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Hemodialysis vascular access is the “lifeline” for patients on hemodialysis. Unfortunately, because of its poor patency and significant complication rate, it is also the “Achilles heel” of hemodialysis. For example, the current unassisted arteriovenous fistula (AVF) maturation rate is only

Central venous catheters are used frequently in patients on hemodialysis as a bridge to a permanent vascular access. They are prone to frequent complications, including catheter-related bloodstream infection, catheter dysfunction, and central vein obstruction. There is a compelling need to develop new drugs or devices to prevent central venous catheter complications. We convened a multidisciplinary panel of experts to propose standardized definitions of catheter end points to guide the design of future clinical trials seeking approval from the Food and Drug Administration. Our workgroup suggests diagnosing catheter-related bloodstream infection in catheter-dependent patients on hemodialysis with a clinical suspicion of infection (fever, rigors, altered mental status, or unexplained hypotension), blood cultures growing the same organism from the catheter hub and a peripheral vein (or the dialysis bloodline), and absence of evidence for an alternative source of infection. Catheter dysfunction is defined as the inability of a central venous catheter to (1) complete a single dialysis session without triggering recurrent pressure alarms or (2) reproducibly deliver a mean dialysis blood flow of >300 ml/min (with arterial and venous pressures being within the hemodialysis unit parameters) on two consecutive dialysis sessions or provide a Kt/V≥1.2 in 4 hours or less. Catheter dysfunction is defined only if it persists, despite attempts to reposition the patient, reverse the arterial and venous lines, or forcefully flush the catheter. Central vein obstruction is suspected in patients with >70% stenosis of a central vein by contrast venography or the equivalent, ipsilateral upper extremity edema, and an existing or prior history of a central venous catheter. There is some uncertainty about the specific criteria for these diagnoses, and the workgroup has also proposed future high-priority studies to resolve these questions.

Paraproteins are monoclonal Igs or their components (light or heavy chains) that are produced by a clonal population of mature B cells, most commonly plasma cells. These paraproteins or monoclonal proteins are secreted into the blood and subsequently filtered by the glomerulus before entering into urine, where they can cause various types of kidney disease, including both glomerular and tubulointerstitial injuries. Furthermore, a monoclonal protein that causes a specific glomerular or tubulointerstitial lesion in a human can reproducibly cause the same pathology when injected into an animal, supporting unique paraprotein characteristics. This Moving Points in Nephrology will provide an update for the Clinical Journal of the American Society of Nephrology readership on some of the clinically relevant kidney lesions associated with monoclonal paraprotein production and the pathophysiology underlying these kidney lesions.

Disorders of plasma and B cells leading to paraproteinemias are associated with a variety of renal diseases. Understanding the mechanisms of injury and associated nephropathies provides a framework that aids clinicians in prompt diagnosis and appropriate adjunctive treatment of these disorders. Glomerular diseases that may be associated with paraproteinemias include amyloid deposition, monoclonal Ig deposition disease, proliferative GN with monoclonal Ig deposits, C3 glomerulopathy caused by alterations in the complement pathway, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemia. Tubular lesions include the classic Fanconi syndrome, light–chain proximal tubulopathy, interstitial fibrosis, and cast nephropathy. These paraproteinemic renal diseases are distinct in their pathogenesis as well as their urinary and kidney biopsy findings. Renal pathology is usually initiated by deposition and direct involvement of the intact monoclonal Ig or Ig fragments with resident cells of the nephron. Our review summarizes current insights into the underlying molecular pathogenesis of these interesting kidney lesions.

Nearly 50% of patients with multiple myeloma develop renal disease, most commonly from AKI caused by cast nephropathy. Development of AKI is associated with poor 1-year survival and reduces the therapeutic options available to patients. There is a great need for more effective therapies. Cast nephropathy is caused by the interaction and aggregation of filtered free light chains and Tamm–Horsfall protein causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of free light chains, because this correlates with renal recovery. Newer chemotherapy agents rapidly lower free light chains and have been referred to as renoprotective. There is additional great interest in using extracorporeal therapies to remove serum free light chains. Small trials initially showed benefit of therapeutic plasma exchange to improve renal outcomes in cast nephropathy, but a large randomized trial of therapeutic plasma exchange failed to show benefit. A newer technique is extended high–cutoff hemodialysis. This modality uses a high molecular weight cutoff filter to remove free light chains. To date, trials of high–cutoff hemodialysis use in patients with cast nephropathy have been encouraging. However, there are no randomized trials showing the benefit of high-cutoff hemodialysis when used in addition to newer chemotherapeutic regimens. Until these studies are available, high-cutoff hemodialysis cannot be recommended as standard of care.

Paraprotein-related kidney disease represents a complex group of diseases caused by an abnormal paraprotein secreted by a clone of B cells. The disease manifestations range from tubulopathies, such as the Fanconi syndrome, to a spectrum of glomerular diseases that can present with varying degrees of proteinuria and renal dysfunction. Diagnosis of these diseases can be challenging because of the wide range of manifestations as well as the relatively common finding of a serum paraprotein, especially in elderly patients. Thus, renal biopsy along with detailed hematologic workup is essential to link the presence of the paraprotein to the associated renal disease. Recent advances in treatment with more effective and targeted chemotherapies, as well as stem cell transplantation, have improved the renal and overall prognosis for many of these disorders.

