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      Inflamação na doença renal crônica: papel de citocinas Translated title: Inflammation in chronic kidney disease: the role of cytokines

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          Abstract

          A doença renal crônica (DRC) é um grave problema de saúde pública cuja prevalência tem aumentado nos últimos anos. Apresenta caráter progressivo e está associada à elevada morbidade e mortalidade. Inúmeros fatores estão associados à instalação e progressão da DRC, tais como obesidade, hipertensão arterial e diabetes mellitus. Além desses fatores, existem evidências de inflamação na fisiopatologia da DRC. Diversas citocinas e quimiocinas têm sido detectadas no plasma e urina de pacientes em estágios precoces da DRC e também relacionadas às complicações da doença. A expressão desses mediadores e a lesão renal sofrem interferência de fármacos como inibidores de enzima conversora de angiotensina (ECA), estatinas e antagonistas de receptores de citocinas. A modulação da resposta imuno-inflamatória pode se tornar alvo para tratamento da DRC. O objetivo deste artigo de revisão foi resumir as evidências científicas do pa-pel da inflamação na DRC, destacando-se os efeitos de citocinas e quimiocinas.

          Translated abstract

          Chronic kidney disease (CKD) is a serious public health problem whose prevalence has increased in the last few years. Its progression is associated with high morbidity and mortality. Several factors are associated with the onset and progression of CKD, such as obesity, hypertension and diabetes mellitus. Beyond these factors, there is evidence of a pathophysiological role for inflammation in CKD. Several cytokines and chemokines have been detected in the plasma and urine of patients at early stages of CKD, and have also been related to CKD complications. The expression of these mediators and renal injury may be influenced by drugs such as angiotensin-converting enzyme inhibitors, statins and antagonists of cytokine receptors. Modulation of the immune-inflammatory response can become a target for CKD treatment. The aim of this study was to review the scientific evidence on the role of inflammation in CKD, especially the effects of cytokines and chemokines.

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          Renal fibrosis: new insights into the pathogenesis and therapeutics.

          Youhua Liu (2006)
          Renal fibrosis is the inevitable consequence of an excessive accumulation of extracellular matrix that occurs in virtually every type of chronic kidney disease. The pathogenesis of renal fibrosis is a progressive process that ultimately leads to end-stage renal failure, a devastating disorder that requires dialysis or kidney transplantation. In a simplistic view, renal fibrosis represents a failed wound-healing process of the kidney tissue after chronic, sustained injury. Several cellular pathways, including mesangial and fibroblast activation as well as tubular epithelial-mesenchymal transition, have been identified as the major avenues for the generation of the matrix-producing cells in diseased conditions. Among the many fibrogenic factors that regulate renal fibrotic process, transforming growth factor-beta (TGF-beta) is one that plays a central role. Although defective matrix degradation may contribute to tissue scarring, the exact action and mechanisms of the matrix-degrading enzymes in the injured kidney have become increasingly complicated. Recent discoveries on endogenous antifibrotic factors have evolved novel strategies aimed at antagonizing the fibrogenic action of TGF-beta/Smad signaling. Many therapeutic interventions appear effective in animal models; however, translation of these promising results into humans in the clinical setting remains a daunting task. This mini-review attempts to highlight the recent progress in our understanding of the cellular and molecular pathways leading to renal fibrosis, and discusses the challenges and opportunities in developing therapeutic strategies.
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            Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease.

            The epidemics of cardiovascular disease, obesity, diabetes, HIV and cancer have all received much attention from the public, media and policymakers. By contrast, chronic kidney disease (CKD) has remained largely a 'silent' epidemic. This is unfortunate because early diagnosis of renal disease based on proteinuria and/or reduced estimated glomerular filtration rate could enable early intervention to reduce the high risks of cardiovascular events, end-stage renal disease (ESRD) and death that are associated with CKD. Given the global increase in the incidence of the leading causes of CKD--hypertension, obesity and diabetes mellitus--better disease management and prevention planning are needed, as effective strategies are available to slow the progression of CKD and reduce cardiovascular risk. CKD may be regarded as a clinical model of accelerated vascular disease and premature ageing, and the risk-factor profile changes during the progression from mild/moderate CKD to ESRD. Although many randomized controlled trials in patients with mild to moderate CKD have shown beneficial effects of interventions aimed at preventing the progression of CKD, most trials have been unable to demonstrate a beneficial effect of interventions aimed at improving outcome in ESRD. Thus, novel treatment strategies are needed in this high-risk patient group. © 2010 The Association for the Publication of the Journal of Internal Medicine.
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              C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease.

              High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4. The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP [stratified into high CRP > or =3.0 mg/L (N= 414) versus low CRP<3.0 mg/L (N= 283)], and serum albumin, with all-cause and cardiovascular mortality. Median follow-up time was 125 months, all-cause mortality was 20% (N= 138) and cardiovascular mortality was 10% (N= 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07-2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13-3.31), but not serum albumin (HR 0.94, 95% CI 0.87-1.02), was an independent predictor of cardiovascular mortality. Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                jbn
                Jornal Brasileiro de Nefrologia
                J. Bras. Nefrol.
                Sociedade Brasileira de Nefrologia (São Paulo )
                2175-8239
                September 2011
                : 33
                : 3
                : 351-364
                Affiliations
                [1 ] Universidade Federal de Minas Gerais Brazil
                Article
                S0101-28002011000300012
                10.1590/S0101-28002011000300012
                22042353
                f310b7cb-3066-488d-ad0b-b09240c5efba

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0101-2800&lng=en
                Categories
                UROLOGY & NEPHROLOGY

                Urology
                Cytokines,Chemokines,Inflammation,Kidney failure, chronic,Citocinas,Quimiocinas,Inflamação,Falência renal crônica

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