Association of ANCA associated vasculitis and rheumatoid arthritis: a lesser recognized overlap syndrome

Background ANCA associated vasculitis (AAV) is an autoimmune disease with significant morbidity and mortality, in which diagnostic delay is associated with worse outcomes. AAV is rarely found in association with other immune mediated diseases. Early recognition of such overlaps enables more timely diagnosis and may impact on disease outcome. We reviewed cases of AAV in which there was an overlap with rheumatoid arthritis (RA). Methods We performed a retrospective analysis of our vasculitis database for patients who had a diagnosis of AAV and RA, and a literature search to find other reported cases of this overlap syndrome. Results We found six subjects who had a diagnosis of RA and developed AAV at a median of 10.5 years (range 4–43 years) after the diagnosis of RA. They had been treated with a mean of 2 disease modifying drugs (0–4) and all had evidence of renal involvement with median creatinine of 227 μmol/l (range 128–700 μmol/l). Only one had a diagnosis of granulomatosis with polyangiitis, while the rest had a clinical diagnosis of microscopic polyangiitis. Half of the patients had positive rheumatoid factor (RhF) at the time of vasculitis diagnosis, three had MPO-ANCA, one PR3-ANCA, and two had ANCA-negative pauci-immune vasculitis. Additionally, we found 29 other cases reported of this overlap, which also most frequently presented with vasculitic renal manifestations, and were frequently RhF positive at the time of AAV diagnosis. Conclusions AAV occurs in subjects with RA rarely, and often with significant delay from the first rheumatological manifestations. Renal involvement is commo

Hyperhomocysteinemia in chronic renal failure

Homocysteine is a sulfur-containing amino acid derived from the metabolism of methionine, whose abnormal accumulation in plasma is a risk factor for vascular disease in the general population and in patients with chronic renal disease. In these patients, the prevalence of individuals with hyperhomocysteinemia is very high, even in the pre-dialysis stage of the disease. The main factor that seems to be implicated on the elevation of homocysteine levels in this population is the renal mass loss, considering that the kidney has an important role in the metabolism of such amino acid. The treatment of hyperhomocysteinemia consists on supplementation of the vitamins that are involved in the homocysteine metabolism (folate, B6 and B12.). However, for chronic renal disease patients, this treatment is not completely effective, because although it promotes reduction of homocysteine levels, the normalization is not reached in the majority of the patients. This study reviews the hyperhomocysteinemia etiology on chronic renal disease, its main determinants, its relationship with vascular diseases, and the modes of treatment.A homocisteína é um aminoácido sulfurado proveniente do metabolismo da metionina, cujo acúmulo anormal no plasma é um fator de risco para doenças vasculares, tanto na população em geral como nos pacientes com insuficiência renal crônica. Nestes, a prevalência de indivíduos com hiperhomocisteinemia é bastante elevada, mesmo na fase não dialítica da doença, em que a função renal está diminuída, mas ainda não é necessário tratamento dialítico. O principal fator que parece estar implicado na elevação dos níveis de homocisteína nestes pacientes com insuficiência renal crônica é a perda da massa renal, já que esta exerce uma importante função no metabolismo desse aminoácido. O tratamento da hiperhomocisteinemia na população em geral consiste na suplementação com as vitaminas envolvidas no seu metabolismo (folato, B6 e B12). Porém, em pacientes com insuficiência renal crônica, este tratamento não é completamente eficaz, pois apesar de promover a redução dos níveis de homocisteína, não alcança a normalização dos mesmos na maioria dos pacientes. Este estudo compreende uma revisão da etiologia da hiperhomocisteinemia na insuficiência renal crônica, sua relação com as doenças vasculares, seus principais determinantes e as formas de tratamento.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

[social Cohesion And Regional Integration: The Mercosur Social Agenda And The Integrationist Social Policy Major Challenges].

