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)

There is evidence that increased excretion of urinary enzymes and low-molecular mass proteins indicate impaired tubular function. The excretion of N-acetyl-beta-D-glucosaminidase (NAG), lysozyme, and ribonuclease in Type I diabetic patients with (n = 19) and without (n = 17) persistent proteinuria (urinary protein excretion greater than 0.5 g/day) was investigated and compared with this excretion in 30 weight- and gender-matched nondiabetic subjects without renal disease. Urinary NAG excretion was significantly higher in diabetic patients with and without persistent proteinuria (1.16 +/- 0.09 and 3.19 +/- 1.2 Umol/L creatinine, respectively) compared to controls (0.37 +/- 0.03 Umol/L creatinine p less than 0.01). In addition, the urinary excretion of lysozyme and ribonuclease was significantly increased in diabetic patients. Urinary NAG was found to correlate positively with albuminuria and proteinuria (r = 0.95 and 0.93, respectively), as well as with ribonuclease and lysozyme (r = 0.93 and 0.60; p less than 0.01) in patients with persistent proteinuria. Furthermore, NAG excretion was significantly related to the duration of diabetes (r = 0.36; p less than 0.05). No relationship existed between urinary NAG and serum creatinine, beta-2-microglobulin, and degree of metabolic control (HbA7). The lysozyme excretion, but not NAG excretion, was significantly related to hypertension in patients with clinical proteinuria. In conclusion, our results suggest a relationship between the development of tubular dysfunction and the impairment of glomerular function in diabetic nephropathy. An increased excretion of NAG and low-molecular mass proteins may indicate early nephropathy
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PMID:Further evidence for tubular dysfunction in insulin dependent diabetes. 252 61

The urinary enzymes alanine amino-peptidase, alkaline phosphatase, gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase and the two urine low-molecular mass proteins lysozyme and ribonuclease were measured in 30 healthy men and 36 insulin-dependent diabetics. 17 diabetics had "clinical proteinuria" (greater than 7.5 g/mol creatinine) and were defined as patients with manifest diabetic nephropathy. The remaining 19 diabetics were without proteinuria. The excretion rates of the two urine proteins and all enzymes except for gamma-glutamyltransferase were the highest in patients suffering from diabetic nephropathy. The excretion rates in both diabetic groups exceeded those of the control group. N-Acetyl-beta-D-glucosaminidase was more often increased than albumin in diabetics without manifest diabetic nephropathy. It is concluded that the tubular dysfunction is an early indicator of the incipient diabetic nephropathy. Thus, tubular parameters, especially the lysosomal enzyme N-acetyl-beta-D-glucosaminidase may be used in follow-up studies of diabetics.
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PMID:[Urine enzymes and low molecular weight proteins as indicators of diabetic nephropathy]. 273 55

We measured the excretion rates of six urinary enzymes that either originate from the proximal renal tubule, like alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), and N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), or that are typical low-molecular-mass proteins, like lysozyme (EC 3.2.1.17) and pancreatic ribonuclease (EC 3.1.27.5). These rates were compared with those of total protein and albumin in urine of 36 insulin-dependent diabetic men and 30 healthy men. Seventeen of the diabetics had "clinical proteinuria," defined as excretion of more than 7.5 g of protein per mole of urinary creatinine (group B). Group A comprised the 19 diabetics without proteinuria. Except for gamma-glutamyltransferase, the excretions of enzymes and proteins were significantly higher in diabetics than in controls and were greater in group B than in group A. N-Acetyl-beta-D-glucosaminidase was the analyte most often increased in group A (89%), followed by albumin and alkaline phosphatase (each 32%). All patients in group B showed increased excretion of N-acetyl-beta-D-glucosaminidase. We conclude from the comparative data that this enzyme may be useful as an early predictor of diabetic nephropathy.
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PMID:Urinary enzymes and low-molecular-mass proteins as indicators of diabetic nephropathy. 289 6

Seeking to study whether measurement of lysozyme (EC 3.2.1.17) in urine by a reliable radioimmunoassay can provide a suitable index of renal tubular function and how lysozymuria develops in temporal relation to proteinuria in diabetic nephropathy, we have compared the urinary excretion of lysozyme and beta 2-microglobulin with the 15-min excretion rate of phenolsulfonphthalein in 39 patients with Type 2 (non-insulin-dependent) diabetes and investigated the temporal relation between the onset of lysozymuria and proteinuria in 15 patients with Type 1 (insulin-dependent) diabetes. The concentrations of lysozyme and beta 2-microglobulin in urine increased in proportion to the decrease in the rate of excretion of phenolsulfonphthalein in these patients. The coefficient of correlation between lysozyme concentration and the 15-min excretion rate of phenolsulfonphthalein (r = -0.70) was higher than that between beta 2-microglobulin concentration and the 15-min excretion rate of phenolsulfonphthalein (r = -0.46). Abnormally high lysozymuria, suggesting the existence of tubular dysfunction, was demonstrated in six of the patients with Type 1 diabetes who showed no proteinuria or only a slight increase in urinary protein excretion. Lysozymuria may thus be added to a list of the indicators for diabetic nephropathy.
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PMID:Determination of urinary lysozyme for potential detection of tubular dysfunction in diabetic nephropathy. 353 May 28