Dialysis care is often associated with poor outcomes including low quality of life (QOL). To improve patient-reported outcomes, incorporation of the patient’s needs and perspective into the medical care they receive is essential. This article provides a framework to help clinicians integrate symptom assessment and other measures such as QOL and frailty scores into a clinical approach to the contemporary supportive care of patients with advanced CKD. This approach involves (1) defining our understanding of kidney supportive care, patient-centered dialysis, and palliative dialysis; (2) understanding and recognizing common symptoms associated with advanced CKD; (3) discussing the concepts of physical function, frailty, and QOL and their role in CKD; and (4) identifying the structural and process barriers that may arise when patient-centered dialysis is being introduced into clinical practice.

Historic migration and the ever–increasing current migration into Western countries have greatly changed the ethnic and cultural patterns of patient populations. Because health care beliefs of minority groups may follow their religion and country of origin, inevitable conflict can arise with decision making at the end of life. The principles of truth telling and patient autonomy are embedded in the framework of Anglo–American medical ethics. In contrast, in many parts of the world, the cultural norm is protection of the patient from the truth, decision making by the family, and a tradition of familial piety, where it is dishonorable not to do as much as possible for parents. The challenge for health care professionals is to understand how culture has enormous potential to influence patients’ responses to medical issues, such as healing and suffering, as well as the physician-patient relationship. Our paper provides a framework of communication strategies that enhance crosscultural competency within nephrology teams. Shared decision making also enables clinicians to be culturally competent communicators by providing a model where clinicians and patients jointly consider best clinical evidence in light of a patient’s specific health characteristics and values when choosing health care. The development of decision aids to include cultural awareness could avoid conflict proactively, more productively address it when it occurs, and enable decision making within the framework of the patient and family cultural beliefs.

This article will demonstrate how to conduct a quality improvement project using the change idea generated in “How To Use Quality Improvement Tools in Clinical Practice: How To Diagnose Solutions to a Quality of Care Problem” by Dr. Ziv Harel and colleagues in this Moving Points feature. This change idea involves the introduction of a nurse educator into a CKD clinic with a goal of increasing rates of patients performing dialysis independently at home (home hemodialysis or peritoneal dialysis). Using this example, we will illustrate a Plan–Do–Study–Act (PDSA) cycle in action and highlight the principles of rapid cycle change methodology. We will then discuss the selection of outcome, process, and balancing measures, and the practicalities of collecting these data in the clinic environment. We will also introduce the PDSA worksheet as a practical way to oversee the progress of a quality improvement project. Finally, we will demonstrate how run charts are used to visually illustrate improvement in real time, and how this information can be used to validate achievement, respond appropriately to challenges the project may encounter, and prove the significance of results. This article aims to provide readers with a clear and practical framework upon which to trial their own ideas for quality improvement in the clinical setting.

To change a particular quality of care outcome within a system, quality improvement initiatives must first understand the causes contributing to the outcome. After the causes of a particular outcome are known, changes can be made to address these causes and change the outcome. Using the example of home dialysis (home hemodialysis and peritoneal dialysis), this article within this Moving Points feature on quality improvement will provide health care professionals with the tools necessary to analyze the steps contributing to certain outcomes in health care quality and develop ideas that will ultimately lead to their resolution. The tools used to identify the main contributors to a quality of care outcome will be described, including cause and effect diagrams, Pareto analysis, and process mapping. We will also review common change concepts and brainstorming activities to identify effective change ideas. These methods will be applied to our home dialysis quality improvement project, providing a practical example that other kidney health care professionals can replicate at their local centers.

Quality improvement involves a combined effort among health care staff and stakeholders to diagnose and treat problems in the health care system. However, health care professionals often lack training in quality improvement methods, which makes it challenging to participate in improvement efforts. This article familiarizes health care professionals with how to begin a quality improvement project. The initial steps involve forming an improvement team that possesses expertise in the quality of care problem, leadership, and change management. Stakeholder mapping and analysis are useful tools at this stage, and these are reviewed to help identify individuals who might have a vested interest in the project. Physician engagement is a particularly important component of project success, and the knowledge that patients/caregivers can offer as members of a quality improvement team should not be overlooked. After a team is formed, an improvement framework helps to organize the scientific process of system change. Common quality improvement frameworks include Six Sigma, Lean, and the Model for Improvement. These models are contrasted, with a focus on the Model for Improvement, because it is widely used and applicable to a variety of quality of care problems without advanced training. It involves three steps: setting aims to focus improvement, choosing a balanced set of measures to determine if improvement occurs, and testing new ideas to change the current process. These new ideas are evaluated using Plan-Do-Study-Act cycles, where knowledge is gained by testing changes and reflecting on their effect. To show the real world utility of the quality improvement methods discussed, they are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis). This provides an example that kidney health care professionals can use to begin their own quality improvement projects.

Live-donor kidney transplantation (LDKT) is the best treatment for eligible people with late-stage kidney disease. Despite this, living kidney donation rates have declined in the United States in recent years. A potential source of this decline is the financial impact on potential and actual living kidney donors (LKDs). Recent evidence indicates that the economic climate may be associated with the decline in LDKT and that there are nontrivial financial ramifications for some LKDs. In June 2014, the American Society of Transplantation’s Live Donor Community of Practice convened a Consensus Conference on Best Practices in Live Kidney Donation. The conference included transplant professionals, patients, and other key stakeholders (with the financial support of 10 other organizations) and sought to identify best practices, knowledge gaps, and opportunities pertaining to living kidney donation. This workgroup was tasked with exploring systemic and financial barriers to living kidney donation. The workgroup reviewed literature that assessed the financial effect of living kidney donation, analyzed employment and insurance factors, discussed international models for addressing direct and indirect costs faced by LKDs, and summarized current available resources. The workgroup developed the following series of recommendations to reduce financial and systemic barriers and achieve financial neutrality for LKDs: (1) allocate resources for standardized reimbursement of LKDs' lost wages and incidental costs; (2) pass legislation to offer employment and insurability protections to LKDs; (3) create an LKD financial toolkit to provide standardized, vetted education to donors and providers about options to maximize donor coverage and minimize financial effect within the current climate; and (4) promote further research to identify systemic barriers to living donation and LDKT to ensure the creation of mitigation strategies.

