin contributes to glomerular basement membrane thickening in diabetes.
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PMID:Glycated albumin stimulates fibronectin and collagen IV production by glomerular endothelial cells under normoglycemic conditions. 934 75

To determine whether urinary albumin to creatinine ratio (Albumin index) and urinary N-acetyl-beta-D-glucosaminidase (NAG) to creatinine ratio (NAG index) in random spot urine samples can be sued to predict the early stage of diabetic nephropathy in the elderly non-insulin dependent diabetic patients, we measured these concentrations in 150 non-diabetics, 61 diabetics without retinopathy and 56 diabetics with retinopathy. All patients with Albustix-positive urine were excluded. Subjects divided into two groups according to whether they were < 60 years (adult group) or > or = 60 years old (old group). Multiple regression analysis was used to investigate the relationship between NAG index or Albumin index (dependent variable) and independent variables (age, systolic blood pressure, duration of diabetes. HbA1c) in diabetic patients. Diabetic patients with retinopathy showed the highest mean Albumin index, followed by diabetic patients without retinopathy and then non-diabetic patients both in adult group and in old group (p < 0.001, p < 0.001, respectively). Diabetic patients with retinopathy showed the highest mean NAG index, followed by diabetic patients without retinopathy and then non-diabetic patients both in adult group and in old group (p < 0.001, p < 0.001, respectively). Albumin index positively correlated with systolic blood pressure, duration of diabetes and HbA1c (r = 0.18, r = 0.35, r = 0.18, respectively). NAG index positively correlated with age, duration of diabetes and HbA1c (r = 0.18, r = 0.25, r = 0.29, respectively). These results suggest that both NAG index and Albumin index in random spot urine samples may serve as early functional indicators of diabetic nephropathy in elderly diabetics.
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PMID:[Microalbumin and N-acetyl-beta-D-glucosaminidase in random spot urine samples as predictors of diabetic nephropathy in the elderly non-insulin dependent diabetic patients]. 943 72

Regulation of mesangial matrix deposition is a dynamic phenomenon involving synthetic and degradative processes. The latter involve a number of matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinases (TIMP). Experimental studies suggest that mesangial matrix degradation is inhibited in diabetic nephropathy, and that this phenomenon has a pathogenic role. The expression of genes for MMP2 and TIMP2 in human diabetic nephropathy was investigated. Reverse transcription polymerase chain reaction was carried out in microdissected glomeruli and tubulo-interstitium obtained from kidney biopsies. We studied 16 NIDDM patients, 5 patients with glomerulonephritis or chronic kidney transplant rejection, and 5 normal control subjects. Albumin excretion rate and renal histology for NIDDM patients were available. Contrary to TIMP2 which was expressed both in tubulo-interstitium and glomeruli in almost all renal biopsies, MMP2 gene down-regulation was observed in glomeruli from all NIDDM patients, irrespective of the albumin excretion rate, and of renal histology. In contrast, this gene was expressed in biopsies from other subjects (chi(2) = 20.6; p = 0.000). In conclusion, this study demonstrates that: 1) in glomeruli of NIDDM patients the MMP2 gene is down-regulated; 2) in biopsies of NIDDM patients the MMP2/TIMP2 pattern is peculiar for NIDDM; 3) the MMP2 gene down-regulation is observed in all NIDDM patients, irrespective of the level of albuminuria and of renal histology. MMP2 gene down-regulation seems to be a molecular epiphenomenon of diabetes, rather than a marker of diabetic nephropathy.
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PMID:Down-regulation of glomerular matrix metalloproteinase-2 gene in human NIDDM. 944 53

