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)

Recently, we have developed a highly sensitive assay system for quantitative measurement of urinary type IV collagen. To obtain a basic evaluation of the assay system we used urine specimens, collected randomly and studied the relation to diabetic nephropathy in patients with non-insulin dependent diabetes mellitus (NIDDM). It was shown that this assay system could measure the samples without concentrating the urine. Urinary sediments which were reported to interfere with the assay could be removed by adding Tris-buffer. In the clinical studies, urinary type IV collagen concentrations were significantly higher in patients with NIDDM regardless of the presence or the absence of albumin. Cases with abnormal values of urinary type IV collagen in the normal albuminuria group were 41.6%, while those with abnormal values of urinary transferrin excretion were 31.0%. Furthermore, among the normal albuminuria group, glycosylated hemoglobin (HbA1c) levels were higher in the groups of abnormal values of urinary type IV collagen than those within the reference values. These results obtained herein suggest that urinary type IV collagen could be a useful marker for the early stage of diabetic nephropathy.
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PMID:[The significance of determination of urinary type IV collagen concentrations from a random urine collection in patients with non-insulin dependent diabetes mellitus]. 956 68

We examined serum and urinary cytokeratin 19 fragment (CYFRA 21-1) levels in patients with diabetic nephropathy as a model of chronic renal failure, to investigate the mechanism of increased serum CYFRA 21-1 levels in chronic renal failure. Serum and urinary CYFRA 21-1 levels in non-insulin-dependent diabetes mellitus (NIDDM) patients with abnormal urinary immunoglobulin G (IgG) levels (>1.1 mg/g x Cr, n=126) were higher than those with normal urinary IgG levels. In NIDDM patients with normal urinary IgG levels (n=81); the urinary albumin or transferrin levels were not related to serum or urinary CYFRA 21-1 levels. We speculate that the increased serum CYFRA 21-1 levels contribute to metabolic abnormality in the kidney itself rather than the decreased urinary excretion per se, and that increased urinary CYFRA 21-1 levels are found in advanced cases of diabetic nephropathy with destruction of the size barrier.
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PMID:Mechanism of increased serum cytokeratin 19 fragment levels in patients with diabetic nephropathy as a model of chronic renal failure. 986 51

An early manifestation of diabetic nephropathy, increased excretion of albumin, is now generally believed to be sufficiently specific, particularly in subjects with diabetes mellitus, to predict the subsequent development of clinically overt diabetic nephropathy. However, certain other proteins besides albumin may also be excreted in abnormal amounts during this early phase of diabetic nephropathy. We evaluated the diagnostic utility of urinary immunoglobulin G (IgG) in patients with diabetic nephropathy by comparing the findings with the clinical stage and renal biopsy specimen. Using 24-hour urine samples, IgG was measured by an enzyme-linked immunosorbent assay. In addition, urine samples were assayed for albumin, transferrin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase. Serum IgG concentration and HbA1c were also evaluated. A total of 197 patients with non-insulin-dependent diabetes mellitus were enrolled in this study. Subjects were grouped according to the rate of urinary albumin excretion (clinical stage). Fifty of these cases were also divided into four groups according to the severity of diffuse glomerular lesions using Gellman's criteria. The urinary excretion of IgG was significantly increased in diabetic patients as compared with the healthy controls. Among diabetic patients, IgG level showed a significant increase with respect to the clinical stage of nephropathy and the progress of glomerular diffuse lesions. In the stage of normoalbuminuria, the urinary excretion of IgG showed a significant increase in parallel with the progress of glomerular diffuse lesions, whereas there was no relationship between the urinary excretion of albumin and the progress of glomerular diffuse lesions. While the excretion of IgG correlated with that of albumin and transferrin, there was no correlation between the excretion of IgG and the other laboratory indices evaluated. These findings indicate that measurement of urinary IgG may be more useful than albuminuria in detecting the early stage of diabetic nephropathy.
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PMID:[Diagnostic significance of urinary immunoglobulin G in diabetic nephropathy]. 1065 27

The exact mechanisms by which growth hormone (GH) damages the kidney inducing diabetic nephropathy has not yet been elucidated. Recently, it has been shown that transferrin has the same diabetogenic effects of GH, being its mediator. Transferrin was studied using immunohistochemistry and immunoelectron microscopy in cases of early diabetic nephropathy, and in controls. Transferrin was only found in diabetic cases in podocytes and Bowman's capsule cells, but also in the tubular cells of both diabetic and non-diabetic controls. Immuno-electron microscopy for the presence of transferrin showed positive signals in the cytoplasm of diabetic podocytes, but not in pedicels. This selective deposition was associated with signs of organelle and cytoskeleton damage. On the basis of previous evidence and present glomerular findings, these results suggest an indirect diabetogenic effect on the kidney by GH mediated through transferrin.
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PMID:Diabetogenic transferrin damages podocytes in early human diabetic nephropathy. 1129 98

