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Abstract Introduction Ideal timing of Renal Replacement Therapy (RRT) discontinuation in Acute Kidney Injury (AKI) is still unknown. We aimed to study the role of creatinine-related variables in predicting RRT successful discontinuation and to propose a clinical predictive score. Methods In this single-centre retrospective study, we evaluated all AKI patients in whom RRT was interrupted for at least 48 hours. Patients who were still RRT-independent 7 days after initial RRT cessation were included in the "Success" group and opposed to the "Failure" group. We evaluated baseline characteristics and variables collected at the time of RRT interruption, as well as the Kinetic estimated Glomerular Filtration Rate (KeGFR), the simple variation in serum Creatinine (ΔsCr), and the incremental creatinine ratio on the first three days after RRT interruption. Multivariable analysis was performed to evaluate prediction of success. Internal validation using a simple binomial generalized regression model with Lasso estimation and 5-fold cross validation method was performed. Results We included 124 patients, 49 in the "Failure" group and 75 in the "Success" group. All creatinine-related variables predicted success in simple and multiple logistic regression models. The best model generated a clinical score based on the odds ratio obtained for each variable and included urine output, non-renal SOFA score, fluid balance, serum urea, serum potassium, blood pH, and the variation in sCr values after RRT discontinuation. The score presented an area under the ROC of 0.86 (95% CI 0.76‒1.00). Conclusion Creatinine variation between the first 2 consecutive days after RRT discontinuation might predict success in RRT discontinuation. The developed clinical score based on these variables might be a useful clinical decision tool to guide hemodialysis catheter safe removal.
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A injúria renal aguda representa um estado de senescência precoce induzida por estresse, e as células-tronco mesenquimais podem ser uma alternativa para seu tratamento. Células-tronco jovens reduzem o fenótipo de envelhecimento em rins quando comparadas a células idosas. O objetivo deste estudo foi avaliar se o tratamento com jovens células-tronco mesenquimais derivadas de cordão umbilical humano podem interferir na senescência renal induzida por lesão de isquemia-reperfusão em ratos. Ratos machos foram submetidos ao modelo de isquemia de artérias renais bilateralmente por 45 minutos, com reperfusão após, e alguns animais receberam 1 X 106 células por via intraperitoneal após 6 horas da indução da lesão. Os animais foram eutanasiados no segundo ou no sétimo dia pós-isquêmico. No segundo dia após a lesão de isquemia-reperfusão, o tratamento com as células melhorou a filtração glomerular e a função tubular, melhorou a expressão renal de aquaporina-2 e reduziu a infiltração de macrófagos nos rins. Proteínas relacionadas à senescência (-galactosidase, p21, p16 e fator de transformação do crescimento ) e microRNAs (mir-29a e miR-34a) estiveram com a expressão aumentada após a isquemia-reperfusão, e houve redução nesses parâmetros com o tratamento. A redução na expressão de Klotho e o estado pró-oxidativo gerados pela isquemia-reperfusão também foram revertidos pelo tratamento. A senescência induzida pela injúria renal aguda é um processo independente de telômeros. Ao sétimo dia pós-lesão, os ratos isquêmicos mantinham defeito de concentração urinária, que foi revertido nos animais tratados. Além disso, o tratamento reduziu o índice de necrose tubular aguda em tecido renal e reduziu o infiltrado macrofágico túbulo-intersticial. O marcador pró-senescência p16 foi completamente restabelecido nos animais tratados...
Acute kidney injury represents a status of premature stress-induced senescence, and mesenchymal stem cells are an alternative for treatment. Young stem cells reduce aging phenotype in kidneys when compared to old cells. The objective of this study was to evaluate if treatment with young human umbilical cord mesenchymal stem cells could interfere in kidney senescence induced by renal ischemia-reperfusion in rats. Male rats were induced to ischemia-reperfusion injury by 45-minutes clamping of both renal arteries; some rats received 1X106 cells intraperitonally six hours later. Rats were euthanatized on post-renal ischemia reperfusion days two and seven. At day 2 after ischemia-reperfusion injury, treatment with cells improved glomerular filtration, tubular function, improved renal expression of aquaporin 2 and decreased macrophage kidney infiltration. Senescence-related proteins (?-galactosidase, p21, p16 and transforming growth factor ?) and microRNAs (miR-29a and miRNA-34a) were overexpressed after ischemia-reperfusion, and reversed by the treatment. The Klotho reduced expression and the pro-oxidative status induced by ischemia-reperfusion were reversed by the treatment. Senescence induced acute kidney injury is a telomere-independent process. At day 7, ischemic rats maintained urinary concentrating defect, which is reversed in treated animals. Moreover, treatment decreased the index of acute tubular necrosis in kidney tissue and decreased macrophage kidney infiltration. Senescence marker p16 was completely restored in treated animals...