The education, evaluation, and support of living donors before, during, and after donation have historically been considered the roles and responsibilities of transplant programs. Although intended to protect donors, ensure true informed consent, and prevent coercion, this structure often leaves referring nephrologists unclear about the donor process and uncertain regarding the ultimate outcome of potential donors for their patients. The aim of this article is to help the referring nephrologist understand the donor referral and evaluation process, help the referring nephrologist understand the responsibilities of the transplant program, and offer suggestions about how the referring nephrologist can help to improve efficiencies in the process of donor education and evaluation. A partnership between referring nephrologists and transplant programs is an important step in advancing living kidney donation. The referring nephrologists are the frontline providers and are in a unique position to offer education about living donation and improve efficiencies in the process. Understanding the donor referral and evaluation process, the responsibilities of the transplant program, and the potential role referring nephrologists can play in the process is critical to establishing such a partnership.

The Best Practice in Live Kidney Donation Consensus Conference held in June of 2014 included the Best Practices in Living Donor Education Workgroup, whose charge was to identify best practice strategies in education of living donors, community outreach initiatives, commercial media, solicitation, and state registries. The workgroup’s goal was to identify critical content to include in living kidney donor education and best methods to deliver educational content. A detailed summary of considerations regarding educational content issues for potential living kidney donors is presented, including the consensus that was reached. Educational topics that may require updating on the basis of emerging studies on living kidney donor health outcomes are also presented. Enhancing the educational process is important for increasing living donor comprehension to optimize informed decision-making.

Despite its superior outcomes relative to chronic dialysis and deceased donor kidney transplantation, live donor kidney transplantation (LDKT) is less likely to occur in minorities, older adults, and poor patients than in those who are white, younger, and have higher household income. In addition, there is considerable geographic variability in LDKT rates. Concomitantly, in recent years, the rate of living kidney donation (LKD) has stopped increasing and is declining, after decades of consistent growth. Particularly noteworthy is the decline in LKD among black, younger, male, and lower-income adults. The Live Donor Community of Practice within the American Society of Transplantation, with financial support from 10 other organizations, held a Consensus Conference on Best Practices in Live Kidney Donation in June 2014. The purpose of this meeting was to identify LKD best practices and knowledge gaps that might influence LDKT, with a focus on patient and donor education, evaluation efficiencies, disparities, and systemic barriers to LKD. In this article, we discuss trends in LDKT/LKD and emerging novel strategies for attenuating disparities, and we offer specific recommendations for future clinical practice, education, research, and policy from the Consensus Conference Workgroup focused on disparities.

Drug-induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupus-like syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Over the years, multiple other agents have been linked to immune-mediated glomerular disease, often with associated autoantibody formation. Certain clinical and laboratory features may distinguish these entities from their idiopathic counterparts, and making this distinction is important in the diagnosis and management of these patients. Here, drug-induced, ANCA-associated vasculitis, drug-induced lupus, and drug-associated membranous nephropathy are reviewed.

Optimizing vascular access outcomes continues to pose a tremendous challenge to nephrologists, surgeons, and radiologists who provide medical care to patients on hemodialysis. There is a huge discrepancy between the optimal vascular access outcome proposed by national guidelines ([1][1]) and the

In an effort to foster innovation and new product development, the American Society of Nephrology and the US Food and Drug Administration partnered to form the Kidney Health Initiative in 2012. Part of the Kidney Health Initiative’s mission is to foster development of therapies by creating a collaborative environment where the US Food and Drug Administration and the greater nephrology community can interact to optimize product evaluation. This particular Kidney Health Initiative project focused on products related to hemodialysis vascular access, with the goal of clarifying appropriate trial end points that could subsequently inform clinical, regulatory, and coverage decisions. Both the lack of common definitions and the lack of consensus on trial end points have been viewed as barriers to innovation in this area. Toward this end, the Kidney Health Initiative convened teams of expert stakeholders to address these issues for each major vascular access category (arteriovenous grafts, arteriovenous fistulas, and central venous catheters), and each team provided recommendations. This commentary provides an overview of the US Food and Drug Administration centers that regulate hemodialysis vascular access and certain laws and regulations that affect these products as well as our perspectives on some of the issues raised and end points proposed by the Kidney Health Initiative teams. The standardized definitions and clinical trial end points proposed by the teams represent an important step forward to improve innovation in this area.

