Kidney Supportive Care in Advanced Chronic Kidney Disease

Key points

•
“Kidney supportive care” (KSC) is replacing the term “kidney palliative care.” KSC is an approach that aims to improve the health-related quality of life (HRQOL) for people and their families for whom kidney disease, either directly or indirectly, substantially impacts their well-being, treatment options, or access to care. This is accomplished through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual. KSC should be provided throughout the continuum of illness, regardless of life expectancy. It can be provided together with therapies intended to prolong life, such as kidney replacement therapy, and requires culturally sensitive shared decision making to prioritize the components of medical care most important to the patient.
•
Dialysis treatment may address some symptoms, such as fatigue, anorexia, nausea, and vomiting, especially for more robust individuals with less comorbidity, but it may do little to address symptom burden and HRQOL in more frail patients or those with multimorbidity. When taken as a whole, symptom burden is similar in predialysis kidney failure patients, those treated with conservative kidney management, and those on chronic dialysis.
•
The Edmonton Symptom Assessment System: Renal is a simple tool to screen for 12 commonly experienced symptoms in CKD using 0 to 10 visual analog scales.
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The aim of symptom management is to ameliorate symptoms that are burdensome and adversely impact the patient’s HRQOL as it is not always necessary or possible to resolve them completely. This usually requires that symptoms be treated to ≤3/10.
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Gabapentin can be used to effectively treat neuropathic pain, restless legs, uremic pruritus, and insomnia if used carefully in low doses and titrated slowly to effect.
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Dialysis is unlikely to benefit patients with significant preexisting functional or cognitive impairment and high levels of comorbidity. These patients are often better cared for with conservative kidney management and careful attention to the principles of KSC.

Despite advances in predialysis care and dialysis technology, people with advanced chronic kidney disease (CKD) continue to have a shortened life expectancy and poor outcomes including physical, emotional, and spiritual suffering, as well as low health-related quality of life (HRQOL). The majority of patients die in acute care facilities, with aggressive care plans in place and without accessing palliative care services. ^, Current end-of-life care practices are not consistent with patients’ preferences. ^,

Supportive care is central to the provision of patient-centered care for patients with chronic diseases. Many countries are placing increased emphasis on the provision of supportive and end-of-life care by “generalist” and community providers as a component of usual care. Therefore kidney supportive care (KSC) is increasingly being recognized as a core clinical competency for the care of patients with advanced CKD. Unfortunately, nephrologists are often not trained adequately to address multifactorial suffering and many of the end-of-life challenges inherent in the care of their patients. Consequently, patients with advanced CKD experience significant unmet care needs. ^, ^, Training in KSC for clinicians treating people with CKD is an urgent priority. This chapter aims to serve as an introduction to KSC and provide some of the foundations for understanding and delivering the key components of KSC.

Defining Kidney Supportive Care

Palliative medicine has undergone many developments over the past several decades and has extended the range of services, the timing of services within the illness trajectory, and the eligible patient groups such that palliative care is no longer limited to terminal care focused primarily on those dying with cancer. Unfortunately, despite the evolution of palliative care over the past several decades, the belief that “palliative care” and “terminal care” are synonymous, such that only patients at the end of life are appropriate for palliative care, remains prevalent among patients, families, and health care providers. ^, This is not appropriate for people with advanced CKD who frequently have high palliative care needs for years before death. For this reason, the term “kidney supportive care” is now preferred. ^, KSC is defined as “an approach that aims to improve the HRQOL for people and their families, for whom kidney disease, either directly or indirectly, substantially impacts their well-being, treatment options, or access to care, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual. This definition is rooted in the World Health Organization (WHO) definition for palliative care. KSC is not restricted to people who withdraw from dialysis or who receive conservative kidney management (CKM). End-of-life care (sometimes referred to as “terminal care” or “hospice care”) is under the umbrella of KSC but is typically limited to the care of people who are believed to be within months of death ( Fig. 61.1 ). Ideally, KSC should be started early so that issues of suffering are addressed as they present. As illness progresses, the need for KSC is likely to increase and will ultimately progress into terminal, end-of-life care.

An illustration shows the four phases of supportive care provided for individuals with kidney diseases from the initial diagnosis phase until the end of life. The illustration depicts a rectangular framework with four colored regions showing patient care from the initial illness to death. The first phase is the broad phase that depicts curative or remittive care with curved borders. The second broad phase denotes kidney supportive care. The third phase leads to a small section labeled terminal or end-of-life care. The final phase is the bereavement phase in which the framework gradually declines and ends. A long arrow below the framework begins from the first phase pointing toward the right side ends at the terminal phase. The first two phases are marked supportive care rather than prognosis. The terminal phase is marked dying phase with a usual prognosis of less than six months. — Fig. 61.1

Key Components of Kidney Supportive Care

KSC requires the culturally sensitive shared decision making to 1. prioritize the components of medical care most important to the individual and 2. ensure those priorities guide clinical decisions. ^, The core components of KSC include symptom management, crisis planning, advance care planning, spiritual care, end-of-life care considerations, and integration with community services. Patient engagement has highlighted many of these issues as top priorities for people with advanced CKD. A comprehensive approach to KSC must also integrate a way to identify patients most likely to benefit from supportive care interventions ( Fig. 61.2 ). Each of these components of KSC is discussed within the context of CKD.

