Exercise and cognitive function in patients with end‐stage kidney disease

In this review we summarize the research pertaining to the role of exercise in preventing cognitive decline in patients with end‐stage kidney disease (ESKD). Impairment in cognitive function, especially in executive function, is common in patients with ESKD, and may worsen with maintenance dialysis as a result of retention of uremic toxins, recurrent cerebral ischemia, and high burden of inactivity. Cognitive impairment may lead to long‐term adverse consequences, including dementia and death. Home‐based and intradialytic exercise training (ET) are among the nonpharmacologic interventions identified to preserve cognitive function in ESKD. Additionally, cognitive training (CT) is an effective approach recently identified in this population. While short‐term benefits of ET and CT on cognitive function were consistently observed in patients undergoing dialysis, more studies are needed to replicate these findings in diverse populations including kidney transplant recipients with long‐term follow‐up to better understand the health and quality of life consequences of these promising interventions. ET as well as CT are feasible interventions that may preserve or even improve cognitive function for patients with ESKD. Whether these interventions translate to improvements in quality of life and long‐term health outcomes, including dementia prevention and better survival, are yet to be determined.     

Improving wellbeing in patients undergoing dialysis: Can meditation help?

Coping with the stress and anxiety caused by end stage kidney disease (ESKD ) symptoms, treatment, restrictions, and social, financial and family stressors, consumes many afflicted with kidney disease. Meditation has been shown to decrease anxiety and stress, and improve wellbeing and quality of life of people with chronic disease. However, the clinical uptake of meditation is low in the ESKD dialysis population. This review describes what meditation and mindful meditation are and how they have been used for people with ESKD . Further research, using active control conditions and larger sample size, is required to identify effective meditation interventions that can improve the wellbeing of our patients and their ability to cope with the demands of ESKD .     

Treatment of Diabetic Sensory Polyneuropathy

No current disease-modifying treatments have been shown definitively in randomized clinical trials to reduce or reverse diabetic sensory polyneuropathy (DSP). It is increasingly recognized that individuals with “prediabetes” or impaired glucose regulation can already have a “small-fiber” neuropathy, or mild DSP, in which sensory axons of both small and larger diameter are damaged. Small-fiber neuropathy is frequently associated with pain, and these patients may present to a neurologist for evaluation before the underlying glucose dysregulation has been diagnosed. It is important to identify these individuals, because aggressive diabetic control and lifestyle interventions can delay the onset of diabetes and may reverse small-fiber neuropathy associated with early diabetes mellitus. Although treatment currently focuses on pain associated with DSP, attention should be paid to potential risk factors for neuropathy. For example, glycemic control and hyperlipidemia should be improved with diet, exercise, and medications. Hypertension that is a risk marker for more severe neuropathy should be treated. Angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers not only treat hypertension but also may directly reduce the progression of neuropathy. Class I or II clinical studies support the use of sodium valproate, pregabalin, duloxetine, amitriptyline, gabapentin, venlafaxine, opioids, and topical capsaicin in treating diabetic neuropathic pain. Pregabalin and gabapentin are relatively well tolerated and have few medication interactions. Sodium valproate has been shown to be effective but is not recommended for use in women of childbearing potential, and patients must be monitored for hepatotoxicity and thrombocytopenia. Tricyclic antidepressants such as amitriptyline are often used for nocturnal pain but require caution in the elderly or anyone with cardiac disease. Venlafaxine and duloxetine successfully treat neuropathic pain independently of their effect on depression. Opioid medications are associated with a high rate of adverse effects but with careful monitoring, they can be effective in treating resistant neuropathic pain. Capsaicin is an effective topical treatment that lacks systemic side effects. The lidocaine patch is effective in relieving pain associated with postherpetic neuralgia, but only class III evidence supports its use for diabetic neuropathic pain. No current Class I or II studies support other treatment modalities.     

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.     

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.     

Are dialysis patients too frail to exercise?

Clinical manifestations of functional and morphological muscular abnormalities in dialysis patients are muscle weakness and low exercise capacity, possibly leading to a sedentary life style with low physical activity. Low cardiorespiratory fitness and muscle atrophy and weakness contribute to the development of frailty and affect patients’ ability to physically navigate their environment. While many dialysis patients may appear too frail to participate in moderate‐to‐vigorous aerobic exercise training, those who can complete such programs appear to derive substantial benefit. Less vigorous aerobic exercise, resistance training, and alternative forms of exercise can also be beneficial. Most patients on dialysis are not too frail to perform resistance exercise of adequate intensity to achieve increases in muscle size and strength, therefore, frailty should not be considered a contraindication to exercise.     

Preemptive kidney transplantation: Has it come of age?

