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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic syndrome (MS) is a known cardiovascular risk factor in the general population and a common problem among renal transplant recipients. This study investigated whether MS after renal transplantation affected long-term graft function. We included 112 transplants at our center between 2000 and 2002. We excluded patients with the presence of pretransplant diabetes or nonstable renal function at 1 year after transplantation. We evaluated parameters such as demographic features, medications, smoking history, body mass index, daily proteinuria, blood pressure, number of HLA mismatches, number of acute rejection episodes, delayed graft function, and laboratory parameters. Patients were followed for a mean of 69.86 +/- 21.94 months. The prevalence of MS was determined using the National Cholesterol Education Program-Adult Treatment Panel III criteria. At 1 year after transplant, 28.6% of subjects had MS, whereas only 10.7% had MS before transplantation. Among 27.7% of patients graft failure had occurred during the follow-up; MS was more frequent among these individuals compared with those displaying stable renal function (51.6% vs 19.8%; P = .002). Older donor age, delayed graft function, acute rejection episodes, smoking history, MS, proteinuria, serum creatinine level, and C-reactive protein were associated with graft failure. Upon multivariate Cox regression analysis, patients with MS at 1 year after transplantation showed an increased risk for graft failure (relative risk, 0.22; 95% confidence interval, 0.06-0.75; P = .016). Older donor age and proteinuria level were other independent risk factors for graft failure. The MS was a prominent risk factor for graft failure. Because MS is a cluster of modifiable risk factors, early identification of patients at risk and intervention in due time may improve graft survival.
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PMID:Metabolic syndrome is related to long-term graft function in renal transplant recipients. 1976 41

Proteinuria is a major health-care problem that affects several hundred million people worldwide. Proteinuria is a cardinal sign and a prognostic marker of kidney disease, and also an independent risk factor for cardiovascular morbidity and mortality. Microalbuminuria is the earliest cue of renal complications of diabetes, obesity, and the metabolic syndrome. It can often progress to overt proteinuria that in 10-50% of patients is associated with the development of chronic kidney disease, ultimately requiring dialysis or transplantation. Therefore, reduction or prevention of proteinuria is highly desirable. Here we review recent novel insights into the pathogenesis and treatment of proteinuria, with a special emphasis on the emerging concept that proteinuria can result from enzymatic cleavage of essential regulators of podocyte actin dynamics by cytosolic cathepsin L (CatL), resulting in a motile podocyte phenotype. Finally, we describe signaling pathways controlling the podocyte actin cytoskeleton and motility and how these pathways can be manipulated for therapeutic benefit.
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PMID:Proteinuria: an enzymatic disease of the podocyte? 1992 1

Accumulating clinical evidence indicates that impaired glucose tolerance is a common phenomenon in essential hypertension. Although recent evidence underscores the role of heme-oxygenase (HO) in diabetes, its effects on insulin sensitivity and glucose metabolism in spontaneously hypertensive rat (SHR), a model of essential hypertension with characteristics of metabolic syndrome including insulin resistance/impaired glucose metabolism remains largely unclear. Here we report the effects of the HO inducer, hemin, and the HO blocker, chromium-mesoporphyrin on insulin sensitivity and glucose metabolism in SHRs. Adult SHRs were severely hypertensive but normoglycemic. Hemin therapy lowered blood pressure, increased plasma insulin, decreased glycemia, and enhanced insulin sensitivity by improving glucose tolerance (ip glucose tolerance test) and insulin tolerance (ip insulin tolerance test) but reduced insulin resistance (homeostasis model assessment index). These effects were accompanied by increased gastrocnemius muscle HO-1, HO activity, cGMP, cAMP alongside antioxidants including bilirubin, ferritin, superoxide dismutase, catalase, and the total antioxidant capacity, whereas oxidative/inflammatory mediators like 8-isoprostane, nuclear-factor-kappaB, activating-protein-1, activating-protein-2, c-Jun-NH2-terminal-kinase, and heme were abated. Furthermore, hemin reduced proteinuria/albuminuria and enhanced the depressed levels of adiponectin, AMP-activated protein-kinase, and glucose transporter-4 in SHRs, suggesting that although SHRs are normoglycemic, insulin signaling and renal function may be impaired. Contrarily, the HO inhibitor chromium-mesoporphyrin exacerbated oxidative stress, aggravated insulin resistance, glucose tolerance, insulin tolerance and nephropathy. Hemin also enhanced HO signaling in Wistar Kyoto and Sprague Dawley rats and increased insulin sensitivity albeit less intensely than in SHRs, suggesting greater selectivity of HO in SHRs with dysfunctional insulin signaling. These results suggest that perturbations of insulin signaling may be a forerunner to hyperglycemia in essential hypertension. By concomitantly potentiating insulin-sensitizing agents, suppressing insulin/glucose intolerance, and abating oxidative stress, HO inducers may prevent metabolic and cardiovascular complications in essential hypertension.
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PMID:Up-regulating the heme oxygenase system with hemin improves insulin sensitivity and glucose metabolism in adult spontaneously hypertensive rats. 2001 31