In the consolidation of the Southern Cone Common Market (MERCOSUR), social policies are still in the embryonic stage. However, since the latter half of the 1990s there has been a speedup in the creation of institutions dedicated to such policies with the Common Market's framework. This article focuses on health policy and the broader social policy system in order to identify the reasons for the imbalance, through three movements: reconstitution of the history of the institutional construction of social policies in MERCOSUR; identification and comparison of the successive strategies for the formulation and implementation of the social integration agenda; and reflection on the current dilemmas and challenges faced by the process. According to the study, MERCOSUR operates with strategies that are difficult to mutually reconcile. On the institutional level, it follows a minimalist strategy, while on the conceptual/ discursive level it adopts a maximalist strategy for supranational unification of social policies. The fact is that it operates a minimalist social policy strategy, since it fails to bring to the field of social integration the debate and proposals on economic and social development models that could sustain the effective construction of regional social citizenship.23 Suppl 2S174-8

New Biomarkers in Acute Tubulointerstitial Nephritis: A Novel Approach to a Classic Condition

Acute tubulointerstitial nephritis (ATIN) is an immunomediated cause of acute kidney injury. The prevalence of ATIN among the causes of acute kidney injury (AKI) is not negligible, especially those cases related to certain drugs. To date, there is a lack of reliable non-invasive diagnostic and follow-up markers. The gold standard for diagnosis is kidney biopsy, which shows a pattern of tubulointerstitial leukocyte infiltrate. The urinalysis findings can aid in the diagnosis but are no longer considered sensitive or specific. Atthe present time, there is a rising attentiveness tofinding trustworthy biomarkers of the disease, with special focus in urinary cytokines and chemokines that may reflect kidney local inflammation. Cell-based tests are of notable interest to identify the exact drug involved in hypersensitivity reactions to drugs, manifesting as ATIN. Certain single-nucleotide polymorphisms in HLA or cytokine genes may confer susceptibility to the disease according to pathophysiological basis. In this review, we aim to critically examine and summarize the available evidence on this topic

Social cohesion and regional integration: the MERCOSUR social agenda and the integrationist social policy major challenges

In the consolidation of the Southern Cone Common Market (MERCOSUR), social policies are still in the embryonic stage. However, since the latter half of the 1990s there has been a speedup in the creation of institutions dedicated to such policies with the Common Market's framework. This article focuses on health policy and the broader social policy system in order to identify the reasons for the imbalance, through three movements: reconstitution of the history of the institutional construction of social policies in MERCOSUR; identification and comparison of the successive strategies for the formulation and implementation of the social integration agenda; and reflection on the current dilemmas and challenges faced by the process. According to the study, MERCOSUR operates with strategies that are difficult to mutually reconcile. On the institutional level, it follows a minimalist strategy, while on the conceptual/ discursive level it adopts a maximalist strategy for supranational unification of social policies. The fact is that it operates a minimalist social policy strategy, since it fails to bring to the field of social integration the debate and proposals on economic and social development models that could sustain the effective construction of regional social citizenship.As políticas sociais se encontram em estágio ainda embrionário nos processos constitutivos do MERCOSUL. Entretanto, desde a segunda metade dos anos 1990, acelerou-se o processo de construção das instituições a elas dedicadas no interior do sistema institucional do mercado comum. Tendo por foco a política de saúde e mais amplamente o sistema de políticas sociais, o artigo rastreia as razões do desequilíbrio através de três movimentos: a reconstituição da trajetória de construção institucional do MERCOSUL social; a identificação e confronto das sucessivas estratégias de formulação e implantação da agenda social da integração; e a reflexão sobre os dilemas e desafios que hoje cercam o tema. O estudo permite afirmar que o MERCOSUL opera com estratégias de difícil conciliação. No plano institucional, orienta-se por uma estratégia minimalista, enquanto que no plano conceitual/discursivo, maneja a estratégia maximalista da unificação supranacional das políticas sociais. O fato é que opera uma estratégia minimalista de políticas sociais, uma vez que abdica de trazer para o campo da integração social o debate e a proposição de modelos de desenvolvimento econômico e social que possam sustentar o processo efetivo de constituição da cidadania social regional.S174S18

