Micro RNA 146a-5p expression in Kidney transplant recipients with delayed graft function / Expressão do Micro RNA 146a-5p em pacientes transplantados renais com disfunção inicial do enxerto

ABSTRACT Introduction: The development of novel non-invasive biomarkers of kidney graft dysfunction, especially in the course of the delayed graft function period would be an important step forward in the clinical practice of kidney transplantation. Methods: We evaluated by RT-PCR the expression of miRNA-146 to -5p ribonucleic micro-acids (miRNAs) in the peripheral blood and renal tissue obtained from kidney transplant recipients who underwent a surveillance graft biopsy during the period of delayed graft function. Results: In biopsy samples, the expression of miR-146a-5p was significantly increased in the group of patients with delayed graft function (DGF) (n = 33) versus stables patients (STA) (n = 13) and patients with acute rejection (AR) (n = 9) (p = 0.008). In peripheral blood samples, a non-significant increase of miR-146a-5p expression was found in the DGF group versus STA and AR groups (p = 0.083). No significant correlation was found between levels of expression in biopsy and plasma. ROC curve analysis revealed an AUC of 0.75 (95% CI: 0.62-0.88) for the renal tissue expression and 0.67 (95% CI 0.52-0.81) for the peripheral blood expression. Conclusion: We conclude that miR-146a-5p expression has a distinct pattern in the renal tissue and perhaps in the peripheral blood in the setting of DGF. Further refinements and strategies for studies should be developed in the field of non-invasive molecular diagnosis of kidney graft dysfunction.

RESUMO Introdução: O desenvolvimento de novos biomarcadores não invasivos para disfunção do enxerto renal, especialmente no decurso da disfunção inicial do enxerto, seria de enorme valia para a prática clínica do transplante renal. Métodos: A técnica de RT-PCR foi utilizada para avaliar a expressão de microRNA 146a-5p no sangue periférico e no tecido renal de receptores de transplante submetidos a biópsia renal de controle no decurso de disfunção inicial do enxerto. Resultados: A expressão de miR-146a-5p estava significativamente aumentada nas amostras de biópsia do grupo de pacientes com disfunção inicial do enxerto (DIE) (n = 33) em relação aos pacientes estáveis (n = 13) e aos com rejeição aguda (RA) (n = 9) (p = 0,008). Foi detectado aumento não significativo da expressão de miR-146a-5p nas amostras de sangue periférico do grupo com DIE em comparação aos pacientes estáveis e com RA (p = 0,083). Não foi identificada correlação significativa entre os níveis de expressão no plasma e na biópsia. A análise da curva COR revelou uma ASC de 0,75 (IC 95%: 0,62-0,88) para a expressão no tecido renal e de 0,67 (IC 95% 0,52-0,81) no sangue periférico. Conclusão: A expressão de miR-146a-5p tem um padrão distinto no tecido renal e talvez no sangue periférico em cenários de DIE. Maiores refinamentos e estratégias adicionais de estudo devem ser desenvolvidos na área do diagnóstico molecular não invasivo da disfunção do enxerto renal.

Micro RNA 146a-5p expression in Kidney transplant recipients with delayed graft function.

INTRODUCTION: The development of novel non-invasive biomarkers of kidney graft dysfunction, especially in the course of the delayed graft function period would be an important step forward in the clinical practice of kidney transplantation. METHODS: We evaluated by RT-PCR the expression of miRNA-146 to -5p ribonucleic micro-acids (miRNAs) in the peripheral blood and renal tissue obtained from kidney transplant recipients who underwent a surveillance graft biopsy during the period of delayed graft function. RESULTS: In biopsy samples, the expression of miR-146a-5p was significantly increased in the group of patients with delayed graft function (DGF) (n = 33) versus stables patients (STA) (n = 13) and patients with acute rejection (AR) (n = 9) (p = 0.008). In peripheral blood samples, a non-significant increase of miR-146a-5p expression was found in the DGF group versus STA and AR groups (p = 0.083). No significant correlation was found between levels of expression in biopsy and plasma. ROC curve analysis revealed an AUC of 0.75 (95% CI: 0.62-0.88) for the renal tissue expression and 0.67 (95% CI 0.52-0.81) for the peripheral blood expression. CONCLUSION: We conclude that miR-146a-5p expression has a distinct pattern in the renal tissue and perhaps in the peripheral blood in the setting of DGF. Further refinements and strategies for studies should be developed in the field of non-invasive molecular diagnosis of kidney graft dysfunction.

