Seminars in nephrology最新文献

Offering and providing effective conservative kidney management (CKM) for patients with end-stage kidney disease who do not want dialysis is a foundational skill that all nephrology fellows should learn during fellowship training. However, the current educational landscape in fellowship training programs is sparse and is not recognized currently as a skill within the Accreditation Council for Graduate Medical Education (ACGME) guidelines. Moreover, there is no standardized curriculum, methods of assessment of this learning objective, and no structure for implementation within general and subspecialty nephrology training programs. In this article, we discuss the current educational resources available for fellowship training programs, including interactive communication skills workshops such as NephroTalk, that address core concepts of CKM and assess communication skills and attitudes of trainees. Additional assessment tools should be prioritized when developing a CKM curriculum, including assessment of symptom management and medical knowledge acquisition. We propose that the ACGME nephrology milestones specifically highlight CKM as an important component within the ACGME nephrology milestones, thus ensuring that trainees understand how and when to offer CKM (knowledge), implement it effectively (skills), and conceptualize it as an appropriate course for patients in a number of varied situations (attitudes). We also outline a subspecialty pathway for palliative nephrology, to align with the recent American Society of Nephrology Task Force Recommendation to provide subspecialty training beyond core competencies, for those interested in pursuit of advanced training that ultimately can shape the CKM landscape in education and policy making.

Thrombotic microangiopathies (TMAs) represent a complex interaction of endothelial and podocyte biology, nephron physiology, complement genetics, and oncologic therapies with host immunology. The complexity of various factors, such as molecular causes, genetic expressions, and immune system mimicking, along with incomplete penetrance, make it difficult to find a straightforward solution. As a result, there may be variations in diagnosis, study, and treatment approaches, and achieving a consensus can be challenging. Here, we review the molecular biology, pharmacology, immunology, molecular genetics, and pathology of the various TMA syndromes in the setting of cancer. Controversies in etiology, nomenclature, and points requiring further clinical, translational, and bench research are discussed. Complement-mediated TMAs, chemotherapy drug–mediated TMAs, TMAs in monoclonal gammopathy, and other TMAs central to onconephrology practice are reviewed in detail. In addition, established and emerging therapies within the US Food and Drug Administration pipeline subsequently are discussed. Finally, a comprehensive review of critical areas of onconephrology clinical practice is presented as practical value to the clinical practitioner and seeds of investigation to be sown among the community of atypical hemolytic uremic syndrome researchers.

Tumor lysis syndrome (TLS) and high-dose methotrexate (HD MTX) toxicity can present with potentially severe complications, including acute kidney injury, in patients with malignancy. Guidelines for using rasburicase and glucarpidase as rescue therapies for TLS and HD MTX toxicity, respectively, are widely used by clinicians intending to mitigate organ toxicity and decrease morbidity and mortality as a consequence of cancer therapy. This review discusses the pathogenesis of TLS and HD MTX–associated toxicity, to understand the mechanism of action of these therapeutic agents and to review the currently available evidence supporting their use.

Pathogenic roles of monoclonal immunoglobulins in kidney disease have been attributed previously to malignant plasma cell and lymphoproliferative disorders such as multiple myeloma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia, or amyloid light chain amyloidosis. Improved technology, advancements in molecular diagnostics, and highly sensitive imaging techniques have established the need to redefine monoclonal gammopathies and the kidney disorders that are associated with monoclonal immunoglobulins regardless of tumor burden. This has led to the establishment of monoclonal gammopathy with renal significance (MGRS). MGRS was defined by the International Kidney and Monoclonal Gammopathy Research Group in 2012 as a clonal proliferative disorder that produces a nephrotoxic monoclonal immunoglobulin and does not meet previously defined hematological criteria for treatment of a specific malignancy. MGRS encompasses a wide array of pathologies with knowledge surrounding its incidence, prognosis, and management continuously increasing. This review examines the current evidence on the diagnosis, prognosis, pathogenesis, and therapy of plasma cell dyscrasias and related MGRS.

Advance care planning, shared decision making, and serious illness conversations are communication processes designed to promote patient-centered care. In onconephrology, patients face a series of complex medical decisions regarding their care at the intersection of oncology and nephrology. Clinicians who aim to ensure that patient preferences and values are integrated into treatment planning must work within a similarly complex care team comprising multiple disciplines. In this review, we describe key decision points in a patient's care trajectory, as well as guidance on how and when to engage in advance care planning, shared decision making, and serious illness discussions. Further research on these processes in the complex context of onconephrology is needed.

Transplant onconephrology is a growing specialty focused on the health care of kidney transplant recipients with cancer. Given the complexities associated with the care of transplant patients, along with the advent of novel cancer therapies such as immune checkpoint inhibitors and chimeric antigen–receptor T cells, there is a dire need for the subspecialty of transplant onconephrology. The management of cancer in the setting of kidney transplantation is best accomplished by a multidisciplinary team, including transplant nephrologists, oncologists, and patients. This review addresses the current state and future opportunities for transplant onconephrology, including the roles of the multidisciplinary team, and related scientific and clinical knowledge.

Magnesium is crucial for various cellular and enzymatic processes, yet it often is overlooked or underappreciated. Hypomagnesemia, a deficiency of magnesium in the blood, is a frequent problem in cancer patients and can lead to severe symptoms and morbidity. In this review, we provide an in-depth analysis of the physiology and regulation of magnesium, and signs and symptoms of hypomagnesemia in cancer patients. We also examine the causes and mechanisms of magnesium imbalances in cancer patients, specifically focusing on cancer-specific therapies that can lead to hypomagnesemia. Finally, we provide updates on the management of hypomagnesemia, including oral and parenteral supplementation, as well as the role of drugs in cases that are resistant to treatment. This review aims to raise awareness among health care providers caring for cancer patients about the significance of monitoring magnesium levels in cancer patients and function as a guide. Future clinical studies should focus on magnesium monitoring, its impact on cancer progression, and its potential for preventing acute kidney injury.

Immune checkpoint inhibitors (ICIs) are now established treatments for advanced cancer and their use is now ubiquitous. The high upside of ICIs is tempered by their toxicity profile affecting almost every organ, including the kidneys. Although acute interstitial nephritis is the major kidney-related adverse effect of checkpoint inhibitors, other manifestations such as electrolyte abnormalities and renal tubular acidosis have been described. With increasing awareness and recognition of these events, the focus has shifted to non-invasive identification of ICI-acute interstitial nephritis, with sophisticated approaches involving biomarkers and immunologic signatures being studied. Although the management of immune-related adverse events with corticosteroids is straightforward, there now are more data to help guide immunosuppressive regimens, ICI rechallenge, and delineate risk and efficacy in special populations such as individuals on dialysis or those who have received a transplant.

Cisplatin is a highly effective chemotherapeutic agent that has been used for more than 50 years for a variety of cancers; however, its use is limited by toxicity, including nephrotoxicity. In this in-depth review, we discuss the incidence of cisplatin-associated acute kidney injury, as well as common risk factors for its development. Cisplatin accumulates in the kidney tubules and causes AKI through various mechanisms, including DNA damage, oxidative stress, and apoptosis. We also discuss the spectrum of nephrotoxicity, including acute and chronic impairment of kidney function, electrolyte disturbances, and thrombotic microangiopathy. We discuss the limited options for the diagnosis, prevention, and management of these complications, along with factors that may impact future therapy with or without cisplatin. We conclude with directions for future research in this expanding and important area.