The mortality among end-stage renal failure (ESRF) patients undergoing renal replacement therapy (RRT) remains high. An important proportion of these patients die shortly after the initiation of RRT. The present study aims to determine the best predictors for the early mortality in a group of 140 ESRF patients who initiated RRT between october 96 and december 99. The mean age of the study group was 61 +/- 13 years, and the mean follow-up time was 20 +/- 12 months. Diabetic nephropathy was the most prevalent etiology of renal failure (30%). The following data, collected immediately before the initiation of RRT, were included as independent variables: demographic and clinical characteristics, including the nutritional status established by the Subjective Global Assessment (SGA), follow-up time in the predialysis clinic (less or longer than 3 months), EPO therapy, vascular access, renal function (creatinine and urea clearances, and Kt/V urea), hematological and biochemical data including serum albumin, bicarbonate, transferrin, PTH and C-Reactive protein, as well as the protein catabolic rate and the percent of lean body mass normalized for ideal body weight, calculated from the 24 h total urine excretion of nitrogen and creatinine. The Cox proportional hazard regression model, stratified for an age over or less than 65 year, was utilized to determine the best predictors for the mortality during the study period. Sixty percent of patients had at least one comorbid condition, and 35% had cardiovascular diseases. Mild-moderate or severe malnutrition was observed in 48% of patients. The creatinine clearance and Kt/V urea before the initiation of RRT were: 9.50 +/- 2.64 ml/min/1.73 m2 and 1.47 +/- 0.44, respectively. Forty-one patients died during the study period (annual death rate: 17%). The best predictor of mortality was the nutritional status assessed by the SGA (OR: 2.32, IC 95% 1.54-3.48, p < 0.0001). In a second analysis in which the SGA was removed from the model, the previous history of cardiovascular diseases (OR: 2.07, CI 95%: 1.06-4.06, p = 0.032), and the percent of lean body mass/ideal weight (OR: 0.96; IC 95%: 0.93-0.99; p = 0.042), proved to be the best predictor of mortality. In conclusion, nutritional indices prior to the initiation of RRT, and the previous history of cardiovascular diseases were the best predictors of the early mortality in this unselected population on dialysis. Because nutritional status appeared to be a marker of the severity of the comorbid conditions, a better control of the number and severity of these comorbid conditions may be the best way for reducing the mortality in patients on RRT.
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PMID:[Predictors of early death during dialysis]. 1147 8

BACKGROUND: Transferrinuria is thought to be a marker for early stages of diabetic nephropathy. Transferrin has also been proposed as a mediator of tubular toxicity because the reabsorption of transferrin results in the release of reactive iron in proximal tubular cells, promoting the formation of hydroxyl radicals. We evaluated the role of urinary transferrin excretion in diabetic patients with early nephropathy by comparing tubulointerstitial injury in renal biopsy specimens. PATIENTS AND METHODS: 45 type 2 diabetic patients with normoalbuminuria (urinary albumin excretion <30 mg/24 h) or microalbuminuria (30-300 mg/24 h) were studied. All patients with microalbuminuria underwent renal biopsy, and the severity of the tubulo-interstitial lesions was determined by a semiquantitative estimate of interstitial fibrosis, tubular atrophy, and interstitial inflammatory infiltrates. Subjects were classified into group A (normoalbuminuria, n=25), group B (microalbuminuria without tubulointerstitial changes, n=11) or group C (microalbuminuria with tubulointerstitial changes, n=9). RESULTS: Urinary transferrin excretion (UTf), as well as UTf/creatinine clearance (Ccr), and transferrin clearance (CTf/Ccr), was significantly higher in groups B and C than in group A, and it was significantly higher in group C than in group B. There were no significant differences in urinary albumin excretion or mesangial expansion rate (MR% estimated by quantitative morphometric studies) between groups B and C. Although urinary beta2-microglobulin excretion was significantly higher in group C than in groups A and B, urinary N-acetyl-beta-D-glucosaminidase activity was significantly higher in groups B and C than in group A. CONCLUSIONS: Increased transferrinuria in the microalbuminuric stage may lead to the development of tubulointerstitial injuries in type 2 diabetic patients.
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PMID:Transferrinuria in type 2 diabetic patients with early nephropathy and tubulointerstitial injury. 1202 Jun 27

To search for biomarkers of IgA nephropathy, protein profiles of urine samples from patients with IgA nephropathy and normal volunteers were compared using two-dimensional DIGE. Most of the 172 spots identified in the urine were serum proteins, and their amounts in IgA nephropathy urine were much higher than those in normal urine; this can be explained as proteinuria caused by glomerular dysfunction. However, only alpha(1)-microglobulin, also one of the major serum proteins, in IgA nephropathy urine was not higher in amount than that in normal urine. We confirmed using ELISA analysis that the amounts of transferrin and albumin in IgA nephropathy and diabetic nephropathy urine were much higher than those in normal urine, whereas the amount of alpha(1)-microglobulin in IgA nephropathy urine was not higher than that in normal urine and was much lower than that in diabetic nephropathy urine. Approximately 50% of alpha(1)-microglobulin forms a complex with IgA in serum. These results suggest that alpha(1)-microglobulin in IgA nephropathy urine is a characteristic protein and might be a biomarker for IgA nephropathy and that alpha(1)-microglobulin might have a relationship with IgA nephropathy pathology.
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PMID:Absence of increased alpha1-microglobulin in IgA nephropathy proteinuria. 1724 5