A flow diagram depicts the approach to kidney supportive care, focuses on quality of life, managing symptoms and prepares both patients and families for end of life care decisions. The flow diagram involves identifying patients to provide bereavement support. A vertical box is labeled on the left includes the Identification of patients most likely to benefit from kidney supportive care, with four vertical boxes beside each labeled as follows: First box: Patients at high risk for death within the next year, which answers No to the Surprise Question, involves Would you be surprised if the patient died in the next 12 months. Second box: General indicators of decline with sub-points: Functional or cognitive decline and repeated unplanned admissions. Third box: Specific clinical indicators with sub-points: Poor tolerance of dialysis with a change in modality, and High physical or psychosocial symptom burden, C K M or withdrawal of dialysis, and Poor or decreasing H R Q O L. Fourth box: Decision making with sub-points Difficulty determining goals of care and Considering withdrawal from dialysis or C K M. An arrow labeled Assess leads to the vertical box labeled Key components of kidney supportive care section, which includes three boxes. First box: Symptom management and relief of suffering with sub-points Physical symptom management and Emotional and psychosocial support, which includes Spiritual support, and Address cultural domains of care where relevant. Second box: Prognostication, which suggests considering clinically relevant outcomes such as Survival, Physical function, H R Q o L, and Cognitive function. Third box: Advance care planning, which includes Goals of care, Identify surrogate decision maker, and Special considerations such as C K M or initiation of dialysis, palliative dialysis, and withdrawal. The Key components of kidney supportive care section transitions with an arrow to Death and then to Bereavement support. A double-headed horizontal arrow at the bottom of the diagram indicates that culturally competent shared decision-making is foundational to the entire process. — Fig. 61.2

Culturally Competent Shared Decision Making

Culturally competent shared decision making is the foundation of KSC and must be incorporated into all components from assessment and management of suffering, sharing prognosis, and advance care planning to delivery of end-of-life care and bereavement support (see Fig. 61.2 ). To relieve suffering and provide care aligned to the preferences and goals of the individual patient, care teams must understand and incorporate the patient’s needs and perspective and adapt the care plan to facilitate integration of the patient’s lifestyle including his or her family and social community. This means allowing the components of medical care deemed most important to the patient to be prioritized. This may require greater emphasis being placed on managing bothersome symptoms rather than maximizing long-term health outcomes such as survival (e.g., balancing the management of dizziness and fatigue with optimal blood pressure control or serum chemistry). As disease progresses, patients’ goals of care often shift to focus almost exclusively on HRQOL rather than survival, with a strong emphasis on emotional, social, and family support. ^, The ethical imperatives of shared decision are discussed further in Chapter 80 .

Culture has enormous potential to influence patients’ beliefs around life and death, healing and suffering, as well as the physician–patient relationship. Cultural sensitivity is particularly important in delivering end-of-life care, and cultural variations in end-of-life preferences have long been noted. In multicultural societies, very different, and often divergent, value systems may be at work, and health care providers will need to be cognizant of these cultural influences. Although a more detailed exploration of how various cultural perspectives may influence the provision of KSC can be found elsewhere, several high-level issues are discussed here.

There are tremendous cross-cultural differences in preferences for decision making. Western cultures tend to promote “patient autonomy,” where the patient is viewed as the best person to make health care decisions. However, many cultures are characterized by strong communal and social bonds where social relationships, rather than individualism, provide the basis for moral judgments. From this perspective, an insistence on self-determination erodes the value placed on personal interconnectedness and challenges the assumption that the patient should make his or her own medical decisions in isolation from their community. In practice, this might mean that the family or community receives and discloses information, even when the patient is competent.

In many parts of the world, the cultural norm is protection of the patient from the truth. This often involves cultural beliefs surrounding the cause and meaning of illness. This can complicate decision making, especially in the context of sharing prognosis. For example, some Aboriginal and Asian cultures prohibit explicit references to dying based on an interpretative framework in which language has the capacity to create reality. Positive thinking is felt to promote health, whereas the delivery of bad news could shorten the life of the patient. Family members may prefer to communicate prognostic information themselves in such a way as to “balance” hope with the bad news. Health care providers need to understand that in some contexts, this may be appropriate.

Cultural views can impact how patients want care to be delivered. Many cultures possess little knowledge of, or have little exposure to, palliative care and may be reluctant to receive this care without understanding the direct benefit to them. Cultural values may also determine who should and who should not be directly involved in providing physical care, with many cultures strongly preferring that family be directly involved. Many non-Western cultures such as traditional Chinese and indigenous cultures view the body, soul, and spirit as an integrated whole in the context of strong interpersonal relationships and may require access to a traditional healer. This may be viewed as similar to access to a hospital chaplain in a Western context.

