Acute kidney injury in a mouse model of meningococcal disease.

INTRODUCTION: Meningococcal disease is associated with high mortality. When acute kidney injury (AKI) occurs in patients with severe meningococcal disease, it is typically attributable to sepsis, although meningococcal disease and lipopolysaccharide release are rarely investigated. Therefore, we evaluated renal tissue in a mouse model of meningococcal disease. METHODS: Female BALB/c mice were induced to AKI by meningococcal challenge. Markers of renal function were evaluated in infected and control mice. RESULTS: In the infected mice, serum concentrations of tumor necrosis factor alpha, interferon gamma, interleukins (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12), and granulocyte-macrophage colony-stimulating factor were elevated, as was renal interstitial infiltration with lymphocytes and neutrophils (p < 0.01 for the latter). Histological analysis showed meningococcal microcolonies in the renal interstitium, without acute tubular necrosis. Infected mice also showed elevated renal expression of toll-like receptor 2, toll-like receptor 4, and Tamm-Horsfall protein. The expression of factors in the intrinsic pathway of apoptosis was equal to or lower than that observed in the control mice. Urinary sodium and potassium were also lower in infected mice, probably due to a tubular defect. CONCLUSION: Our findings corroborate those of other studies of AKI in sepsis. To our knowledge, this is the first time that meningococci have been identified in renal interstitium and that the resulting apoptosis and inflammation have been evaluated. However, additional studies are needed in order to elucidate the mechanisms involved.

Uromodulin: a new biomarker of fetal renal function?

INTRODUCTION: Obstructive uropathies are main diseases affecting the fetus. Early diagnosis allows to establish the appropriate therapy to minimize the risk of damage to kidney function at birth. Biochemical markers have been used to predict the prognosis of renal function in fetuses. Uromodulin, also known by Tamm-Horsfall protein (THP) is exclusively produced in the kidneys and in normal conditions is the protein excreted in larger amounts in human urine. It plays important roles in kidneys and urinary tract. Also it participates in ion transport processes, interact with various components of the immune system and has a role in defense against urinary tract infections. Moreover, this protein was proved to be a good marker of renal function in adult patients with several renal diseases. OBJECTIVE: To evaluate if uromodulin is produced and eliminated by the kidneys during fetal life by analyzing fetal urine and amniotic fluid and to establish correlation with biochemical parameter of renal function already used in Fetal Medicine Center at the Clinic Hospital of UFMG (CEMEFE/HC). METHODS: Between 2013 and 2015, were selected 29 fetuses with indication of invasive tests for fetal diagnosis in monitoring at the CEMEFE/HC. RESULTS: The determination of uromodulin was possible and measurable in all samples and showed statistically significant correlation with the osmolarity. CONCLUSION: There was a tendency of lower levels of Uromodulin values in fetuses with severe renal impairment prenatally. Thus, high levels of this protein in fetal amniotic fluid or fetal urine dosages possibly mean kidney function preserved.

Uromodulin: a new biomarker of fetal renal function? / Uromodulina: um novo biomarcador de função renal fetal?

Abstract Introduction: Obstructive uropathies are main diseases affecting the fetus. Early diagnosis allows to establish the appropriate therapy to minimize the risk of damage to kidney function at birth. Biochemical markers have been used to predict the prognosis of renal function in fetuses. Uromodulin, also known by Tamm-Horsfall protein (THP) is exclusively produced in the kidneys and in normal conditions is the protein excreted in larger amounts in human urine. It plays important roles in kidneys and urinary tract. Also it participates in ion transport processes, interact with various components of the immune system and has a role in defense against urinary tract infections. Moreover, this protein was proved to be a good marker of renal function in adult patients with several renal diseases. Objective: To evaluate if uromodulin is produced and eliminated by the kidneys during fetal life by analyzing fetal urine and amniotic fluid and to establish correlation with biochemical parameter of renal function already used in Fetal Medicine Center at the Clinic Hospital of UFMG (CEMEFE/HC). Methods: Between 2013 and 2015, were selected 29 fetuses with indication of invasive tests for fetal diagnosis in monitoring at the CEMEFE/HC. Results: The determination of uromodulin was possible and measurable in all samples and showed statistically significant correlation with the osmolarity. Conclusion: There was a tendency of lower levels of Uromodulin values in fetuses with severe renal impairment prenatally. Thus, high levels of this protein in fetal amniotic fluid or fetal urine dosages possibly mean kidney function preserved.

Resumo Introdução: Uropatias obstrutivas estão entre as principais doenças que acometem o feto. O diagnóstico precoce destas doenças permite estabelecer a terapêutica adequada, visando minimizar os riscos de danos à função renal no nascimento. Os marcadores bioquímicos têm sido utilizados na predição do prognóstico da função renal em fetos. A uromodulina, também chamada de proteína de Tamm-Horsfall (THP), é produzida exclusivamente nos rins, e em condições normais, é a proteína excretada em maior volume na urina humana. Ela desempenha importantes funções nos rins e trato urinário. Participa dos processos de transporte de íons, interage com vários componentes do sistema imunológico e possui papel na defesa contra infecções do trato urinário. Além disso, se mostrou um bom biomarcador de função renal em adultos portadores de diversas doenças renais. Objetivos: Avaliar se a uromodulina é produzida e eliminada pelos rins durante a vida fetal através da análise de urina fetal e líquido amniótico, além de estabelecer correlação com o parâmetro bioquímico de função renal já utilizado no Centro de Medicina Fetal do Hospital das Clínicas da UFMG (CEMEFE/HC). Métodos: Entre 2013 e 2015, foram selecionados 29 fetos com indicação de exames invasivos para diagnóstico fetal em acompanhamento no CEMEFE/HC. Resultados: A dosagem da uromodulina foi possível e quantificável em todas as amostras e mostrou correlação significativa com a osmolaridade. Conclusão: A uromodulina mostrou uma tendência em apresentar valores reduzidos em fetos com grave comprometimento renal no pré-natal. Assim, valores elevados desta proteína em dosagens de urina fetal ou líquido amniótico podem significar uma função renal preservada.