Recent trends in the diagnosis, treatment, and classification of collagen IV-associated kidney disease are likely to result in increasing numbers of people in adult nephrology practices who have a confirmed diagnosis of...Recent trends in the diagnosis, treatment, and classification of collagen IV-associated kidney disease are likely to result in increasing numbers of people in adult nephrology practices who have a confirmed diagnosis of Alport syndrome. These trends include the increasing use of genetic testing in the diagnostic evaluation of people with hematuria, focal segmental glomerulosclerosis, and chronic kidney disease of unknown etiology; early treatment with inhibitors of the renin-angiotensin-aldosterone system to delay kidney failure; and application of an expanded definition of Alport syndrome based on genotype rather than phenotype. This commentary discusses these trends and their implications for the adult nephrologist.
A substantial number of patients with focal segmental glomerulosclerosis (FSGS) have a pathogenic genetic mutation in a podocyte protein as the cause of their disease. The mutations can affect a wide range of cell functi...A substantial number of patients with focal segmental glomerulosclerosis (FSGS) have a pathogenic genetic mutation in a podocyte protein as the cause of their disease. The mutations can affect a wide range of cell functions including the actin cytoskeleton, cell adhesion and motility, mitochondrial function, and nuclear pore proteins. The likelihood of a genetic cause declines with age, from approximately 30% in children and adolescents to 10% in adulthood, and the specific proteins involved and the pattern of inheritance differ in the 2 age groups. The presence of a genetic cause for FSGS can have important clinical ramifications including the need for a diagnostic kidney biopsy, medical management, and the risk of recurrent disease after kidney transplantation. This review summarizes the spectrum of genetic causes of nephrotic syndrome, primarily FSGS, in adults with a focus on diagnosis, presentation, and management.
Monoclonal gammopathies occur secondary to a broad range of clonal B lymphocyte or plasma cell disorders, producing either whole or truncated monoclonal immunoglobulins. The kidneys are often affected by these monoclonal...Monoclonal gammopathies occur secondary to a broad range of clonal B lymphocyte or plasma cell disorders, producing either whole or truncated monoclonal immunoglobulins. The kidneys are often affected by these monoclonal proteins, and, although not mutually exclusive, can involve the glomeruli, tubules, interstitium, and vasculature. The nephrotoxic potential of these monoclonal proteins is dependent on a variety of physicochemical characteristics that are responsible for the diverse clinicopathologic manifestations, including glomerular diseases with organized deposits, glomerular diseases with granular deposits, and other lesions, such as C3 glomerulopathy and thrombotic microangiopathy with unique pathophysiologic features. The diseases that involve primarily the tubulointerstitial and vascular compartments are light chain cast nephropathy, light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulin-induced nephropathy with distinct acute and chronic clinicopathologic features. The diagnosis of a monoclonal gammopathy-related kidney disease is established by identification of an underlying active or more commonly, low-grade hematologic malignancy, serologic evidence of a monoclonal gammopathy when detectable, and most importantly, monoclonal protein-induced pathologic lesions seen in a kidney biopsy, confirming the association with the monoclonal protein. Establishing a diagnosis may be challenging at times, particularly in the absence of an overt hematologic malignancy, with or without monoclonal gammopathy, such as proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Overall, the treatment is directed against the underlying hematologic disorder and the potential source of the monoclonal protein.
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 dos...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.
Patients with cancer and kidney disease experience a range of symptoms that impact their quality of life. Pain, fatigue, decreased appetite, and depression are all common in this population. Kidney palliative care is pat...Patients with cancer and kidney disease experience a range of symptoms that impact their quality of life. Pain, fatigue, decreased appetite, and depression are all common in this population. Kidney palliative care is patient-centered medical care focused on reducing symptoms and defining individualized goals of care for patients and their families. Pharmacologic management of pain in patients with cancer and kidney disease requires recognition of the type of pain, its cause, and the risks and benefits of different medication classes. This review describes basic symptom management options as well as considerations for discussing goals of care, prognosis, and end of life.
Adv Chronic Kidney Dis
· 2022 Mar · PMID 35817526
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Full text
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...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.
Anemia is a common medical problem among patients with cancer and chronic kidney disease (CKD). Although anemia in patients with CKD is often treated with iron and erythropoietin-stimulating agents, there are controversi...Anemia is a common medical problem among patients with cancer and chronic kidney disease (CKD). Although anemia in patients with CKD is often treated with iron and erythropoietin-stimulating agents, there are controversies with regard to the use of erythropoietin-stimulating agents in cancer patients. In this article, we review the treatment of anemia in patients with cancer and CKD, in addition to summarizing the current guidelines in treatment of anemia in these patients.
