Journal of The American Society of Nephrology最新文献

Mechanical circulatory support is used to augment circulatory flow in cardiogenic shock and end-stage heart failure. Support can last from hours for temporary mechanical circulatory support to years for durable mechanical circulatory support. The physiologic relationship of heart and kidney function and the epidemic of cardio-kidney-metabolic disease lead to frequent use of simultaneous mechanical circulatory support and extracorporeal KRT (dialysis). The need for dialysis can range from short periods of AKI in cardiogenic shock to long-term dialysis for individuals who receive left ventricular assist devices (LVADs) for destination therapy in advanced heart failure and progress to CKD G5 with replacement therapy. Changes in technology, clinical evidence, and organ transplantation have led to major changes in mechanical circulatory support use. With temporary mechanical circulatory support, devices and clinical situations vary widely, with intra-aortic balloon pumps, microaxial flow pumps, and venoarterial extracorporeal membrane oxygenation providing different levels of circulatory support. Considerations for dialysis, whether for AKI or CKD G5, are discussed. In durable mechanical circulatory support, LVADs are now used primarily for permanent therapy, and most LVAD recipients survive for more than 5 years, time in which kidney dysfunction can develop or progress. Outpatient dialysis with LVADs is performed for both AKI and for CKD G5, with in-center intermittent hemodialysis, peritoneal dialysis, or home hemodialysis. This article discusses considerations specific to dialysis in temporary and durable circulatory support, including the challenging aspects of volume management and complication risks. Concurrent mechanical circulatory support and dialysis present diverse clinical challenges in patients with complex medical needs. Meeting this challenge requires close cooperation and shared decision making incorporating cardiologists, nephrologists, other medical professionals, patients, and their caregivers.

Ferroptosis is a distinct necrotic form of regulated cell death caused by a breakdown in membrane redox homeostasis. Accumulating evidence highlights a central role for ferroptosis in both acute and chronic kidney diseases, with proximal tubule cells being the primary target. It is tightly controlled by an intricate network of metabolic pathways for iron, lipid, and redox homeostasis, all of which are highly affected by kidney diseases. Moreover, recent studies have demonstrated that several human kidney disease genes modulate cellular susceptibility to ferroptosis by altering these metabolic pathways, underscoring ferroptosis as a potential therapeutic target to improve patient outcomes. Mechanistic studies have defined the cysteine-glutathione-glutathione peroxidase 4 (GPX4) axis as the central defense against ferroptosis. GPX4 detoxifies membrane phospholipid hydroperoxides, thus preventing iron-dependent lipid peroxidation chain reactions and damage to the plasma membrane. When GPX4 is overwhelmed, toxic lipid peroxides accumulate and disrupt membrane integrity-a process known as ferroptotic stress-ultimately leading to plasma membrane rupture and cell death. In this review, we provide a conceptual framework for understanding how ferroptotic stress contributes to kidney disease progression and how it can be therapeutically targeted. We highlight recent evidence that ferroptotic stress not only triggers cell death but also significantly affects the surviving proximal tubule cells. We discuss sex-specific differences in ferroptosis and explore the implications of female resilience to ferroptosis for identifying new therapeutic strategies. By integrating mechanistic insights into ferroptotic stress with new experimental observations, this review underscores ferroptosis as both a pathogenic driver and a promising therapeutic target in kidney disease.