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Recent Advances in the Management of Vascular Calcification in Patients with End-Stage Renal Disease.
Nitta, K, Ogawa, T, Hanafusa, N, Tsuchiya, K
Contributions to nephrology. 2019;:62-72
Abstract
BACKGROUND Vascular calcification (VC) is common in patients with chronic kidney disease (CKD) including end-stage renal disease (ESRD). The pathogenesis of VC is complex, resulting in increased arterial stiffening, which is associated with cardiovascular mortality. In addition to traditional cardiovascular risk factors, CKD patients also have a number of non-traditional cardiovascular risk factors that may play an important role in the pathogenesis of VC. SUMMARY Management of CKD-mineral bone disorder using conventional therapeutic approaches, which include restricting dietary phosphate, administering phosphate binders, and using active vitamin D and calcimimetics, may inhibit the progression of VC, but these approaches remain controversial because recommended biochemical targets are difficult to achieve. Current treatment strategies focus on correcting abnormal calcium, phosphate, parathyroid hormone, and vitamin D levels in ESRD patients. Novel therapies for addressing VC include magnesium and vitamin K supplementation, which are currently being investigated in randomized controlled trials. This review summarizes current treatment strategies and therapeutic targets for the management of VC in patients with ESRD. Key Messages: A better understanding of the potential therapeutic approaches to VC may lead to improved mortality rates among patients with CKD including those on dialysis. Fetuin-A inhibits VC by binding to the nanoparticles of calcium and phosphate, preventing mineral accretion. These particles are known as calciprotein particles and may provide an important pathway for mineral transport and clearance. This review article summarizes the current management of VC in patients with ESRD.
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Risks, benefits, and ethical questions associated with transplanting kidneys from hepatitis C virus-infected donors into hepatitis C virus-negative patients.
Goldberg, D, Reese, PP
Seminars in dialysis. 2019;(2):179-186
Abstract
Utilization of kidneys from hepatitis C virus (HCV)-infected deceased donors has the potential to increase the number of kidney transplants by 500-1000 (or more) each year. This increase in the number of kidney transplants offers major opportunities to extend survival and improve quality of life for patients infected with HCV, as well as uninfected recipients. However, due to a lack of prospective safety and efficacy data on a sufficient number of HCV-negative recipients who received a kidney from a HCV-infected donor, as well as key logistical barriers, the practice of transplanting HCV-infected organs into uninfected recipients is not yet ready to be considered as standard of care. Ongoing research coupled with a collaboration between insurers and transplant centers might bring positive-into-negative transplant into the realm of standard of care in well-informed transplant candidates, regardless of HCV status.
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Ethical Issues in Pragmatic Cluster-Randomized Trials in Dialysis Facilities.
Goldstein, CE, Weijer, C, Taljaard, M, Al-Jaishi, AA, Basile, E, Brehaut, J, Cook, CL, Grimshaw, JM, Lacson, E, Lindsay, C, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2019;(5):659-666
Abstract
A pragmatic cluster-randomized trial (CRT) is a research design that may be used to efficiently test promising interventions that directly inform dialysis care. While the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials provides general ethical guidance for CRTs, the dialysis setting raises additional considerations. In this article, we outline ethical issues raised by pragmatic CRTs in dialysis facilities. These issues may be divided into 7 key domains: justifying the use of cluster randomization, adopting randomly allocated individual-level interventions as a facility standard of care, conducting benefit-harm analyses, gatekeepers and their responsibilities, obtaining informed consent from research participants, patient notification, and including vulnerable participants. We describe existing guidelines relevant to each domain, illustrate how they were considered in the Time to Reduce Mortality in End-Stage Renal Disease (TiME) trial (a prototypical pragmatic hemodialysis CRT), and highlight remaining areas of uncertainty. The following is the first step in an interdisciplinary mixed-methods research project to guide the design and conduct of pragmatic CRTs in dialysis facilities. Subsequent work will expand on these concepts and when possible, argue for a preferred solution.
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Long-Term Risks of Intravenous Iron in End-Stage Renal Disease Patients.
Kshirsagar, AV, Li, X
Advances in chronic kidney disease. 2019;(4):292-297
Abstract
Patients with end-stage renal disease on dialysis commonly receive intravenous iron to treat anemia along with erythropoiesis-stimulating agents. While studies of intravenous iron have demonstrated efficacy in raising hemoglobin, the quantity of administered intravenous iron has raised concerns about iron overload leading to long-term toxicities. The goal of this review is to understand recent trends in intravenous iron use, potential mechanisms of iron toxicity, and to evaluate the available evidence in the literature for potential long-term cardiovascular and infectious complications. We include findings from the recently published landmark clinical trial of intravenous iron for patients receiving hemodialysis to contextualize treatment recommendations.
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5.
Tenapanor: First Approval.
Markham, A
Drugs. 2019;(17):1897-1903
Abstract
The selective sodium hydrogen exchanger 3 (NHE3) inhibitor tenapanor is being developed by Ardelyx Inc. for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) [under the tradename IBSRELA®] and for hyperphosphataemia in patients with chronic kidney disease (CKD) on dialysis or with end stage renal disease (ESRD). Based on positive results from the phase III T3MPO trial program, tenapanor was recently approved in the USA for the treatment of IBS-C in adults. This article summarises the milestones in the development of tenapanor leading to this first approval.
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Successful multiple-exchange peritoneal dialysis in a patient with severe hematological toxicity by methotrexate: case report and literature review.