This paper is part of the Clinical Trial Endpoints for Dialysis Vascular Access Project of the American Society of Nephrology Kidney Health Initiative. The purpose of this project is to promote research in vascular access by clarifying trial end points which would be best suited to inform decisions in those situations in which supportive clinical data are required. The focus of a portion of the project is directed toward arteriovenous access. There is a potential for interventional studies to be directed toward any of the events that may be associated with an arteriovenous access’ evolution throughout its life cycle, which has been divided into five distinct phases. Each one of these has the potential for relatively unique problems. The first three of these correspond to three distinct stages of arteriovenous access development, each one of which has been characterized by objective direct and/or indirect criteria. These are characterized as: stage 1—patent arteriovenous access, stage 2—physiologically mature arteriovenous access, and stage 3—clinically functional arteriovenous access. Once the requirements of a stage 3—clinically functional arteriovenous access have been met, the fourth phase of its life cycle begins. This is the phase of sustained clinical use from which the arteriovenous access may move back and forth between it and the fifth phase, dysfunction. From this phase of its life cycle, the arteriovenous access requires a maintenance procedure to preserve or restore sustained clinical use. Using these definitions, clinical trial end points appropriate to the various phases that characterize the evolution of the arteriovenous access life cycle have been identified. It is anticipated that by using these definitions and potential end points, clinical trials can be designed that more closely correlate with the goals of the intervention and provide appropriate supportive data for clinical, regulatory, and coverage decisions.

Membranoproliferative GN represents a pattern of injury seen on light microscopy. Historically, findings on electron microscopy have been used to further subclassify this pathologic entity. Recent advances in understanding of the underlying pathobiology have led to a proposed classification scheme based on immunofluorescence findings. Dysregulation of the complement system has been shown to be a major risk factor for the development of a membranoproliferative GN pattern of injury on kidney biopsy. Evaluation and treatment of this complex disorder rest on defining the underlying mechanisms.

The last decade has seen major progress in understanding the pathogenesis as well as the prognosis and treatment of patients with IgA nephropathy (IgAN). Although the diagnostic criterion of a kidney biopsy demonstrating dominant or codominant IgA deposition remains unchanged, much more is known about the genetic and environmental factors predisposing to disease development and progression. These advances have led to the identification of novel diagnostic and prognostic markers. Among the most promising clinically are genetic profiling, quantification of galactose-deficient IgA1 levels, and measurement of anti-IgA1 immunoglobulins. While targeted treatment for IgAN remains elusive, there is mounting evidence for therapeutic interventions that alter the disease course. The appropriate validation and integration of these discoveries into clinical care represent a major challenge, but one that holds tremendous promise for refining prognostication, guiding therapy, and improving the lives of patients with IgAN.

Summary Membranous nephropathy (MN) is an autoimmune disease usually associated with a nephrotic syndrome and it may progress to ESRD in the long term. Its etiology is often unknown (idiopathic MN), whereas other cases have a recognizable etiology (secondary MN). In idiopathic MN, the glomerular lesions are mainly caused by autoantibodies against a podocyte membrane protein, the M-type of phospholipase A2 receptor 1. The natural course of idiopathic MN is quite varied with spontaneous complete or partial remissions a relatively common occurrence. Patients with asymptomatic non-nephrotic proteinuria seldom progress and need only conservative management. Those with persistent full-blown nephrotic syndrome and those with declining renal function are candidates for specific treatment with any of several regimens. Cyclical therapy with alternating monthly intravenous and oral glucocorticoids combined with a cytotoxic agent can induce remission and preserve renal function in the long term. Cyclosporine or tacrolimus can induce remission, but relapses are frequent after the drug withdrawal. Mycophenolate mofetil monotherapy seems to be ineffective, but may be beneficial when administered together with steroids. The experience with adrenocorticotropic hormone, natural or synthetic, is limited to a few studies with short-term follow-up, but high rates of remission can be seen after prolonged treatment. A high rate of remission and good tolerance have also been reported with rituximab. Patients with moderate renal insufficiency may also benefit from treatment, but at a price of frequent and serious side effects. With these limitations in mind, idiopathic MN may be considered a treatable disease in many patients.

As judged by the American College of Radiology Appropriateness Criteria, renal Doppler ultrasonography is the most appropriate imaging test in the evaluation of AKI and has the highest level of recommendation. Unfortunately, nephrologists are rarely specifically trained in ultrasonography technique and interpretation, and important clinical information obtained from renal ultrasonography may not be appreciated. In this review, the strengths and limitations of grayscale ultrasonography in the evaluation of patients with AKI will be discussed with attention to its use for (1) assessment of intrinsic causes of AKI, (2) distinguishing acute from chronic kidney diseases, and (3) detection of obstruction. The use of Doppler imaging and the resistive index in patients with AKI will be reviewed with attention to its use for (1) predicting the development of AKI, (2) predicting the prognosis of AKI, and (3) distinguishing prerenal azotemia from intrinsic AKI. Finally, pediatric considerations in the use of ultrasonography in AKI will be reviewed.

Because of its noninvasive nature and provision of quantitative measures of a wide variety of physiologic parameters, functional magnetic resonance imaging (MRI) shows great potential for research and clinical applications. Over the past decade, application of functional MRI extended beyond detection of cerebral activity, and techniques for abdominal functional MRI evolved. Assessment of renal perfusion, glomerular filtration, interstitial diffusion, and parenchymal oxygenation turned this modality into an essential research and potentially diagnostic tool. Variations in many renal physiologic markers can be detected using functional MRI before morphologic changes become evident in anatomic magnetic resonance images. Moreover, the framework of functional MRI opened a window of opportunity to develop novel pathophysiologic markers. This article reviews applications of some well validated functional MRI techniques, including perfusion, diffusion-weighted imaging, and blood oxygen level-dependent MRI, as well as some emerging new techniques such as magnetic resonance elastography, which might evolve into clinically useful tools.

Hemodialysis vascular access dysfunction is a major source of morbidity for patients with ESRD. Development of effective approaches to prevent and treat vascular access failure requires an understanding of the underlying mechanisms, suitable models for preclinical testing, systems for targeted delivery of interventions to maximize efficacy and minimize toxicity, and rigorous clinical trials that use appropriate outcome measures. This article reviews the substantial progress and ongoing challenges in developing novel treatments for arteriovenous vascular access failure and focuses on localized rather than systemic interventions.