Many people from rural and remote areas wish to die at home connected to land and family for strong cultural reasons yet are relocated for end-of-life care. For indigenous people, relocation at the end of life is an extremely frightening experience. Culture also plays a role in the expression of suffering and grief, with many cultures being reluctant to complain of pain. Others are not comfortable with frank, direct styles of communication and therefore may not express suffering or grief overtly as this may be seen as inappropriate. In these cases, emotional containment does not mean indifference or a lack of suffering.

Culturally competent shared decision making requires that clinicians and patients jointly consider best clinical evidence in light of a patient’s specific health characteristics and values within the framework of the patient’s and family’s cultural beliefs. In increasingly diverse societies, the challenge for health care professionals is to understand how these numerous cultural differences shape the care for an individual patient. Cross-cultural communication strategies required to address this have recently been explored ^, and are summarized in Table 61.1 . Cross-cultural communication starts with understanding one’s own beliefs, values, and experiences and then acknowledging individual cultural traditions, which may be sharply divergent. Health care professionals also need to recognize the diversity of beliefs and practices within cultural groups. The process of acculturating may complicate this, and many people will hold blended cultural perspectives. Health care professionals therefore must be careful not to assume the preferences of individuals on the basis of their cultural group. When uncertain about how a patient or family perceives a situation, it is best simply to ask. ^,

Table 61.1

Strategies for Culturally Competent Shared Decision Making

From Brown EA, Bekker HL, Davison SN, et al. Supportive care: communication strategies to improve cultural competence in shared decision making. Clin J Am Soc Nephrol . 2016;11:1902–1908.

Task	Communication Strategy	Additional Considerations
Understand one’s own beliefs, values, and experiences	Having an awareness of individual differences from that of the patient is important to create a respectful and nonbiased dialogue. It will also help resolve conflict when differences with patients’ beliefs and wishes arise.	Consider one’s perspective as a clinician and the influence of the health care system and institution within which one delivers care.
Understand the patient’s experience	Ask about the patient as a person, where they are from, and degree of integration within the ethnic community. Assess how the patient interprets his or her condition (i.e., the cause and impact).	This includes asking what their most important concerns are now that they have this illness. This establishes the groundwork for negotiating mutually acceptable goals for care.
Acknowledge individual cultural traditions	Ask about the patient’s health beliefs, values, practices, and cultural communication etiquette. This includes attitudes toward truth telling. Avoid generalizing a patient’s beliefs or values on the basis of cultural norms.	The “RISK” reduction assessment is a helpful strategy to ascertain the level of cultural influence for a patient.
Giving information	Ask–Tell–Ask (this strategy can extend to many of the tasks described here): Ask the patient’s understanding of his or her illness, what kind of information the patient and/or family needs, and how they want the information told. Tell (give) information concisely, avoid jargon, and disclose only one to three pieces of information at any given time. Ask what the patient understands or will take away from the conversation.	The final ask ensures the information has been understood and invites the patient and family to share concerns or explore lingering questions. Are there language barriers or low health literacy barriers that may hinder understanding and shared decision making?
Determine the level of patient engagement in decision making	Assess preferences for decision making and who will be involved.	Explicitly explore preferences for family-centered versus individual-centered decision making.
Address trust concerns	Be nonjudgmental, transparent, and avoid defensiveness.	The goal is to create an atmosphere of mutual respect and avoid misunderstanding.
Address resources needs	Ask what tangible resources they need to navigate the health care system. Ask if assistance is available to them and their family in their community.	This may be influenced by language, level of education, socioeconomic status, and their social support networks.

Prognostication

Estimating and communicating prognosis is required for shared decision making. Being able to prognosticate accurately helps health care professionals identify high-risk patients, facilitate discussions regarding the need for targeted KSC services, and align care pathways to best meet an individual’s needs. Given that KSC focuses on the individual patient’s priorities, patient-specific prognoses for relevant outcomes beyond survival, such as the impact of treatments on HRQOL, physical function, hospital-free survival, and symptoms, are needed.

Studies have shown that despite patients wanting to discuss their prognosis, it is often not done. ^, Prognostication is challenging in CKD given the great variation in individual illness trajectories. Accurate prognostic models are limited, and nephrologists struggle to explain illness complexity and predict clinical trajectories. ^, Although there is a large volume of data on prognostic markers, individually these factors are often of little practical relevance. Only a small number of studies have attempted to combine these factors into clinically useful prognostic tools. A recent review highlights the limits and deficiencies of currently available prognostic tools, ^, which are outlined in Table 61.2 . These tools are limited to progression of kidney failure and survival on dialysis. They do not prognosticate outcomes for people receiving CKM, nor do they address patient or family concerns of HRQOL, function, and symptom burden.

