Epidemiology of end-stage kidney disease

End-stage kidney disease (ESKD) is a common and morbid disease that affects patients’ quality and length of life, representing a large portion of health care expenditure in the United States. These patients commonly have associated diabetes and cardiovascular disease, with high rates of cardiovascular-related death. Management of ESKD requires renal replacement therapy via dialysis or transplantation. While transplantation provides the greatest improvement in survival and quality of life, the vast majority of patients are treated initially with hemodialysis. However, outcomes differ significantly among patient populations. Barriers in access to care have particularly affected at-risk populations, such as Black and Hispanic patients. These patients receive less pre-ESKD nephrology care, are less likely to initiate dialysis with a fistula, and wait longer for transplants—even in pediatric populations. Priorities for ESKD care moving into the future include increasing access to nephrology care in underprivileged populations, providing patient-centered care based on each patient’s “life plan,” and focusing on team-based approaches to ESKD care. This review explores ESKD from the perspective of epidemiology, costs, vascular access, patient-reported outcomes, racial disparities, and the impact of the COVID-19 crisis.     

Public policy and programs – Missing links in growing home dialysis in the United States

Patients with end-stage kidney disease (ESKD) require dialysis or a kidney transplant for survival and over 760 000 patients now benefit from these therapies in the United States. Dialysis in the United States in the late 1960s and early 1970s was often done in the home. After the advent of Medicare coverage for ESKD in 1972 and the subsequent easier access to center based hemodialysis, the use of home modalities dramatically declined. This stands in contrast to home dialysis uptake in other industrialized healthcare systems where both peritoneal dialysis and home hemodialysis are more frequently used. Characteristics unique to the US healthcare system as well as the cultures of providers (physicians and dialysis providers) and recipients of ESKD care are hypothesized as the main reasons for observed differences in home dialysis use. To address these issues, the Centers for Medicare and Medicaid Services have recently proposed new payment programs under an Executive Order from the President of the United States, with the explicit goal of increasing the number of patients using home dialysis. This perspective outlines policy opportunities and programs with a proven track record of home dialysis growth in other countries or hypothesized promise based on identified barriers and needs.     

Achieving equity in dialysis care and outcomes: The role of policies

Socially disadvantaged persons, including racial and ethnic minorities, individuals with low incomes, homeless persons, and non-US citizens bear a disproportionate burden of end-stage kidney disease (ESKD). Inequities in nephrology referral, vascular access, use of home dialysis modalities, kidney transplantation, and mortality are prominent. Public policies, including the Patient Protection and Affordable Care Act, end-stage renal disease Quality Incentive Program, and the Prospective Payment System, were enacted to improve healthcare access and dialysis care. Here, we highlight inequities in dialysis care and outcomes, how current ESKD and other public policies may influence or exacerbate these inequities, and gaps in the literature needed to inform future policies toward achieving equity in ESKD. We give special attention to the 2019 Advancing American Kidney Health Executive Order, which has high potential to radically transform dialysis care.     

Barriers to providing optimal dialysis care for undocumented immigrants: Policy challenges and solutions

Access to hemodialysis for undocumented immigrants with end stage renal disease (ESRD) is widely variable across the United States and highly dependent upon state policy. Some states have enacted policies to provide coverage for standard dialysis to undocumented immigrants, while other states do not provide coverage. Patients living in some states which do not provide coverage rely on emergency federal coverage through the Emergency Medical Treatment and Active Labor Act. However, this act requires that patients present with an acute, life-threatening condition in order to receive dialysis, which is then referred to as “emergency-only hemodialysis” (EoHD). Because EoHD requires patients to present in life-threatening condition, patients who rely on EoHD suffer from debilitating physical symptoms and psychosocial distress. Undocumented immigrants who receive EoHD also have staggeringly higher mortality rates than those who receive standard hemodialysis. Moreover, in comparison with standard dialysis, EoHD results in greater health care utilization and higher health care costs. Therefore, EoHD represents a very low value care practice, providing substandard care at a greater cost. Policy change is urgently needed to provide undocumented immigrants with ESRD access to the standard of care; that is, three-times weekly standard hemodialysis or peritoneal dialysis.     

