Advances in Chronic Kidney Disease

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...

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...

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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...

No abstract text is available yet for this article.

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...

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...

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...

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 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...

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...

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...

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...

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...

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...

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...

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...

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...

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...