Table 61.2

Prognostic Tools Relevant to Kidney Supportive Care

Data Source	Population Studied	Parameter	C-Statistic
Progression of CKD to Kidney Failure Defined as Need for Dialysis or Preemptive Kidney Transplantation: Kidney Failure Risk Equation
Two Canadian cohorts ^, A total of 31 multinational cohorts from the CKD Prognosis Consortium	Development and initial validation with 3449 and 4942 Canadian patients with G3-5 CKD, respectively. Additional validation in 721,357 multinational participants with G3-5 CKD	Four-variable model: age, gender, eGFR, and ACR Currently available for free online ( https://www.qxmd.com/calculate/calculator_308/kidney-failure-risk-equation-4-variable )	Pooled data from the 31 multinational cohorts 2-year prediction: 0.9 (95% CI 0.89-0.92) 5-year prediction: 0.88 (95% CI 0.86-0.90)
		Eight-variable model: age, gender, eGFR, ACR, calcium, phosphate, bicarbonate, and albumin	Pooled data from the 31 multinational cohorts 2-year prediction: 0.89 (95% CI 0.88-0.91) 5-year prediction: 0.87 (95% CI 0.85-0.88)
3 Months’ Survival after Dialysis Start
USRDS	69,441 incident patients aged ≥67 years	Age, albumin, assistance with ADL, nursing home, cancer, heart failure, and hospitalization Currently available for free online ( https://qxmd.com/calculate/3-month-mortality-in-incident-elderly-esrd-patients )	0.681 (95% CI 0.676-0.686)
USRDS	69,441 incident patients aged ≥67 years	A more comprehensive version adds gender, race, central vein dialysis catheter use, early nephrology referral, albumin, creatinine, peripheral vascular disease, and alcohol abuse	0.712 (95% CI 0.706-0.718)
French REIN registry	28,496 incident patients aged ≥75 years	Gender, age, congestive heart failure, severe peripheral vascular disease, dysrhythmia, severe behavioral disorders, active malignancy, serum albumin, and impaired mobility	0.749 (95% CI 0.743-0.755)
Catalan renal registry	1365 incident diabetic adult patients	Age, functional autonomy, heart disease, and central catheter as vascular access	0.77 (95% CI 0.742-0.798)
6 Months’ Survival after Dialysis Start
French REIN registry	4142 incident patients aged ≥75 years	BMI, diabetes, congestive heart failure, peripheral vascular disease, dysrhythmia, active malignancy, severe behavioral disorder, dependency for transfers, and initial context of dialysis start	0.70 (95% CI 0.671-0.729)
6 Months’ Survival on Hemodialysis
New England HD clinics	1026 adult-prevalent patients. External validation in 1372 prevalent patients	Age, dementia, peripheral vascular disease, serum albumin, and the “surprise question” Currently available for free online ( https://qxmd.com/calculate/calculator_135/6-month-mortality-on-hd )	0.80 (95% CI 0.73-0.88)

ACR, Urine albumin-to-creatinine ratio; ADL, activities of daily living; BMI, body mass index; CI, confidence interval; CKD, chronic kidney disease; C-statistic, concordance (C)-statistic (which corresponds to the area under receiver operating characteristic curve, ranges from 0 to 1 depending on accuracy of discrimination); eGFR, estimated glomerular filtration rate; G3-5, estimated glomerular filtration rate category 3-5; HD, hemodialysis; REIN, Renal Epidemiology and Information Network; USRDS, United States Renal Data System.

As the field of prognostication moves forward, new markers may enhance current approaches. These may include identifying a decline in physical function using tools, such as gait speed, a modified Karnofsky activity scale, activities of daily living, or frailty scores. Repeat hospitalizations, a decline in HRQOL scores, reduced nutritional scores, reduced appetite, and lower body weight ^, may all be simple and reliable means for independently identifying CKD patients at risk for early death or poor health outcomes. Ideally, these prognostic tools would be used alongside patient decision aids to help in the shared decision-making process. Accurate prognostication will likely provide better opportunities to meet patients’ and families’ needs in the final years and months of life. New models, however, will need to be evaluated in different clinical and cultural contexts.

Symptom Assessment and Management

Symptom assessment and management are integral components of KSC. Advanced CKD is associated with a high symptom burden, and patients often experience complex clusters of symptoms, such as pruritus, pain, restless legs, fatigue, anorexia, nausea, insomnia, anxiety, and depression. Research suggests that symptom burden is more important than objective clinical parameters in determining HRQOL in people with CKD. Symptom burden was shown to account for 29% to 44.6% of the impairment in dialysis patients’ physical HRQOL scores and 39% to 48.7% of their impairment in mental HRQOL scores. Although dialysis treatment may address some uremic symptoms, it may do little to address symptom burden and HRQOL in more frail patients and chronic inflammation, malnutrition, and frailty continue to progress regardless of whether dialysis is started or not. At a population level, 1 year of dialysis did not result in an improvement in overall symptom burden or HRQOL. The patients who tend to do the best are those with limited comorbidity; they tend to have low symptom burden until shortly before needing dialysis and experience the more typical uremic symptoms of anorexia, nausea, vomiting, and fatigue, and these can quickly improve after starting dialysis. Kidney Disease: Improving Global Outcomes recommends incorporating regular global symptom screening using validated tools such as the ESAs-r:Renal (Edmonton Symptom Assessment System: Renal) into routine clinical practice and the incorporation of systematic, stepwise approaches to managing these symptoms. ^,