Neuromuscular Disease in the Dialysis Patient: An Update for the Nephrologist

Neuromuscular disease is an extremely common complication of end-stage kidney disease (ESKD), manifesting in almost all dialysis patients, and leading to weakness, reduced exercise capacity, and disability. Recent studies have suggested that hyperkalemia may underlie the development of neuropathy. As such, maintenance of serum K⁺ within normal limits between periods of dialysis in ESKD patients manifesting early neuropathic symptoms may reduce neuropathy development and progression. For patients with more severe neuropathic syndromes, increased dialysis frequency or a switch to high-flux dialysis may prevent further deterioration, while ultimately, renal transplantation is required to improve and restore nerve function. Exercise training programs are beneficial for ESKD patients with muscle weakness due to neuropathy or myopathy, and are capable of improving exercise tolerance and quality of life. Specific treatments have recently been evaluated for symptoms of autonomic neuropathy, including sildenafil for impotence and midodrine for intra-dialytic hypotension, and have been shown to be effective and well tolerated. Other important management strategies for neuropathy include attention to foot care to prevent callus and ulceration, vitamin supplementation, and erythropoietin. Treatment with membrane-stabilizing agents, such as amitryptiline and gabapentin, are highly effective in patients with painful neuropathy.     

Frequent vascular access thrombosis in a patient with end stage kidney disease on hemodialysis

Vascular access thrombosis (VAT) is common among patients receiving hemodialysis and leads to missed dialysis treatments, hospitalizations, catheter placement, and graft/fistula abandonment. This article reviews the association between hypercoagulability and VAT and the high prevalence of hypercoagulable states in end-stage kidney disease (ESKD). This article reviews the role of antithrombotic and anticoagulant medications in preventing VAT. The article concludes by reviewing the unique challenges of using vitamin K antagonists in patients with ESKD.     

Vascular access should be tailored to the patient

A cornerstone of hemodialysis treatment is the creation of a functional and durable dialysis vascular access. Every patient with chronic kidney disease should have a plan of renal replacement therapy and access site protection. Factors having a crucial impact on vascular access selection include age, comorbidity, vessel quality, prognosis, dialysis urgency, and surgeon’s preferences. Our medical group have reviewed these factors in our patients and, based on recently published data, developed a clinical decision tree for dialysis access in the chronic kidney disease patient. Vascular access care should be patient-centered with the aim to maximize patient survival without loss of vascular access options; and not focused only the primary patency rates of dialysis access procedures.     

Vascular access in kidney transplant recipients

Vascular access is an important element in the overall care provided to kidney transplant recipients. The transplanted kidney is not indestructible, and chronic kidney disease after transplantation may result in needing another transplant or beginning dialysis. Commonly used vascular accesses, like peripheral and central lines, can preclude the creation of future, permanent dialysis access. Therefore, there is urgent need to preserve vessels for the future access needs for hemodialysis among kidney transplant recipients without functional vascular access for dialysis. Moreover, the proper care of functional vascular access among kidney transplant recipients is crucial. In this review article, we will address the common vascular access procedures and complications among kidney transplant recipients.     

Barriers to kidney transplantation in ESKD

Kidney transplantation is the ideal treatment option for patients with end-stage kidney disease (ESKD). Since there is clear mortality benefit to receiving a transplant regardless of comorbidities and age, the gold standard of care should focus on attaining kidney transplantation and minimizing, or better yet eliminating, time on dialysis. Unfortunately, only a small percentage of patients with ESKD receive a kidney transplant. Several barriers to kidney transplantation have been identified. Barriers can largely be grouped into three categories: patient-related, physician/provider-related, and system-related. Several barriers fall into multiple categories and play a role at various levels within the healthcare system. Acknowledging and understanding these barriers will allow transplant centers and dialysis facilities to make the necessary interventions to mitigate these disparities, optimize the transplant evaluation process, and improve patient outcomes. This review will discuss these barriers and potential interventions to increase access to kidney transplantation.     