The benefits of preemptive kidney transplantation are manifold. By avoiding complications associated with dialysis, preemptive kidney transplantation offers significant benefits in terms of patient welfare and societal cost-saving. Patients transplanted preemptively also tend to enjoy better patient and graft survival, especially when done with a living-donor organ. While dialysis exposure limited to 6 to 12 months may not significantly impact post-transplant outcomes, longer period of dialysis has been shown to increase the risk of mortality, delayed graft function, acute rejection, and death-censored graft loss. The benefits of preemptive transplantation also extend to different age groups and end-stage kidney disease (ESKD) diagnoses. However, multiple barriers have prevented wider adoption of preemptive transplantation as the primary treatment of ESKD around the world. Timely preparation for ESKD and identification of living donors should be encouraged in all patients with advanced chronic kidney disease to increase the chance of preemptive transplantation.     

Polyneuropathy with impaired glucose tolerance: Implications for diagnosis and therapy

Opinion statement Prediabetes is associated with a length-dependent polyneuropathy that typically is sensory predominant and painful. A diagnosis of prediabetes should be sought in patients with otherwise idiopathic sensory-predominant neuropathy by doing a 2-hour oral glucose tolerance test. Fasting plasma glucose of 100 to 125 mg/dL or 2-hour glucose 140 to 199 mg/dL (impaired glucose tolerance) constitutes prediabetes. Most patients with neuropathy associated with prediabetes (NAP) are obese and show metabolic manifestations of insulin resistance, including hyperlipidemia and hypertension. Appropriate treatment addresses hyperglycemia, insulin resistance, and neuropathic pain. Professionally administered individualized diet and exercise counseling (modeled on the Diabetes Prevention Program) has been shown to be more effective than glucose-lowering medications in preventing progression from impaired glucose tolerance to diabetes, and is the mainstay of treatment for all patients with NAP. The goals of this therapy should be a 5% to 7% reduction in weight and an increase to 30 minutes of moderate exercise five times weekly. Patients with prediabetes are at increased risk for myocardial infarction, stroke, and peripheral vascular disease. Therefore, risk reduction with control of hypertension and hyperlipidemia is essential. Neuropathic pain troubles nearly every patient with NAP, and often limits aerobic exercise. No trials have specifically addressed the patient population with NAP, and neuropathic pain treatment closely follows recommendations for diabetic neuropathy. Gabapentin, lamotrigine, and tricyclic antidepressants are well-validated first-line therapies. Adjunctive therapy with opioids, nonsteroidal anti-inflammatory drugs often are necessary. Diet and exercise seem to reduce neuropathic pain in patients with NAP.     

The role of physical therapy in improving physical functioning of renal patients

Although not traditionally a part of the dialysis team, physical therapists can play an important role in improving the quality of life for dialysis patients. Physical therapists are trained to evaluate the presence of a functional problem such as back pain, muscle weakness, limited range of motion, balance disorder, alteration in gait, joint pain, neuropathic pain, sensory disturbance, loss of functional mobility, or alteration in posture. Many of these conditions are prevalent in the dialysis population. This article describes how a patient is referred to physical therapy, and once referred, how the patient is evaluated and treated, including goal setting and progression. It is thought that early referral of dialysis patients to physical therapy may prevent some of the functional deterioration typically seen in this population. The incorporation of physical therapy as part of the routine treatment plan may help dialysis staff to address many of the regular nonspecific complaints of fatigue, malaise, pain, and discomfort commonly experienced by dialysis patients.     

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.     

Chronic kidney disease in the general population

End-stage kidney disease (ESKD), defined as the need for dialysis, receipt of a transplant, or death from chronic kidney failure, generally affects fewer than 1% of the population. However ESKD is the end result of chronic kidney disease (CKD), a widely prevalent but often silent condition with elevated risks of cardiovascular morbidity and mortality and a range of metabolic complications. A recently devised classification of CKD has facilitated prevalence estimates that reveal an "iceberg" of CKD in the community, of which dialysis and transplant patients are the tip. Hypertension, smoking, hypercholesterolemia, and obesity, currently among the World Health Organization's (WHO's) top 10 global health risks, are strongly associated with CKD. The factors, together with increasing diabetes prevalence and an aging population, will result in significant global increases in CKD and ESKD patients. Treatments now available effectively reduce the rate of progression of CKD and the extent of comorbid conditions and complications. The challenges are (1) to intervene effectively to reduce the excess burden of cardiovascular morbidity and mortality associated with CKD, (2) to identify those at greatest risk for ESKD and intervene effectively to prevent progression of early CKD, and (3) to ultimately introduce cost-effective primary prevention to reduce the overall burden of CKD. The vast majority of the global CKD burden will be in developing countries, and policy responses must be both practical and sustainable in these settings.     

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.     

Immigration status and end-stage kidney disease: Role of policy and access to care

Immigration status is an important mitigating factor in determining the provision of dialysis and kidney-related care. Immigrants make up the largest uninsured group in the country. For immigrants with end-stage kidney disease (ESKD), dialysis access varies by insurance type and by state, leading to great variability in the availability of kidney care. In some states, undocumented immigrants may only qualify for hemodialysis when critically ill (emergency hemodialysis), which is associated with higher mortality, hospital length of stay, and cost, in addition to an emotional burden on patients, their caregivers, and healthcare professionals. Barriers to effective care for immigrants with ESKD include immigration status, insurance access, and availability of pre-end stage kidney disease care, vascular access, and transplant. Effective strategies for improving dialysis care for immigrants include advocacy at the state and federal level, broadening definitions under Emergency Medicaid, and improving benefits for home therapies and transplantation options.     

