Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the study was to assess TGF-beta and IL-6 urinary excretion (measured with EIA) in 12 IDDM patients (7 F, 5 M, age 20-49 yrs, mean = 33.08) with albuminuria or microalbuminuria. Control group consists of 27 IDDM patients (12 F, 15 M, age 24-59 yrs. mean = 39.5) without albuminuria or microalbuminuria. Urinary excretion of IL-6 was significantly higher (p < 0.05) in IDDM patients with albuminuria (mean = 7.43 +/- 8.29 pg/mg creatinine) than in control group (mean = 3.74 +/- 2.64 pg/mg creatinine). Urinary excretion of TGF-beta was also higher (but not significantly in IDDM patients with albuminuria or microalbuminuria (mean = 42.0 +/- 30.0 pg/mg creatinine) than in control group (mean = 27.0 +/- 20.0 pg/mg creatinine). The data indicate that IL-6 and TGF-beta could be involved in the development of diabetic nephropathy.
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PMID:[Increased urinary excretion of transforming growth factor beta and interleukin-6 in patients with diabetic nephropathy]. 913 74

We investigated whether a relationship exists between circulating transforming growth factor beta -1 (TGF-beta(1)), collagen type I metabolism, microalbuminuria, and left ventricular hypertrophy in essential hypertension and whether the ability of the angiotensin II type 1 receptor antagonist losartan to correct microalbuminuria and regress left ventricular hypertrophy in hypertensives is related to changes in TGF-beta(1) and collagen type I metabolism. The study was performed in 30 normotensive healthy controls and 30 patients with never-treated essential hypertension classified into 2 groups: those with microalbuminuria (urinary albumin excretion >30 and <300 mg/24 h) associated with left ventricular hypertrophy (left ventricular mass index >116 g/m(2) for men and >104 g/m(2) for women) (group B; n=17) and those without microalbuminuria or left ventricular hypertrophy (group A; n=13). The measurements were repeated in all patients after 6 months of treatment with losartan (50 mg once daily). The serum concentration of TGF-beta(1) was measured by a 2-site ELISA method, and the serum concentrations of carboxy-terminal propeptide of procollagen type I (a marker of collagen type I synthesis) and carboxy-terminal telopeptide of collagen type I (a marker of collagen type I degradation) were measured by specific radioimmunoassays. The duration of hypertension and baseline values of blood pressure were similar in the 2 groups of patients. No differences in serum TGF-beta(1), carboxy-terminal propeptide of procollagen type I, and carboxy-terminal telopeptide of collagen type I were found between normotensives and group A of hypertensives. Serum TGF-beta(1), carboxy-terminal propeptide of procollagen type I, and the ratio of carboxy-terminal propeptide of procollagen type I to carboxy-terminal telopeptide of collagen type I were increased (P<0.05) in group B of hypertensives compared with group A of hypertensives and normotensives. No differences in carboxy-terminal telopeptide of collagen type I were found among the 3 groups of subjects. After treatment with losartan, microalbuminuria and left ventricular hypertrophy persisted in 6 patients (then considered nonresponders) and disappeared in 11 patients (then considered responders) from group B. Compared with nonresponders, responders exhibited similar control of blood pressure and higher (P<0.05) blockade of angiotensin II type 1 receptors (as assessed by a higher increase in plasma levels of angiotensin II). Whereas TGF-beta(1), carboxy-terminal propeptide of procollagen type I, and the ratio of carboxy-terminal propeptide of procollagen type I to carboxy-terminal telopeptide of collagen type I decreased (P<0.05) in responders, no changes in these parameters were observed in nonresponders. These findings show that an association exists between an excess of TGF-beta(1), stimulation of collagen type I synthesis, inhibition of collagen type I degradation, and cardiorenal damage in a group of patients with essential hypertension. In addition, our results suggest that the ability of losartan to blunt the synthesis of TGF-beta(1) and normalize collagen type I metabolism may contribute to protect the heart and the kidney in a fraction of patients with essential hypertension.
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PMID:Transforming growth factor beta in hypertensives with cardiorenal damage. 1104 Feb 29

