UMLS:C0033687 - FACTA Search

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

The clustering of cardiovascular risk factors was noted already a century ago, but it is only recently that a link between the CV risk cluster and insulin resistance has been postulated - a proposal which is not unanimously accepted. There is no doubt, however, that obesity per se impacts on renal function and the risk of chronic kidney disease (CKD). Particularly obesity early in life is an important predictor of CKD in adult life, but in adults as well a high body mass index (BMI) is an independent predictor of ESRD. The BMI threshold is lower in Asians. The link between obesity and CKD is not fully explained by the association between obesity and diabetes or hypertension respectively. Obesity is associated with increased glomerular filtration rate and renal blood flow, glomerulomegaly and in extreme cases focal segmental glomerulosclerosis. The causal role of obesity is underlined by the effect of weight loss on proteinuria and glomerular hyperfiltration. An even better predictor than BMI is visceral obesity (waist circumference). For kidney disease in the metabolic syndrome it is relevant that insulin resistance is linked to salt sensitivity and increased tubular reabsorption of sodium. Recent evidence points to adverse effects of aldosterone on podocytes, mediated by reactive oxygen species and resulting from hypothetical stimulants of aldosterone synthesis by visceral adipocytes.
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PMID:Metabolic syndrome and kidney disease. 1818 98

The aim of this study was to evaluate the relationship between the diagnosis of metabolic syndrome (MetS) or its components and the prevalence of microvascular and macrovascular complications in 130 Japanese type 2 diabetic patients. Out of the 130 patients, 58.5% satisfied the criteria of the MetS as defined by the IDF guideline. The results of logistic regression analysis with adjustment for three variables (age, gender and duration of diabetes) revealed that the presence of MetS as defined by the IDF guideline was not independently related to the presence of proliferative retinopathy, proteinuria, neuropathy, or macrovascular disease in the diabetic patients. The waist circumference per se was not associated with diabetic neuropathy, retinopathy, nephropathy, or macrovascular diseases. These results suggest that neither the presence of MetS, as defined by the IDF guideline, nor the waist circumference was associated with the presence of either microvascular or macrovascular complications in Japanese type 2 diabetic patients.
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PMID:Neither the presence of metabolic syndrome as defined by the IDF guideline nor an increased waist circumference increased the risk of microvascular or macrovascular complications in Japanese patients with type 2 diabetes. 1820 78

Aldosterone is traditionally viewed as a hormone regulating electrolyte and blood pressure homeostasis by acting on the distal nephron. Accumulating evidence suggests that aldosterone also plays pathogenetic roles in cardiovascular and renal injury. For example, aldosterone is a potent inducer of proteinuria. We demonstrated that podocyte injury underlies the pathogenesis of proteinuria in aldosterone-infused rats on a high salt diet. Mineralocorticoid receptor was detected in the podocytes in vivo and in vitro, and aldosterone caused induction of its effector kinase Sgk1, activation of NADPH oxidase and generation of reactive oxygen species. Selective aldosterone blocker eplerenone, as well as antioxidant tempol, ameliorated aldosterone-induced podocyte injury and proteinuria. Aldosterone was also involved in the podocyte damage and proteinuria of metabolic syndrome model SHR/NDmcr-cp. Adipocyte-derived aldosterone releasing factors were suggested to contribute to the aldosterone excess of this model. Furthermore, high salt diet markedly worsened the renal injury of SHR/NDmcr-cp. Although salt lowered serum aldosterone levels, it caused MR activation in the kidney. Accordingly, eplerenone dramatically improved the salt-evoked nephropathy. Taken together, aldosterone blockers can be an excellent therapeutic strategy for the treatment of podocyte injury, proteinuria, and cardiovascular and renal complications, not only in high aldosterone states but also in patients with activated MR signaling in the target tissue, whose circulating aldosterone level is not necessarily high. Addition of aldosterone blockers in patients treated with ACEIs or ARBs are also promising, because of "aldosterone breakthrough" phenomenon. Careful monitoring of hyperkalemia is necessary, especially in patients with impaired renal function.
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PMID:Aldosterone and glomerular podocyte injury. 1831 76

