Pathophysiology of acute renal failure.
ABSTRACT Acute renal failure (ARF) is a common renal disease affecting up to 5% of all hospitalized patients, with a higher prevalence of 10-30% in patients in critical care units (1-3). Despite advances in the management of critically ill patients and technological advances in renal replacement therapy, the high mortality of patients with ARF has not changed over the last decades and remains above 50% (4-6). Moreover, as a consequence of more advanced medical therapy and more complicated surgical interventions in older and multimorbid patients, the number of patients with ARF is increasing (1, 4, 5). Moreover, ARF itself increases the risk to develop additional complications that can be deleterious. Recently, an independent association between ARF and mortality has been shown in patients following administration of radiocontrast media in an intensive care unit and in patients following cardiac surgery (6, 7). Following radiocontrast media the mortality of patients with ARF was increased five fold and following cardiac surgery sixteen-fold as compared to patients with the same underlying disease without ARF. The pathophysiology of ischemic ARF is reviewed with the emphasis on the following mechanisms: Increased fractional excretion of sodium, Activation of tubuloglomerular feedback, Cytoskeletal disruption, Tubular obstruction, Vascular mechanisms. The following mediators will also be discussed: Calcium, Cysteine proteases, Nitric oxide, Adhesion receptors and integrins.
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ABSTRACT: AIMS: The meta-analysis of recent small animal experiments of mesenchymal stem/stromal cells (MSC) therapy for impaired kidney could provide significant clues to design large animal experiments as well as human clinical trials. METHODS: A total of 21 studies was analyzed. These, were indexed from PubMed and Embase databases. All data were analyzed by RevMan 5.1 and SPSS 17.0. Pooled analysis and multivariable meta-regression were calculated by random effects models. Heterogeneity and publication bias across the studies were also explored. RESULTS: Pooled analysis showed elevated serum creatinine (Scr) reduction in the animal models of renal failure followed MSC therapy. By exploratory multivariable meta-regression, significant influence factors of Scr reduction were the time point of Scr measurement [early measurement showed greater reduction than the late (p=0.005)] and the route of MSC delivery [arterial delivery of MSCs caused greater reduction in elevated Scr, when compared with the intra-renal delivery and intravenous injection (p=0.040)]. Subgroup analysis showed there tended to be greater reduction in Scr with higher MSC number (>10(6) ), the renal ischemia-reperfusion injury (IRI) model, and late administration (>1 day) after injury. CONCLUSION: The present meta-analysis confirmed that MSC therapy could improve impaired renal function. MSCs might get obvious effect in the early stage of renal injuries after arterial delivery. Further, this meta-analysis may provide important clues for animal experiments even for human clinical trials in MSC studies.Nephrology 12/2012; · 1.69 Impact Factor
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ABSTRACT: Acute kidney injury (AKI) has been recognized as one of the most complex clinical complications in modern medicine, and ischemia/reperfusion (I/R) injury is well-known as a main reason of AKI. In addition, AKI leads to important systemic consequences such as acute lung injury. This study was designed to investigate the role of erythropoietin (EPO) on kidney function makers and tissue damage; and lung endothelial permeability and lung water content (LWC) in bilateral renal I/R injury model in rats. Male Wistar rats were randomly divided into three groups of sham, I/R, and I/R treated with EPO (I/R + EPO) groups. The I/R and I/R + EPO groups were subjected to bilateral renal I/R injury; however, only the I/R + EPO group received EPO (500 IU/kg, i.p.) 2 h before ischemia surgery, and the same dose was continued once a day for 3 days after ischemia. The sham group underwent a surgical procedure without ischemia process. The blood urea nitrogen (BUN) and serum creatinine (Cr) levels, kidney tissue damage score (KTDS), and kidney weight (KW) per 100 g body weight significantly increased in I/R group (P < 0.05). EPO administration decreased levels of BUN and Cr significantly (P < 0.05), and KTDS and KW insignificantly (P = 0.1). No significant differences in kidney and serum levels of malondialdehyde, and lung vascular permeability and LWC were observed between the groups. The serum and kidney levels of nitrite were not significantly different between I/R and sham groups; however, administration of EPO increased the renal level of nitrite (P < 0.05). EPO protected the kidney against I/R injury; however, it may not protect the lung tissue from the damage induced by renal I/R injury in rats.International journal of preventive medicine 06/2013; 4(6):648-55.
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ABSTRACT: BACKGROUND:Acute kidney injury (AKI) is a common complication of noncardiac surgery and is associated with excess morbidity and mortality. Perioperative hemoglobin concentrations are strongly associated with surgical mortality, but little is known about their relationship with AKI. We studied hemoglobin concentration before and 24 hours after surgery and its association with AKI.METHODS:We performed a single-center observational cohort study using clinical and administrative data from the Cleveland Clinic, Cleveland, OH. In patients with normal preoperative renal function, we examined the association between the outcome of AKI and the exposures of preoperative hemoglobin concentration and decrements in hemoglobin concentration in the first 24 hours after surgery using logistic regression and controlling for important confounding variables.RESULTS:We included 27,381 patients who had 33,330 noncardiac surgeries. AKI developed in 2478 (7.4%) surgeries. Preoperative hemoglobin concentrations were <12.0 g/dL in 9566 (29%) patients. Hemoglobin concentrations decreased by >4.0 g/dL in 10,808 (32%) patients. Compared with patients with a preoperative hemoglobin >12.0 g/dL, the adjusted odds ratio (OR) for AKI was 2.01 (95% confidence interval [CI], 1.8-2.3) for those with a preoperative hemoglobin between 10.1 and 12.0 g/dL and was 3.7 (95% CI, 2.6-5.4) for those with a preoperative hemoglobin <8.0 g/dL. Compared with patients who did not have a decrease in postoperative hemoglobin, a decrement of 1.1 to 2.0 g/dL was associated with an adjusted OR of 1.51 (95% CI, 1.15-1.98), and a decrement of >4.0 g/dL with an OR of 4.7 (95% CI, 3.6-6.2) for AKI.CONCLUSIONS:Low preoperative and early postoperative decrements in hemoglobin concentrations are strongly associated with postoperative AKI in a graded manner. Given the frequency of low perioperative hemoglobin and decreases in hemoglobin concentration, research is needed to determine whether there are safe treatment strategies to mitigate the risk of AKI.Anesthesia and analgesia 09/2013; · 3.08 Impact Factor