Diabetic nephropathy is major long-term complication of diabetes mellitus a social and civilization-related disease. At present, the most sensitive and non-invasive indicator of the progression of diabetic nephropathy is microalbuminuria. Morphological features such as accumulation of extracellular matrix proteins, thickening of glomerules' basement membranes are prior to microalbuminuria. The aim of our clinical study was to establish whether urine and serum TGF-beta 1 and IL-6 levels may be significant in prognosing and evaluating a risk for developing diabetic nephropathy. The trial was carried out in 68 patients with type II diabetes mellitus and a group of 10 healthy subjects served as control. Urine and serum TGF-beta 1 concentrations were evaluated, as well as, basic laboratory parameters. After one-year-observation serum creatinine level and microalbuminuria value were investigated in 60 patients with type II diabetes mellitus. In patients with type II diabetes mellitus both urine and serum TGF-beta 1 and IL-6 were elevated. After one-year-observation of patients with type II diabetes mellitus it was established that the increase of serum creatinine concentrations values were higher in those patients, whose initial TGF-beta 1 levels exceeded normal values. A positive correlation between urine TGF-beta 1 level and the progression of renal failure measured by the increase of serum creatinine level was observed. In conclusion, our findings indicate that urine TGF-beta 1 and IL-6 levels may be a good prognostic factor of the development of diabetic nephropathy in the course of diabetes mellitus.
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PMID:[Cytokines in noninvasive diagnostics of diabetic nephropathy progression]. 1262 78

Discordant findings are reported on the left ventricular transforming growth factor-beta(1) (TGF-beta(1)) mRNA levels in various rat models. Left ventricular TGF-beta(1) mRNA levels did not differ between spontaneously hypertensive rats (SHR) and normal rats, between deoxycorticosterone (DOCA)-salt and sham-operated hypertensive rats, but were increased in stroke-prone spontaneously hypertensive rats (SHRSP) and in post-myocardial infarction (MI) rats. Renal cortical TGF-beta(1) mRNA levels were, however, higher in DOCA-salt hypertensive rats. Angiotensin II subtype 1 receptor antagonism (AT(1)R) and angiotensin converting enzyme inhibition (ACEI) decreased left ventricular and vascular smooth muscle TGF-beta(1) mRNA levels in SHR and renal TGF-beta(1) mRNA in DOCA-salt hypertensive rats and in SHRSP. In post-MI rats ventricular TGF-beta(1) mRNA decreased by AT(1)R antagonism. In essential hypertensive patients, TGF-beta(1) protein as well as TGF-beta(1) mRNA levels are hyperexpressed. The TGF-beta(1) overproduction in hypertension can be attributed to various factors such as elevated angiotensin II, increased systemic blood pressure (BP) per se, increased fluid shear stress and a differential expression of TGF-beta(1) linked to DNA polymorphism in the promoter. The Arg(25) polymorphism in the TGF-beta(1) gene is associated with higher BP. A higher plasma TGF-beta(1) concentration is found in hypertensive patients with microalbuminuria and left ventricle hypertrophy. In these patients, AT(1)R antagonism and ACEI reduced these plasma TGF-beta(1) levels significantly.
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PMID:Association between transforming growth factor-beta and hypertension. 1285 Mar 97

We evaluated association between hyperinsulinemia/insulin resistance and microalbuminuria in the insulin-resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rat. OLETF rats showed glomerular hyperfiltration (an increase in creatinine clearance and a decrease in fractional excretion of Na) and microalbuminuria at the insulin-resistant prediabetic stage, and both were related to expression of transforming growth factor (TGF)-beta(1) and extracellular matrix protein such as fibronectin and collagen (a(1)) IV. Cilostazol, a selective type III cyclic nucleotide phosphodiesterase (PDE) inhibitor, normalized glomerular hyperfiltration and microalbuminuria with a parallel decline of TGF-beta(1) and extracellular matrix protein mRNA expression. Cilostazol may be beneficial to lessen early glomerular nephropathy in a state of hyperinsulinemia/insulin resistance.
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PMID:Cilostazol, a phosphodiesterase inhibitor, reduces microalbuminuria in the insulin-resistant Otsuka Long-Evans Tokushima Fatty rat. 1553 93