In the absence of significant research, we performed a prospective study to examine the association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The study cohort comprised a total of 8329 healthy men, with normal baseline kidney functions and no proteinuria, working in a semiconductor manufacturing company and its 13 affiliates. Alcohol intake was assessed with a self-reported questionnaire. Biochemical tests for liver and metabolic function and abdominal ultrasonography were done. Chronic kidney disease was defined as either the presence of proteinuria or a glomerular filtration rate (GFR) of <60 mL/min per 1.73 m(2). Cox proportional hazards model was used to estimate hazard ratios in the model for CKD. During 26717.1 person-years of follow-up, 324 men developed CKD. Nonalcoholic fatty liver disease was associated with the development of CKD (crude relative risk, 2.18; 95% confidence interval [CI], 1.75-2.71); and this relationship remained significant even after adjustment for age, GFR, triglyceride, and high-density lipoprotein cholesterol (adjusted relative risk [aRR], 1.55; 95% CI, 1.23-1.95). The association between NAFLD and incident CKD was evident in the NAFLD group with elevated serum gamma-glutamyltransferase (GGT) (aRR, 2.31; 95% CI, 1.53-3.50), even after adjustment for age, GFR, triglyceride, and high-density lipoprotein cholesterol, but not in the NAFLD group without elevated GGT (aRR, 1.09; 95% CI, 0.79-1.50) (P = .008 for interaction). To summarize, NAFLD with elevated GGT concentration was associated with an increased CKD risk among nondiabetic, nonhypertensive Korean men, irrespective of metabolic syndrome.
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PMID:Nonalcoholic fatty liver disease predicts chronic kidney disease in nonhypertensive and nondiabetic Korean men. 1832 62

Metabolic syndrome, which is caused by obesity, is now a global pandemic. Metabolic syndrome is an aggregation of hypertension, diabetes and dyslipidaemia. Insulin resistance is a key factor in the development of these components of metabolic syndrome. Concerning the mechanism for the development of hypertension in metabolic syndrome, the lack of insulin resistance in the kidney increases sodium reabsorption by hyperinsulinaemia, leading to sodium retention in the body, and resultant salt-sensitive hypertension. Moreover, hyperaldosteronism, which is caused by adipocyte-derived aldosterone-releasing factors, induces not only salt-sensitive hypertension, but also proteinuria in obese hypertensive rats. Salt loading markedly aggravates proteinuria and induces cardiac diastolic dysfunction in obese hypertensive rats, suggesting that salt and aldosterone exert unfavourable synergistic actions on the cardiovascular system, possibly through the overproduction of oxidative stress. In turn, reactive oxygen species (ROS), which are induced by adipokines such as tumour necrosis factor-alpha, non-esterified fatty acids, angiotensinogen etc., can activate the mineralocorticoid (MR) receptor, in an aldosterone-independent fashion. Therefore, aldosterone/MR activation plays a key role not only in the development of salt-sensitive hypertension, but also in cardiovascular injury in metabolic syndrome, possibly through its function as a feed-forward system.
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PMID:Aldosterone in salt-sensitive hypertension and metabolic syndrome. 1843 32