Failure of hemodialysis access is caused mostly by venous intimal hyperplasia, a fibro-muscular thickening of the vessel wall. The pathogenesis of venous neointimal hyperplasia in primary arteriovenous fistulae consists of processes that have been identified as upstream and downstream events. Upstream events are the initial events producing injury of the endothelial layer (surgical trauma, hemodynamic shear stress, vessel wall injury due to needle punctures, etc.). Downstream events are the responses of the vascular wall at the endothelial injury that consist of a cascade of processes including leukocyte adhesion, migration of smooth muscle cells from the media to the intimal layer, and proliferation. In arteriovenous fistulae, the stenoses occur in specific sites, consistently related to the local hemodynamics determined by the vessel geometry and blood flow pattern. Recent findings that the localization of these sites matches areas of disturbed flow may add new insights into the pathogenesis of neointimal hyperplasia in the venous side of vascular access after the creation of the anastomosis. The detailed study of fluid flow motion acting on the vascular wall in anastomosed vessels and in the arm vasculature at the patient-specific level may help to elucidate the role of hemodynamics in vascular remodeling and neointimal hyperplasia formation. These computational approaches may also help in surgical planning for the amelioration of clinical outcome. This review aims to discuss the role of the disturbed flow condition in acting as upstream event in the pathogenesis of venous intimal hyperplasia and in producing subsequent local vascular remodeling in autogenous arteriovenous fistulae used for hemodialysis access. The potential use of blood flow analysis in the management of vascular access is also discussed.

Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development.

Heart failure remains the leading cause of hospitalization in older patients and is considered a growing public health problem with a significant financial burden on the health care system. The suboptimal efficacy and safety profile of diuretic-based therapeutic regimens coupled with unsatisfactory results of the studies on novel pharmacologic agents have positioned ultrafiltration on the forefront as an appealing therapeutic option for patients with acute decompensated heart failure (ADHF). In recent years, substantial interest in the use of ultrafiltration has been generated due to the advent of dedicated portable devices and promising results of trials focusing both on mechanistic and clinical aspects of this therapeutic modality. This article briefly reviews the proposed benefits of ultrafiltration therapy in the setting of ADHF and summarizes the major findings of the currently available studies in this field. The results of more recent trials on cardiorenal syndrome that present a counterpoint to previous observations and highlight certain limitations of ultrafiltration therapy are then discussed, followed by identification of major challenges and unanswered questions that could potentially hinder its more widespread use. Future studies are warranted to shed light on less well characterized aspects of ultrafiltration therapy and to further define its role in ADHF and cardiorenal syndrome.

Summary The cardiorenal syndrome has recently been defined as “disorders of the heart and kidney whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other.” The syndrome is extremely common and independently associated with poor clinical outcomes. However, no pharmacological therapy has been shown to improve its outcomes. Unfortunately, the mechanisms that initiate the development of renal dysfunction in heart failure are still debated. This review tries to clarify some of the misunderstanding regarding the principle hemodynamic factors that drive the kidneys to retain salt and water. Clin J Am Soc Nephrol 8: 1800–1807, 2013. doi: 10.2215/CJN.04090413

International audience; In using a patient-centered approach, neither a clinician nor a prognostic score can predict with absolute certainty how well a patient will do or how long he will live; however, validated prognostic scores may improve accuracy of prognostic estimates, thereby enhancing the ability of the clinicians to appreciate the individual burden of disease and the prognosis of their patients and inform them accordingly. They may also facilitate nephrologist's recommendation of dialysis services to those who may benefit and proposal of alternative care pathways that might better respect patients' values and goals to those who are unlikely to benefit. The purpose of this article is to discuss the use as well as the limits and deficiencies of currently available prognostic tools. It will describe new predictors that could be integrated in future scores and the role of patients' priorities in development of new scores. Delivering patient-centered care requires an understanding of patients' priorities that are important and relevant to them. Because of limits of available scores, the contribution of new prognostic tools with specific markers of the trajectories for patients with CKD and patients' health reports should be evaluated in relation to their transportability to different clinical and cultural contexts and their potential for integration into the decision-making processes. The benefit of their use then needs to be quantified in clinical practice by outcome studies including health-related quality of life, patient and caregiver satisfaction, or utility for improving clinical management pathways and tailoring individualized patient-centered strategies of care. Future research also needs to incorporate qualitative methods involving patients and their caregivers to better understand the barriers and facilitators to use of these tools in the clinical setting. Information given to patients should be supported by a more realistic approach to what dialysis is likely to entail for the individual patient in terms of likely quality and quantity of life according to the patient's values and goals and not just the possibility of life prolongation.

Paraproteins are monoclonal Igs that accumulate in blood as a result of abnormal excess production. These circulating proteins cause a diversity of kidney disorders that are increasingly being comanaged by nephrologists. In this review, we discuss paraprotein-related diseases that affect the glomerulus. We provide a broad overview of diseases characterized by nonorganized deposits, such as monoclonal Ig deposition disease (MIDD), proliferative GN with monoclonal Ig deposits (PGNMID), and C3 glomerulopathy, as well as those characterized by organized deposits, such as amyloidosis, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemic GN, and rarer disorders, such as monoclonal crystalline glomerulopathies, paraprotein–related thrombotic microangiopathies, and membranous-like glomerulopathy with masked IgGκ deposits. This review will provide the nephrologist with an up to date understanding of these entities and highlight the areas of deficit in evidence and future lines of research.

