Abstract
Chronic kidney disease (CKD) is a growing global issue, currently affecting approximately 10% of the population. Optimal care of these patients must encompass their complex medical issues, aiming not only to delay progression of disease but also to manage symptoms and complications of their CKD and comorbidities, facilitate timely and smooth transition to renal replacement therapy, and support conservative management choice in patients who opt for this. Furthermore, care should include advocacy for the patient and support of their social and psychological needs. Due to the complex and multifaceted needs of patients with CKD, a multidisciplinary clinic allows longitudinal follow-up of these patients, allowing continuity of care and utilization of the skills of multiple team members including doctors, nurses, social workers, pharmacists, and other allied health members. Patients with CKD come from varied socioeconomic and educational backgrounds, with variable health literacy and educational needs, and a team approach with well-defined roles, responsibilities, and objectives is a logical and effective way of caring for these patients. Through this approach, it is hoped that improved outcomes for patients with CKD may be achieved.
Keywords
advanced care planning, dialysis modality, education, health literacy, longitudinal care, multidisciplinary clinic, multidisciplinary team, renal conservative management, renal replacement therapy
Outline
Introduction, 121
Staging and Terminology for Chronic Kidney Disease and Effect on Need for Coordinated Care, 122
Overview of Chronic Kidney Disease Clinic, 122
Philosophical Basis, 122
Role of Multidisciplinary Clinics, 123
Structure and Definition of Multidisciplinary Clinics, 124
Key Goals of Chronic Kidney Disease Care, 124
Diagnosis, 124
Education, 124
Delay of Kidney Disease Progression, 125
Management of Comorbidities, 125
Preparation for Kidney Replacement Therapy, 128
Modality Selection, 128
Vascular Access Creation, 129
Timely Initiation, 129
Independent Therapies, 130
In-Center Hemodialysis, 130
Transplant, 130
Maximum Conservative Management, 131
Advanced Care Planning, 131
Clinic Logistics, 131
Services, 131
Key Components of the Clinic, 131
Individual Roles, 132
Chronic Kidney Disease Clinic Role in Longitudinal Care: Different Stages of Chronic Kidney Disease, 132
Chronic Kidney Disease Clinic Role in Parallel Care: Integrating With Other Caregivers, 133
Other Benefits of the Chronic Kidney Disease Clinic and Organized Protocol-Based Care, 133
Recent and Future Studies, 134
Conclusion, 135
Introduction
Chronic kidney disease (CKD) is defined by the Kidney Disease Improving Global Outcomes (KDIGO) as an abnormality of kidney structure or function that is present for greater than 3 months and has implications for health . CKD affects 10% of the global population. The numbers of people affected are growing exponentially, and certain populations from low-income backgrounds and geographical areas such as Asia and Africa are disproportionately affected. CKD is an increasingly common cause of morbidity and mortality, climbing from the 27th greatest contributor to global deaths in 1990 to the 18th greatest in 2010. United States Renal Data System (USRDS) data suggest that mortality in patients with CKD is greater than double that of patients without CKD, at 111.2 per 1000 patient years (after adjusting for age, sex, and race) in 2014. Likewise, hospitalization rates are much higher among patients with CKD compared with those without, with the 2014 USRDS data showing it to be two to three times higher. In the United States, the crude incidence rate of end-stage kidney disease (ESKD) was 370 per million per year in 2014, and the number of dialysis and transplant patients rose by 3.5% from 2013. Caring for patients with CKD and ESKD is costly, with 2014 estimates of cost per person per year in the United States equaling $32,586 for transplant patients, $73,612 for peritoneal dialysis patients, and $87,638 for hemodialysis patients.
Both awareness and adoption of CKD guidelines are generally considered to be suboptimal among nonnephrologist physicians. International CKD guidelines may only be accessible in around 50% of cases, and the availability of renal registries may be extremely low in developing countries.
Historically, the focus of CKD care was to coordinate placement of vascular access, to attend to uremic symptoms and complications, and to provide dialysis. However, it is increasingly recognized that conditions associated with CKD, such as anemia and malnutrition, and comorbidities such as diabetes and hypertension, may result in significant morbidity, even if the patient does not progress to ESKD. Thus the goals of therapy are to (1) delay progression of CKD; (2) delay and treat known cardiovascular disease (CVD) comorbidities; (3) manage uremic symptoms (such as fatigue, pruritis, anorexia) and complications (such as anemia, CKD-mineral bone disease [CKD-MBD], malnutrition, and hypertension); (4) educate and engage patients and families in modality choice; (5) initiate timely kidney replacement therapy, including timely placement of access or transplant workup (including preemptive transplantation where feasible); and (6) facilitate goals of care discussions and patient autonomy in decision making and support a conservative approach to CKD management where this is in line with patient wishes. Each of these goals requires education and effective communication between patients and caregivers and comanagement by different health professionals, including nursing and allied health. With the main aim to maintain health, it is essential that the structure of the clinic reflect all goals and the demand for communication and investigation to ensure success.