Many global symptom assessment tools of varying length have been used in CKD studies. For clinical utility it is important that these tools are valid, reliable, and sufficiently short and simple to minimize patient and staff burden. They must be appropriate for use in high-risk patients who are frail with cognitive impairment. In the case of pain, 0- to 100-mm visual analog scales or 0 to 10 numeric rating scales are advised based on extensive literature around what constitutes clinically important differences in pain intensity. Core domains that should be assessed when managing pain include pain intensity, function, HRQOL, and adverse events. ^,

Several self-reported HRQOL measures have also been used for CKD patients. Some are generic measures, whereas others are disease specific such as the Kidney Dialysis Quality of Life (KDQOL) Questionnaire and the shorter version (KDQOL-SF). These multidimensional tools focus on physical and emotional symptoms, burden of disease and effects on daily life, cognitive function, work status, sexual function, quality of social interaction and social support, staff encouragement, and patient satisfaction. Unfortunately, they are burdensome, requiring interviewer assistance and substantial time to complete. Although such tools provide comprehensive HRQOL information, they are perhaps more suited to a research environment where dedicated staff can help with the administration and complex scoring. To embed a HRQOL measure into routine clinical care, simple tools that can be interpreted easily by staff will most likely be required. ^, ^, Generic and disease-specific measures have been shown to perform similarly in assessing changes in HRQOL in people on hemodialysis, and an Oxford review of patient-reported outcome measures in CKD recommended EQ-5D-5L for use in this patient population. Recommendations for symptom assessment tools that can be used in routine clinical care are outlined in Table 61.3 .

Table 61.3

Recommendations for Clinical Symptom Assessment Tools for Use in People With Advanced Chronic Kidney Disease

Description	Clinical Utility
Global Symptom Assessment
Edmonton Symptom Assessment System–Revised: Renal (ESAS-r: Renal) ^, ^,
A 0-10 NRS for 12 symptoms: pain, activity, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath, pruritus, sleep, and restless legs. It also has a place to capture “other problems.” The scale for each symptom is anchored by the words “no” and “severe” at 0 and 10, respectively. The sum of all scores makes up the overall symptom distress score ranging from 0-120.	This is a short, practical tool for global symptom screening, which can be rapidly and repeatedly completed by patients and therefore incorporated easily into routine clinical care, even for patients who are preterminal. It has been translated into several languages. It uses the 0-10 NRS advised for the assessment of pain intensity.
Palliative Care Outcome Scale–Renal (POS-Renal)
Assesses 17 symptoms: pain, shortness of breath, weakness or lack of energy, nausea, vomiting, poor appetite, constipation, mouth problems, drowsiness, poor mobility, itching, difficulty sleeping, restless legs or difficulty keeping legs still, anxiety, depression, changes in skin, and diarrhea. These are rated in terms of their impact on the patient over the past week using a 0 (not at all) to 4 (overwhelmingly) Likert scale.	This tool is slightly longer than the ESAS-r: Renal but is simple to use. It has been translated into several languages. A disadvantage is that is does not use the 0-10 NRS that is advised for assessing pain and does not assess fatigue, which is one of the most prevalent and bothersome symptoms for people with advanced CKD. The concept of weakness is not the same as fatigue.
Multidimensional Pain Assessment
The Brief Pain Inventory (BPI)
Assesses the location, type (nociceptive vs. neuropathic), and intensity of pain. It also evaluates the impact of pain on the core domains of function and HRQOL. Specifically, it explores the impact of pain on general activity, mood, walking ability, work, relationships, sleep, and enjoyment of life. The standard 32-question instrument has been condensed to a 9-question short form.	This tool has been used successfully in clinical and research settings internationally to assess pain once identified as a problem. The short form is simple to use with minimal respondent burden, and seriously ill patients have been successful in completing it. The Interference Scale of the BPI has been recommended by IMMPACT for the assessment of physical functioning, one of the core pain assessment domains. A change of 1 point on the Interference Scale is considered the minimally clinically important change. ^, It has been translated into several languages.
Health-Related Quality of Life Assessment
5-Level EuroQol 5 Dimension (EQ-5D-5L)
This generic HRQOL measure has 2 parts: 1. EQ-5D descriptive system and 2. EQ VAS. The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: “no problems,” “slight problems,” “moderate problems,” “severe problems,” and “extreme problems.” The EQ VAS records the patient’s self-rated health on a vertical 0- to 100-mm VAS, where the endpoints are labeled “The best health you can imagine” and “The worst health you can imagine.”	This short, practical tool for assessing HRQOL is available in more than 130 languages.

CKD, Chronic kidney disease; HRQOL, health-related quality of life; IMMPACT, Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials; NRS, numerical rating scale; VAS, visual analog scale.

