MicroRNAs in toxic acute kidney injury: Systematic scoping review of the current status

Abstract

Acute kidney injury induced by nephrotoxic agents is common, increasing in incidence and associated with considerable morbidity and mortality in developing countries. MicroRNAs are stable biomarkers that can be detected in extracellular fluids. This systematic scoping review aims to describe published research on urinary and circulating microRNAs in toxic acute kidney injury in both animal and human studies. We conducted a literature search, using EMBASE and Medline, for articles on urinary and circulating microRNA in nephrotoxic injuries to February 2020. A total of 21 publications studied acute kidney injury from 12 different toxic agents. Cisplatin was the most common nephrotoxic agent (n = 10), followed by antibiotics (n = 4). There were no randomized controlled trials. An increase in urinary miR‐218 predicted acute kidney injury in six different studies, suggesting it is a promising biomarker for nephrotoxin‐induced acute kidney injury. There were many factors that prevented a more comprehensive synthesis of microRNA performance including highly variable models, no consistent protocols for RNA isolation, cDNA synthesis and PCR amplification, and variability in normalization methods using reference controls. In conclusion, while microRNAs are promising biomarkers to study nephrotoxic acute kidney injury, the replication of most positive findings is not assessable due to deficient reporting of negative outcomes. A very narrow range of poisons have been studied, and more human data are required. In particular, further studies are needed on the most important causes of nephrotoxic injury, such as pesticides, chemicals, snake envenoming, and medicines other than aminoglycosides and cisplatin.

Data Normalization of Urine miRNA Profiling from Head and Neck Cancer Patients Treated with Cisplatin

“…Whether for one sample or another, to date, there has been no consensus on the reference miRNA that should be used. For example, many studies still use creatinine as a normalizer when evaluating the expression profile of urinary miRNAs [ 25 ]. However, especially in the case of AKI patients (the participants considered in this study), it is known that creatinine has important deficiencies in terms of its specificity and sensitivity [ 26 ].…”

Oxalato De Cálcio

“…A variação relativa dos níveis séricos de creatinina é um parâmetro de grande importância para diagnóstico precoce da IRA, sendo fundamentada pelos estágios da KDIGO para estadiamento ((KDIGO). 2012).Muitos estudos têm sido desenvolvidos no intuito de detectar a injúria renal aguda associada a envenenamentos por animais através de novos biomarcadores urinários, vasculares e técnicas de identificação de microRNAs, ALBUQUERQUE P. L. M , SHIHANA, BARRON et al 2021, SHIHANA, WONG et al 2021…”

MicroRNAs como possíveis biomarcadores de nefrotoxicidade induzida pela cisplatina em pacientes com câncer de cabeça e pescoço

“…obtido é dado em fold change, ou seja, quantas vezes o miRNA alvo apresentou expressão aumentada ou diminuída no grupo com RAM renal em comparação ao grupo sem RAM renal.Conforme detalhado no item "1.5.3. Creatinina como biomarcador", as múltiplas variáveis às quais a creatinina está sujeita tornam inadaqueado assumir que a excreção de creatinina urinária é constante no indivíduo com nefrotoxicidade por cisplatina; (além disso, como mostrado pela revisão de Shihana et al, ainda não há um consenso sobre o seu uso ou não na normalização(228)). Por este motivo, optou-se por por não realizar a normalização dos valores de 2 -ΔCt por creatinina urinária.3.6.6.…”