In diabetic nephropathy the extent of matrix accumulation in both glomeruli and the interstitium correlates strongly with the degree of renal insufficiency and proteinuria. Factors responsible for the deposition and accumulation of extra cellular matrix material within the kidney are therefore of considerable interest. Such factors include the potent fibrotic cytokine TGF-beta. We measured serum TGF-beta1 in patients with various stages of diabetic nephropathy, and correlated its level with different biochemical parameters. The study was conducted on: Group I: 30 patients with diabetic nephropathy (Subgroup IA: 20 patients with microalbuminuria; Subgroup IB: 10 patients with overt nephropathy), Group II: 19 diabetic patients without nephropathy (positive control), Group III: 20 healthy volunteers (negative control). Serum creatinine, Fasting and postprandial blood glucose, Fasting serum cholesterol, Glycated haemoglobin (HbA1c), Microalbumin estimation in urine, Serum TGF-beta1 estimation were done for all the studied groups. Our results showed a statistically significantly higher serum TGF-beta1 level in patients with diabetic nephropathy versus diabetic patients without nephropathy (mean +/- SD, 47.66 +/- 21.92 and 27.07 +/- 15.46 respectively) (P<0.001). Also in patients with diabetic nephropathy versus healthy controls (mean +/- SD, 47.66 +/- 21.29 and 27.05 +/- 8.95 respectively) (P<0.001). While serum TGF-beta1 concentrations were almost similar in diabetic patients without nephropathy and in healthy controls. Serum TGF-beta1 was statistically significantly higher in patients with overt nephropathy versus patients with microalbuminuria (mean+/-SD, 73.5 +/- 2.41 and 34.9 +/- 12.41) (P<0.001). Serum TGF-beta1 was significantly positively correlated with albumin excretion rate, fasting and postprandial blood glucose levels, serum cholesterol and HbA1c, these correlations were only found in diabetic patients with nephropathy but not in those without nephropathy or the control group. (r=0.86, P<0.001, r=0.444, P<0.05, r=0.375, P<0.05, r=0.532, P <0.01, r=0.696, P<0.001 respectively. HbA1c was found to be predictor of 68% of changes of serum TGF-beta1 (P<0.001) and serum cholesterol was predictor of 73% of changes of serum TGF-beta1 concentration (P<0.01). In conclusion, our results suggest that TGF-beta1 may play a key role in the development and progression of diabetic nephropathy. Accordingly, it may be also directly implicated in the functional deterioration of the kidney functions seen in patients with diabetic nephropathy, therefore beside proper glycemic control, strategies aiming at antagonizing TGF- beta1 for example by the use of specific antibodies or a specific inhibitor of TGF-beta1 may help to prevent the development or attenuate the progression of nephropathy in diabetic patients.
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PMID:Transforming growth factor-beta 1 in diabetic nephropathy. 1673 45

Endothelin (ET) receptor blockade delays the progression of diabetic nephropathy; however, the mechanism of this protection is unknown. Therefore, the aim of this study was to test the hypothesis that ET(A) receptor blockade attenuates superoxide production and inflammation in the kidney of diabetic rats. Diabetes was induced by streptozotocin (diabetic rats with partial insulin replacement to maintain modest hyperglycemia [HG]), and sham rats received vehicle treatments. Some rats also received the ETA antagonist ABT-627 (sham+ABT and HG+ABT; 5 mg/kg per d; n = 8 to 10/group). During the 10-wk study, urinary microalbumin was increased in HG rats, and this effect was prevented by ET(A) receptor blockade. Indices of oxidative stress, urinary excretion of thiobarbituric acid reactive substances, 8-hydroxy--deoxyguanosine, and H2O2 and plasma thiobarbituric acid reactive substances were significantly greater in HG rats than in sham rats. These effects were not prevented by ABT-627. In addition, renal cortical expression of 8-hydroxy--deoxyguanosine and NADPH oxidase subunits was not different between HG and HG+ABT rats. ETA receptor blockade attenuated increases in macrophage infiltration and urinary excretion of TGF-beta and prostaglandin E2 metabolites in HG rats. Although ABT-627 did not alleviate oxidative stress in HG rats, inflammation and production of inflammatory mediators were reduced in association with prevention of microalbuminuria. These observations indicate that ETA receptor activation mediates renal inflammation and TGF-beta production in diabetes and are consistent with the postulate that ETA blockade slows progression of diabetic nephropathy via an anti-inflammatory mechanism.
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PMID:Endothelin A receptor blockade reduces diabetic renal injury via an anti-inflammatory mechanism. 1716 19