Diagnosis of the type of glomerular disease that causes the nephrotic syndrome is necessary for appropriate treatment and typically requires a renal biopsy. The goal of this study was to identify candidate protein biomarkers to diagnose glomerular diseases. Proteomic methods and informatic analysis were used to identify patterns of urine proteins that are characteristic of the diseases. Urine proteins were separated by two-dimensional electrophoresis in 32 patients with FSGS, lupus nephritis, membranous nephropathy, or diabetic nephropathy. Protein abundances from 16 patients were used to train an artificial neural network to create a prediction algorithm. The remaining 16 patients were used as an external validation set to test the accuracy of the prediction algorithm. In the validation set, the model predicted the presence of the diseases with sensitivities between 75 and 86% and specificities from 92 to 67%. The probability of obtaining these results in the novel set by chance is 5 x 10(-8). Twenty-one gel spots were most important for the differentiation of the diseases. The spots were cut from the gel, and 20 were identified by mass spectrometry as charge forms of 11 plasma proteins: Orosomucoid, transferrin, alpha-1 microglobulin, zinc alpha-2 glycoprotein, alpha-1 antitrypsin, complement factor B, haptoglobin, transthyretin, plasma retinol binding protein, albumin, and hemopexin. These data show that diseases that cause nephrotic syndrome change glomerular protein permeability in characteristic patterns. The fingerprint of urine protein charge forms identifies the glomerular disease. The identified proteins are candidate biomarkers that can be tested in assays that are more amenable to clinical testing.
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PMID:Urine biomarkers predict the cause of glomerular disease. 1730 Nov 91

Serum cystatin C (CysC) has been proposed as a potentially superior marker for the evaluation of renal function because it was more sensitive and accurate for the estimation of glomerular filtration rate (GFR) than other markers. We evaluated the clinical usefulness of CysC in diabetic nephropathy. The study was performed on 414 Japanese diabetic patients. We compared serum CysC levels with serum creatinine levels, urinary concentrations of albumin, transferrin and type IV collagen, and creatinine clearance (Ccr). Then, the correlation between serum CysC levels and high-sensitivity C-reactive protein (H-CRP) levels were examined. When the patients were classified by renal function, 19% of the patients were free from nephropathy, 49% had microalbuminuria, 28% had persistent proteinuria, and 4% had end stage renal disease. The serum CysC levels increased with the progression of nephropathy, and significantly higher in overt nephropathy, but not significant in early nephropathy. Serum CysC levels were well-correlated with H-CRP levels in the patients without nephropathy. These results indicate that serum CysC would be practical for the evaluation of renal function in diabetic patients with overt nephropathy but not early nephropathy and might be related with a risk for cardiovascular events in patients without nephropathy.
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PMID:Serum cystatin C in diabetic patients. Not only an indicator for renal dysfunction in patients with overt nephropathy but also a predictor for cardiovascular events in patients without nephropathy. 1798 Sep 29

Selectivity index (SI) has been reported to reflect the selectivity of proteinuria, and it has a relationship with tubulointerstitial damage. Moreover it has a predictive value on functional outcome. However, it is necessary to measure serum IgG, serum transferrin, urinary IgG, and urinary transferrin to calculate SI. We measured urinary micro-cholesterol (mCHO) levels in sixty-three patients with proteinuria (urinary total protein > or = g/gCr) and compared urinary mCHO/total protein(uTP) ratio and SI. The patients' diseases were minimal change nephrotic syndrome (MCNS, n = 12), focal and segmental glomerular sclerosis (FSGS, n = 12), membranous nephropathy (MN, n = 17), and diabetic nephropathy (DMN, n = 22). Urinary mCHO levels were measured by the ECC method using cholesterol ester hydrolase (CEH) and cholesterol dehydrogenase, and this method was performed conveniently by automatic analyzer. No correlation was observed between urinary mCHO/gCr and serum lipid levels. There was no difference of urinary protein levels among each disease group. We found urinary mCHO/uTP ratio has a good positive correlation with SI(R = 0.722, p < 0.001). Although the difference between ROC curves of SI and urinary mCHO/uTP ratio in distinguishing MCNS from other diseases (FSGS+MN+DMN) did not reach the statistical significance, the area under the curve was larger for mCHO/uTP ratio. These results suggest that measurement of urinary mCHO by ECC method can be a simple and useful tool for predicting selectivity of proteinuria and lipoprotein-loading tubulopathy.
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PMID:[Clinical significance of urinary cholesterol/total protein ratio as a marker of selectivity of proteinuria: comparison with selectivity index]. 1931 16


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