Tempol is a redox-cycling nitroxide that promotes the metabolism of many reactive oxygen species (ROS) and improves nitric oxide bioavailability. It has been studied extensively in animal models of oxidative stress. Tempol has been shown to preserve mitochondria against oxidative damage and improve tissue oxygenation. Tempol improved insulin responsiveness in models of diabetes mellitus and improved the dyslipidemia, reduced the weight gain and prevented diastolic dysfunction and heart failure in fat-fed models of the metabolic syndrome. Tempol protected many organs, including the heart and brain, from ischemia/reperfusion damage. Tempol prevented podocyte damage, glomerulosclerosis, proteinuria and progressive loss of renal function in models of salt and mineralocorticosteroid excess. It reduced brain or spinal cord damage after ischemia or trauma and exerted a spinal analgesic action. Tempol improved survival in several models of shock. It protected normal cells from radiation while maintaining radiation sensitivity of tumor cells. Its paradoxical pro-oxidant action in tumor cells accounted for a reduction in spontaneous tumor formation. Tempol was effective in some models of neurodegeneration. Thus, tempol has been effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage and many of the diseases associated with aging. Indeed, tempol given from birth prolonged the life span of normal mice. However, presently tempol has been used only in human subjects as a topical agent to prevent radiation-induced alopecia.
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PMID:Effects of tempol and redox-cycling nitroxides in models of oxidative stress. 2015 67

Obese persons with metabolic syndrome often have associated with salt-sensitive hypertension, microalbuminuria, and cardiac dysfunction, and the plasma aldosterone level in one-third of metabolic syndrome patients is clearly elevated. Hyperaldosteronism, which may be caused at least partially by certain adipocyte-derived factors, contributes to the development of proteinuria in obese hypertensive rats, and salt loading aggravates the proteinuria and induces cardiac diastolic dysfunction because of inadequate suppression of plasma aldosterone level. However, mineralocorticoid receptor (MR) antagonists prevent salt-induced renal and cardiac damage, suggesting that aldosterone excess and a high-salt diet exert an unfavorable synergistic action on the kidney and heart. In Dahl salt-sensitive rats, however, despite appropriate suppression of plasma aldosterone with a high-salt diet, salt loading paradoxically activated renal MR signaling, and the renal injury was markedly prevented by MR antagonists. Accordingly, we discovered an alternative pathway of MR activation in which Rac1, a small GTP-binding protein, activates MRs. Salt loading activates renal Rac1 in Dahl salt-sensitive rats, and Rac1 in turn induces MR activation, which results in renal injury, and the renal injury has been found to be prevented by Rac1 inhibitors. Moreover, several metabolic syndrome-related factors induce Rac1 activation, and one of them, hyperglycemia, activates MRs via Rac1 activation. Consistent with this, Rac1 inhibitors attenuated the proteinuria and renal injury in obese hypertensive animals. Thus, both salt and obesity activate Rac1 and cause MR activation. Abnormal activation of the aldosterone/MR pathway plays a key role in the development of salt-sensitive hypertension and renal injury in metabolic syndrome.
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PMID:Mineralocorticoid receptors, salt-sensitive hypertension, and metabolic syndrome. 2017 94

Obesity is fast becoming a bane for the present civilization, as a result of sedentary lifestyle, atherogenic diet, and a susceptible thrifty genotype. The concept of metabolic syndrome, which is a constellation of metabolic disturbances, has crystallized over the last 80 years with the aim of identifying those at greater risk of developing type 2 diabetes and cardiovascular disease. These patients have visceral obesity and insulin resistance characterized by hypertyriglyceridemia. Recently, it has been realized that they are also at an increased risk of chronic renal disease. Release of adipocytokines leads to endothelial dysfunction. There is also activation of systemic and local renin-angiotensin-aldosterone system, oxidative stress, and impaired fibrinolysis. This leads to glomerular hyperfiltration, proteinuria, focal segmental glomerulosclerosis (FSGS), and ultimately end-stage renal disease (ESRD). Treatment consists of lifestyle modifications along with optimal control of blood pressure, blood sugar and lipids. Metformin and thiazolidenidiones reduce insulin resistance; while angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria and have a renoprotective effect. Exciting new medical therapies on the horizon include rimonabant a cannabinoid receptor type 1 antagonist, soy proteins, and peroxisome proliferator-activated receptor (PPAR) agonist. Bariatric surgery for morbid obesity has also been shown to be effective in treating metabolic syndrome.
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PMID:Metabolic syndrome and chronic kidney disease. 2036 11