Women with a history of preeclampsia are characterized by vascular dysfunction and an increased risk of cardiovascular disease. In the present study we investigated whether insulin sensitivity is decreased in women with previous preeclampsia and whether it is associated with endothelium-dependent and/or -independent vasodilation and/or features of metabolic syndrome. Twenty-eight nonobese women with previous severe preeclampsia and 20 women with a previous normotensive pregnancy were studied 5 to 6 years after the index pregnancy. Vasodilation was measured by venous occlusion plethysmography after intra-arterial infusions of sodium nitroprusside and acetylcholine and insulin sensitivity by the intravenous glucose tolerance test using the minimal model technique. The women were tested for lipid profile, inflammatory status and endothelial activation. Insulin sensitivity did not differ between the groups (P=0.24). Insulin sensitivity correlated positively to endothelium-dependent vasodilation only in the patient group in both low (beta=0.59; P=0.04) and high (beta=0.53; P=0.04) concentrations of acetylcholine and in a high concentration of sodium nitroprusside (beta=0.0007; P=0.006). In multivariate analysis, the waist/hip ratio (P=0.04) and serum triglycerides (P=0.04) had the most effect on insulin sensitivity in the patient group. Gestational weeks at the onset of preeclamptic hypertension (P=0.02) and proteinuria (P=0.02) associated positively with insulin sensitivity together with first-trimester body mass index (P=0.008) and maximum diastolic blood pressure during preeclampsia (P=0.005). The present study indicates a relation between insulin sensitivity with vascular dilatory function in women with previous preeclampsia. Furthermore, early onset preeclampsia correlates with impaired insulin sensitivity later in life.
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PMID:A relationship between insulin sensitivity and vasodilation in women with a history of preeclamptic pregnancy. 1857 72

Metabolic syndrome and obesity have causative roles in the development of chronic kidney disease (CKD). CKD leads to end-stage renal disease (ESRD), cardiovascular disease and death. The prevalence of metabolic syndrome is increasing worldwide in both developing and developed countries. Early detection and treatment of metabolic syndrome would be a cost-effective strategy to target the increasing prevalence of ESRD. Therefore, subjects with metabolic syndrome are candidates for CKD screening via dipstick proteinuria testing and serum creatinine measurements. The international community is beginning to share information on CKD through World Kidney Day, Kidney Disease Improving Global Outcomes, Commission for the Global Advancement of Nephrology, International Society of Nephrology and other scientific societies. The Japanese Society of Nephrology initiated the Asian Forum of CKD Initiative 2007 to discuss regional issues related to CKD in Asian countries. The clinical effects of metabolic syndrome vary among ethnic groups. A fundamental scientific question is the ethnic factor for calculating the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease Study equation. The incidence and prevalence of CKD are closely related with lifestyle factors such as diet, exercise, tobacco use, as well as other cultural differences. Research on the relationship between CKD and metabolic syndrome may provide clues to better understand the role of lifestyle-related factors and the age-related decline in GFR.
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PMID:Metabolic syndrome and chronic kidney disease: a Japanese perspective on a worldwide problem. 1858 18

The metabolic syndrome is a risk factor for the development of chronic kidney disease. Angiotensin II type 1 receptor blockers (ARBs) and thiazolidinediones (TZDs) provide renovascular protection, probably in the metabolic syndrome. However, the effect of both agents administered together in patients with metabolic syndrome remains to be determined. The aim of this study was to assess the effects of ARB plus TZD combination therapy in Zucker obese rats fed a high-protein diet, an animal model of metabolic syndrome and renal injury. Zucker obese rats were fed a high-protein diet (OHP; n=6), a high-protein diet containing candesartan, an ARB (OHP+C; n=6), or a high-protein diet containing both candesartan and pioglitazone (OHP+CP; n=6) for 12 weeks. Systolic blood pressure and urinary protein excretion were measured throughout the study, and renal histology and immunohistochemistry were assessed at 12 weeks. OHP rats developed hypertension (157+/-4 mmHg) and proteinuria (178+/-44 mg/d), and these conditions were significantly ameliorated by candesartan (to 143+/-3 mmHg and 84+/-25 mg/d, respectively). Pioglitazone enhanced the antihypertensive and anti-proteinuric effects of candesartan (121+/-3 mmHg, 16+/-8 mg/d, respectively). Histologically, candesartan ameliorated glomerulosclerosis, podocyte injury, interstitial fibrosis and monocyte/macrophage infiltration into the tubulointerstitium in the kidneys of OHP rats. Pioglitazone abrogated residual interstitial fibrosis in the kidneys of OHP+C rats. Our results suggested that pioglitazone augmented the antihypertensive, anti-proteinuric and possibly renal anti-fibrotic actions of candesartan in Zucker obese rats fed a high-protein diet. The combination therapy of ARB and TZD may protect against renal injury in patients with metabolic syndrome.
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PMID:Pioglitazone enhances the antihypertensive and renoprotective effects of candesartan in Zucker obese rats fed a high-protein diet. 1863 87

