Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glomerular and proximal tubular function of the diabetic kidney was investigated. The urinary excretion (relative clearance) of albumin, a marker of glomerular function, and retinol binding protein (RBP), a low molecular weight (LMW) protein and marker of proximal tubular function, was determined in insulin-dependent diabetics. No correlation between the relative clearances of albumin and RBP was observed. LMW proteinuria without microalbuminuria was observed in 27 patients which suggests that tubular dysfunction may be an early stage in the development of diabetic nephropathy. Microalbuminuria was found in 16 patients while a mixed type of proteinuria (microalbuminuria and LMW proteinuria) was present in 56 patients several of whom had advanced nephropathy with elevated serum levels of RBP and creatinine. It is suggested that a combination of tubular and glomerular malfunction may be responsible for some cases of mixed proteinuria.
 ...
PMID:Relationship between the urinary excretion of albumin and retinol-binding protein in insulin-dependent diabetics. 318 Apr 84

Tubular damage as suggested by enzymuria and tubular proteinuria is a recognized feature of glomerulonephritis (GN) with clinical proteinuria and both incipient and overt diabetic nephropathy (DN). However, little is known about the presence of tubulopathy in patients with primary GN, microalbuminuria [albumin excretion (AER) 30-300 mg/d] and microhematuria. Three groups were studied. The GN group comprised 17 (2 F) patients with biopsy-proven GN with microalbuminuria. The DN group comprised 35 (14 F) patients with incipient diabetic nephropathy with AER 30-300 mg/d, and controls comprised 38 (15 F) normal subjects with normal AER < 30 mg/d. Serum creatinine, albuminurinuria, transferrinuria, and markers of tubular damage such as urinary excretion of N-acetyl-glucosaminidase (NAG), leucine aminopeptidase (LAP), gamma-glutamyl transferase (gGT), and retinol binding protein (RBP) were measured. GN and DN had comparable degrees of albuminuria, transferrinuria, and LAP excretion, and these were significantly higher than controls. Serum creatinine was significantly higher in GN than DN and controls. DN had significantly higher NAG and RBP, and lower gGT than GN and controls. In both GN and DN groups, both glomerular proteins correlated with each other and NAG correlated significantly to LAP and gGT. Albuminuria correlated to tubular enzymuria in GN group but not in patients with DN. The results suggest that tubular damage is less marked in microalbuminuric patients with GN than those with DN despite similar degree of glomerular proteinuria. The pattern of tubulopathy is also different in the two groups, indicating differences in the pathogenesis of tubular damage in these two clinical settings.
 ...
PMID:Tubular damage in microalbuminuric patients with primary glomerulonephritis and diabetic nephropathy. 777 Jun 43

The brush-border of the human renal proximal tubule is extremely sensitive to toxic, ischaemic and inflammatory insults. A monoclonal antibody to a brush-border antigen (BB-50) had been shown to identify increased urinary excretion of BB-50 (UBB-50) among workers exposed to heavy metals and hydrocarbons as well as patients on cisplatin and patients with early diabetic nephropathy. This study describes the use of this antibody to quantify UBB-50 among lead exposed workers. The study population consisted of 154 workers from a factory manufacturing lead stabilisers. Of these 91 workers had less than 6 months of exposure and formed the control group. The remaining 63 workers with a median exposure of 3 years formed the exposed group. Several blood lead (PbB) indices were used as exposure indices. These include the most recent PbB (PbBrec), a time-integrated blood lead index (PbBint), an absolute change in recent PbB (PbB delta), a relative change in PbB (PbB delta%), as well as the number of times the PbB measurements were above 40, 50 and 60 micrograms/100 ml (PbB40, PbB50, PbB60 respectively). Urinary levels of beta-2-microglobulin (U beta 2m), alpha-1-microglobulin (U alpha 1m), retinol binding protein (URBP), albumin (UAlb), activity of total N-acetyl-D-beta-glucosaminidase (NAG-T) and heat stable NAG isoenzyme (NAG-B) were measured along with the serum beta 2m (S beta 2m). Through stepwise analysis, UBB-50 was best correlated with PbBint, PbB40 and PbB delta% (r2, 0.271). Of these, PbBint and PbB40 had about twice the contribution to the variation in UBB-50.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Urinary excretion of tubular brush-border antigens among lead exposed workers. 784 42