The aim of treatment is to ameliorate symptoms that are burdensome and adversely impact the patient’s HRQOL as it is not always necessary or possible to resolve them completely. It is important to acknowledge this and negotiate with the patient an acceptable level of symptom control. For pain, there is good evidence to suggest that targeting a pain of <33/100 mm on a visual analog scale or 3/10 on a numeric rating scale or a change in pain intensity of at least 30% (moderate benefit) or 50% (substantial benefit) will deliver worthwhile HRQOL benefits. Given the synergistic and interrelated nature of symptoms experienced in advanced CKD, an approach to care that addresses overall symptom burden is likely to improve HRQOL even if each individual symptom has not resolved completely. For example, a moderate reduction in pain may be sufficient to improve sleep, improve mood, and increase the ability to cope with health challenges, resulting in a substantial improvement in function and HRQOL. Recommendations for the management of common symptoms in CKD are outlined in Table 61.4 . These recommendations are appropriate for people with kidney failure who have yet to start dialysis, people who are receiving CKM, and for people on hemodialysis. ^, A general stepwise approach to symptom management involves 1. ruling out contributing factors, 2. maximizing the use of nonpharmacologic interventions, and 3. considering pharmacologic interventions if symptoms continue to impact adversely the patient’s HRQOL.

Table 61.4

Symptom Management for People with Advanced Chronic Kidney Disease ^,

Restless Legs Syndrome
Address Possible Contributing Factors	Nonpharmacologic Management	Pharmacologic Management	Additional Considerations
Anemia Iron deficiency Hyperphosphatemia Medications such as dopamine antagonists, antidepressants, and opioids (some of these drugs are commonly prescribed at end of life, e.g., haloperidol and opioids)	Abstinence from stimulants (e.g., alcohol, caffeine, and nicotine) Mental alerting activities (e.g., puzzles and games) Good sleep hygiene Exercise	First line: gabapentin (50-300 mg daily) 2-3 hours before sleep, especially if concomitant pruritus, insomnia, and/or neuropathic pain are reported Second line: nonergot-derived dopamine agonists (pramipexole 0.125 mg daily, ropinirole 0.25 mg daily, rotigotine transdermal patch 1-3 mg) given 2 hours before sleep At the end of life if swallowing is problematic: consider midazolam 1 mg subcutaneously q4h PRN	The most common side effects of gabapentin are drowsiness, dizziness, confusion, fatigue, and occasionally peripheral edema Nonergot-derived dopamine agonists have shown success in reducing symptoms in idiopathic RLS, but there are limited data in uremic RLS. Side effects might include headache, insomnia, and nausea. Augmentation may occur with long-time use. Benzodiazepines are not a first-line treatment for RLS, but there is some limited evidence for their use. If the patient is experiencing refractory RLS causing significant sleep disturbance or if benzodiazepines may potentially treat concurrent symptoms (e.g., anxiety), they could be considered.
Uremic Pruritus
Address Possible Contributing Factors	Nonpharmacologic Management	Pharmacologic Management	Additional Considerations
Anemia Iron deficiency Hyperphosphatemia Hypercalcemia Other: xerosis, drug hypersensitivities, allergies, infestations, contact dermatitis, or inflammation	Good skin care and moisturizers (e.g., baths with lukewarm water, pat dry and moisturize within 2 minutes; gentle soaps with no fragrances or additives) Keep skin cool Humid environment Avoid scratching—keep fingernails short, encourage gentle massage, and wear gloves at night Consider complimentary therapies (e.g., phototherapy [UVB] 3 times weekly for a 3-week trial; acupuncture. Little evidence exists for these alternative therapies.	Topical	Topical
		Capsaicin 0.025% or 0.03% ointment Pramoxine 1% Menthol/camphor/phenol—0.3% each γ-Linolenic acid cream 2.2%	These agents can be applied two times daily (four times daily for capsaicin). Capsaicin may cause burning to the area initially. Menthol, camphor, and phenol are separate products that can be added to most creams. All 3 may be added together, commonly with a 0.3% concentration for each.
		Systemic	Systemic
		First line: gabapentin (50-300 mg daily) 2-3 hours before sleep. Second line: tricyclic antidepressant such as doxepin 10 mg daily at night	The most common side effects of gabapentin are drowsiness, dizziness, confusion, fatigue, and occasionally peripheral edema. Potential adverse effects of tricyclic antidepressants include dizziness, blurred vision, constipation, and urinary retention. There is an increased risk of confusion and sedation, particularly in older adults.
Nausea and Vomiting
Address Possible Contributing Factors	Nonpharmacologic Management	Pharmacologic Management	Additional Considerations
Metabolic disturbances (e.g., uremia) Medications (e.g., opioids and SSRI antidepressants) Gastrointestinal disturbances (e.g., constipation and delayed gastric emptying)	Manage constipation Encourage good oral hygiene Smaller, more frequent meals; eat meals slowly Avoid alcohol Avoid foods that are greasy, spicy, or excessively sweet Minimize aromas (e.g., cooking odors, perfumes, and smoke) Encourage relaxed, upright position after eating to facilitate digestion Loose-fitting clothing Consider complementary therapies (e.g., relaxation techniques, acupressure, and use of ginger)	First line: Ondansetron 4-8 mg every 8 hours as needed Second line: metoclopramide 2.5 mg every 4 hours as needed (first-line therapy if nausea is due to delayed gastric emptying) Third line: olanzapine 2.5 mg every 8 hours as needed OR haloperidol 0.5 mg every 8 hours as needed Fourth line: for persistent and severe nausea, consider increasing haloperidol to 1.0 mg (maximum 5 mg in 24 hours) OR replacing with methotrimeprazine 5 mg orally or 6.25 mg subcutaneously every 8 hours as needed	Ondansetron can be constipating. Haloperidol, metoclopramide, and olanzapine are all dopamine antagonists: Avoid prescribing them together. They can also exacerbate RLS. They all cross the blood-brain barrier, and extrapyramidal symptoms are possible. Haloperidol has a higher risk of extrapyramidal symptoms than metoclopramide and olanzapine. Increasing the dose of methotrimeprazine may lead to levels of drowsiness that the patient may find unacceptable and should be discussed with the patient and/or family