Optimal vascular access planning begins when the patient is in the predialysis stages of CKD. The choice of optimal vascular access for an individual patient and determining timing of access creation are dependent on a multitude of factors that can vary widely with each patient, including demographics, comorbidities, anatomy, and personal preferences. It is important to consider every patient's ESRD life plan (hence, their overall dialysis access life plan for every vascular access creation or placement). Optimal access type and timing of access creation are also influenced by factors external to the patient, such as surgeon experience and processes of care. In this review, we will discuss the key determinants in optimal access type and timing of access creation for upper extremity arteriovenous fistulas and grafts.

Despite significant improvements in preoperative patient evaluation and surgical planning, vascular access failure in patients on hemodialysis remains a frequent and often unforeseeable complication. Our inability to prevent this complication is, in part, because of an incomplete understanding of how preexisting venous and arterial conditions influence the function of newly created arteriovenous fistulas and grafts. This article reviews the relationship between three preexisting vascular pathologies associated with CKD (intimal hyperplasia, vascular calcification, and medial fibrosis) and hemodialysis access outcomes. The published literature indicates that the pathogenesis of vascular access failure is multifactorial and not determined by any of these pathologies individually. Keeping this observation in mind should help focus our research on the true causes responsible for vascular access failure and the much needed therapies to prevent it.

Vascular access dysfunction remains a major cause of morbidity and mortality in hemodialysis patients. At present there are few effective therapies for this clinical problem. The poor understanding of the pathobiology that leads to arteriovenous fistula (AVF) and graft (AVG) dysfunction remains a critical barrier to development of novel and effective therapies. However, in recent years we have made substantial progress in our understanding of the mechanisms of vascular access dysfunction. This article presents recent advances and new insights into the pathobiology of AVF and AVG dysfunction and highlights potential therapeutic targets to improve vascular access outcomes.

To achieve sustainable change, quality improvement initiatives must become the new way of working rather than something added on to routine clinical care. However, most organizational change is not maintained. In this next article in this Moving Points in Nephrology feature on quality improvement, we provide health care professionals with strategies to sustain and support quality improvement. Threats to sustainability may be identified both at the beginning of a project and when it is ready for implementation. The National Health Service Sustainability Model is reviewed as one example to help identify issues that affect long-term success of quality improvement projects. Tools to help sustain improvement include process control boards, performance boards, standard work, and improvement huddles. Process control and performance boards are methods to communicate improvement results to staff and leadership. Standard work is a written or visual outline of current best practices for a task and provides a framework to ensure that changes that have improved patient care are consistently and reliably applied to every patient encounter. Improvement huddles are short, regular meetings among staff to anticipate problems, review performance, and support a culture of improvement. Many of these tools rely on principles of visual management, which are systems transparent and simple so that every staff member can rapidly distinguish normal from abnormal working conditions. Even when quality improvement methods are properly applied, the success of a project still depends on contextual factors. Context refers to aspects of the local setting in which the project operates. Context affects resources, leadership support, data infrastructure, team motivation, and team performance. For these reasons, the same project may thrive in a supportive context and fail in a different context. To demonstrate the practical applications of these quality improvement principles, these principles are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis).

Quality improvement is a common lexicon among practicing nephrologists. However, most clinical nephrologists have not received formal training in quality improvement methodology. However, the effect of performance measurement and data reporting in medicine and clinical nephrology has increased

International audience; Comprehensive conservative (nondialytic) kidney care is widely recognized and delivered but until recently, has not been clearly defined. We provide a clear definition of comprehensive conservative care. This includes interventions to delay progression of kidney disease and minimize complications as well as detailed communication, shared decision making, advance care planning, and psychologic and family support. It does not include dialysis. Limited epidemiologic evidence from Australia and Canada indicates that, for every new person diagnosed with ESRD who receives dialysis or transplant, there is one new person who is managed conservatively (either actively or not). For older patients (those >75 or 80 years old) who have higher levels of comorbidity (such as diabetes and heart disease) and poorer functional status, the survival advantage of dialysis may be limited, and comprehensive conservative management may be considered; however, robust comparative evidence remains limited. Considerations of symptoms, quality of life, and hospital-free days are as or sometimes more important for patients and families than survival. There is some evidence that communication about possible conservative management options is generally insufficient, even where comprehensive conservative care pathways are already established. Symptom control and the cost-effectiveness of interventions are addressed in the companion papers within this Moving Points in Nephrology series. There is almost no evidence about which models of care and which interventions might be most beneficial in this population; future research on these areas is much needed. Meanwhile, consistency in definition of comprehensive conservative care and basing interventions on existing evidence about survival, symptoms, quality of life, and experience will maximize patient-centered and holistic care.