Nephropathy is a frequent complication of long term diabetes. Diabetic nephropathy is the major determinant of premature morbidity and mortality both in insulin-dependent (IDDM) and in non-insulin dependent-diabetes mellitus (NIDDM). There is good evidence that genetic predisposition plays a major role in development of diabetic nephropathy. This hypothesis is based on the observation that diabetic nephropathy clusters within families, both in IDDM and NIDDM. Components of the renin-angiotensin system (RAS) are plausible candidate genes to examine for a association with microalbuminuria and diabetic nephropathy. In this study we compared the distribution of PstI melting polymorphism at the ACE locus among NIDDM patients with diabetic nephropathy and in patients who, despite long duration of NIDDM, remain without this complication. The 220 NIDDM patients for whom DNA was available were classified into two groups according to their renal status: normoalbuminuric control subjects (n = 80) who are NIDDM patients with an A/C ratio < 2.5 and nephropathy cases (n = 140) who are NIDDM patients with A/C ratio > 2.5. Albumin excretion rate was assayed by radioimmunoassay. HbA1c was assayed using HPLC methods, creatinine--using Jaffe methods and DNA analysis using PCR reaction, and then after the amplification product was digested with PstI enzyme. The study revealed that PstI sequence differences ("+/= and -") in the ACE gene do not contribute to genetic susceptibility to diabetic nephropathy in NIDDM.
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PMID:[Is PstI polymorphism of the angiotensin I converting enzyme gene associated with nephropathy development in non-insulin-dependent diabetes mellitus (preliminary study)]. 949 4

Albumin modified by Amadori glucose adducts, formed in increased amounts in diabetes, stimulates collagen IV production and gene expression in renal glomerular mesangial cells, and induces mesangial matrix accumulation accompanied by increased mRNA encoding alpha 1 (IV) collagen and fibronectin in diabetic animals. These effects contribute to the pathogenesis of diabetic nephropathy, and resemble biologic activities of the cytokine TGF-beta 1, which also has been causally implicated in diabetic renal disease. We postulated that Amadori-modified glycated albumin modulates TGF-beta 1 expression in mesangial cells, and that TGF-beta 1 participates in mediating the glycated albumin-induced increases in mesangial cell matrix production. To test this hypothesis, we measured mRNA encoding TGF-beta 1, the TGF-beta Type II receptor and fibronectin, a key matrix component of the TGF-beta 1 tissue response, after incubation of mesangial cells with glycated albumin. Steady state levels of the mRNAs encoding for these proteins were stimulated when mesangial cells were cultured in the presence of albumin containing Amadori glucose adducts compared with levels in cells cultured with the nonglycated, glucose-free counterpart. The glycated protein-induced changes in mRNA expression were observed with concentrations of glycated albumin encompassing those found in clinical specimens and in media containing physiologic (5.5 mM) glucose concentrations, indicating that they were due to the glucose-modified protein and not to a hyperglycemic milieu. Further, they were accompanied by increased translated fibronectin protein, which was prevented with TGF-beta neutralizing antibody, as was the glycated albumin-induced increase in fibronectin mRNA. The findings indicate that Amadori-modified glycated albumin stimulates mesangial cell TGF-beta 1 gene expression by mechanisms that are operative under normoglycemic conditions. These data provide the first link between elevated glycated serum albumin concentrations and increased TGF-beta 1 bioactivity in the pathogenesis of mesangial matrix accumulation in diabetes.
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PMID:Glycated albumin stimulates fibronectin gene expression in glomerular mesangial cells: involvement of the transforming growth factor-beta system. 950 8

An activated renal endothelin (ET) system is implicated in the pathogenesis of renal fibrosis, as recently shown in ET-1 transgenic mice. Because progressive renal fibrosis is also a major finding in diabetic nephropathy, we analyzed the activity of the renal ET system in rats with streptozotocin-induced diabetes mellitus and the effect of blocking the ETA receptor, using the orally active ETA antagonist LU 135252. The effects of long-term treatment with LU 135252 were compared with those of an ACE inhibitor. Plasma and urinary ET-1 concentrations were measured. Progression of diabetic nephropathy was analyzed by measuring urinary albumin and protein excretion. Urinary ET-1 excretion was significantly elevated as early as 7 days after induction of diabetes and increased further. The daily urine volume was significantly correlated with urine ET-1 excretion. Treatment with LU 135252 significantly decreased the ET-1 excretion by more than 50%, whereas ACE inhibition resulted only in a mild decrease. Albumin excretion was significantly decreased after ACE inhibition, whereas ETA inhibition resulted in a nonsignificant decrease. Urinary ET and albumin excretion probably reflect independent mechanisms of renal damage in diabetes.
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PMID:Renal endothelin system in diabetes: comparison of angiotensin-converting enzyme inhibition and endothelin-A antagonism. 959 22