Serum albumin as nutritional marker of hemodialysis patients

The prevalence of protein-energy malnutrition is high in patients with chronic renal failure on long-term hemodialysis therapy. Among several parameters available for the assessment of nutritional status, albumin has been the most commonly used given its strong association with morbidity and mortality in those patients. However, many factors such as age, comorbidities, hypervolemia and body losses, can affect the serum albumin concentration. Furthermore, the albumin metabolism can be altered in the presence of inflammation, a common condition in this group of patients. Thus, this communication aimed to address the general aspects of albumin and discuss its usefulness for assessing nutritional status in chronic renal failure patients undergoing hemodialysis.A prevalência de desnutrição protéico-energético em pacientes com insuficiência renal crônica submetidos à terapia de hemodiálise é elevada. Dentre os diversos parâmetros disponíveis para a avaliação do estado nutricional, a albumina tem sido o mais comumente utilizado para este fim visto a sua estreita associação com a morbidade e mortalidade nesta população. No entanto, vários fatores como idade, comorbidades, hipervolemia e perdas corpóreas podem influenciar as concentrações séricas de albumina. Além disso, na vigência de inflamação, condição comumente presente neste grupo de pacientes, o metabolismo da albumina pode encontrar-se alterado, influenciando os seus níveis plasmáticos. Sendo assim, esta comunicação tem como objetivo abordar os aspectos gerais da albumina e discutir a sua utilização na avaliação do estado nutricional de pacientes com insuficiência renal crônica submetidos à hemodiálise.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPM, Depto. de MedicinaUNIFESP, EPMSciEL

T-lymphocyte in ANCA-associated vasculitis: what do we know? A pathophysiological and therapeutic approach

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune condition that commonly causes kidney impairment and can be fatal. The key participation of B-lymphocytes as ANCA producers and neutrophils as target of these antibodies is widely described as the mechanism of endothelial damage in this disease. There has been a rising interest in the role of T-lymphocytes in AAV in recent years. Evidence is strong from animal models, and T-lymphocytes can be found infiltrating kidney tissue and other tissue sites in AAV patients. Furthermore, the different subsets of T-lymphocytes are also key players in the aberrant immune response observed in AAV. Polarization towards a predominant Th1 and Th17 response in the acute phase of the disease has been described, along with a decline in the number of T-regulatory lymphocytes, which, in turn, show functional impairment. Interactions between different T-cell subsets, and between T-cells and neutrophils and B-cells, also enhance the inflammatory response, constituting a complex network. Novel therapies targeting T-cell immunity are emerging in this scenario and may constitute an interesting alternative to conventional therapy in selected patients. This review aims to summarize the available evidence regarding T-cell imbalances and functional impairment, especially focusing on renal involvement of AAV

Short-term effects of a very-low-protein diet supplemented with ketoacids in nondialyzed chronic kidney disease patients

Objective: To evaluate the effects on the nutritional and metabolic parameters of a very-low-protein diet supplemented with ketoacids (VLPD+KA) in comparison with a conventional low-protein diet (LPD) in chronic kidney disease (CKD) patients.Design: Prospective, randomized, controlled clinical study.Setting: Outpatient Clinic of the Nephrology Division of Federal University of São Paulo, Brazil.Subjects: the study involved 24 patients with advanced CKD ( creatinine clearance <25 ml/min) that were randomly assigned to either a VLPD+KA (VLPD+KA group, 12 patients) or to a conventional LPD with 0.6 g/kg/day ( LPD group, 12 patients). the patients were followed for 4 months.Results: Nutritional status was adequately maintained with both diets for the studied period. Protein intake and serum urea nitrogen decreased significantly only in the VLPD+KA group ( from 0.68 +/- 0.17 to 0.43 +/- 0.12 g/kg/day, P<0.05; from 61.4 +/- 12.8 to 43.6 +/- 14.9 mg/dl, P<0.001; respectively). Ionized calcium did not change in the VLPD+KA group but tended to decrease in the LPD group. Serum phosphorus tended to decrease in the VLPD+KA group probably as a result of a significant reduction in dietary phosphorus (529 +/- 109 to 373 +/- 125 mg/day, P<0.05) associated to the phosphorus-binding effect of the ketoacids. No change in these parameters was found in the LPD group. Serum parathormone increased significantly only in the LPD group (from 241 +/- 138 to 494 +/- 390 pg/ ml, P<0.01). the change in PTH concentration was negatively correlated with changes in ionized calcium concentration ( r = - 0.75, P = 0.02) and positively correlated with changes in serum phosphorus ( r = 0.71, P = 0.03) only in the LPD group.Conclusion: This study indicates that a VLPD+KA can maintain the nutritional status of the patients similarly to a conventional LPD. Besides, an improvement in calcium and phosphorus metabolism and a reduction in serum urea nitrogen were attained only with the VLPD+KA. Thus, VLPD+KA can constitute another efficient therapeutic alternative in the treatment of CKD patients.Sponsorship: This study was supported by CAPES, Oswaldo Ramos Foundation and Fresenius Kabi, Ltda.Universidade Federal de São Paulo, Nutr Program, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Nutr Program, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilWeb of Scienc