Tubular damage is a recognized feature of both overt diabetic nephropathy and glomerulonephritis. However, the pattern and mechanism of tubular damage in the two clinical settings remain unclear. Two groups of patients with macroalbuminuria (albuminuria > 300 mg/day) were studied. Group 1 comprised 41 patients with biopsy proven primary glomerulonephritis and group 2 comprised 28 patients with clinical diabetic nephropathy due to insulin dependent diabetes mellitus. Serum creatinine, creatinine clearance, glomerular proteinuria (albuminuria and transferrinuria), markers of tubular damage such as urinary excretion of lysosomal enzyme (N-acetyl glucosaminidase), brush border enzymes (leucine aminopeptidase and gamma-glutamyl transferase) and retinol binding protein (tubular protein) were measured. Both groups were comparable in serum creatinine, creatinine clearance, glomerular proteinuria and excretion of N-acetyl-glucosaminidase. However, a significantly higher degree of tubular brush border enzymuria and a lower level of tubular proteinuria were seen in group 1 than in group 2. In group 1, albuminuria correlated to tubular enzymuria and tubular proteinuria. However, there was no correlation in diabetic patients between parameters of glomerular and tubular damage or dysfunction. The data presented suggested that the pattern of tubulopathy is different in patients with comparable degree of macroalbuminuria due to diabetic nephropathy and glomerulonephritis. Moreover, in diabetic nephropathy contrary to glomerulonephritis, markers of tubular damage are unrelated to glomerular proteinuria. This may suggest different mechanisms of tubular damage in the two clinical settings. We recommended that in all patients with proteinuria, particularly those with diabetic nephropathy, markers of renal tubular damage may be useful in monitoring the course of their disease.
 ...
PMID:Tubulopathy with macroalbuminuria due to diabetic nephropathy and primary glomerulonephritis. 786 56

It is well established that the detection of microalbuminuria in a patient with diabetes mellitus indicates the presence of glomerular involvement in early renal damage. Recent studies have demonstrated that there is also a tubular component to renal complications of diabetes, as shown by the detection of renal tubular proteins and enzymes in the urine. In fact, tubular involvement may precede glomerular involvement, as several of these tubular proteins and enzymes are detectable even before the appearance of microalbuminuria. This review looks at the studies reported so far on serum and urinary markers of diabetic nephropathy, both glomerular and tubular, and their roles in the early detection of renal damage. The advantages and disadvantages of some of these markers are also discussed. The markers reviewed include (1) glomerular--transferrin, fibronectin, and other components of glomerular extracellular matrix, and (2) tubular--low molecular weight proteins (beta 2 microglobulin, retinol binding protein, alpha 1 microglobulin, urine protein 1), other proteins such as Tamm-Horsfall protein, beta 2 glycoprotein-1, urinary enzymes (N-acetyl-beta-D-glucosaminidase, cholinesterase, gamma glutamyltranspeptidase, alanine aminopeptidase), and tubular brush-border antigen.
 ...
PMID:Markers of diabetic nephropathy. 944 15

Urinary samples were concentrated rapidly and efficiently and were used to develop several protein assays that may be of value in monitoring individuals with progressive renal disorders. Transforming growth factor-beta1 (TGF-11) and retinol binding protein (RBP) were measured with modification of commercially available methods used to assay serum specimens; type 3 collagen (T3C) was measured with a new immunonephelometric assay. The precision characteristics of these assays are comparable with those reported for microalbuminuria. The clinical utility of measuring a panel of these markers was demonstrated in urine samples from 16 control subjects and from 46 individuals with insulin-dependent diabetes mellitus (IDDM) with various albumin excretion rates (AERs). TGF-beta1 and T3C were used as markers of cytokine expression and of the renal fibrogenic process, whereas RBP excretion served as a marker of tubular injury or dysfunction. Compared with controls, T3C excretion was significantly increased in 18 normoalbuminuric and further increased in 13 microalbuminuric (AER 20 < or = 200 microg/min) IDDM subjects. RBP excretion was increased in macroalbuminuric IDDM subjects (AER >200 microg/min, overt nephropathy). Significant correlations were also found between AER and RBP in all but macroalbuminuric individuals, whereas TGF-beta1 correlated with T3C excretion in controls and in normoalbuminuric diabetic subjects. Urinary RBP but not AER was an excellent predictor of diabetic nephropathy as defined by serum creatinine (P = 0.0001). This underscores the importance of an early tubulopathy in the subsequent development of glomerulopathy and overt nephropathy. The data suggest that longitudinal monitoring of a panel of urinary markers such as that used in the current study may better define their relevance in progressive glomerulosclerosis and may also provide greater insight into the mechanisms underlying such process.
 ...
PMID:Urinary measurement of transforming growth factor-beta and type IV collagen as new markers of renal injury: application in diabetic nephropathy. 959 Mar 67

