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)

Immunofluorescence staining in unfixed or fixed renal biopsy specimens were evaluated in nine patients with diabetic nephropathy in order to elucidate if immunofluorescence staining is applicable in fixed renal tissues in such patients. Renal biopsy specimens were embedded in gelatin or paraffin matrix. Renal biopsy specimens embedded in paraffin matrix were digested with 0.05% protease. Immunofluorescent studies of kidney tissues were performed by staining with FITC-labeled heavy chain specific anti-human IgG, IgA, IgM, acute phase reactant (APR) proteins such as alpha 1-anti-trypsin (alpha 1-AT), haptoglobin (Hpt) and beta-lipoprotein (beta-Lp) antisera, and then examined with a fluorescent microscope. Linear and nodular deposition of IgG, IgA, IgM, alpha 1-AT, Hpt, and beta-Lp were observed in the glomerular capillary walls of the renal specimens embedded in paraffin matrix. The staining patterns in specimens embedded in paraffin matrix was similar to that embedded in gelatin matrix. There was no significant difference in the intensity or distribution of IgG, IgM, alpha 1-AT, and beta-Lp deposition among the two different conditions of immunofluorescence in patients with diabetic nephropathy. It was suggested that immunofluorescence staining in renal biopsy specimens embedded in paraffin matrix after digestion with protease is useful for the evaluation of IgG, IgM, APR proteins, and beta-Lp in glomeruli from patients with diabetic nephropathy.
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PMID:Immunofluorescence staining in unfixed or fixed renal biopsy specimens from patients with diabetic nephropathy. 241 46

The levels of immunoglobulins, complement components and APR proteins including alpha 1-antitrypsin (alpha 1-AT), alpha 1-acid glycoprotein (alpha 1-AG), alpha 2-macroglobulin (alpha 2-MG) and haptoglobin (Hpt) in the sera, as well as glycosylated or nonglycosylated protein fractions of these proteins in the sera, were examined by laser nephelometry in 49 patients with diabetes mellitus. Immunofluorescence studies of immunoglobulins, beta-lipoprotein (beta-Lp), complement components and APR proteins in the kidney and skin tissues of patients with diabetic nephropathy were performed to elucidate whether such factors might play a role in the development of the vascular changes in this disease. The levels of alpha 1-AT and alpha 2-MG in the sera as well as glycosylated or nonglycosylated protein fractions of these proteins in the sera from patients with diabetic nephropathy, were significantly greater than those in healthy adults. Marked linear deposition of these proteins in the glomerular or dermal vascular walls was observed in the same patients. In particular, IgG and alpha 1-AT were accumulated in the glomeruli of patients with the nodular type of this disease. The intensity of alpha 1-AT or IgG deposition in glomerular capillary walls treated with a high concentration (4 mol) of NaCl was markedly decreased in such patients. It appeared that serum APR proteins with or without glycosylation underwent exudation into the glomerular and dermal vascular walls, and then accumulated in these walls in patients with diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunopathological analysis of acute phase reactant (APR) proteins in glomeruli from patients with diabetic nephropathy. 247

The 24-h urine excretion and renal clearance of albumin, alpha I-acid glycoprotein, transferrin, IgG, IgA and haptoglobin were studied in 30 albustix-negative diabetics with no clinical data for diabetic nephropathy aiming at the precise characterization of proteinuria in patients with diabetes mellitus. The diabetic patients were divided into two groups - 15 patients with newly diagnosed diabetes and 15 - with a longer duration of diabetes. Thirteen healthy subjects, at the same mean age, served as a control group. The results reveal increase of the clearances and 24-h excretion of the proteins studied in the patients with diabetes mellitus, in those with a short duration of the disease including, with authentic difference for albumin, transferrin, IgG and haptoglobin among the patients with a longer duration of the disease and the healthy controls and authentic difference for albumin between those with the newly diagnosed diabetes and the healthy control. The possible prognostic significance of the indices studied is discussed as well as their importance for the early diagnosis of diabetic nephropathy.
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PMID:[Urinary excretion and renal clearance of several specific plasma proteins in diabetics]. 361 8

The solubilization of renal deposits of IgG and other serum proteins by fresh human sera or human gamma-globulin was studied in patients with diabetic nephropathy. Renal biopsy specimens were from 10 patients with diabetic nephropathy. These specimens were incubated with fresh sera obtained from the same patients and healthy adults or human gamma-globulin at 37 degrees C for 1 hr in plastic test tubes. The sections were stained with FITC-labeled heavy chain specific anti-human IgG, alpha 1-antitrypsin, haptoglobin and beta-lipoprotein antisera, and then examined with a fluorescent microscope. It was demonstrated that fresh human sera or gamma-globulin significantly solubilized glomerular deposits of IgG and other serum proteins in patients with diabetic nephropathy. It was postulated that solubilization of protein deposits in glomeruli requires the same substances detected in vitro in the kidney tissues from patients with diabetic nephropathy.
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PMID:Solubilization of intraglomerular deposits of serum proteins by fresh human sera or gamma-globulin in patients with diabetic nephropathy. 608 25