Without passion man is a mere latent force and possibility, like the flint which awaits the shock of the iron before it can give forth its spark. Henri-Frederic Amiel, 1821–1881 For most physicians, medicine as a professional journey is driven by passion. Medical student essays speak passionately about healing the sick; comforting the bereaved; discovering new insights; and developing new paradigms for diagnosis, prognostic markers, and therapeutics. Academic health centers (AHCs) provide the home for this passion to be nurtured and honed among its trainees, and fueled among its faculty. However, in response to enormous pressures over the past 40 yr, ACHs have increasingly shifted the focus from faculty-relevant issues to strategic considerations about competitive market forces, reimbursement shortfalls, increasing regulatory oversight and compliance requirements, and extramural funding levels. As increasingly complex enterprises, AHCs have been slow to adjust with regard to revising promotion and tenure policies, establishing mentoring and faculty development programs, and creating bridge funding mechanisms, leaving relationships between academic leadership and faculty strained. Under the weight of all these forces, faculty passion and career satisfaction has steadily diminished, particularly among the most junior members. Recent reviews of academic medical faculty indicate that approximately 42% are seriously considering leaving academic medicine in the next 5 yr and that 40% reported that their career was not progressing satisfactorily (1). Career satisfaction is threatened by the lack of time for teaching, scholarship, and personal and professional self-renewal (2–6). In addition to the rapidly changing economic and regulatory environments, AHCs are also affected by the evolving social environment, in which generational differences define distinct approaches to career and family (7). By and large, department chairs and senior faculty are Baby Boomers. Born between 1945 and 1962, Boomers work hard out of loyalty, expect long-term employment, pay their “dues,” …

Vitamin D functions in the body through both an endocrine mechanism (regulation of calcium absorption) and an autocrine mechanism (facilitation of gene expression). The former acts through circulating calcitriol, whereas the latter, which accounts for more than 80% of the metabolic utilization of the vitamin each day, produces, uses, and degrades calcitriol exclusively intracellularly. In patients with end-stage kidney disease, the endocrine mechanism is effectively disabled; however, the autocrine mechanism is able to function normally so long as the patient has adequate serum levels of 25(OH)D, on which its function is absolutely dependent. For this reason, calcitriol and its analogs do not constitute adequate replacement in managing vitamin D needs of such patients. Optimal serum 25(OH)D levels are greater than 32 ng/mL (80 nmol/L). The consequences of low 25(OH)D status include increased risk of various chronic diseases, ranging from hypertension to diabetes to cancer. The safest and most economical way to ensure adequate vitamin D status is to use oral dosing of native vitamin D. (Both daily and intermittent regimens work well.) Serum 25(OH)D can be expected to rise by about 1 ng/mL (2.5 nmol/L) for every 100 IU of additional vitamin D each day. Recent data indicate that cholecalciferol (vitamin D(3)) is substantially more potent than ergocalciferol (vitamin D(2)) and that the safe upper intake level for vitamin D(3) is 10,000 IU/d.

Vascular calcification is widespread, particularly in patients with chronic kidney disease, who receive, among other treatments, active vitamin D supplements. Emerging evidence indicates that vascular calcification is a regulated process that resembles embryonic endochondral osteogenesis, involving osteoblastic differentiation of vascular smooth muscle cells. In experimental animal models, high dosages of vitamin D consistently promote vascular calcification. In particular, the vitamin D-fed rat is frequently used as a model to assess putative regulators of calcific vasculopathy. The artery wall calcification in these animals most likely results from multiple mechanisms involving systems physiology of the complex, bone-vascular-renal-endocrine axis. Genetically engineered mice with upregulated vitamin D signaling pathways have also shed light on the molecular intermediaries, including fibroblast growth factor-23 and transcriptional intermediary factor 1-alpha. In contrast to the studies of animals, studies of humans show that vitamin D has an inverse relationship or little effect. This difference between in vitro and in vivo findings is most likely, again, due to the complex, systemic feedback regulatory mechanisms that control calcium-phosphate metabolism. Recent epidemiologic evidence suggests that there is a narrow range of vitamin D levels in which vascular function is optimized. Levels above or below this range seem to confer a significant increase in risk for cardiovascular disease. There is some evidence to suggest that dietary vitamin D may be carried by lipoprotein particles into cells of the artery wall and atherosclerotic plaque, where it may be converted to active form by monocyte-macrophages. These findings raise interesting questions regarding the effects of vitamin D intake on atherosclerotic calcification and cardiovascular risk.

Hemodynamic shock (HS) is a clinical syndrome that is commonly observed in hospitalized patients. Prompt recognition and intervention are the cornerstones of mitigating the dire consequences of HS. Untreated HS usually leads to death. Unlike other types of clinical syndromes ( e.g. , chest pain), for which a clinical diagnosis is made before treatment is initiated in earnest, the treatment of shock often occurs concurrently or ahead of the diagnostic process. The maintenance of end-organ perfusion is critical to prevent irreversible organ injury and failure, and this frequently requires the use of fluid resuscitation and vasopressors. A complete review of all of the signs and symptoms, diagnosis, and treatment of HS has been reviewed in detail elsewhere (1). This article provides a concise summary of how to approach the patient in HS, diagnostic and therapeutic decision making, and the use of vasopressors. In addition, the effects of vasopressors on end organs with particular focus on renal hemodynamics is reviewed. HS is classically described as “an acute clinical syndrome initiated by ineffective perfusion, resulting in severe dysfunction of organs vital to survival” (1). As clinicians, we take great pains to teach our trainees that shock is not just hypotension, but that shock represents hypoperfusion of end organs. This rationale leads to the common refrain: “Normotensive patients can often suffer from shock.” The clinical manifestations of HS are related directly to the end organs that are not receiving adequate perfusion and can be categorized on the basis of the organ affected. Besides hypotension, the classic signs and symptoms of HS are tachycardia, relative hypotension (a decrease in baseline BP of 40 mmHg), tachypnea, cool and clammy extremities, oliguria, dysglycemia, and delirium (1). Patients who are hypotensive (systolic BP