When ESKD complicates the management of pain

Pain is one of the most common symptoms reported by patients with end-stage kidney disease (ESKD) and negatively impacts their health-related quality of life (HRQOL), dialysis adherence, healthcare utilization, and mortality. There are a number of patient-related and health system-related barriers that make it very challenging to treat pain in these patients. Moreover, the limited availability of efficacious and safe nonopiate analgesic options has led to over-use of opioids in this population. We propose a framework for pain assessment and tailored treatment using nonpharmacological and pharmacological approaches to optimize pain management and opioid use. Additionally, we recommend system-level changes to improve care coordination and pain management in ESKD patients.     

Barriers to optimal vascular access for hemodialysis

Vascular access is the Achilles heel for hemodialysis (HD). An arteriovenous fistula (AVF), considered the optimal access for HD, rather than a graft or central venous catheter (CVC) caused the “Fistula First” initiative to dominate quality assessment. However, this initiative had the unintended consequence of increasing the proportion of less desirable catheters, leading to “Fistula First, Catheter Last”. But as the end-stage kidney disease (ESKD) population expanded with aging, sicker patients, individual assessment of the appropriate access changed the paradigm to KDOQI’s “Patient First: ESKD Life-Plan” to attain the “right access, in the right patient, at the right time, for the right reasons”. However, such a goal has proved elusive because the optimal vascular access does not currently exist. Thus, ESKD care providers attempting to offer the “right access” must weigh the barriers to achieving the most optimal access to suit each of their HD patients. The barriers are based on shortcomings related specifically to each of the three vascular accesses and to characteristics of each ESKD patient's demographics, physical factors, quality of life, and cost considerations. This article will describe these barriers so that clinicians caring for ESKD patients initiating or receiving HD provide the most optimal vascular access for that specific patient.     

Physician access and early nephrology care in elderly patients with end-stage renal disease

Early nephrology care may improve treatment outcomes of patients with end-stage renal disease. We sought to examine if physician access affects early nephrology care defined as visiting a nephrologist 12 to 4 months before initiating dialysis. The study population consisted of elderly patients starting hemodialysis whose demographic characteristics and initial dialysis therapy were derived from form 2728 files of the Centers for Medicare & Medicaid Services. Early nephrology care, chronic kidney disease and co-morbidities along with access to local non-nephrologist physicians and nephrologists were identified based on Medicare claims and/or United States 2000 Census data. About one-third of elderly patients received early nephrology care prior to initiating dialysis. Patients living in an area with a large number of non-nephrologist physicians or living relatively far away from a nephrologist had a lower likelihood of getting early nephrology care prior to initiating dialysis while those in an area with more practicing nephrologists were more likely to get early nephrology care. The study shows that physician access significantly influences the use of early nephrology care among elderly patients progressing to end-stage renal disease in the United States.     

When ESKD complicates the management of diabetes mellitus

Given the increased incidence and prevalence of ESKD (end-stage kidney disease) attributed to diabetes mellitus, it is important to consider the physiological and global sociodemographic factors that give rise to unique challenges in providing excellent care to this population. The individual with diabetes and ESKD faces alterations of glucose homeostasis that require close therapeutic attention, as well as the consideration of safe and effective means of maintaining glycemic control. Implementation of routine monitoring of blood glucose and thoughtful alteration of the individual’s hypoglycemic drug regimen must be employed to reduce the risk of neurological, cardiovascular, and diabetes-specific complications that may arise as a result of ESKD. Titration of insulin therapy may become quite challenging, as kidney replacement therapy often significantly impacts insulin requirements. New medications have significantly improved the ability of the clinician to provide effective therapies for the management of diabetes, but have also raised an equal amount of uncertainty with respect to their safety and efficacy in the ESKD population. Additionally, the clinician must consider the challenges related to the delivery of kidney replacement therapy, and how inter-modality differences may impact glycemic control, diabetes, and ESKD-related complications, and issues surrounding dialysis vascular access creation.     