The aim of the study was to determine in a rat model of streptozotocin-induced diabetic nephropathy the expression of: WT-1 (for podocyte loss in the glomerulus), TGF-beta 1 (for tissue damage), caspase-3 and bax (for glomerular apoptosis) and the possible protective effects of an angiotensin II type 1 receptor blocker. Three groups of male Wistar albino rats were used. The first group consisted of non-diabetic control rats. The second group was the untreated diabetic rats. The third group consisted of diabetic rats treated with Irbesartan, which is an angiotensin II receptor antagonist, widely used in treatment for hypertension. Immunohistochemical stainings for TGF-beta 1, bax, caspase-3 and WT-1 were performed. The microalbuminuria levels of the Irbesartan-treated diabetic group were lower than those of the untreated diabetic group (P<0.01). The immunostaining of TGF-beta 1, bax and caspase-3 was decreased in glomeruli of the Irbesartan-treated diabetic group compared to the untreated diabetic group. WT-1 immunopositive podocyte numbers were found to be significantly lower in the untreated diabetic group than in the other groups (P<0.01). In the Irbesartan-treated diabetic group, the WT-1 immunopositive cell numbers were higher compared to the untreated diabetic group (P<0.01). We conclude that the decrease in the number of podocytes is an early marker of diabetic nephropathy, AT1 receptor blocker has renoprotective effects on the regulation of renal hemodynamics and on the control of tissue damage by preventing podocyte loss, which leads to decrease of bax and caspase-3 expressions of apoptosis related proteins, and may prevent glomerular cell apoptosis via angiotensin II.
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PMID:The effects of angiotensin-II receptor blockers on podocyte damage and glomerular apoptosis in a rat model of experimental streptozotocin-induced diabetic nephropathy. 2126 61

The glomerular capillary endothelium is highly specialized to support the selective filtration of massive volumes of plasma. Filtration is driven by Starling forces acting across the glomerular capillary wall, and depends on its large surface area and extremely high water permeability. Glomerular endothelial cells are extremely flat and perforated by dense arrays of trans-cellular pores, the fenestrae. This phenotype is critical for the high glomerular water permeability and depends on podocyte-derived VEGF, as well as TGF-beta. Endothelial cell-derived PDGFB, in turn, is necessary for the establishment of mesangial cells, which sculpt the glomerular loop structure that underlies the large filtration surface area. In pre-eclampsia, inhibition of the VEGF- and TGF-beta signaling pathways leads to endothelial swelling and loss of fenestrae, reducing the glomerular filtration rate. Similarly, in the thrombotic microangiopathies, glomerular endothelial cell injury coupled with inappropriate VWF activation leads to intracapillary platelet aggregation and loss of the flat, fenestrated phenotype, thus reducing the glomerular filtration rate. Normally, a remarkably small fraction of albumin and other large plasma proteins passes across the glomerular capillary wall despite the massive filtration of water and small solutes. An elaborate glycocalyx, which covers glomerular endothelial cells and their fenestrae forms an impressive barrier that, together with other components of the glomerular capillary wall, prevents loss of plasma proteins into the urine. Indeed, microalbuminuria is a marker for endothelial glycocalyx disruption, and most forms of glomerular endothelial cell injury including pre-eclampsia and thrombotic microangiopaties can cause proteinuria.
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PMID:Glomerular endothelium: a porous sieve and formidable barrier. 2246 80