Diabetic nephropathy (DN) is usually characterized by glomerular dysfunction, with microalbuminuria as an early indicator. Urinary excretion of smaller molecular weight proteins such as n-acetyl-beta-glucosaminidase (beta-NAG) and retinol binding protein (RBP) indicate proximal tubular dysfunction, and may identify diabetic patients at risk of developing diabetic nephropathy. In a trial to assess renal tubular function, urinary excretion of beta-NAG (by colorimetric assay) and RBP (by ELISA) were determined in 59 type 1 diabetic patients (mean age 15 +/- 3.2 yr). Of the 59 patients, 11 were microalbuminuric while 48 had normal urinary albumin excretion (UAE). Patients were compared with 40 matched healthy subjects. Diabetic patients with microalbuminuria (n = 11) had concomitant renal tubular disorder indicated by high urinary beta-NAG in all (100%) and RBP in 10 (90.9%) of them. Meanwhile, patients without microalbuminuria (n = 48) had both tubular markers excreted in urine in significantly higher amounts than controls (mean beta-NAG = 6.88 vs. 3.76 U/g Cr, p < 0.001; RBP = 386.6 vs. 151.8 microg/dL, p < 0.001). Among those patients, 29 (61%) had raised urinary beta-NAG activity, and 39 (82%) had increased loss of RBP in urine. A significant correlation was found between urinary beta-NAG and RBP in normoalbuminuric patients (r = 0.66, p < 0.001), as well as between each of the two tubular markers and HbA1c (r = 0.83, p < 0.001). At 30 and 36 months of follow-up, two out of 48 (4.2%) diabetic patients developed persistent microalbuminuria. Both had elevated baseline HbA1C, and urinary beta-NAG. In conclusion, proximal tubular dysfunction may occur independent of glomerular alteration. Whether tubular markers precede the development of microalbuminuria needs further study.
 ...
PMID:Urinary excretion of n-acetyl-beta-D-glucosaminidase and retinol binding protein as alternative indicators of nephropathy in patients with type 1 diabetes mellitus. 1501 73

We investigated the relationship between the levels of serum albumin (ALB), serum transthyretin (TTR) or retinol binding protein (RBP) and those of serum cystatin C or clinical gradings in patients with diabetic nephropathy. Serum samples were obtained from 85 patients with type 2 diabetic nephropathy in our hospital. The levels of serum ALB, TTR, RBP and cystatin C were measured by the Dade Behring assay system using the automated Dade Behring Nephelometer II (BN II). The grades of diabetic nephropathy were classified into five groups according to Report of the Ministry of Health and Welfare, Japan. The serum levels of RBP showed a significant correlation between the serum levels of cystatin C and the grades of diabetic nephropathy. However, the serum levels of TTR were not significantly correlated with those of serum cystatin C or the grades of diabetic nephropathy. In this study, the serum levels of TTR were not influenced by renal function although those of RBP and ALB were influenced by renal function. In spite of clinical usefulness in the nutritional assessment of healthy controls and hemodialysis patients, RBP and ALB are not suitable nutrition marker in patients with chronic renal failure. However, TTR is suitable marker in patients with chronic renal failure.
 ...
PMID:[Effective usage of nutrition assessment proteins in patients with diabetic nephropathy]. 1505 7

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.
 ...
PMID:Urine biomarkers predict the cause of glomerular disease. 1730 Nov 91

Plasma retinol-binding protein 4 (RBP4) may be a new adipokine linked to obesity-induced insulin resistance and type 2 diabetes. The impact of diabetic nephropathy on plasma RBP4 levels, however, is not known. We tested the hypothesis that microalbuminuria is associated with elevated plasma concentrations of RBP4 in type 2 diabetic subjects. Retinol, its binding protein and transthyretin (TTR) were measured in the plasma and urine of 62 type 2 diabetic subjects, 26 of whom had microalbuminuria. The results were compared to 35 healthy control subjects. Despite no differences in plasma retinol, concentrations of the RBP4 were significantly elevated in plasma of diabetic patients and significantly higher in those with microalbuminuria. The higher plasma levels of the binding protein in subjects with microalbuminuria were accompanied by both significantly elevated plasma TTR and increased urinary levels of RBP4. There were no correlations of plasma-binding protein levels and parameters of insulin resistance. Our study suggests that plasma RBP4 levels in type 2 diabetic patients are affected by incipient nephropathy. Therefore, further studies evaluating RBP4 as a regulator of systemic insulin resistance and type 2 diabetes will need to take renal function into consideration.
 ...
PMID:Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients. 1756 82


1 2 Next >>