To assess the validity of urine albumin concentration (UAC) and the urine albumin:creatine ratio (UACR) in a random urine specimen (RUS) for screening diabetic nephropathy in Korea, a total of 105 ambulatory diabetes mellitus patients (male:female, 52:53), ages 40-75 years (median 59 years) collected 105 RUSs after completing a timed 24 hour urine collection. Albumin was measured by immunonephelometry. According to the timed urinary albumin excretion rate (UAER) measured in the 24 hour collection (criterion standard), samples were classified normoalbuminuric (UAER < 20 micrograms/min; n = 50), microalbuminuric (UAER 20-200 micrograms/min; n = 30), and macroalbuminuric (UAER > 200 micrograms/min; n = 25). The receiver operating characteristics (ROC) curve of UAC and UACR in a RUS for screening of microalbuminuria (normo- and microalbuminuric samples; n = 80) and macroalbuminuria (micro- and macroalbuminuric samples; n = 55) were plotted. Pearson's coefficients of correlation of 24 hour UAER vs. UAC and UACR were 0.81 and 0.75, respectively (P < 0.001). The point of intersection with a 100%-to-100% diagonal for microalbuminuria were as follows: 31.0 mg/l for UAC and 32.5 mg/g for UACR; for macroalbuminuria 181 mg/l for UAC and 287.3 mg/g for UACR. The sensitivity and specificity of the cut-off points for microalbuminuria were 77% and 82% for UAC and 77% and 92% for UACR. The sensitivity and specificity of the cut-off points for macroalbuminuria were 84% and 90% for UAC and 88% and 90% for UACR. In present study, no difference was observed when comparing the performance of UAC and UACR based on a statistical comparison by McNemar test. The repeated measurements of UAC and UACR in the same individual were statistically similar and were correlated with each other. Based on these results, albumin measurements (UAC and UACR) in a RUS were considered as a valid test for screening diabetic nephropathy.
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PMID:The validity of random urine specimen albumin measurement as a screening test for diabetic nephropathy. 1019 5

Currently, neither the American Diabetes Association nor the Kidney Foundation consider the results of a positive dipstick urine test for protein, a semi-quantitative measurement, in the final evaluation of diabetic nephropathy. Instead, they require a quantitative test. The object of this study was to assess whether a positive semi-quantitative test could accurately substitute for a quantitative one to evaluate renal disease. We determined the proportion of urine samples dipstick positive for protein that had an albumin:creatinine ratio of 30 microg/mg or more, the recommended value for the diagnosis of microalbuminuria (incipient nephropathy). Albumin:creatinine ratios were measured in urine samples from 19 diabetic and 51 nondiabetic patients in which the dipstick test for protein was positive. Twelve of 24 (50%) urine samples trace positive for protein by a dipstick method had albumin:creatinine ratios of 30 microg/mg or more, whereas 42 of 46 (91%) urine samples greater than or equal to 1+ for protein exceeded that ratio. The results were similar in the two groups of patients. The positive predictive value for a test result more than or equal to 1+ for protein was 91%. We conclude that in contrast to the recommendations of the American Diabetes Association and the National Kidney Foundation, dipstick positive proteinuria of more than or equal to 1+ can substitute for an albumin:creatinine ratio. An algorithm for this more cost-effective approach to the diagnosis of diabetic nephropathy is suggested.
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PMID:Relationship between dipstick positive proteinuria and albumin:creatinine ratios. 1023 10


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