Breathlessness
Address Possible Contributing Factors	Nonpharmacologic Management	Pharmacologic Management	Additional Considerations
Anxiety Anemia Infection Volume overload leading to pulmonary edema	Sit in an upright position (e.g., 45 degrees) Position by a window or use a fan to blow air gently across the face Maintain a humid environment Pursed lip breathing Supplemental oxygen Complementary therapies (e.g., relaxation techniques, and music) Consider role of diet such as sodium and fluid restriction if patient is volume overloaded	If patient is intravascularly volume overloaded: diuretic such as a loop diuretic—furosemide. Occasionally patients may require combination diuretic therapy—consider adding metolazone Near the end of life: low doses of opioids are the most effective treatment For breathlessness that is episodic and primarily associated with a specific activity, consider fentanyl 12.5 μg subcutaneously or sublingually PRN For shortness of breath that is more constant or unpredictable in nature, consider hydromorphone 0.5 mg PO (0.2 mg subcutaneously) every 4 hours around the clock and every hour as needed	Due to accumulation of metabolites, opioids should always be started at a low dose and monitored closely for adverse effects Due to its fast action, fentanyl works well in cases where breathlessness is predictable
Fatigue and Sleep Disturbances
Address Possible Contributing Factors	Nonpharmacologic Management	Pharmacologic Management	Additional Considerations
Fatigue Vitamin D deficiency Metabolic acidosis Hyperphosphatemia Secondary hypothyroidism Anemia Malnutrition Mood disorders Sleep disturbances Sleep disturbances Other symptoms (e.g., restless legs, pruritus, pain, and breathlessness) Cognitive impairment Medications Generalized insomnia Mood disorders Sleep apnea	Fatigue Exercise Nutrition and hydration management Energy-conservation strategies Good sleep hygiene (e.g., avoid stimulants before bed, avoid napping during the day, and save the bedroom for sleep) Cognitive and psychological approaches (e.g., relaxation therapy, delegating, and setting limits) Complementary treatments (e.g., acupressure, massage, and acupuncture)	Sleep disturbances First line: consider low-dose gabapentin (50-300 mg at night), especially if the patient has concomitant neuropathic pain, RLS, or uremic pruritus Second line: Doxepin 10 mg at bedtime, especially if concomitant pruritus or neuropathic pain reported Third line: cautiously consider mirtazapine 7.5 mg or zopiclone 3.75-5 mg at night or melatonin 2-5 mg at night	Reassess medications after 2-4 weeks. Avoid over-the-counter sleep aids and benzodiazepines if possible. Specifically, avoid mirtazapine if taking tramadol or antidepressants. Monitor doxepin for anticholinergic side effects (e.g., dizziness, blurred vision, constipation, urinary retention, and cardiac arrhythmias). Evidence for melatonin is limited and inconclusive. Ideally, all of these medications should be prescribed for short-term use only
Nociceptive Pain
Address Possible Contributing Factors	Nonpharmacologic Management	Pharmacologic Management	Additional Considerations
Determine cause for pain and consider appropriate investigations	Physical therapies (e.g., physical therapy, aerobic exercise, stretching, massage, acupressure, and acupuncture) Behavioral therapies (e.g., cognitive behavioral therapy—most commonly used behavioral therapy), biofeedback, relaxation techniques, psychotherapy/individual or group counseling, guided imagery, mindfulness-based stress reduction Interventional and surgical (e.g., ablative techniques, nerve blocks, and trigger point injections)	Step 1: Acetaminophen/paracetamol, maximum of 3 g daily. If pain is localized to a small joint, consider a topical NSAID (e.g., diclofenac gel 5% or 10% two to three times daily). Step 2: ADD an opioid to step 1 in very low doses. Hydromorphone starting at 0.5 mg PO (0.2 mg subcutaneously) every 4-6 hours; buprenorphine/fentanyl/methadone	Trial each step for 1-4 weeks before progressing, depending on pain severity Before starting an opioid, consider completing an opioid risk tool and order a bowel routine to avoid constipation (e.g., PEG 3350). All opioids should be started at low doses, monitored carefully for adverse effects and overall benefit, and titrated slowly (see Table 61.5 )
Neuropathic Pain
Address Possible Contributing Factors	Nonpharmacologic Management	Pharmacologic Management	Additional Considerations
Determine cause for pain and consider appropriate investigations	As for nociceptive pain	Start with adjuvant therapy. First line: gabapentin, pregabalin (calcium channel α2–Δ ligands) Second line: tricyclic antidepressants, amitriptyline starting at 10–25 mg daily or doxepin starting at 10 mg daily If more analgesia is required in addition to adjuvant therapy, add a nonopioid and then proceed with low dose of an opioid and titrate as described for nociceptive pain	Methadone may be effective for severe neuropathic pain because of its activity against the NMDA receptor antagonism

NMDA, N -methyl- d -aspartate; NSAID, nonsteroidal antiinflammatory drug; PO, per os; q4h, every 4 hours; PRN, as needed; RLS, restless legs syndrome; SSRI, selective serotonin reuptake inhibitor; UVB, short-wave ultraviolet B.