This chapter describes the principles of chronic disease management and a model of integrated multidisciplinary team-based care structured on these goals. The structure and function of a clinic-based approach for the comprehensive care of patients with CKD are outlined, and the potential uses of such a clinic are also discussed. The described structure and function may serve as a template for the development of such clinics. To ensure a context for such a clinic, we also review the evidence and rationale supporting this concept.
Staging and Terminology for Chronic Kidney Disease and Effect on Need for Coordinated Care
The 2012 KDIGO guideline suggested a classification of CKD based on cause, glomerular filtration rate (GFR) category and albuminuria category. After determining the etiology of the kidney disease, patients can be assigned to six different GFR categories ( Table 8.1 ), and three different albuminuria categories ( Table 8.2 ), to assess in two dimensions: severity and prognosis. The aim of this classification system was to recognize the importance of other markers of CKD, such as albuminuria or structural kidney abnormalities, which can occur even when GFR is preserved. Recognition of CKD as a spectrum of disease, and these abnormalities as points along this spectrum, may permit the earlier identification and intervention of CKD in individuals, thereby providing the greatest opportunity to reduce morbidity and mortality.
| GFR category | GFR (mL/min/1.73 m 2 ) | Terms |
|---|---|---|
| G1 | ≥90 | Normal or high |
| G2 | 60–89 | Mildly decreased, compared with young adult level |
| G3a | 45–59 | Mildly to moderately decreased |
| G3b | 30–44 | Moderately to severely decreased |
| G4 | 15–29 | Severely decreased |
| G5 | <15 | End-stage kidney failure |
| Category | Albumin/creatinine ratio (ACR) (mg/mmol) | ACR (mg/g) | Terms |
|---|---|---|---|
| A1 | <3 | <30 | Normal to mildly increased |
| A2 | 3–30 | 30–300 | Moderately increased, compared with young adult level |
| A3 | >30 | >300 | Severely increased, compared with young adult level |
The adoption of a universal language and terminology, initially through the 2002 National Kidney Foundation–sponsored Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines, and more recently through the aforementioned KDIGO guidelines, has helped facilitate knowledge acquisition by the medical community, patients, and public bodies and has improved research clarity and applicability. The KDIGO staging system has helped clarify the previously used terms ( predialysis, progressive renal disease, progressive renal insufficiency ), which were often confusing and sometimes misleading.
The estimates of populations with CKD generated from the new CKD classification system and the accompanying public awareness campaign around the world have helped identify the large burden of CKD that exists. The focus on earlier identification has identified a large number of patients whose CKD would have remained undetected much longer based on creatinine levels alone, and thus there is the need to create appropriately structured care delivery systems as described herein, including the education of other healthcare providers in CKD care. Furthermore, evidence has accumulated regarding the need for more proactive care and for the early institution of strategies to delay CKD progression, as well as CVD risk reduction, which is the most common cause of death among the CKD population. As a result, CKD screening and prevention strategies should be employed alongside management strategies in high-risk populations, such as people with diabetes. Kidney health promotion campaigns and education have already been shown to be effective in reducing rates of ESKD in Taiwan, Uruguay, and Chile.
Overview of Chronic Kidney Disease Clinic
Philosophical Basis
In contrast to the case of diabetes or heart failure, the role of a multidisciplinary clinic in facilitating the care of patients with CKD has not been clearly defined. Thus data to support the concept and implementation are often drawn from experience with other chronic diseases. Clinics for the care of CKD should be based on the fundamental principle of ensuring the delivery of longitudinal, complex care to a large, diverse group of individuals. This requires that the structure of the clinic and services offered optimize communication within and between individuals, including the patient and other physicians and allied health teams. One of the key roles of the care should be to integrate medical, psychological, and social aspects of chronic disease to optimize patient outcomes.
Health literacy is defined by the Institute of Medicine as “the degree to which individuals can obtain, process and understand the basic health information and services they need to make appropriate health decisions.” It represents a complex set of skills that allow an individual to optimize their healthcare interactions, which encompasses not only their numeracy, reading, and writing (print literacy) and listening and speaking (oral literacy) but also their cultural and conceptual knowledge as applied to health information, and their personal skills and confidence, which allow individuals to take action on healthcare issues.