Currently, there is no effective treatment for diabetic microangiopathy. We have been examining, therefore, the effects of lysozyme on the renal conditions of spontaneous diabetic mice (NSY mice). We assessed the changes in glomerulus following the administration of lysozyme, using the thickness of the glomerular capillary basement membrane as an indicator. Littermate, male F19 NSY mice were divided into two groups. One of the groups (Group L) was treated with lysozyme; the other control group (Group C) with physiological saline. Group L received a daily intramuscular injection of lysozyme solution for 4 or 8 weeks. The thickness of the glomerular capillary basement membrane was measured in order to assess the effect of lysozyme administration. In the 4-week series, the thickness was 4783 +/- 1760 A in Group C and 3266 +/- 777 A in Group L, while in the 8-week series it was 6011 +/- 2043 A in Group C and 3540 +/- 431 A in Group L. In both series of Group L, a distinct inhibitory effect on the basement membrane thickening was found. The present findings suggest that lysozyme may be effective in human diabetic nephropathy. However its clinical usefulness must be confirmed in future studies.
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PMID:The inhibitory effect of lysozyme on the glomerular basement membrane thickening in spontaneous diabetic mice (NSY mice). 373 16

Proteinuria is one of the bad prognostic indices in renal disease. This study compares the pattern of protein excretion in 10 patients with IgA nephropathy (IgAN), 10 patients with chronic glomerulonephritis approaching end-stage renal failure (ESRF) who still had proteinuria and 10 other patients with diabetic nephropathy (DN) with proteinuria but normal renal function. The pattern of proteinuria was analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing (IEF) and assayed for orosomucoid, alpha-1-microglobulin, retinol-binding protein, lysozyme, beta-2-microglobulin and N-acetyl-beta-D-glucosaminidase activity. Our data showed much similarity in the pattern of proteinuria between the DN and ESRF groups but significant differences with the IgAN group. The pattern of proteinuria in the IgAN group reflects glomerulonephritis whereas the similar pattern between the ESRF and DN groups may reflect hyperfiltration as well as tubular injury.
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PMID:Pattern of proteinuria in tubular injury and glomerular hyperfiltration. 939 12

Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications. The purpose of this study was to examine the novel coumarin-aspirin compound XLF-III-43 in the inhibition of AGE formation in diabetic nephropathy. In vitro analysis showed XLF-III-43 in a dose-dependent manner decreased glucose induced formation of glycation adducts on albumin and inhibited AGE-lysozyme crosslinking. The streptozotocin-induced diabetic rats were used to investigate the beneficial effects of XLF-III-43 treatment on diabetic nephropathy. Administration of XLF-III-43 significantly decreased (P<0.05) blood urea nitrogen and urinary albumin excretion. Moreover, XLF-III-43 ameliorated kidney hypertrophy, mesangial expansion and glomerulosclerosis in diabetic rats relative to untreated model group. These data correlated with decreased both AGE and downstream markers of AGE stress (TGF-beta1, CTGF, fibronectin and collagen IV fibrolysis) in kidneys of diabetic rats. These data support further development of XLF-III-43 for prevention of nephropathy via inhibition of AGE formation consequent to chronic hyperglycemia.
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PMID:XLF-III-43, a novel coumarin-aspirin compound, prevents diabetic nephropathy in rats via inhibiting advanced glycation end products. 1989 8

Urinary lactic dehydrogenase, alkaline phosphatase and lysozyme determinations were performed on 70 patients with various kidney diseases such as acute and chronic pyelonephritis, acute and chronic glomerulonephritis, idiopathic nephrotic syndrome, diabetic nephropathy, nephrosclerosis, lupus nephritis, analgesic nephropathy, gouty nephropathy, renal tuberculosis, renal lithiasis, and polycystic kidneys. Fifty-three of these patients had elevated levels of urinary lactic dehydrogenase, but this was not of any value in determining the etiology of the renal disease. Similarly, the elevation of alkaline phosphatase in 23 of the 70 had no etiological significance. Neither of these determinations was significant in indicating the degree of renal functional impairment or prognosis. The urinary lysozyme was significantly elevated in only five of the 70 patients and was of no value in indicating the presence or the seriousness of the underlying renal disease.
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PMID:Urinary lactic dehydrogenase, alkaline phosphatase and lysozyme studies in renal disease. 2032 65

Diabetic nephropathy is the leading cause of chronic renal disease and one of the major causes of cardiovascular mortality. Evidence suggests that its progression is due to the chronic hyperglycemia consequent to the production and accumulation of advanced glycation endproducts (AGEs). Lysozyme was shown to posses AGE-sequestering properties and the capacity to reduce the severity of the early stage manifestations of the diabetic nephropathy. This study was aimed to contribute to the understanding the molecular mechanisms of lysozyme effectiveness in the diabetic nephropathy, using an in-vitro cellular model, represented by the HK-2 cells, human proximal tubular epithelial cells. Lysozyme significantly reduced the AGE-induced IL-6 mRNA and an ELISA assay showed also a decreased release of the functional protein with a dose-dependent trend. In addition, lysozyme prevented macrophage recruitment, suggesting its capacity to elicit an anti-inflammatory action. We may conclude that the protective action of lysozyme on the nephrotoxic effects of AGE may depend, at least in part, on its ability to prevent the production and release of inflammatory mediators, such as IL-6 and to reduce macrophage recruitment in the inflammatory sites.
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PMID:Human recombinant lysozyme downregulates advanced glycation endproduct-induced interleukin-6 production and release in an in-vitro model of human proximal tubular epithelial cells. 2449 50