Abstract
Acute kidney injury (AKI) is a disease entity of major importance, affecting approximately 6% of all patients on the intensive care unit. The mortality rate exceeds 60%. AKI is related to several underlying conditions, including sepsis, nephrotoxicity or major surgery. Ischaemia reperfusion injury or hypoxic conditions may lead to severe injury of the kidney and is associated with a steep decline in survival rates of patients. At present, AKI is diagnosed on the basis of creatinine levels and urine output. Novel markers and knowledge of their pathophysiological role is of major importance for targeted therapeutic interventions. Noncoding RNAs (ncRNAs) have recently been introduced and are the subject of intensive research initiatives. They are arbitrarily separated into small ncRNAs (≤200 nucleotides) and long ncRNAs (lncRNAs, ≥200 nucleotides). Whereas small ncRNAs such as microRNAs have been extensively studied over the past several years, investigations into the role of linear lncRNAs and circular RNAs (circRNAs) are largely lacking. The present review article therefore aims to elucidate in detail the role of microRNAs, lncRNAs and circRNAs in animal models as well as patients with ischaemic AKI and to describe their use as biomarkers as well as their potential use as therapeutics.
Highlights
Acute kidney injury (AKI) is associated with considerable morbidity and was identified previously as an independent risk factor for mortality of patients [1]
According to this suggested classification, lncRNAs are classified as: (1) signal lncRNAs, which are spatiotemporally transcribed in response to developmental cues, cellular context or diverse stimuli; (2) decoy lncRNAs, which impact on transcriptional regulation by titrating away transcription factors and other proteins from chromatin; (3) guide lncRNAs, which sequester ribonucleoprotein complexes and direct them to chromatin and other specific targets; and (4) scaffold lncRNAs, which interact with multiple partners to form a chromatin modifying complex [34, 35]
Arid2-IR = AT-rich interactive domain-containing protein 2 intronic region; hypoxia-inducible factor-1α (HIF-1α) = ; IL-1β = interleukin-1β; MALAT1 = metastasis associated lung adenocarcinoma transcript 1; Nuclear factor-κB (NF-κB) = nuclear factor-κB; PRINS = psoriasis susceptibility-related RNA gene induced by stress; RANTES = regulated on activation, normal T cell expressed and secreted; TapsAKI = transcript predicting survival in AKI
Summary
Acute kidney injury (AKI) is a disease entity of major importance, affecting approximately 6% of all patients on the intensive care unit. Noncoding RNAs (ncRNAs) have recently been introduced and are the subject of intensive research initiatives. They are arbitrarily separated into small ncRNAs (≤200 nucleotides) and long ncRNAs (lncRNAs, ≥200 nucleotides). Whereas small ncRNAs such as microRNAs have been extensively studied over the past several years, investigations into the role of linear lncRNAs and circular RNAs (circRNAs) are largely lacking. The present review article aims to elucidate in detail the role of microRNAs, lncRNAs and circRNAs in animal models as well as patients with ischaemic AKI and to describe their use as biomarkers as well as their potential use as therapeutics
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