It is clear that patients who have poor health literacy and a poor understanding of their health conditions and management have worse outcomes, including lower likelihood of receiving kidney transplantation and increased mortality. Limited health literacy is common, and prevalence can range between 12% and 20% among patients with CKD and ESKD. Certain groups of patients may be particularly at risk of poor outcomes due to poor health literacy, as limited health literacy has been demonstrated to have an independent association with low socioeconomic status, nonwhite ethnicity, poor English fluency, and comorbidities in patients with kidney disease. Kidney transplant recipients are less likely to have poor health literacy, particularly those who have received preemptive transplantation and live-donor transplantation. This may suggest that the intensive education process typically performed pretransplant could improve health literacy and lead to better clinical outcomes. Causality cannot be established, however, as it is possible that health literacy directly affects access to transplantation, where patients with higher health literacy at baseline are better equipped to seek live kidney donors and have regular medical follow-up to allow preemptive transplantation. In any case, improving health literacy among patients with CKD is likely to result in better clinical outcomes.
Adult learning operates five assumptions: (1) adults are independent and self-directing; (2) adults have accumulated a great deal of experience, which is a rich resource for learning; (3) adults value learning that integrates with the demands of their everyday life; (4) adults are more interested in immediate, problem-centered approaches than subject-centered ones; and (5) adults are more motivated to learn by internal drives than by external ones. Knowles and colleagues suggested seven principles of adult learning based on these, including (1) establishing a safe and effective learning environment, (2) involving learners in mutual planning of methods and learning content, (3) involving learners in identifying their own needs, (4) facilitating learners to define their own learning objectives, (5) encouraging learners to identify and use resources appropriately to achieve their objectives, (6) supporting learners to carry out their own learning plans, and (7) allowing learners to critically reflect on and evaluate their own learning. The importance of the application of these principles in the development and application of tools for use in multidisciplinary clinics should be emphasized.
Role of Multidisciplinary Clinics
Early referral to a nephrologist is associated with a lower chance of needing to commence dialysis by temporary vascular access, increased uptake of independent therapies such as peritoneal dialysis, reduced hospitalization rates, and reduced mortality compared with late nephrology referral. Moreover, multidisciplinary nephrology clinics have been shown to be cost-effective compared with general nephrology clinics, especially when patients were referred early, leading to increased life-years free of dialysis and fewer days spent in hospital. KDIGO provides recommendations for criteria for referral to a nephrologist ( Box 8.1 ); however, the decision to refer must be considered on a case-by-case basis.
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Acute kidney injury (AKI) or abrupt sustained fall in glomerular filtration rate (GFR);
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GFR <30 mL/min/1.73 m 2 ;
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a consistent finding of significant albuminuria (albumin/creatinine ration [ACR] >300 mg/g;
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progression of chronic kidney disease (CKD) (irrespective of GFR);
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urinary red cell casts, red blood cell >20 per high-power field sustained and not readily explained;
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CKD and hypertension refractory to treatment with four or more antihypertensive agents;
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persistent abnormalities of serum potassium;
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recurrent or extensive nephrolithiasis; or
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hereditary kidney disease.
Given the multiplicity of goals of CKD care, the complexity of treatment options, wide disparities in patient health literacy, and patient educational needs, it is clear that a team of individuals is required to achieve optimal management. Treatment targets, such as blood pressure, may be reached by involving expert nurses, pharmacists, or other members of the team in conjunction with the physician. Thus a team approach with well-defined roles, responsibilities, and objectives appears to be both logical and practical. Improved patient care and outcomes due to a multidisciplinary team clinic have been demonstrated in disciplines such as endocrinology, cardiology, rheumatology, and oncology. Similarly, compared with standard care by a nephrologist alone, there is evidence that a multidisciplinary care team approach is beneficial for both children and adults with CKD.
Structure and Definition of Multidisciplinary Clinics
Formal Multidisciplinary Team
A multidisciplinary team is defined as nurses, nurse educators, dietitians, pharmacists, social workers, and physicians who are allied in a formal relationship and who interact with the patient and each other. Although it is recognized that there are a number of different configurations due to funding and local healthcare system issues, for the purpose of definition, this team is readily identifiable as dedicated (part time or full time) to CKD care.
Informal Multidisciplinary Resources
Nurses, social workers, dietitians, pharmacists, and physicians associated with the kidney team to whom patients are referred may constitute informal resources, because there is no defined team or expectation of standardization of team interactions with each other or the patient. In such an arrangement, patient access is dependent on individual patient needs, and the group of individuals may or may not interact as a team or necessarily be involved with longitudinal follow-up of patients. Each team member is able to interact with the patient on a regular basis as necessary, but coordination with other team members is not necessary to its structure.
