Advances in chronic kidney disease最新文献

Cancer is a leading cause of death in patients with kidney transplantation. Patients with kidney transplants are 10- to 200-times more likely to develop cancers after transplant than the general population, depending on the cancer type. Recent advances in cancer therapies have dramatically improved survival outcomes; however, patients with kidney transplants face unique challenges of immunosuppression management, cancer screening, and recurrence of cancer after transplant. Patients with a history of cancer tend to be excluded from transplant candidacy or are required to have long cancer-free wait time before wait-listing. The strategy of pretransplant wait time management may need to be revisited as cancer therapies improve, which is most applicable to patients with a history of multiple myeloma. In this review, we discuss several important topics in transplant onconephrology: the current recommendations for pretransplant wait times for transplant candidates with cancer histories, cancer screening post-transplant, post-transplant lymphoproliferative disorder, strategies for transplant patients with a history of multiple myeloma, and novel therapies for patients with post-transplant malignancies. With emerging novel cancer treatments, it is critical to have multidisciplinary discussions involving patients, caregivers, transplant nephrologists, and oncologists to achieve patient-oriented goals.

Paraneoplastic glomerular diseases (GNs) are rare manifestations in patients with underlying hematologic and solid organ malignancies and can occur before or after the detection of cancer. In the absence of established algorithms for investigation and reliable tests, they remain difficult to diagnose. Given the heterogeneity and infrequency of cases, the pathogenesis of most paraneoplastic GNs is poorly understood. Most of our recent understanding of paraneoplastic GNs has emerged from the discovery of target antigens in membranous nephropathy such as thrombospondin type-1 domain-containing protein 7A and neural epidermal growth factor-like 1 protein that appear to be promising in differentiating a primary vs paraneoplastic cause of membranous nephropathy. Treatment of paraneoplastic GNs is usually directed at the underlying malignancy. This review will focus on the epidemiology, pathogenesis, and diagnosis of paraneoplastic glomerular processes.

Patients with malignancies have a high prevalence of kidney disease and are often treated with antineoplastic agents that undergo kidney metabolism or excretion or clearance via renal replacement therapies. Thus, the dosing of these agents, including classic chemotherapeutic drugs, targeted therapies, and immunotherapy, must take into account patients’ kidney function. In this review, we will discuss the pitfalls of accurate measurement of kidney function and how kidney disease affects both pharmacodynamic and pharmacokinetic properties of drugs. Lastly, we will discuss specific agents and summarize current dosing strategies for use in patients with chronic kidney disease and end-stage kidney disease.

Sickle cell disease causes several kidney manifestations. They include defects in urine concentration, impaired handling of potassium and hydrogen ion, albuminuria, acute kidney injury, and chronic kidney disease to name a few. Glomerular hyperfiltration, tubular hyperfunctioning, endothelial damage from repeated sickling and vaso-occlusive episodes, and iron-induced proinflammatory changes in the glomerular mesangium and tubulointerstitium are some of the mechanisms of kidney damage. Albuminuria is one of the most and common clinical features of kidney disease and progresses with age. Kidney disease in patients with sickle cell is associated with increased mortality. Annual screening for proteinuria starting at age 10 years and limiting the use of nonsteroidal anti-inflammatory agents and the use of angiotensin-converting enzyme inhibitors may help in early detection and delaying the progression of kidney disease. Adequate hydration, angiotensin-converting enzyme inhibitors, and adequate control of sickle cell are the main stay of treatment for albuminuria. The hemoglobin goal for patients with sickle cell nephropathy is lesser (10 g/dL) than that for patients with chronic kidney disease due to other causes given that a higher hemoglobin level increases viscosity and the risk of precipitating vaso-occlusive episodes. A multidisciplinary approach is recommended for managing patients with sickle cell and kidney diseases.

Oncosurgery is a surgical specialty that focuses on the diagnosis, staging, and management of cancer and cancer-related complications. Acute kidney injury is a common and important complication related to oncologic surgery, associated with longer hospital length of stay, greater costs, increased risk of incident or progressive chronic kidney disease (CKD), and higher mortality. The pathogenesis of oncosurgery-related acute kidney injury is multifactorial and determined by different variables, including patient characteristics (comorbidities, volume status, age, pre-existing CKD), specific cancer type or location, surgical procedure involved, as well as intrinsic neuroendocrine and hemodynamic responses to anesthesia and/or surgery. Early nephrology evaluation may be helpful to assist with preservation of kidney function and prevention of further kidney injury.