Unraveling the podocyte injury in lupus nephritis: Clinical and experimental approaches.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with renal involvement in over half of the cases. In lupus nephritis (LN), podocytes are injured at the structural and molecular level. Spontaneous or induced animal models of SLE can reproduce the glomerular damage, similar to what is observed in humans. In this review, murine models focusing the podocyte injury were summarized, and therapeutic strategies to protect the podocyte cell were explored. METHODS: Using the PubMed and MEDLINE databases from 1950 to 2015, literature search was conducted by article title and abstract, combining the following key words: "systemic lupus erythematosus," "lupus nephritis," "animal model," "podocyte injury," and "treatment." RESULTS: Published or in-press eligible studies that were published as full-length articles in English-language journals were considered. Articles were summarized according to podocyte structure and function, the podocyte injury resulting from spontaneous (NZB/W F1 hybrid, MRL/lpr, and BXSB-Yaa mice) or induced (chronic graft-versus-host disease and pristane) mice models of LN, and the protective effects of drug treatments on podocyte cell structure and function reported in these models. CONCLUSIONS: Murine models of SLE have proven useful for better comprehension of the multiple mechanisms involved in systemic autoimmunity that leads to LN. These critical tools should be considered when target therapies are designed to control this disorder.

Intra- and interindividual iodine excretion in 24 hours in individuals in southern Brazil: a cross-sectional study.

AIMS: To evaluate the variability of 24-hour urinary iodine (UI) excretion intra- and interindividually on three days of a week in healthy subjects, living in southern Brazil, and the correlation among the urinary excretion of iodine and sodium. METHODS: Cross-sectional study, including 47 volunteers: 18 individuals with one, 15 individuals with two and 14 individuals with three 24-hour urine samples. Iodine, creatinine and Na(+) excretion in urine during 24-hour were measured. RESULTS: Mean height, weight, BMI and 24-hour urinary excretion of creatinine were higher in men. UI and urinary sodium were correlated (n = 89, r = 0.524, p = 0.000). UI excretion varied widely, both inter- and intraindividually, on the 3 days of the week, but the mean excretion of UI was similar. In single individuals, the ratio between the maximum and minimum 24-hour UI excretion (m/m) ranged from 1.03 to 2.87, and the median coefficient of variation (CV) was 21% (P25 = 7.0% and P75 = 36.8%), with a range of 1%-51%. 24-hour UI excretion varied greatly among individuals on Sunday (CV = 47.5% and m/m = 7.75), Monday (CV = 38.7% and m/m = 4.60) and Thursday (CV = 40.4% and m/m = 4.50). UI was adequate in the group of 14 people, however, the UI excretion of two women suggested iodine intake persistently below that recommended by WHO. CONCLUSION: The variability of 24-hour UI excretion on different days in the same individual is lower than that observed among individuals.

Hormônio de estimulação da tireóide (TSH) e correlações laboratoriais / Thyroid stimulating hormone (TSH) and laboratorials correlations

A secreção hipofisária de TSH regula a secreção de T4 (tiroxina) e T3 (triiodotironina) que, por sua vez, exercem “feed-back” negativo no controle de secreção dos hormônios da tireóide, sendo que, a medida que ocorre um aumento na secreção de T3 e T4, o metabolismo celular aumenta. Este aumento promove, em nível de hipotálamo, redução na secreção de TRF (fator de liberação da tireotrofina), provocando uma redução na secreção de TSH pela adeno-hipófise e, redução de T3 e T4 pela tireóide, reduzindo o metabolismo basal celular. Desta forma, quando a função hipotálamo-hipofisária está intacta, pequenas alterações nas concentrações dos hormônios tireoideanos livres resultam em grandes concentrações séricas de TSH, tornando o mesmo melhor indicador de alterações discretas da produção tireoideana. Os valores de referência de TSH para estereóideanos são: 0,4-4 µUI/mL; para hipotireoidismo: <0,01 µUI/mL e para hipertireoidismo: 7,1-≥75 µUI/mL. Em um Hospital de médio porte na cidade de Porto Alegre, no Setor de Imunologia, foram coletados os resultados de TSH de 1130 pacientes no período de maio de 2007 até julho de 2007, analisando a adequação dos valores de referência e relatando sua repercussão clínica. A análise revelou a importância de resultados laboratoriais na clínica desses pacientes