Atherosclerosis is accelerated in people with systemic lupus erythematosus, and the presence of dysfunctional, pro-inflammatory high-density lipoproteins is a marker of increased risk. We developed a mouse model of multigenic lupus exposed to environmental factors known to accelerate atherosclerosis in humans - high-fat diet with or without injections of the adipokine leptin. BWF1 mice were the lupus-prone model; BALB/c were non-autoimmune controls. High-fat diet increased total serum cholesterol in both strains. In BALB/c mice, non-high-density lipoprotein cholesterol levels increased; they did not develop atherosclerosis. In contrast, BWF1 mice on high-fat diets developed increased quantities of high-density lipoproteins as well as elevated high-density lipoprotein scores, indicating pro-inflammatory high-density lipoproteins; they also developed atherosclerosis. In the lupus-prone strain, addition of leptin increased pro-inflammatory high-density lipoprotein scores and atherosclerosis, and accelerated proteinuria. These data suggest that environmental factors associated with obesity and metabolic syndrome can accelerate atherosclerosis and disease in a lupus-prone background.
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PMID:Pro-inflammatory high-density lipoproteins and atherosclerosis are induced in lupus-prone mice by a high-fat diet and leptin. 2041 Jan 56

Recent clinical and experimental studies have shown that aldosterone is a potent inducer of proteinuria and that mineralocorticoid receptor (MR) antagonists confer efficient antiproteinuric effects. We identified glomerular epithelial cells (podocytes) as novel targets of aldosterone; activation of MR injures podocytes possibly via oxidative stress, resulting in disruption of glomerular filtration barrier, proteinuria, and progression of chronic kidney disease. We also demonstrated that SHR/cp, a rat model of metabolic syndrome, was susceptible to podocyte injury and proteinuria. Aldosterone excess caused by adipocyte-derived aldosterone-releasing factors was suggested to underlie the nephropathy. High salt intake augmented MR activation in the kidney and exacerbated the nephropathy. Furthermore, we identified an alternative pathway of MR activation by small GTPase Rac1. RhoGDIalpha knockout mice, a model with Rac1 activation in the kidney, showed albuminuria, podocyte injury, and glomerulosclerosis. Renal injury in the knockout mice was accompanied by enhanced MR signaling in the kidney despite normoaldosteronemia, and was ameliorated by an MR antagonist, eplerenone. Moreover, Rac-specific inhibitor significantly reduced the nephropathy, concomitantly with repression of MR activation. In vitro transfection studies provided direct evidence of Rac1-mediated MR activation. In conclusion, our findings suggest that MR activation plays a pivotal role in the pathogenesis of chronic kidney disease in metabolic syndrome, and that MR may be activated both aldosterone dependently (via aldosterone-releasing factors) and independently (via Rac1). MR antagonists are promising antiproteinuric drugs in metabolic syndrome, although long-term effects on renal outcomes, mortality, and safety need to be established.
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PMID:Activation of the aldosterone/mineralocorticoid receptor system in chronic kidney disease and metabolic syndrome. 2053 72

Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share common features. Both are associated with visceral obesity, type 2 diabetes mellitus, metabolic syndrome, and insulin resistance. However, the relationship between NAFLD and CKD is poorly understood. We examined the prevalence of and risk factors for CKD in patients with NAFLD. We analyzed 174 Japanese patients with liver biopsy-proven NAFLD using a cross-sectional design. Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min per 1.73 m(2) and/or overt proteinuria. Of 174 NAFLD patients, 92 (53%) exhibited histologic characteristics of nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD; and 82 (47%) had non-NASH NAFLD. Chronic kidney disease was present in 24 (14%) of 174 NAFLD patients. The prevalence of CKD was significantly higher in NASH patients (19 of 92; 21%) than non-NASH patients (5 of 82; 6%). The presence of CKD was associated with a higher body mass index and the presence of hypertension and NASH. Our results demonstrated a high prevalence of CKD among patients with NASH.
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PMID:Nonalcoholic steatohepatitis and increased risk of chronic kidney disease. 2081 13

Aldosterone has emerged as a deleterious hormone in the kidney, for example as a potent inducer of proteinuria. We identified the podocyte, the final filtration barrier in the glomerulus, as a novel target of aldosterone. Activation of the mineralocorticoid receptor (MR) in the podocyte disrupts the filtration barrier and induces proteinuria. Recent clinical and experimental studies have shown the efficacy of MR antagonism in reducing albuminuria in patients or rodent models of type 1 and type 2 diabetes. We assessed the pathogenic role of aldosterone in SHR/NDmcr-cp, a rat model of type 2 diabetes/metabolic syndrome. Podocyte injury and proteinuria were early manifestations of nephropathy in this model, and were exacerbated by high-salt feeding. Inappropriate activation of the aldosterone/MR system, possibly via adipocyte-derived aldosterone releasing factors, underlay the renal damage. Furthermore, we identified Rac1, a Rho family small GTPase, as a novel ligand-independent activator of MR. This alternative pathway of MR activation, indeed, contributed to podocyte injury in proteinuric kidney disease. In conclusion, MR can be activated by several different pathways, both aldosterone-dependently and -independently, leading to podocyte impairment and progression of proteinuric kidney disease. MR antagonists are promising anti-proteinuric drugs in diabetes, although hyperkalemia is a concern.
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PMID:Endocrinological aspects of proteinuria and podocytopathy in diabetes: role of the aldosterone/mineralocorticoid receptor system. 2106 6


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