Aristizabal-Alzate, A, Nieto-Rios, JF, Ocampo-Kohn, C, Serna-Higuita, LM, Bello-Marquez, DC, Zuluaga-Valencia, GA
Jornal brasileiro de nefrologia. 2019;(3):427-432
Abstract
Methotrexate is an effective medication to control several diseases; however, it can be very toxic, being myelosuppression one of its main adverse effects, which increases in severity and frequency in patients with renal failure. We present the case of a 68-year-old man with chronic, end-stage renal disease associated with ANCA vasculitis, under treatment with peritoneal dialysis, who received the medication at a low dose, indicated by disease activity, which presented as a complication with severe pancytopenia with mucositis that improved with support measures and multiple-exchange peritoneal dialysis. We reviewed 20 cases published to date of pancytopenia associated with methotrexate in patients on dialysis and found high morbidity and mortality, which is why its use in this type of patient is not recommended. However, when this complication occurs, a therapeutic option could be the use of multiple-exchange peritoneal dialysis in addition to supportive therapy for drug-related toxicity, although it is recognized that studies are required to show the role of multiple-exchange peritoneal dialysis in the removal of this medication.
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A swan song for Kt/Vurea.
Vanholder, R, Van Biesen, W, Lameire, N
Seminars in dialysis. 2019;(5):424-437
Abstract
Dialyzer clearance of urea multiplied by dialysis time and normalized for urea distribution volume (Kt/Vurea or simply Kt/V) has been used as an index of dialysis adequacy since more than 30 years. This article reviews the flaws of Kt/V, starting with a lack of proof of concept in three randomized controlled hard outcome trials (RCTs), and continuing with a long list of conditions where the concept of Kt/V was shown to be flawed. This information leaves little room for any conclusion other than that Kt/V, as an indicator of dialysis adequacy, is obsolete. The dialysis patient might benefit more if, instead, the nephrology community concentrates in the future on pursuing the optimal dialysis dose that conforms with adequate quality of life and on factors that are likely to affect outcomes more than Kt/V. These include residual renal function, volume status, dialysis length, ultrafiltration rate, the number of intra-dialytic hypotensive episodes, interdialytic blood pressure, serum potassium and phosphate, serum albumin, and C reactive protein.
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8.
Assessment and Management of Hypertension among Patients on Peritoneal Dialysis.
Vaios, V, Georgianos, PI, Liakopoulos, V, Agarwal, R
Clinical journal of the American Society of Nephrology : CJASN. 2019;(2):297-305
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Abstract
Approximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.
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Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and End-Stage Renal Disease.
Nishimura, M, Hsu, JC
The American journal of cardiology. 2018;(1):131-140
Abstract
Over the past decade, there have been tremendous advancements in anticoagulation therapies for stroke prevention in patients with atrial fibrillation (AF). Although the non-vitamin K antagonist oral anticoagulants (NOACs) demonstrated favorable clinical outcomes compared with warfarin overall, the decision to anticoagulate and the choice of appropriate agent in patients with AF and concomitant chronic kidney disease (CKD) or end-stage renal disease (ESRD) are a particularly complex issue. CKD and ESRD increase both the risk of stroke and bleeding, and since all of the NOACs undergo various levels of renal clearance, renal dysfunction inevitably affects the pharmacokinetics of the drug in each patient. Furthermore, the randomized controlled clinical trials of each NOAC versus warfarin often did not include patients with advanced CKD or ESRD. In this focused review, we describe the available evidence supporting the use of NOACs for prevention of stroke in patients with AF with concomitant advanced CKD or ESRD. Although questions of safety and appropriate use of these new agents in CKD and ESRD remain, NOACs offer a significant step forward in the anticoagulation management of at-risk patients with AF.
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Dialysis Patient-Centeredness and Precision Medicine: Focus on Incremental Home Hemodialysis and Preserving Residual Kidney Function.
Gedney, N, Kalantar-Zadeh, K
Seminars in nephrology. 2018;(4):426-432
Abstract
An exponential interest in incremental transition to dialysis recently has emerged in lieu of outright three times/wk hemodialysis initiation as the standard of care. Incremental dialysis is consistent with precision medicine, given individualized dialysis dose adjustment based on patient's dynamic needs, leading to reduced patient suffering from longer or more frequent dialysis treatments and improved health-related quality of life. It includes twice-weekly or less frequent hemodialysis treatments with or without a low-protein diet on nondialysis days, or a shorter (<3 h) hemodialysis treatment three times per week or more frequent treatments, a useful approach for home hemodialysis initiation. Peritoneal dialysis also can be initiated incrementally with a shorter dwell time, less daily solution volume, or therapy for fewer than 7days per week. Subsequent transition to more frequent or more intense dialysis therapy within several months or longer will counter worsening fluid retention and uremia, for example, whenever residual urea clearance decreases to less than 2mL/min or if urine volume reaches less than 500mL/d, especially if loss of nocturia ensues. There are many advantages to using precision medicine tools to institute incremental dialysis protocols including preservation of residual kidney function, adhering to patient preference, and allowing for a greater patient-centeredness. Incremental dialysis may become the treatment of choice in End-stage renal disease Seamless Care Organizations (ESCO). This article also features a home hemodialysis patient's experience as a real-world scenario of how individualization of dialysis therapy based on unique patient characteristics and adjustment and shortening of hemodialysis treatment time and frequency led to improved patient experience, compliance with treatment regimen, and increased urine output, and the role of future ESCOs.