Seminars in Nephrology

Children with end-stage kidney disease (ESKD) face a lifetime of complex medical care, alternating between maintenance chronic dialysis and kidney transplantation. Kidney transplantation has emerged as the optimal treatment of ESKD for children and provides important quality of life and survival advantages. Although transplantation is the preferred therapy, lifetime exposure to immunosuppression among children with ESKD is associated with increased morbidity, including an increased risk of cancer. Following pediatric kidney transplantation, cancer events occurring during childhood or young adulthood can be divided into two broad categories: post-transplant lymphoproliferative disorders and non-lymphoproliferative solid tumors...

Cancer is one of the most devastating complications of kidney transplantation and constitutes one of the leading causes of morbidity and mortality among solid organ transplantation (SOT) recipients. Immunosuppression, although effective in preventing allograft rejection, inherently inhibits immune surveillance against oncogenic viral infections and malignancy. Adoptive cell therapy, particularly immune effector cell therapy, has long been a modality of interest in both cancer and transplantation, though has only recently stepped into the spotlight with the development of virus-specific T-cell therapy and chimeric antigen receptor T-cell therapy...

Kidney transplant recipients are at increased risk of malignancy as a result of immunosuppression and are increasingly exposed to checkpoint inhibitors (CPIs). However, CPI therapy can precipitate allograft rejection. This review aims to summarize the current literature describing the epidemiology, immunological mechanisms, diagnosis, and treatment of CPI-associated allograft rejection.Initial studies of CPIs suggested allograft rejection post commencement of CPIs occured commonly (40-60%), occurring between 2 and 6 weeks after CPI initiation, with a cancer response rate approaching 50%...

Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma...

Cancer has been identified by kidney transplant recipients as a critically important outcome. The co-occurrence of cancer and kidney transplantation represents a complex intersection of diseases, symptoms, and competing priorities for treatments. Research that focuses on biochemical parameters and clinical events may not capture the priorities of patients. Patient-centered research can improve the relevance and efficiency of research and is particularly pertinent in the setting of cancer and kidney transplantation to facilitate shared decision-making in complex clinical situations...

Post-transplant lymphoproliferative disorders (PTLDs) are a heterogenous set of unregulated lymphoid cell proliferations after organ or tissue transplant. A majority of cases are associated with the Epstein-Barr virus and higher intensity of pharmacologic immunosuppression. The clinical presentations are numerous. The diagnosis is ideally by histology, except in cases where the tumor is inaccessible to biopsy. While some pre-emptive therapies and treatment strategies are available have reasonable success are available, they do not eliminate the high morbidity and significant mortality after PTLD...

Amyloidosis is a heterogeneous disorder characterized by abnormal protein aggregate deposition that often leads to kidney involvement and end-stage kidney disease. With advancements in diagnostic techniques and treatment options, the prevalence of patients with amyloidosis requiring chronic dialysis has increased. Kidney transplantation is a promising avenue for extending survival and enhancing quality of life in these patients. However, the complex and heterogeneous nature of amyloidosis presents challenges in determining optimal referral timing for transplantation and managing post-transplantation course...

End-stage kidney disease patients who are referred for transplant undergo an extensive evaluation process to ensure their health prior to transplant due in part to the shortage of available organs. Although management and surveillance guidelines exist for malignancies identified in the transplant and waitlist populations, less is written about the management of premalignant lesions in this population. This review covers the less common premalignant lesions (intraductal papillary mucinous neoplasm, gastrointestinal stromal tumor, thymoma, and pancreatic neuroendocrine tumor) that can be found in the transplant candidate population...

Recent advances in the treatment of plasma cell disorders (PCDs) have provided a wealth of therapy alternatives and improved overall survival tremendously. Various types of PCDs are associated with kidney injury and end-stage kidney disease in a considerable number of patients. Kidney transplantation (KTx) is the best option for renal replacement therapy in select patients in terms of both quality of life parameters and overall survival. Even with modern therapies, all PCDs carry the risk of hematologic progression, whereas histologic recurrence and graft loss are other prevailing concerns in these patients...

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Urinary tract infections are the most common bacterial infections encountered by health care professionals. In women, the lifetime incidence of urinary tract infections may be up to 40% to 50%, of whom a further 40% may have recurrent infections. Urinary tract infections are associated with significant morbidity and potential mortality-they may be complicated by frequent recurrences, kidney damage, sepsis, and preterm birth, as well as collateral damage of antimicrobial use, which includes Clostridium difficile colitis and selection of drug-resistant organisms...

