scholarly journals Circulating Long Noncoding RNA TapSAKI Is a Predictor of Mortality in Critically Ill Patients with Acute Kidney Injury

2015 ◽  
Vol 61 (1) ◽  
pp. 191-201 ◽  
Author(s):  
Johan M Lorenzen ◽  
Celina Schauerte ◽  
Jan T Kielstein ◽  
Anika Hübner ◽  
Filippo Martino ◽  
...  

Abstract BACKGROUND Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating gene expression. Intriguingly, these RNA transcripts are detectable and stable in the blood of patients with cancer and cardiovascular disease. We tested whether circulating lncRNAs in plasma of critically ill patients with acute kidney injury (AKI) at inception of renal replacement therapy were deregulated and might predict survival. METHODS We performed a global lncRNA expression analysis using RNA isolated from plasma of patients with AKI, healthy controls, and ischemic disease controls. This global screen revealed several deregulated lncRNAs in plasma samples of patients with AKI. lncRNA-array–based alterations were confirmed in kidney biopsies of patients as well as in plasma of 109 patients with AKI, 30 age-matched healthy controls, and 30 disease controls by quantitative real-time PCR. RESULTS Circulating concentrations of the novel intronic antisense lncRNA TrAnscript Predicting Survival in AKI (TapSAKI) (P < 0.0001) were detectable in kidney biopsies and upregulated in plasma of patients with AKI. Cox regression and Kaplan–Meier curve analysis revealed TapSAKI as an independent predictor of 28-day survival (P < 0.01). TapSAKI was enriched in tubular epithelial cells subjected to ATP depletion (P = 0.03). CONCLUSIONS The alteration of circulating concentrations of lncRNAs in patients with AKI supports TapSAKI as a predictor of mortality in this patient cohort.

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
William Beaubien-Souligny ◽  
Alan Yang ◽  
Gerald Lebovic ◽  
Ron Wald ◽  
Sean M. Bagshaw

Abstract Background Frailty status among critically ill patients with acute kidney injury (AKI) is not well described despite its importance for prognostication and informed decision-making on life-sustaining therapies. In this study, we aim to describe the epidemiology of frailty in a cohort of older critically ill patients with severe AKI, the outcomes of patients with pre-existing frailty before AKI and the factors associated with a worsening frailty status among survivors. Methods This was a secondary analysis of a prospective multicentre observational study that enrolled older (age > 65 years) critically ill patients with AKI. The clinical frailty scale (CFS) score was captured at baseline, at 6 months and at 12 months among survivors. Frailty was defined as a CFS score of ≥ 5. Demographic, clinical and physiological variables associated with frailty as baseline were described. Multivariable Cox proportional hazard models were constructed to describe the association between frailty and 90-day mortality. Demographic and clinical factors associated with worsening frailty status at 6 months and 12 months were described using multivariable logistic regression analysis and multistate models. Results Among the 462 patients in our cohort, median (IQR) baseline CFS score was 4 (3–5), with 141 (31%) patients considered frail. Pre-existing frailty was associated with greater hazard of 90-day mortality (59% (n = 83) for frail vs. 31% (n = 100) for non-frail; adjusted hazards ratio [HR] 1.49; 95% CI 1.11–2.01, p = 0.008). At 6 months, 68 patients (28% of survivors) were frail. Of these, 57% (n = 39) were not classified as frail at baseline. Between 6 and 12 months of follow-up, 9 (4% of survivors) patients transitioned from a frail to a not frail status while 10 (4% of survivors) patients became frail and 11 (5% of survivors) patients died. In multivariable analysis, age was independently associated with worsening CFS score from baseline to 6 months (adjusted odds ratio [OR] 1.08; 95% CI 1.03–1.13, p = 0.003). Conclusions Pre-existing frailty is an independent risk factor for mortality among older critically ill patients with severe AKI. A substantial proportion of survivors experience declining function and worsened frailty status within one year.


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