Navegando por Assunto "Acute kidney injury"

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Epigenetic regulation of the N-terminal truncated isoform of matrix metalloproteinase-2 (NTT-MMP-2) and Its presence in renal and cardiac diseases.
(2021) Cruz, Juliana de Oliveira; Silva, Alessandra Oliveira; Ribeiro, Jessyca Milene; Luizon, Marcelo Rizzatti; Ceron, Carla Speroni
Several clinical and experimental studies have documented a compelling and critical role for the full-length matrix metalloproteinase-2 (FL-MMP-2) in ischemic renal injury, progressive renal fibrosis, and diabetic nephropathy. A novel N-terminal truncated isoform of MMP-2 (NTT-MMP-2) was recently discovered, which is induced by hypoxia and oxidative stress by the activation of a latent promoter located in the first intron of the MMP2 gene. This NTT-MMP-2 isoform is enzymatically active but remains intracellular in or near the mitochondria. In this perspective article, we first present the findings about the discovery of the NTT-MMP-2 isoform, and its functional and structural differences as compared with the FL-MMP-2 isoform. Based on publicly available epigenomics data from the Encyclopedia of DNA Elements (ENCODE) project, we provide insights into the epigenetic regulation of the latent promoter located in the first intron of the MMP2 gene, which support the activation of the NTT-MMP-2 isoform. We then focus on its functional assessment by covering the alterations found in the kidney of transgenic mice expressing the NTT-MMP-2 isoform. Next, we highlight recent findings regarding the presence of the NTT-MMP-2 isoform in renal dysfunction, in kidney and cardiac diseases, including damage observed in aging, acute ischemia-reperfusion injury (IRI), chronic kidney disease, diabetic nephropathy, and human renal transplants with delayed graft function. Finally, we briefly discuss how our insights may guide further experimental and clinical studies that are needed to elucidate the underlying mechanisms and the role of the NTT-MMP-2 isoform in renal dysfunction, which may help to establish it as a potential therapeutic target in kidney diseases.
Evaluation of the prevalence and factors associated with acute kidney injury in a pediatric intensive care unit.
(2021) Louzada, Cibelle Ferreira; Ferreira, Alexandre Rodrigues
Objective To assess the prevalence of acute kidney injury in pediatric intensive care unit according to diagnostic criteria – pediatric risk, injury, failure, loss, end-stage renal disease, Acute Kidney Injury Network and Acute Kidney Injury Work Group, or Kidney Disease: Improving Global Outcomes –, and determining factors associated with acute kidney injury as well as its outcome. Methodology This was a cross-sectional monocentric observational study, including patients aged between 29 days and 17 years who were admitted to the pediatric intensive care unit between January 1, 2012 and December 31, 2016. To evaluate the association between the study variables and acute kidney injury, the log-binomial generalized univariate and multivariate linear models were adjusted. Results The study included 1131 patients, with prevalence of acute kidney injury according to the Acute Kidney Injury Network and Kidney Disease: Improving Global Outcomes criteria of 12.6% and of 12.9% according to the pediatric risk, injury, failure, loss, end-stage renal disease. In the multivariate analysis of older children (PR 1.007, 95% CI: 1.005–1.009), sepsis (PR 1.641, 95% CI: 1.128–2.387), demand for ventilatory support (PR 1.547, 95% CI: 1.095–2.186), and use of vasoactive amines (PR 2.298, 95% CI: 1.681–3.142) constituted factors associated with statistical significance to the development of acute kidney injury. The mortality rate among those with acute kidney injury was 28.7%. Conclusion Older children, diagnosis of sepsis, demand for ventilatory support, and use of vasoactive amines were correlated with a higher risk of developing acute kidney injury. The mortality associated with acute kidney injury was elevated; it is crucial that all measures that ensure adequate renal perfusion are taken for patients with risk factors, to avoid the installation of the disease.