Canadian survey of clinical status at dialysis initiation 1998-1999: a multicenter prospective survey

AIMS: The current growth in end-stage kidney disease populations has led to increased efforts to understand the impact of status at dialysis initiation on long-term outcomes. Our main objective was to improve the understanding of current Canadian nephrology practice between October 1998 and December 1999. METHODS: Fifteen nephrology centers in 7 provinces participated in a prospective data collection survey. The main outcome of interest was the clinical status at dialysis initiation determined by: residual kidney function, preparedness for chronic dialysis as measured by presence or absence of permanent peritoneal or hemodialysis access, hemoglobin and serum albumin. Uremic symptoms at dialysis initiation were also recorded, however, in some cases these symptom data were obtained retrospectively. RESULTS: Data on 251 patients during 1-month periods were collected. Patients commenced dialysis at mean calculated creatinine clearance levels of approximately 10 ml/min, with an average of 3 symptoms. 35% of patients starting dialysis had been known to nephrologists for less than 3 months. These patients are more likely to commence without permanent access and with lower hemoglobin and albumin levels. Even of those known to nephrologists, only 66% had permanent access in place. CONCLUSIONS: Patients commencing dialysis in Canada appear to be doing so in relative concordance with published guidelines with respect to timing of initiation. Despite an increased awareness of kidney disease, a substantial number of patients continues to commence dialysis without previous care by a nephrologist. Of those who are seen by nephrologists, clinical and laboratory parameters are suboptimal according to current guidelines. This survey serves as an important baseline for future comparisons after the implementation of educational strategies for referring physicians and nephrologists.     

ATTENTION: Workforce shortages as a barrier to optimal dialysis

Providing optimal end-stage kidney disease (ESKD) management requires an adequately trained and sufficiently staffed workforce, including doctors, nurses, and patient care technicians (PCTs). The growing need for ESKD services for a surging population of dialysis-dependent patients has made obvious a workforce crisis affecting nephrology. For a multitude of reasons, the physician workforce supply available to provide dialysis care has failed to expand commensurate with patients need in recent years. Of most importance, fewer US trainees are choosing to enter nephrology, and fewer international medical graduates are available to fill training program rosters. Equally important but less frequently cited are occupational shortages of trained dialysis nurses and PCTs. This article brings attention to this complex workforce shortage and addresses the limited information available regarding how it might constitute a barrier to optimal dialysis care.     

Interleukin-6 gene expression in peripheral blood mononuclear cells from patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis

To compare the interleukin-6 (IL-6) gene expression in the peripheral blood mononuclear cells (PBMCs) and plasma IL-6 levels in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with those in patients undergoing hemodialysis. Eleven hemodialysis patients, 10 CAPD patients, 15 non-dialyzed patients with end-stage kidney disease (ESKD), and 7 healthy controls were included in this study. PBMCs were collected by differential centrifugation. Plasma IL-6 concentration was measured by enzyme immunoassay. Plasma IL-6 levels were significantly increased in the hemodialysis and CAPD patients as compared with non-dialyzed ESKD patients and normal subjects (p < 0.01). Following hemodialysis, plasma IL-6 levels exceeded those before hemodialysis. No significant difference was found in plasma IL-6 levels in CAPD patients and in hemodialysis patients when blood was drawn before hemodialysis. Low but steady-state levels of IL-6 mRNA expression were observed in the non-dialyzed ESKD patients. The expression of IL-6 mRNA in PBMCs was significantly increased in the patients undergoing hemodialysis or CAPD as compared with the non-dialyzed ESKD patients. The PBMC IL-6 mRNA was significantly lower in CAPD patients than in hemodialysis patients (p < 0.01). A significant correlation was found between the plasma concentration of IL-6 and the expression of IL-6 mRNA in PBMCs from patients undergoing hemodialysis or CAPD (p < 0.01). The hemodialysis or CAPD procedure contributed to the increase in PBMC IL-6 mRNA expression and plasma IL-6 concentration. CAPD treatment stimulated the production of IL-6 to a lesser extent than hemodialysis treatment.     