No Multidisciplinary Team
Nurses, social workers, pharmacists, and dietitians may or may not be available to the patient. There is an absence of team structure or function.
Key Goals of Chronic Kidney Disease Care
This section describes the key goals of comprehensive CKD care, including diagnosis, education, delay of progression, identification and treatment of comorbidities associated with CKD, and complications of CKD. The institution of primary prevention strategies, including vaccination programs and the preparation of patients for kidney replacement therapy as appropriate, is also discussed. The goals described are comprehensive and complex, thus the need for a structured delivery system with protocols, such as delivery in formal longitudinal clinic care.
Diagnosis
The first goal of the nephrology clinic team should be to attempt to establish or confirm a diagnosis and to determine the rate of progression of kidney disease. A review of current medications is necessary to ensure the absence of nephrotoxic medications. Past medical and family history should be investigated, with effort to elucidate the presence of systemic disease including diabetes, vascular disease, connective tissue disorders, infections, and malignancy. Kidney disease may be multifactorial in nature, and consideration should be given to the possibility of several contributory factors.
The nephrologist should ensure that appropriate tests have been undertaken to establish a diagnosis. In early visits, reversible causes of kidney disease should be sought, even if a chronic etiology is suspected, especially if there has been a rapid decline in kidney function. For example, noninvasive imaging may be helpful to rule out potentially reversible obstructive causes. Invasive tests, such as kidney biopsy, may be performed when needed to establish diagnosis or guide treatment.
Education
CKD education covers a broad range of topics and skills ( Box 8.2 ). Patient education and awareness are integral components of the clinic. Education is important from a decision-making perspective and to alleviate fear and psychological suffering. In addition, people who have received disease and management education are more likely to take an active part in their care, with better outcomes noted in other chronic health conditions, especially for those previously failing to meet treatment goals. Ongoing feedback to increase patient knowledge regarding interventions and their outcomes has been demonstrated to improve effectiveness of treatment in the case of dyslipidemia. Patients receiving comprehensive education programs in the predialysis period are more likely to opt for independent dialysis therapies, including peritoneal dialysis and home hemodialysis. In the present and emerging technological era, promising new opportunities for education exist, such as computer-based, online, mobile phone applications, and virtual environment training.
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Explanation of normal kidney function, blood pressure, and laboratory test results and their significance
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Explanation of specific disease conditions, symptoms, and complications of CKD
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Dietary teaching
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Diabetes education, if appropriate
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Facilitating medication knowledge and adherence
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Discussions about vein preservation in preparation for future vascular access (avoiding blood taking and intravenous cannulae on selected side)
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Anemia management education, including risks and benefits of iron and erythrocyte-stimulating agents (ESAs), teaching of self-administration, and provision of educational materials to the primary care provider
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Discussions about self-management, values, and decision-making considerations.
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Discussion of choices for treating end-stage kidney disease, including conservative therapy, hemodialysis, peritoneal dialysis, and discussion of the benefits of home-based modalities, if appropriate
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Discussion about option of kidney transplantation (live or deceased donor), if appropriate
Ideally, education should also involve family members or support-network individuals. Education should commence in early stages of CKD, to allow patients a better understanding of their disease and to equip them with knowledge and skills so they can best preserve kidney function and avoid complications of CKD for as long as possible. As CKD progresses, education must expand and intensify to include more complex management concepts, such as preparations for dialysis.
Delay of Kidney Disease Progression
The cornerstone of CKD care is to delay progression of kidney disease and thereby to reduce complications related to kidney failure, including death and ESKD. This involves treatment of the primary kidney disease, if possible, as well as optimizing factors and systemic disease that may otherwise contribute to CKD progression. Lastly, management also involves the avoidance of future kidney insults where possible, such as hypotension, hypovolemia, and nephrotoxic medications. Although guidelines exist regarding management targets for intervention, treatment goals and methods must be individualized, with consideration of risks versus benefits for each patient ( Table 8.3 ).