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

The haptoglobin (Hp) genotype is a major determinant of progression of nephropathy in individuals with diabetes mellitus (DM). The major function of the Hp protein is to bind and modulate the fate of extracorpuscular hemoglobin and its iron cargo. We have previously demonstrated an interaction between the Hp genotype and the DM on the accumulation of iron in renal proximal tubule cells. The primary objective of this study was to determine the intracellular localization of this iron in the proximal tubule cell and to assess its potential toxicity. Transmission electron microscopy demonstrated a marked accumulation of electron-dense deposits in the lysosomes of proximal tubules cells in Hp 2-2 DM mice. Energy-dispersive X-ray spectroscopy and electron energy loss spectroscopy were used to perform elemental analysis of these deposits and demonstrated that these deposits were iron rich. These deposits were associated with lysosomal membrane lipid peroxidation and loss of lysosomal membrane integrity. Vitamin E administration to Hp 2-2 DM mice resulted in a significant decrease in both intralysosomal iron-induced oxidation and lysosomal destabilization. Iron-induced renal tubular injury may play a major role in the development of diabetic nephropathy and may be a target for slowing the progression of renal disease.
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PMID:Poor lysosomal membrane integrity in proximal tubule cells of haptoglobin 2-2 genotype mice with diabetes mellitus. 2274 5

Diabetic nephropathy (DN) is the leading cause of end stage renal disease and dialysis worldwide. Despite aggressive treatment, the number of patients on hemodialysis due to type 1 and type 2 diabetes mellitus is increasing annually. The lack of reliable animal models that mimic human disease has delayed the identification of specific factors that cause or predict DN. Different investigators around the world are testing different murine models. Validation criteria for early and advanced DN, phenotypic methods, background strain have recently been developed. Establishment of an authentic mouse model of DN will undoubtedly facilitate the understanding of the underlying genetic mechanisms that contribute to the development of DN and to study new treatments. Here we describe the characteristics of our new mouse model with type 1 diabetes mellitus and different haptoglobin genotypes that can mimic human DN.
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PMID:Is the Hp 2-2 diabetic mouse model a good model to study diabetic nephropathy? 2349 May 97

Diabetic nephropathy is the leading cause of end-stage renal disease. The urinary albumin to creatinine ratio is used as a predictor for the development of nephropathy but it is neither sensitive nor specific. Here we used liquid chromatography/mass spectrometry on urine of eight normoalbuminuric patients with type 2 diabetes from the VA Diabetes Trial to identify candidate markers for loss of renal function. Initial verification of seven markers (agrin, haptoglobin, mannan-binding lectin serine protease 2, LAMP-2, angiotensinogen, NGAL, and uromodulin) in the urine of an additional 30 patients showed that haptoglobin was the best predictor of early renal functional decline. We then measured this in the urine of 204 patients with type 2 diabetes who did not yet have significant kidney disease (estimated glomerular filtration rate stage 2 or better and an albumin to creatinine ratio <300 mg/g). In comparing the highest to lowest tertiles, the odds ratio for having early renal function decline was 2.70 (CI: 1.15, 6.32) using the haptoglobin to creatinine ratio compared with 2.50 (CI 1.14, 5.48) using the albumin to creatinine ratio after adjusting for treatment group and use of ACE inhibitors. Addition of the haptoglobin to creatinine ratio to a model using the albumin to creatinine ratio to predict early renal function decline resulted in improved predictive performance. Thus, the haptoglobin to creatinine ratio may be useful to predict patients with type 2 diabetes at risk of nephropathy before the development of macroalbuminuria or reduced glomerular filtration rate.
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PMID:Urine haptoglobin levels predict early renal functional decline in patients with type 2 diabetes. 2372 3

As a prognostic biomarker for progression of diabetic nephropathy, albuminuria fails in terms of sensitivity and specificity. Better urinary or plasma biomarkers are needed that can predict which diabetic patients are at highest risk for progression. Bhensdadia et al. report proteomic investigations that identified urinary haptoglobin as a potential prognostic biomarker for progressive diabetic nephropathy. Although as a single marker urinary haptoglobin adds little to albuminuria, together the two appear to provide better diagnostic accuracy than albuminuria alone.
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PMID:How to find a prognostic biomarker for progressive diabetic nephropathy. 2353 33

Diabetes mellitus (DM) is associated with increased oxidative stress due to elevated glucose levels in the plasma. Glucose promotes glycosylation of both plasma and cellular proteins with increased risk for vascular events. Diabetic patients suffer from a higher incidence of cardiovascular complications such as diabetic nephropathy. Haptoglobin (Hp) is an antioxidant plasma protein which binds free hemoglobin, thus preventing heme-iron mediated oxidation. Two alleles exist at the Hp gene locus (1 and 2) encoding three possible Hp genotypes that differ in their antioxidant ability, and may respond differently to vitamin E treatment. Several clinical studies to have shown that Hp 1-1 genotype is a superior antioxidant to the Hp 2-2 genotype and Hp 2-2 genotype is associated with a higher incidence of cardiovascular disease. Vitamin E was found to have beneficial effect in patient and mice with Hp 2-2 genotype. In this review we have summarized the results of our studies in patients with diabetic nephropathy treated with vitamin E and in diabetic mice with different haptoglobin genotypes.
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PMID:Vitamin E and diabetic nephropathy in mice model and humans. 2425 94


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