Prognosis and risk factors for cardiac valve calcification in Chinese end-stage kidney disease patients on combination therapy with hemodialysis and hemodiafiltration

BackgroundCardiac valve calcification (CVC) is an important risk factor for cardiovascular complications. However, limited data are available concerning the prevalence, clinical features and risk factors for CVC in end-stage kidney disease (ESKD) patients. In this study, we aimed to assess these parameters in Chinese ESKD patients receiving combination therapy with hemodialysis and hemodiafiltration.MethodsWe conducted a cross-sectional study on 293 ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration at the First Affiliated Hospital of Chongqing Medical University from October 2014 to December 2015. CVC was evaluated via echocardiography.ResultsESKD patients with CVC had a higher prevalence of diabetes mellitus, aortic and/or coronary artery calcification, arrhythmia, heart failure and coronary heart disease; increased systolic, diastolic and pulse pressure; longer duration of hemodialysis and hypertension; reduced hemoglobin, albumin and high-density lipoprotein cholesterol levels; and increased serum calcium and calcium-phosphorus product levels compared with those without CVC. Logistic regression analysis showed that increased dialysis duration (p = 0.006, OR = 2.25), serum calcium levels (p = 0.046, OR = 2.04) and pulse pressure (p < 0.001, OR = 3.22), the presence of diabetes (p = 0.037, OR = 1.81) and decreased serum albumin levels (p = 0.047, OR = 0.54) were risk factors for CVC. The correlation analysis indicated a significantly increased CVCs prevalence with an increase prevalence of heart failure, aortic and coronary artery calcification.ConclusionsCVC represents a common complication and a danger signal for cardiovascular events in ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration. The presence of diabetes, increased pulse pressure, long dialysis duration, hypoalbuminemia and high serum calcium levels were independent risk factors for CVC.     

INTERLEUKIN-6 GENE EXPRESSION IN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM PATIENTS UNDERGOING HEMODIALYSIS OR CONTINUOUS AMBULATORY PERITONEAL DIALYSIS

To compare the interleukin-6 (IL-6) gene expression in the peripheral blood mononuclear cells (PBMCs) and plasma IL-6 levels in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with those in patients undergoing hemodialysis.

Eleven hemodialysis patients, 10 CAPD patients, 15 non-dialyzed patients with end-stage kidney disease (ESKD), and 7 healthy controls were included in this study. PBMCs were collected by differential centrifugation. Plasma IL-6 concentration was measured by enzyme immunoassay.

Plasma IL-6 levels were significantly increased in the hemodialysis and CAPD patients as compared with non-dialyzed ESKD patients and normal subjects (p < 0.01). Following hemodialysis, plasma IL-6 levels exceeded those before hemodialysis. No significant difference was found in plasma IL-6 levels in CAPD patients and in hemodialysis patients when blood was drawn before hemodialysis. Low but steady-state levels of IL-6 mRNA expression were observed in the non-dialyzed ESKD patients. The expression of IL-6 mRNA in PBMCs was significantly increased in the patients undergoing hemodialysis or CAPD as compared with the non-dialyzed ESKD patients. The PBMC IL-6 mRNA was significantly lower in CAPD patients than in hemodialysis patients (p < 0.01). A significant correlation was found between the plasma concentration of IL-6 and the expression of IL-6 mRNA in PBMCs from patients undergoing hemodialysis or CAPD (p < 0.01).

The hemodialysis or CAPD procedure contributed to the increase in PBMC IL-6 mRNA expression and plasma IL-6 concentration. CAPD treatment stimulated the production of IL-6 to a lesser extent than hemodialysis treatment.     

When ESKD complicates cancer screening and cancer treatment

End-stage kidney disease (ESKD) affects the recommended screening, incidence, treatment, and mortality of cancer. Cancer occurring in a patient with ESKD can influence candidacy for kidney transplantation as well as dialysis decision-making and cancer treatment. Certain cancers are more common among ESKD patients, notably, viral-mediated cancers that are associated with human papilloma or hepatitis viruses, and urothelial cancers associated with analgesic and Balkan nephropathies. Solid tumors are not believed to occur more frequently in ESKD patients. The presence of ESKD may confer a higher risk of post-surgical complications as well as mortality. The cost-effectiveness of cancer screening depends upon individual cancer risk and estimated overall survival. The high mortality associated with ESKD argues against routine cancer screening in dialysis patients. Cancer treatment in ESKD may be complicated by the need to avoid, adjust doses of and/or coordinate the timing of administration of imaging contrast, chemotherapy, and immunotherapy with dialysis treatments. There is a general dearth of information on the treatment of cancer in ESKD patients. These issues will be discussed, and some general guidelines presented based upon the current literature.