| Treatment Target | Treatment Options | |
|---|---|---|
| Blood pressure and renin-angiotensin-aldosterone system (RAAS) interruption | If urine ACR <3 mg/mmol: ≤140 mmHg systolic and ≤90 mmHg diastolic If urine ACR >3 mg/mmol: ≤130 mmHg systolic and ≤ 80mmHg diastolic Minimizing proteinuria in people with diabetes and urine ACR 3 to 30 mg/g, and in all individuals with AER >30 mg/g | Antihypertensive medications ACE inhibitor or ARB in people with diabetes and urine ACR 30 to 300 mg/g, and in all individuals with ACR >300 mg/g Fluid status management with dialysis |
| Reducing risk of AKI | Avoiding AKI | Careful consideration when performing investigations or procedures which may increase risk of AKI Careful management of patients with intercurrent illnesses that may increase risk of AKI Provision of educational material for patients regarding AKI risks |
| Protein intake | If GFR <30 mL/min/1.73 m 2 : ≤0.8 g/kg/d If at risk of CKD progression: <1.3 g/kg/d | Dietary protein limitation, avoid excess while providing sufficient intake for adequate nutrition |
| Glycemic control | HbA 1c <7% for prevention of diabetic kidney disease HbA 1c 7%–8% with established CKD | Dietary modification Oral Various hypoglycemic agents Injectable Insulin Glucagon-like peptide -1 receptor agonists |
| Salt intake | <90 mmol (<2 g) per day | Dietary salt restriction |
| Lifestyle | Physical activity compatible with cardiovascular health and tolerance ≥30 min, 5 times per wk BMI 20–25 kg/m 2 (according to country specific demographics) Nonsmoker | Physical activity Dietary modification Bariatric surgery (in appropriate patients) Smoking cessation |
| Additional dietary advice | Dependent on individual | Individualized dietary advice regarding phosphate and potassium intake when indicated |
Management of Comorbidities
These topics are covered in-depth in other, dedicated chapters. This section will identify how multidisciplinary clinics can help facilitate optimal care.
Cardiovascular Disease
Patients with CKD are more likely to have cardiovascular risk factors, including smoking, obesity, hypertension, dyslipidemia, hyperuricemia, anemia, elevated glycosylated hemoglobin, chronic inflammation with elevated C-reactive protein (CRP), and albuminuria. Patients with CKD are at an increased risk of cardiovascular events and death, and this risk increases with declining GFR. In fact, CVD is the most common cause of death in the CKD population, accounting for close to 50% of deaths, and mortality due to CVD may be 10 to 30 times higher in dialysis patients compared with the general population. Furthermore, not only is declining GFR a predictor for CVD, but albuminuria is also an independent predictor for CVD-related death, even at low levels. Again, the risk of major cardiovascular events has been shown to increase with increasing levels of proteinuria.
Patients with CKD therefore require assessment and therapy for vascular disease and associated risk factors. It should be noted that many risk factors for CVD are also associated with the risk of progression of CKD. Traditional risk factors, such as hypertension, smoking, obesity, and diabetes, are common in the CKD population; thus risk factor reduction strategies used to prevent CVD in the general population can be applied to patients with CKD and may have the added effect of slowing the progression of kidney disease. However, these risk factors fail to adequately explain the increased cardiovascular risk among patients with CKD, and management strategies used in the general population, such as aspirin and statins, do not always result in similar benefits in the CKD population. Other nontraditional risk factors, such as calcific vascular disease, volume overload, and uremic toxins, may help account for the disproportionately increased risk among patients with CKD.
Multidisciplinary clinics may help facilitate cardiovascular risk reduction by enhancing the adherence to a healthy lifestyle and medication use and by complementing other cardiovascular risk reduction strategies that patients may receive in other circumstances (i.e., from primary care or other specialists).
Anemia
Anemia in CKD patients is due to reduced erythropoietin production by the kidneys, reduced red cell life span, functional iron deficiency, and chronic inflammation. Anemia is an important predictor of morbidity and mortality in the dialysis population and has been associated with ischemic heart disease, left ventricular hypertrophy, congestive heart failure, reduced quality of life, and increased mortality.
Erythrocyte-stimulating agents (ESAs) are currently recommended in patients with CKD who are iron replete to achieve partial correction of anemia. There have been several studies investigating the optimal target hemoglobin for patients with CKD who are treated with ESAs. Several large randomized controlled trials have evaluated clinical outcomes with ESA use to achieve normal versus near-normal hemoglobin targets, including the Correction of Hemoglobin and Outcomes in REnal Insufficiency (CHOIR), Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE), and Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) studies. Overall, the evidence has suggested that targeting normal hemoglobin levels with ESA use does not result in a significant difference in mortality, cardiovascular events, or progression to ESKD, but may be associated with a higher risk of hypertension and vascular complications, including stroke and vascular access thrombosis. As a result, KDIGO recommends that ESAs generally should not be used to target a hemoglobin of greater than 11.5 g/dL, and should not be used to intentionally increase the hemoglobin to greater than 13.0 g/dL.