The burden of sepsis on our health care system is significant, with approximately 750,000 cases per year in the United States, 215,000 resultant deaths, and annual costs of $16.7 billion nationally (1). Organ failure is a significant contributor to mortality, with renal failure occurring in approximately 15% of patients (2). In a large registry of critically ill patients with acute renal failure, in 19% of whom was sepsis identified as the presumed cause, in-hospital mortality was 37% with a combined outcome of death or dialysis dependence in 50% (3). Clinicians are challenged to manage this disease in an aging population with multiple comorbidities, immunosuppression, and a changing pattern of causative microorganisms (2,4). The increasing incidence of sepsis and the unacceptably high mortality rates associated with the disease have led to global efforts to understand pathophysiology, improve early diagnosis, and standardize management (5). Understanding the spectrum of the disease is important for gauging severity, determining prognosis, and developing methods for standardization of care in sepsis. At an international consensus conference in 1991, sepsis was defined as the systemic inflammatory response syndrome (SIRS) with a suspected source of infection. SIRS is defined as two or more of the following perturbations: Temperature >38 or 90 beats per minute; respiratory rate >20 breaths per minute or Paco2 12,000/mm3, 10% immature band forms. Organ dysfunction and hypoperfusion abnormalities characterize severe sepsis, and septic shock includes sepsis-induced hypotension despite adequate fluid resuscitation (6). These definitions allowed for a more uniform approach to clinical trials, hypothesis generation, and the care of the patient with sepsis. The use of SIRS criteria for the identification of sepsis have been believed by many to be arbitrary and nonspecific. In 2001, …

Live donor kidney transplantation (LDKT) is a superior option for most patients with ESRD compared with dialysis and deceased donor kidney transplantation ([1][1]). Much effort occurs in transplant and nephrology communities to educate and advocate for early transplant referral and live donor

Drugs and toxins frequently are associated with the development of various types of acute kidney disease and CKD. Although medications are a widely known cause of tubulointerstitial damage, drug-related glomerular injury is not well appreciated but nonetheless, important. Glomerular damage that occurs after exposure to medications can be caused by direct cellular injury involving the mesangial, endothelial, or visceral epithelial cells (podocytes). Examples include nodular glomerulosclerosis associated with smoking and endothelial injury with thrombotic microangiopathy from a number of medications. Podocyte injury with the development of a minimal change or FSGS lesion has also been described with various medications. Glomerulopathies may also be associated with drug-induced immune-mediated processes. Through various pathways, drugs may promote the formation of a number of antibodies, which may, ultimately, affect the glomerulus. Examples include lupus-like renal lesions and ANCA-related pauci-immune vasculitis. It is critical to recognize these conditions early, because in many patients, there is improvement in renal parameters on stopping the offending medication.

Over the last several decades, despite advances in predialysis care and dialysis technology, people with advanced CKD continue to have a high symptom burden, shortened life expectancy, and substantial physical, emotional, and spiritual suffering ([1][1]). Unfortunately, most nephrologists are not

Diseases of the glomerulus have always held a special place of interest for nephrologists. At first glance the glomerulus is a simple filtering structure connected to a couple of pipes, like so many manmade fluid-filtering systems. Of course, on closer inspection, advancement in science has revealed

Ultrasound is commonly used in nephrology for diagnostic studies of the kidneys and lower urinary tract and to guide percutaneous procedures, such as insertion of hemodialysis catheters and kidney biopsy. Nephrologists must, therefore, have a thorough understanding of renal anatomy and the sonographic appearance of normal kidneys and lower urinary tract, and they must be able to recognize common abnormalities. Proper interpretation requires correlation with the clinical scenario. With the advent of affordable, portable scanners, sonography has become a procedure that can be performed by nephrologists, and both training and certification in renal ultrasonography are available.

Autosomal-dominant polycystic kidney disease is a systemic disorder and the most common hereditary renal disease, which is characterized by cyst growth, progressive renal enlargement, and development of renal failure. The cystic nature of autosomal dominant polycystic kidney disease and its renal and extrarenal complications (kidney stones, cyst hemorrhage, intracerebral aneurysm, liver cysts, cardiac valve abnormalities, etc.) give radiologic imaging studies a central role in the management of these patients. This article reviews the indications, comparative use, and limitation of various imaging modalities (ultrasonography, magnetic resonance imaging, computerized tomography scan, Positron emission tomography scan, and renal scintigraphy) for the diagnosis and management of complications in autosomal dominant polycystic kidney disease. Finally, this work provides evidence for the value of total kidney volume to predict disease progression in autosomal dominant polycystic kidney disease.

Nonmaturation of new arteriovenous fistulas (AVFs) remains a major barrier to increasing AVF use in hemodialysis patients ([1][1]). Our current clinical paradigm views nonmaturing AVF as a plumbing problem, with efforts directed at augmenting access flow by surgical or percutaneous interventions ([2

Kidney transplantation can be associated with various complications that vary from vascular complications to urologic disorders to immunologic adverse effects. In evaluating the recipient with graft dysfunction, clinicians can choose among several imaging modalities, including ultrasonography, nuclear medicine studies, computed tomography, and magnetic resonance imaging. This review discusses the evaluation of the kidney transplant recipient using these imaging procedures, emphasizing the clinical diagnostic utility and role of each modality. A kidney biopsy is often required as a gold standard for diagnostic purposes. However, because of the inherent risks of a kidney biopsy, noninvasive imaging in diagnosing causes of graft dysfunction is a highly desired tool used and needed by the transplant community. Because the diagnostic accuracy varies depending on the time course and nature of the transplant-related complication, this review also addresses the advantages and limitations of each modality. The recent advances in kidney transplant imaging techniques and their clinical implications are also discussed.