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.     

Medication management in dialysis: Barriers and strategies

People with end-stage kidney disease (ESKD) who require chronic dialysis are often reliant on complicated medication regimens to manage their health conditions. Due to the complexities of the advanced kidney disease, underlying comorbidities, and special instructions, medication regimens for patients on dialysis put patients at high risk for medication therapy problems related to safety, effectiveness, appropriateness, and adherence. This article explores the factors that affect optimal medication use for people on dialysis, including the broader drug use system, and offers recommendations around medication reconciliation, medication review, deprescribing, and considering social determinants of health to improve medication management among patients with ESKD.     

Exercise and physical activity for people receiving peritoneal dialysis: Why not?

People with end‐stage kidney disease (ESKD) receiving peritoneal dialysis (PD) are physically inactive leading to low physical function and poor health outcomes. Guidelines recommend that nephrologists encourage PD patients to increase their activity levels; however, PD patients are often discouraged from participating in exercise programs because of perceived barriers and a lack of precision about the appropriate exercise regimen. This review suggests ways forward to assist nephrology professionals to encourage PD patients to exercise, instead of creating barriers. The paper draws on the literature in addition to the experience of programs in France, the United States, and Australia to demonstrate the possibilities when considering increasing physical activity in this group.     

Schwannoma of the posterior tibial nerve: the problem of delay in diagnosis

Schwannomas are the most common tumours of the sheath of peripheral nerves. The clinical diagnosis is usually straightforward, but may be delayed for many years in a schwannoma of the posterior tibial nerve. The symptoms are often attributed to entrapment neuropathy or to lumbosacral radiculopathy. We describe 25 patients with a schwannoma of the posterior tibial nerve. Only three were diagnosed within a year of presentation. The mean time to diagnosis was 86.5 months with a median of 48 months (2 to 360). All the patients complained of pain, which was felt specifically in the sole of the foot in 18. A Tinel sign was detected in all 25 patients. MRI confirmed the diagnosis in all the cases in which it had been undertaken. Surgical resection of the lesion abolished the neuropathic pain. In patients with a long history of neuropathic pain in the lower limb in whom lumbar and pelvic lesions have been excluded, a benign tumour of the sheath of a peripheral nerve may explain the symptoms. Surgical resection of the tumour is safe and effective.     

Breaking the adherence barriers: Strategies to improve treatment adherence in dialysis patients

Nonadherence to therapy (dietary/fluid restrictions, medications, and dialysis treatment), is common in patients with end-stage kidney disease (ESKD) undergoing dialysis. It is associated with a higher risk of mortality and adverse outcomes. Clinical trials evaluating adherence improvement interventions have largely addressed patient-related factors by employing educational/cognitive, counselling/behavioral, psychological strategies, or combinations thereof. A major barrier to progress in addressing ESKD-related adherence is the difficulty in comparing these trials due to the highly diverse nature of interventions and adherence outcomes. Surrogate outcomes like changes in inter-dialysis weight gain or phosphate levels are frequently used without adjusting for confounders, with the potential for biased efficacy estimates. A majority of trials reported improvement in some adherence measures, but some of the same studies showed no improvement in other adherence markers, questioning the validity of outcome measurement. Among the interventions, cognitive/behavioral strategies, combination strategies, and individually delivered interventions may have some advantages. Relapse of nonadherence, which is common on follow-up, should be managed to sustain long-term adherence. Technology-based interventions hold great future potential for addressing ESKD nonadherence. Streamlining intervention strategies and standardizing outcome measures in future clinical trials will provide reliable guidance to manage nonadherence effectively, which may improve clinical outcomes in dialysis patients.     

Rehabilitation of the Geriatric Dialysis Patient

Dialysis is offered to patients with end‐stage renal disease as a life‐sustaining therapy. However, studies have shown that elderly patients experience high rates of functional disability, hospitalization, institutionalization, and mortality on chronic dialysis therapy, and that the initiation of dialysis is in fact associated with an acceleration in functional decline. These findings have sparked debate about the utility of dialysis for elderly renal patients. In this article, it is proposed that geriatric rehabilitation can prevent, reverse or delay the onset of functional disability and associated adverse outcomes in older dialysis patients, and thus should be incorporated routinely into standard geriatric dialysis care. We outline the causes of disability in elderly dialysis patients, and demonstrate the potential impact of rehabilitation using a case scenario. Models of rehabilitation that have been shown to be effective in improving outcomes for elderly renal and nonrenal populations, including inpatient rehabilitation, exercise training, falls prevention, and home‐based models, are reviewed.