To maintain hemoglobin in the target range, regular blood tests are required. Pharmacists and doctors can then review blood work results and make adjustments to doses if needed. Nursing staff are also vital to this process, first to educate patients in how to self-administer ESAs, decreasing the number of clinic visits required, and to facilitate administration of ESAs for those patients who are unable to self-administer due to dexterity, cognitive issues, or other concerns. In addition, nurses are an important bridge to communicate and reinforce changes in dose or administration to patients.
CKD-MBD
Hyperphosphatemia, hypercalcemia, and hyperparathyroidism observed in ESKD have been independently associated with increased mortality. It is likely that disordered calcium/phosphate metabolism contributes to the excessively high incidence of CVD in patients with CKD. Vessel wall calcification, as well as atherosclerotic plaque with high calcium component, has been demonstrated in patients with CKD.
Phosphate-binding treatments have been the mainstay of managing calcium/phosphate abnormalities in the past, with calcium-based binders generally being used as a first line due to their low cost and availability. More recently, however, evidence has suggested that calcium-based phosphate binders may contribute to vascular calcification and to increased cardiovascular events and mortality. The use of noncalcium-based binders is becoming more common, and newer products are also being developed, including sevelamer, lanthanum, and iron-based binders. However, limited is known about the long-term effects and complications of these medications. Moreover, phosphate-lowering therapy, though effective at normalizing biochemical CKD-MBD parameters, has not demonstrated a mortality benefit thus far. As such, the most recent, updated KDIGO guidelines on CKD-MBD management suggest aiming for normal phosphate levels, avoiding hypercalcemia, and restricting both the use of calcium-based phosphate binders and dietary phosphate intake.
The input of dieticians and nurse educators is vital to ensure that patients have adequate knowledge about their dietary goals and to assist them with strategies to reduce excessive phosphate intake, thereby reducing the need for calcium-based binders and patients’ pill burden.
Nutrition
Malnutrition is common in patients in later stages of CKD. There is a strong association between decreased albumin and worse nutritional status, with adverse outcomes including increased mortality. Unfortunately, albumin is a late indicator of malnutrition and is a negative acute phase reactant. Acidosis also contributes to protein breakdown and mineral metabolism aberrations. Thus assessment of nutritional status cannot be adequately performed by only using biochemical markers, but also requires the expertise of a dietitian.
Reduced protein diets have been extensively studied as a means to slow the progression of kidney disease, with mixed results. Metaanalyses and a large, randomized trial suggest that the effect may be slight and there is a potential for protein malnutrition, which would result in adverse outcomes. The optimal level of dietary protein restriction to derive maximal benefits and avoid harm is not clear, and protein restriction to slow CKD progression is controversial, especially in advanced CKD. A reasonable approach is to limit protein with a goal to avoid excess while providing sufficient intake for adequate nutrition. Thus the KDIGO guidelines currently suggest protein intake of 0.8 g/kg/day in adults with a GFR <30 mL/min/1.73 m 2 , when accompanied with appropriate education, and that adults at risk of CKD progression should avoid high protein intake of >1.3 g/kg/day.
Formulation of a dietary plan that optimizes nutritional state, individually caters to a patient’s nutritional needs (whether that be weight loss or weight gain), and avoids excessive loads of nutritional elements that may add to complications in patients with CKD (such as phosphate, potassium, and salt) is challenging and requires dietetics expertise. Furthermore, ensuring adherence to a prescribed diet is difficult and requires frequent, continuous input from dietitians and nurse educators. This becomes only more important as the patient approaches ESKD, because worsening malnutrition may become the principal indication to initiate dialysis.
Primary Prevention
The main content for the topics in this section is covered in-depth by other dedicated chapters. This section will identify how multidisciplinary clinics can help facilitate optimal care.
Primary prevention strategies are also important in the management of patients with CKD and may sometimes be overlooked due to the time-intensive management of conditions associated with uremia and its complications. Vaccinations, lipid-lowering agents and other CVD primary prevention strategies, diabetes control, smoking cessation, and lifestyle modification are important. This section briefly reviews these strategies in CKD patients.
Vaccinations
Infection is the second leading cause of death among patients on dialysis. As a result, patients with CKD may benefit from immunization against communicable diseases, including pneumococcal infections and influenza, which are common sources of morbidity and mortality in hospitalized patients and those with chronic illnesses. Vaccination programs have been less successful among CKD patients compared with the general population, both in terms of implementation and response to vaccine. Reasons for poor response include malnutrition, uremia, and the generally immunosuppressed state of patients with CKD.