Sodium and potassium disorders are pervasive in patients with cancer. The causes of these abnormalities are wide-ranging, are often primary or second-order consequences of the underlying cancer, and have prognostic impli...Sodium and potassium disorders are pervasive in patients with cancer. The causes of these abnormalities are wide-ranging, are often primary or second-order consequences of the underlying cancer, and have prognostic implications. The approach to hyponatremia should focus on cancer-related etiologies, such as syndrome of inappropriate antidiuretic hormone, to the exclusion of other causes. Hypernatremia in non-iatrogenic forms is generally due to water loss rather than excessive sodium intake. Debilitated or dependent patients with cancer are particularly vulnerable to hypernatremia. Hypokalemia can occur in patients with cancer due to gastrointestinal disturbances, resulting from decreased intake or increased losses. Renal losses can occur as a result of excessive mineralocorticoid secretion or therapy-related nephrotoxicity. The approach to hyperkalemia should be informed by historical and laboratory clues, and pseudohyperkalemia is particularly common in patients with hematological cancers. Hyperkalemia can be seen in primary or metastatic disease that interrupts the adrenal axis. It can also develop as a consequence of immunotherapy, which can cause adrenalitis or hypophysitis. Tumor lysis syndrome (TLS) is defined by the development of hyperkalemia and is a medical emergency. Awareness of the electrolyte abnormalities that can befall patients with cancer is vital for its prompt recognition and management.
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 surge...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.
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 multimerizat...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.
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...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.
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, inc...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.
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 a...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.
Hematopoietic stem cell transplantation (SCT) provides a curative option for the treatment of several malignancies. Its growing use is associated with an increased burden of kidney disease. Acute kidney injury is usually...Hematopoietic stem cell transplantation (SCT) provides a curative option for the treatment of several malignancies. Its growing use is associated with an increased burden of kidney disease. Acute kidney injury is usually seen within the first 100 days of transplantation and has an incidence ranging between 12 and 73%, with the highest rate in myeloablative allogeneic SCT. A large subset of patients after SCT develop chronic kidney disease. They can be broadly classified into thrombotic microangiopathy, nephrotic syndrome, and calcineurin toxicity. Dialysis requirement after SCT is associated with mortality exceeding 80%. Given the higher morbidity and mortality related to development kidney disease, nephrologists need to be aware of the various causes and best treatment options.
The Executive Order on Advancing American Kidney Health aimed to slow the progression of kidney disease, increase access to kidney transplantation, and expand home dialysis. In order to support the kidney health strategy...The Executive Order on Advancing American Kidney Health aimed to slow the progression of kidney disease, increase access to kidney transplantation, and expand home dialysis. In order to support the kidney health strategy laid out by the Advancing American Kidney Health, the National Institutes of Health, the National Institute of Diabetes, and Digestive, and Kidney Diseases, as well as other funding agencies must dedicate robust research funding to kidney disease. Currently, federal research investment for kidney health is less than 1% of Medicare fee-for-service expenditures for Americans with kidney disease. To address disparities in federal research funding, nephrology organizations are working together to advocate for increased federal commitment to kidney disease research. Underfunding of kidney disease research impedes scientific opportunities and innovation and prevents the collaboration of young investigators with research faculty that can accelerate the exodus of talent within the nephrology research workforce. This review provides an overview of the current state of federal research funding for kidney disease within the United States. In addition, we discuss ongoing advocacy efforts and programs that aim to increase federal funding for kidney-related research and accelerate the development of new and better therapies.
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....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.
Kidney transplant policy has not historically been considered a domain of nephrology policy; despite that, the US transplant system is marked by missed opportunities that prevent patients from accessing a kidney transpla...Kidney transplant policy has not historically been considered a domain of nephrology policy; despite that, the US transplant system is marked by missed opportunities that prevent patients from accessing a kidney transplant. Policymakers in the federal government are focused on growing the inadequate supply of kidneys, especially on increasing procurement of deceased donor organs, and reducing kidney discards. There are many more challenges in transplantation that require the attention of experts in nephrology policy, whether in the Administration, Congress, advocacy organizations, or clinical practice. Thoughtful policy solutions are needed to improve transplant equity, balance competing patient desires, increase living donation, develop and implement measures of transplant center performance, and create an infrastructure for the long-term management of transplant recipients.
The number and percentage of patients dialyzing at home has steadily increased during the past decade, and federal policy initiatives have driven interest to a new high. However, the mere utilization of home dialysis doe...The number and percentage of patients dialyzing at home has steadily increased during the past decade, and federal policy initiatives have driven interest to a new high. However, the mere utilization of home dialysis does not ensure better outcomes for patients and care partners. Although public reporting systems for dialysis quality are mature and robust, the incorporation of home dialysis quality in those systems is immature; the advent of the End-Stage Renal Disease Treatment Choices payment model brings this problem into sharp relief. The home dialysis modalities present both common and unique targets for quality measurement. For both modalities, therapy duration (or its inverse, technique failure) is a potential target. For peritoneal dialysis, peritonitis, catheter complications, and residual kidney function are additional targets; for home hemodialysis, vascular access infections, dialysis adequacy, and treatment adherence are targets. Patient-reported experience measures are also important; this domain is a long-standing disparity, as in-facility hemodialysis patients have been routinely surveyed for several years. The statistical aspect of quality measurement in home dialysis requires some adaptation, as the typical home dialysis program is small, thus presenting a threat to reliability; pooling programs may be necessary. Ultimately, promoting high-quality home dialysis will likely increase utilization of home dialysis.