Chronic Pain Management

Although detailed information on the management of chronic or persistent pain is beyond the scope of this chapter, some general principles are worth highlighting. Chronic pain can be defined as any painful condition that persists for more than 3 months. Dialysis patients may also experience recurring episodes of acute pain, such as pain from needling fistulas or intradialytic steal syndrome, intradialytic headaches, and cramps. These acute pains tend to be associated with tissue damage but typically have no progressive pattern, last a predictable period, subside as healing occurs, and are episodic with periods without pain. By contrast, chronic pain is present for long periods and is often out of proportion with the extent of the originating injury. It is more likely to result in functional impairment and disability, psychological distress, sleep deprivation, and poor HRQOL.

Nonpharmacologic therapies are a vital part of managing chronic pain and are typically required to augment pharmacologic treatments to achieve adequate relief (i.e., multimodal therapy). They may also be used as stand-alone therapies. Examples are outlined briefly in Table 61.4 . Core principles in developing a treatment plan for chronic pain include explaining the nature of the chronic pain condition, setting appropriate goals, and developing a comprehensive treatment approach and plan for adherence. Medication should not be the sole focus of treatment and should only be used when needed, in conjunction with other nonpharmacologic modalities, to meet treatment goals. Optimal patient outcomes often require multiple approaches used in concert, coordinated via a multidisciplinary team.

There are five essential principles for the pharmacologic management of pain. These are described in Table 61.5 . Of particular importance is the careful selection of analgesics when prescribing for people with advanced CKD. Many analgesics and their metabolites are excreted by the kidney through glomerular filtration, tubular secretion, or both. People with CKD are at risk for accumulation of toxic metabolites if not monitored carefully. The choice of an appropriate initial therapeutic strategy depends on an accurate evaluation of the cause of the pain and the type of chronic pain syndrome. In particular, neuropathic pain should be distinguished from nociceptive pain ( Table 61.6 ). For most patients with advanced CKD, the initial treatment of neuropathic pain involves calcium channel α2–δ ligands (e.g., gabapentin and pregabalin) or tricyclic antidepressants (see Table 61.4 ). Opioid medications are considered second-line agents for neuropathic pain. By contrast, the pharmacologic approach to nociceptive pain primarily involves nonopioid and opioid analgesics if nonpharmacologic strategies are insufficient. The opioids that are generally considered safer for use in people with advanced CKD are hydromorphone, buprenorphine, fentanyl, and methadone, with doses started low, titrated slowly, and the patient monitored carefully for analgesia, adverse effects, overall function, and HRQOL (see Table 61.4 ).

Table 61.5

Five Principles of Pain Management in Advanced Chronic Kidney Disease (CKD)

Principle	Description	Specific Considerations in Advanced CKD
“By mouth”	Oral administration is the safest and therefore preferred. Patient comfort and effectiveness must be considered. If ingestion or absorption is uncertain, analgesics need to be given by alternative routes, such as transdermal, rectal, or subcutaneous.	Hemodialysis patients have easy intravenous access. However, this is to be avoided as the route of administration for analgesics to optimize safety and minimize the risk of abuse and addiction.
“By the clock”	For continuous or predictable pain, analgesics should be given regularly. Additional “breakthrough” or “rescue” medication should be available on an “as needed” (PRN) basis in addition to the regular dose.	Some patients with mild pain may achieve adequate pain relief with analgesic dosing post-hemodialysis only. An example would be mild neuropathic pain dosed with gabapentin post hemodialysis.
“By the ladder”	Pharmacologic management proceeds stepwise from a nonopioid (step 1) to a very low dose of an opioid (step 2) using a modified WHO analgesic ladder. There are no good options for “weak” opioids for people with advanced CKD.	Careful selection of analgesics for each step of the ladder, taking into account the degree of kidney failure, is critical (see Table 61.4 ). Sustained-release preparations are generally not recommended in people with advanced CKD.
“For the individual”	There is large variability in patients’ response to analgesics. The “correct” dose is the amount needed to relieve the pain without producing intolerable side effects. Evaluation and recording of benefits and toxicity are essential.	Chronic pain is often experienced in the context of numerous other physical, psychosocial, and spiritual concerns including end-of-life issues. Close attention to these other issues must not be forgotten as part of the pain management strategy.
“Attention to detail”	Pain changes over time; therefore there is the need for ongoing reassessment. Side effects should be explained and managed actively (e.g., constipation).	There are no studies on the long-term use of analgesics in people with CKD. Careful attention must be paid to efficacy and safety. The impact on overall symptom burden, physical function, emotional state, cognition, and HRQOL should be assessed routinely.