Risk factors for new-onset diabetes after transplantation (NODAT) need to be assessed in large cohorts. We retrospectively evaluated the impact of early (3 and 6 months after transplantation) proteinuria, urinary albumin excretion (UAE) and arterial pressure on NODAT in 828 Caucasian renal transplant recipients (median follow-up: 5.3 years; 5832 patient-years). The 10- and 20-year incidence of NODAT was 15.0% and 22.0%, respectively. Low-grade (<1 g/day) (HR: 2.04 [1.25-3.33], p = 0.0042) and very low-grade (<0.3 g/day) (HR: 2.21 [1.32-3.70], p = 0.0025) proteinuria were independent risk factors for NODAT. There was a dose-dependent relationship across UAE categories (increasing risk from normoalbuminuria to macroalbuminuria) with NODAT. Tacrolimus, sirolimus and beta-blockers (HR: 1.86 [1.07-3.22], p = 0.0277) were significantly associated with NODAT even after multiple adjustments, but not diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Systolic arterial pressure (HR per 10 mmHg: 1.16 [1.03-1.29], p = 0.0126) and pulse pressure (HR: 1.26 [1.12-1.43], p = 0.0002) were associated with NODAT. Only pulse pressure remained significant after adjustments. Patients at highest risks had early proteinuria and pulse pressure >60 mmHg. Early low-grade proteinuria and pulse pressure (in addition to beta-blockers) constitute independent risk factors for NODAT; they may be markers of the metabolic syndrome and/or vascular damage in renal transplant recipients.
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PMID:Early pulse pressure and low-grade proteinuria as independent long-term risk factors for new-onset diabetes mellitus after kidney transplantation. 1869 75

We examined the hypothesis that senescence represents a proximate mechanism by which the kidney is damaged in type 2 diabetic nephropathy (DN). As a first step, we studied whether the senescence-associated beta-galactosidase (SA-beta-Gal) and the cell cycle inhibitor p16INK4A are induced in renal biopsies from patients with type 2 DN. SA-beta-Gal staining was approximately threefold higher (P < 0.05) than in controls in the tubular compartment of diabetic kidneys and correlated directly with body mass index and blood glucose. P16INK4A expression was significantly increased in tubules (P < 0.005) and in podocytes (P = 0.04). Nuclear p16INK4A in glomeruli was associated with proteinuria (P < 0.002), while tubular p16INK4A was directly associated with body mass index, LDL cholesterol, and HbA1c (P < 0.001-0.05). In a parallel set of experiments, proximal tubule cells passaged under high glucose presented a limited life span and an approximately twofold increase in SA-beta-Gal and p16INK4A protein. Mean telomere lengths decreased approximately 20% as an effect of replicative senescence. In addition, mean telomere decreased further by approximately 30% in cells cultivated under high glucose. Our results show that the kidney with type 2 diabetic nephropathy displays an accelerated senescent phenotype in defined renal cell types, mainly tubule cells and, to a lesser extent, podocytes. A similar senescent pattern was observed when proximal tubule cell cultures where incubated under high-glucose media. These changes are associated with shortening tubular telomere length in vitro. These findings indicate that diabetes may boost common pathways involving kidney cell senescence, thus reinforcing the role of the metabolic syndrome on biological aging of tissues.
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PMID:Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy. 1876 88

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