The incidence of hematologic malignancies is on the rise worldwide. Kidney disease is ubiquitous in patients with hematologic malignancies, encompassing a wide spectrum of disorders involving each kidney compartment, including the vasculature, tubules, interstitium, and glomerulus, and there is significant overlap of kidney involvement with each hematologic malignancy. Vascular disorders include both microvascular and macrovascular damage, via thrombotic microangiopathy, hyperleukocytosis, hyperviscosity, and cryoglobulinemia. The tubulointerstitial compartment may be affected by prerenal azotemia and acute tubular injury, but malignant infiltration, tumor lysis syndrome, extramedullary hematopoiesis, cast nephropathy, granulomatous interstitial nephritis, and lysozymuria should be considered in certain populations. Obstructive uropathy may occur due to nephrolithiasis or retroperitoneal fibrosis. Glomerular disorders, including membranoproliferative, membranous, minimal change, and focal segmental glomerulosclerosis, can rarely occur. By understanding how each compartment may be affected, care can best be optimized for these patients. In this review, we summarize the widely varied etiologies of kidney diseases stratified by kidney compartment and hematologic malignancy, focusing on demographics, pathology, pathophysiology, mechanism, and outcomes. We conclude with common electrolyte abnormalities associated with hematologic malignancies.

Thrombotic microangiopathies (TMAs) have in common a terminal phenotype of microangiopathic hemolytic anemia with end-organ dysfunction. Thrombotic thrombocytopenic purpura results from von Willebrand factor multimerization, Shiga toxin–mediated hemolytic uremic syndrome causes toxin-induced endothelial dysfunction, while atypical hemolytic uremic syndrome results from complement system dysregulation. Drug-induced TMA, rheumatological disease–induced TMA, and renal-limited TMA exist in an intermediate space that represents secondary complement activation and may overlap with atypical hemolytic uremic syndrome clinically. The existence of TMA without microangiopathic hemolytic features, renal-limited TMA, represents an undiscovered syndrome that responds incompletely and inconsistently to complement blockade. Hematopoietic stem cell transplant-TMA represents another more resistant form of TMA with different therapeutic needs and clinical course. It has become apparent that TMA syndromes are an emerging field in nephrology, rheumatology, and hematology. Much work remains in genetics, molecular biology, and therapeutics to unravel the puzzle of the relationships and distinctions apparent between the different subclasses of TMA syndromes.

Three years ago, the Advancing American Kidney Health executive order launched a substantial effort with the goals of delaying the progression of kidney disease while also increasing kidney transplantation and the utilization of home dialysis. Included among the initiatives created by this executive order are two new payment models under the supervision of the Centers for Medicare & Medicaid Services Innovation Center. The End Stage Renal Disease Treatment Choices model is a mandatory payment model impacting nephrologists and dialysis providers in many regions across the country. The Kidney Care Choices model offers nephrologists four voluntary options for participation in value-based care. The early experience of two large kidney care organizations highlights the improvements these payment models have demonstrated over prior kidney care payment models while also suggesting additional opportunities for improvement. These models offer nephrologists the opportunity to partner with other providers and deliver patient-centered care across the kidney care continuum. The models represent another step toward value-based care and, if successful, should yield great benefits for patients with kidney disease.

While patients with end-stage kidney disease have benefited from innovations in clinical therapeutics and care delivery, these changes have been primarily incremental and have not fundamentally transformed care delivery. Dialysis markets are highly concentrated, which may impede innovation. Unique features of the dialysis industry that have contributed to consolidation can help to explain links between consolidation and innovation. We discuss these unique features and then provide a framework for considering the effects of consolidation on innovation in dialysis that focuses on the following economic considerations: (1) industry characteristics, composition, and stage of consolidation, (2) innovation characteristics and relative profitability, (3) the role of government regulation, and (4) innovation from smaller providers and new entrants. We present examples of how these considerations have influenced the adoption of alternative dialysis technologies such as peritoneal dialysis and erythropoietin-stimulating agents, and we discuss how consolidated markets can both help and hinder recent policy initiatives to transform dialysis care delivery. Only by considering these important drivers of consolidation, future efforts can be successful in transforming end-stage kidney disease care.