Variations in vaccination dose and dosing schedule to increase response rates in dialysis patients have been tried with reasonable success, which could be implemented among patients at all stages of CKD. In the case of hepatitis B, KDIGO recommends that patients with a GFR <30 mL/min/1.73 m 2 and risk of CKD progression should be vaccinated. Intradermal hepatitis B vaccination may be able to achieve higher rates of seroconversion and higher peak antibody titers and thus should be considered for patients who do not respond to intramuscular vaccination, especially those in high-risk populations. In general, patients with higher GFR levels are more likely to seroconvert after hepatitis B vaccination ; thus it is clear that early identification of CKD and provision of comprehensive care is invaluable.
Aspirin
The use of low-dose aspirin to prevent cardiovascular events is widespread in the general population; however, results in the literature are inconsistent as to whether aspirin therapy results in a clinically significant effect on either cardiovascular or all-cause mortality in patients with CKD. In addition, aspirin therapy may increase the risk of bleeding. As a result, it remains unclear whether aspirin therapy is beneficial in patients with CKD, and this therapy is currently recommended only for secondary prevention in patients with known coronary artery disease, not as primary prevention in patients with CKD.
Dyslipidemia
Like aspirin, statin use for correcting dyslipidemia and reducing cardiovascular risk has become extremely common in the general population. Studies including the Prospective Pravastatin Pooling (PPP) project, the Deutsche Diabetes Dialyse (4D) study, and A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events (AURORA) have evaluated the use of statins in patients with CKD and found that statins are effective in lowering cholesterol levels; however, these studies did not show convincing reductions in cardiovascular events or mortality. More recently (2011) the Study of Heart and Renal Protection (SHARP) trial evaluated combined statin and ezetimibe use in patients with CKD in the largest, prospective, double-blind, placebo-controlled trial to date, and found a significant reduction in major atherosclerotic events and stroke in the treatment group. However, this trial did exclude patients with a history of cardiovascular events, limiting its applicability to many CKD patients. Although the study demonstrated effectiveness of the lipid-lowering strategy in CKD patients, that effect was proportional to the reduction in cholesterol (as in other populations). In those patients who were on dialysis, the proportional reduction was lower and the benefit smaller. As a result, the most recent KDIGO guidelines recommend initiation of statin use for primary prevention of cardiovascular events only in non–dialysis-dependent CKD patients and also recommend the continuation, but not initiation, of statins for patients with CKD on dialysis or kidney transplant, in those who have not had a previous CVD event. In addition, the guidelines recommend that statin dose should not be titrated up to achieve a target low-density lipoprotein (LDL) due to the lack of benefit with higher doses, and therefore that monitoring follow-up LDL levels is not necessary.
Diabetes Control
Optimal diabetes management should be encouraged and facilitated with referral to a diabetes program if possible. Intensive glucose control in both type 1 and type 2 diabetes may prevent or stabilize the early stages of microvascular complications, including CKD, and the benefits from early intensive glucose control appear to be sustained even years later, in a so-called “legacy effect.” However, despite reductions in progression of albuminuria and microvascular disease, tight glycemic control is not associated with a reduced risk of kidney failure, major cardiovascular events, or death in the CKD population.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have gained recent attention through the EMPA-REG OUTCOME trials, a large, randomized, double-blind, placebo-controlled trial, where empagliflozin was associated reduced cardiovascular events and death in patients with diabetes, and was also associated with slower progression of CKD in diabetic patients. The canagliflozin cardiovascular assessment study (CANVAS) confirmed these results with canagliflozin, another SGLT2 inhibitor. These agents represent a new therapeutic direction for prevention, and possibly treatment, of CKD in diabetes. These agents appear to produce beneficial effects beyond glycemic control to reduce risk of CVD and CKD progression.
Lifestyle Modification and Rehabilitation
Smoking cessation is recommended for reducing cardiovascular and malignancy risk, but also because cigarette smoking is associated with CKD progression. Obesity, poor diet, and sedentary lifestyle contribute to diabetes, hypertension, and vascular disease. Patients with CKD should be encouraged to maintain a healthy weight, and those who are able should be encouraged to increase physical activity because this has been demonstrated to result in improved aerobic capacity, cardiovascular function, and health-related quality of life.
Multidisciplinary clinics therefore offer another opportunity to assist patients with lifestyle interventions through facilitating and encouraging healthy diet, smoking cessation, and individual appropriate exercise interventions.
Preparation for Kidney Replacement Therapy
Individuals with progressive CKD require timely preparation for either kidney replacement therapy (dialysis or transplantation) or conservative care. Creating and implementing these care plans is an iterative process that takes time and requires a multidisciplinary team approach. The different modalities should be seen as complementary, and individuals may transition through several modalities. Home-based therapies that foster independent care are encouraged. The optimal timing of dialysis initiation remains unknown but is usually influenced by a combination of low estimated GFR (eGFR), patient symptoms, and careful clinical evaluation. Close follow-up of patients at the later stages of CKD, with objective assessment of global functioning, permits appropriate timing of dialysis initiation.
