Contributions to nephrology
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The pathogenesis of sepsis-induced acute kidney injury (AKI) is not fully understood, and may involve altered systemic hemodynamics and renal circulation, renal hypoxia and perhaps direct tubular toxicity. Oxidative stress, induced by systemic and intrarenal generation of reactive oxygen species (ROS) can directly exert renal parenchymal damage and may intensify renal microvascular and functional dysregulation, with a feedforward loop of hypoxia and ROS generation. Herein we review compelling evidence that sepsis is associated with systemic and intrarenal intense oxidative and nitrosative stress with a depletion of antioxidant capacity. ⋯ Though oxidative and nitrosative stress are likely to participate in the pathogenesis of sepsis-induced AKI, it is impossible to clearly identify their isolated independent role and renal-specific effect since there are complex interactions involved linking various affected organs, ROS generation with altered systemic hemodynamics, compromised microcirculation, hypoxia and distorted cellular function. Facing this complex disease entity, alleviation of oxidative stress single-handedly is unlikely to be effective in the prevention of sepsis-associated renal dysfunction. However, the addition of antioxidants to a comprehensive treatment strategy seems a reasonable approach.
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Despite the identification of several of the cellular mechanisms thought to underlie the development of acute kidney injury (AKI), the pathophysiology of AKI is still poorly understood. It is clear, however, that instead of a single mechanism being responsible for its etiology, AKI is associated with an entire orchestra of failing cellular mechanisms. Renal microcirculation is the physiological compartment where these mechanisms come together and exert their integrated deleterious action. ⋯ Under pathological conditions, such as inflammation, shock or sepsis, however, the renal microcirculation becomes compromised, which results in a disruption of the homeostasis of nitric oxide, reactive oxygen species, and oxygen supply and utilization. This imbalance results in these compounds exerting pathogenic effects, such as hypoxemia and oxidative stress, resulting in further deterioration of renal microcirculatory function. Our hypothesis is that this sequence of events underlies the development of AKI and that integrated therapeutic modalities targeting these pathogenic mechanisms will be effective therapeutic strategies in the clinical environment.
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Sepsis-induced acute kidney injury (AKI) is the most common form of AKI observed in critically ill patients. AKI mortality in septic critically ill patients remains high despite our increasing ability to support vital organ systems. This high mortality is partly due to our poor understanding of the pathophysiological mechanisms of sepsis-induced AKI. ⋯ Sepsis-induced renal microvascular alterations (vasoconstriction, capillary leak syndrome with tissue edema, leukocytes and platelet adhesion with endothelial dysfunction and/or microthrombosis) and/or an increase in intra-abdominal pressure could contribute to an increase in RVR. Further studies are needed to explore the time course of renal microvascular alterations during sepsis as well as the initiation and development of AKI. Doppler ultrasonography combined with the calculation of the resistive indices may indicate the extent of the vascular resistance changes and may help predict persistent AKI and determine the optimal systemic hemodynamics required for renal perfusion.
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Comparative Study Controlled Clinical Trial
Comparison of efficacy between continuous hemodiafiltration with a PMMA high-performance membrane dialyzer and a PAN membrane hemofilter in the treatment of septic shock patients with acute renal failure.
The aim of this study was to investigate whether continuous hemodiafiltration (CHDF) with a high-performance membrane dialyzer made of polymethylmethacrylate (PMMA-CHDF) in the treatment of septic shock patients with acute renal failure (ARF) is clinically relevant. 30 patients were treated with PMMA-CHDF. 13 patients treated with CHDF used a hemofilter made of polyacrylonitrile membrane (PAN-CHDF). Systolic blood pressure significantly increased in the PMMA-CHDF group following 24 h of treatment (p < 0.01), whereas it did not improve in the PAN-CHDF group. Urine volume significantly increased in the PMMA-CHDF group following 24 h of treatment which was more than in the PAN-CHDF group (p < 0.05). 28-day survival was 83.3% in the PMMA-CHDF group and 30.8% in the PAN-CHDF group, respectively (p < 0.01). We can assume that PMMA-CHDF in the treatment of septic shock patients with ARF is clinically relevant.
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Pediatric acute kidney injury (AKI) epidemiology has shifted from primary kidney disease to secondary to another organ system illness or its treatment with nephrotoxic medications. Similar to adult patients, critically ill children with AKI with multiorgan failure exhibit high mortality rates, yet conducting interventional trials to prevent, treat or mitigate the effects of AKI in children have been hampered by relatively low event rates and the reliance on serum creatinine as the biomarker of AKI. However, recent advancements in standardizing the AKI definition via the pediatric modified RIFLE criteria, multicenter collaboration via the Prospective Pediatric CRRT Registry Group and multiple validation studies of novel AKI biomarkers in children have provided the essential components to evaluate preventive and therapeutic strategies to attack pediatric AKI as a disease state. The scope of this article is to review the advancements in the study of pediatric AKI over the past decade and offer a compelling and bright view of what is on the horizon for the prevention, treatment and rehabilitation of AKI in kids.