Kidney transplant often is complicated by infections in the recipient from therapy-related and patient-related risk factors. Infections in kidney transplant recipients are associated with increased morbidity, mortality, and allograft dysfunction. There is a predictable timeline after kidney transplant regarding the types of pathogens causing infections, reflecting the net state of immunosuppression. In the early post-transplant period, bacterial infections comprise two thirds of all infections, followed by viral and fungal infections...

Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) are commonly used to prevent clotting of the hemodialysis extracorporeal circuit and optimize hemodialysis adequacy. There is no consensus on the optimal dosing for UFH and LMWHs during hemodialysis. In clinical practice, semiquantitative clotting scoring of the dialyzer and venous chamber may help to guide UFH and LMWH dose adjustment. Laboratory monitoring has not been shown to improve clinical outcomes and is therefore not routinely indicated in most hemodialysis patients...

Patients with end-stage kidney disease (ESKD) experience a high thrombotic risk but are also at increased risk of bleeding. There is an unmet need for safer antithrombotic therapy in patients with ESKD on hemodialysis. Factor XI (FXI) represents an attractive therapeutic target for anticoagulation because of the potential to mitigate the bleeding risks associated with currently approved anticoagulants, especially in patients at high risk of bleeding. FXI inhibition is also an attractive option in settings where coagulation is activated by exposure of the blood to artificial surfaces, including the extracorporeal circuit during hemodialysis...

An adequate knowledge of anticoagulants used to prevent clotting in the extracorporeal circuit is crucial to provide optimal hemodialysis. Drugs can potentially prevent extracorporeal circuit clotting, but administration, half-life, and potential side effects differ. However, there is a lack of concise recommendations to guide anticoagulation and to avoid side effects. Because of the development of newer anticoagulant agents, direct thrombin inhibitors, and heparinoids, some of the side effects related to heparin may be overcome, but a deeper knowledge of these newer drugs is necessary...

Maintaining patency of the extracorporeal hemodialysis (HD) circuit is a prerequisite to perform HD. Unfractionated heparin and low-molecular-weight heparins are the most used anticoagulants in maintenance HD, but their administration comes with a major trade-off of bleeding complications. This narrative review article discusses technical factors impacting on HD circuit patency, such as tubings, dialyzer membranes, priming practices, and treatment settings. Strategies for monitoring extracorporeal circuit clotting during and after treatment are also reviewed, as these are essential tools for optimizing anticoagulation...

The development of biocompatible membranes, aiming to limit the inflammatory response, oxidative stress, and coagulability during hemodialysis, has been an important step in reducing dialysis-related adverse outcomes. This includes a reduction in the risk of clotting of the extracorporeal circuit, thus enabling hemodialysis with a reduced dose or even without systemic anticoagulant drugs in patients with an increased bleeding risk. In this article, we summarize the in vitro research and clinical evidence on the antithrombotic properties of vitamin E- and heparin-coated membranes...

Human immunodeficiency virus (HIV) and tuberculosis (TB) are the leading infectious causes of death globally. The combined brunt of these diseases is experienced mainly in low-income and lower-middle-income countries. HIV/TB have devastating effects on the kidneys, leading to accelerated decline of kidney function as well as mortality. Managing the triad of TB/HIV and kidney disease is challenging. We discuss the epidemiology of HIV/TB coinfection and the kidney and the key mechanisms of kidney disease including genetic susceptibility...

Infection-related glomerulonephritis is an immunologically mediated glomerular injury after an infection. Glomerulonephritis may occur with the infection or after a variable latent period. Poststreptococcal glomerulonephritis (PSGN) is the prototype of infection-related glomerulonephritis. The streptococcal antigens, nephritis-associated plasmin-like receptor and streptococcal exotoxin B, have emerged as major players in the pathogenesis of PSGN. Although PSGN is the most common infection-related glomerulonephritis in children, in adults, glomerulonephritis is secondary to bacteria such as staphylococci, viruses such as hepatitis C, and human immunodeficiency virus, and, rarely, parasitic infections...

Cardiovascular diseases are highly prevalent among patients on dialysis. For these diseases, antiplatelets and antithrombotic therapies including heparin, vitamin K antagonists, and direct oral anticoagulants, are being used. However, the benefit-risk balance of these therapies could differ for dialysis patients compared with the general population. This review article focuses on the bleeding risk associated with the use of heparin, antiplatelets, vitamin K antagonists, and direct oral anticoagulants in patients receiving hemodialysis...