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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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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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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Several cellular and molecular targets and mechanisms have been investigated in preclinical studies of acute kidney injury (AKI), but translation in successful clinical studies has failed to date. This article reviews many issues that have limited this and the potential future perspectives in AKI prevention and treatment. ⋯ Preclinical models of AKI should closely mimic the complexity of human AKI, considering the importance of several comorbidities in determining the clinical course and outcomes in the human disease. Moreover, studies should test novel interventions in models where AKI is already established, instead of focusing only at primary prevention. AKI definitions and endpoints in animal studies should be similar to those applied in clinical studies; in particular, AKI biomarkers should be implemented to guide patient selection for clinical trials and monitor intervention efficacy. In this scenario, cell-cycle arrest biomarkers have been widely investigated as AKI predictors in both preclinical and clinical studies and they serve as useful tools for future interventional studies. A better understanding of human AKI through a large collection of biological samples and kidney biopsies and omics applications, and an iterative relationship between preclinical and clinical studies are critical steps to improve future preclinical models and clinical trials. Finally, given the great variability in clinical manifestation of AKI, a strong collaboration between research centers and industry is recommended. Key messages: Several methodological issues have hampered the translation of basic research findings in clinical studies, and overcoming these obstacles is necessary to achieve success.
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The incidence of acute kidney injury (AKI) will in the future remain high, partly due to an increase in comorbidities and other AKI favoring factors such as the rise in high-risk diagnostic and therapeutic interventions. AKI has emerged as a major public health concern with high human and financial costs. It has recently been demonstrated that patients surviving an AKI episode show increased all-cause mortality, chronic kidney disease (CKD), ESRD, cardiovascular events, and reduced quality of life. ⋯ There are at present no clear guidelines on which patients should be referred and on the elements of post AKI care that may improve non-renal and renal outcomes. In this review, we discuss several points of concern in post-AKI management and propose an algorithm on post-AKI care, mainly based on the renal recovery pattern at discharge from the hospital. Potential opportunities to improve care include appropriate risk stratification, close monitoring of kidney function, management of CKD complications, blood pressure control, medication reconciliation, and education of patients and non-nephrologists on AKI and its downstream complications.