Nephron
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Review
Immunomodulatory and Kidney-Protective Effects of the Human Chorionic Gonadotropin Derivate EA-230.
The systemic inflammatory response following infectious or non-infectious insults is related to morbidity (including acute kidney injury) and mortality. Pregnancy is associated with immunotolerance and an increased glomerular filtration rate. ⋯ Furthermore, an excellent safety profile of EA-230 was observed in phase 1 studies in humans, and the immunomodulatory effects of EA-230 were recently demonstrated in a phase IIa study during human experimental endotoxemia. A prospective double-blind placebo-controlled randomized trial in 180 patients undergoing elective CABG-surgery with or without valve surgery is currently conducted to investigate the immunomodulatory and renoprotective properties of EA-230.
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Acute kidney injury (AKI) is a frequent complication of both cardiac and major non-cardiac surgery. AKI is independently associated with morbidity, mortality, and long-term adverse events including chronic kidney disease in postsurgical patients. Since specific treatment options for kidney failure are very limited, early identification, diagnosis, and renal support strategies are key steps to improve patients' outcome. ⋯ According to current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, AKI diagnosis is based on 2 functional markers, serum creatinine increase and urine output decrease, that are not renal-specific and have important limitations. However, preoperative risk stratification for postoperative AKI and/or early diagnosis after surgery could be the best way to apply preventive or timely supportive therapeutic measures. Clinical prediction scores, renal functional reserve assessment, and new biomarkers of kidney stress (suppression of tumorigenicity-2, insulin-like growth factor binding protein-7, tissue inhibitor metalloproteinase-2) may help the clinicians to identify patients at risk of AKI and that could benefit from the application of nephroprotective bundles suggested by the KDIGO guidelines. In severe AKI patients with oligoanuria and fluid accumulation, renal replacement therapy is the only supportive measure even if mode and timing remain open to investigation. Key messages: Perioperative AKI is an important and underdiagnosed complication. Identifying patients at high risk of AKI and diagnosing AKI early are major goals. Preventive interventions are mainly based on the KDIGO guidelines and bundles. Furthermore, a personalized multidisciplinary approach should always be considered to minimize the progression of disease and the complications related to kidney damage.
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Iron is critical for fundamental biologic functions such as cell division and mitochondrial electron transport. However, by the virtue of its ability to donate electrons, iron is probably the most effective oxidant in biologic systems. ⋯ To avoid damage from iron-mediated oxidative injury or ferroptosis, multiple defense mechanisms exist including iron binding proteins and robust glutathione-dependent intracellular pathways. Hepcidin, through its ability to sequester iron within macrophages and induce H-ferritin, serves as an endogenous protective molecule against ferroptosis. Key Messages: Recent studies have demonstrated the protective role of hepcidin in both ischemic reperfusion injury and heme-mediated models of acute kidney injury (AKI). Ferroptosis-inhibiting drugs and hepcidin offer exciting novel prospects to treat AKI.
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Perioperative acute kidney injury is a common problem. While clinical trials seek to evaluate the impact of interventions on a variety of primary and secondary endpoints with the aim of implementing this knowledge to improve perioperative outcomes, the use of valid and relevant endpoints within clinical trials is of critical importance to achieving this goal. Suitable endpoints must be validated for the study population and in light of the clinical context under investigation while also considering regulatory requirements that govern the licensing of new therapeutic agents as well as the values of patients whose outcomes we seek to improve. ⋯ The Standardized Endpoints in Perioperative Medicine (StEP) initiative is an international collaboration whose goal is to identify and recommend a suite of clearly and precisely defined endpoints across multiple domains, specifically suited for use in perioperative clinical trials. The current review describes the rationale, goals and the planned pathway of the StEP renal subgroup. Development of a set of standardized and core renal endpoints, valid and relevant for use in the perioperative context, precisely defined and yet with sufficient flexibility to encourage broad uptake and application should facilitate high-quality and practice-changing perioperative research into the future.
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Review Meta Analysis
Effect of ultrafiltration versus intravenous furosemide for decompensated heart failure in cardiorenal syndrome: a systematic review with meta-analysis of randomized controlled trials.
Ultrafiltration is an adjunctive treatment for decompensated heart failure patients with cardiorenal syndrome. The efficacy and safety of ultrafiltration in the patient cohort are still unknown. ⋯ Ultrafiltration is a safe and effective strategy in the treatment of cardiorenal syndrome without increasing the risk of renal deterioration.