Modality Selection
Predialysis counseling programs provided through the CKD clinic may help patients chose a dialysis modality, confront the prospect of dialysis, and prepare themselves for life on dialysis. Education and knowledge influence both readiness to decide and decision making itself. A multidisciplinary team should identify possible barriers to various modalities, including physical, visual, cognitive, psychological, and social problems, and help overcome such barriers where possible by adequate care, education, and psychological counseling. Predialysis nurses have an important role in supporting patients who must make decisions when kidney replacement therapy is needed. Dialysis modalities include hemodialysis, either in-center or at home, peritoneal dialysis (peritoneal dialysis), including continuous ambulatory peritoneal dialysis (CAPD), and automated peritoneal dialysis (APD). The selection of dialysis modality is influenced by a number of factors, including availability and accessibility, patient comorbidities, socioeconomic circumstances, the patient’s living situation, and the method of clinician financial reimbursement.
Suboptimal preparation for kidney replacement therapy can result in a high rate of hospitalizations in patients with advanced CKD, low uptake of home dialysis or preemptive transplantation, urgent hospitalization to initiate dialysis, and decreased likelihood of commencing dialysis with an arteriovenous fistula (AVF). A number of factors may contribute, including fragmented treatment, poorly delivered patient education, healthcare infrastructure, inadequate communication among healthcare providers, and delayed decision making. Both time and healthcare support are necessary for patients to process their dialysis options. In one study, around 25% of patients were undecided about modality choice, despite receiving predialysis education. Stage of behavioral change has been shown to influence patients’ ability to make medical treatment-related decisions and act on the basis of those decisions. As a result, there is a need for structured dialysis decision-making education tools that facilitate patient behavioral change and support the multidisciplinary team in addressing the diverse lifestyle barriers and learning requirements of patients.
The availability of a comprehensive predialysis education program has been shown to facilitate increased uptake of home-based therapies among CKD patients, particularly in centers with established home dialysis programs. Home-based dialysis (home hemodialysis and peritoneal dialysis) has been associated with improved quality of life and cost-effectiveness compared with in-center hemodialysis. Despite this, the overall uptake remains low, with 90% of patients with ESKD in the United States undertaking in-center dialysis, compared with less than 10% on home dialysis. Reasons for this are multifactorial and include patient comorbidities, late referral to a nephrologist, inadequate dialysis modality education, and unfavorable social circumstances. Furthermore, it has been reported that CKD patients who select home dialysis (especially peritoneal dialysis) as their initial modality of choice may still end up initiating dialysis in-center and are more likely to start with a central venous catheter (CVC) as opposed to an AVF. Thus there is a need to develop and test the effectiveness of comprehensive and standardized education programs to address this issue. Through the CKD clinic, there should be ongoing evaluation of patients’ expectations, reinforcement of modality choice, and ongoing education of patients regarding benefits and timing to improve preparedness for home dialysis.
In terms of dialysis therapies, observed survival is generally highest in patients treated with home hemodialysis. There is currently no compelling evidence to show a difference in survival between in-center hemodialysis and peritoneal dialysis. Studies attempting to compare survival outcomes between these two modalities have been mainly observational in nature and yielded variable results due to selection bias, flawed study design, variances in mortality effects with time from initiation of dialysis, differences in patient comorbidities, and other factors. Although several studies have found an early survival benefit associated with peritoneal dialysis, this has been largely attributed to higher baseline residual kidney function and less comorbidity.
Transplantation is the optimal treatment for kidney replacement therapy and is associated with improved cost effectiveness, patient survival, and quality of life. Living versus deceased kidney donation affords an increased survival benefit to both recipient and graft, in addition to facilitating earlier transplantation. At any given time, approximately 50% to 60% of patients receiving dialysis are eligible for transplantation, but estimates are not available for those with earlier stages of CKD. A significant proportion of patients may be ineligible for transplantation, such as those with extensive vascular calcification or severe CVD. Preemptive transplantation, that is, before the need for dialysis, is only generally an option for patients with an available living donor. In the United States approximately 30% of transplants are from living donors, with one-fifth of these being unrelated to the recipient.
It is generally preferred that patients commence dialysis either on peritoneal dialysis, or hemodialysis using an AVF rather than a CVC. This is especially relevant in today’s reimbursement environment, where patients with optimal starts can lead to healthcare savings of tens of thousands of dollars per year. For this reason, modality selection should be explored with the patient in a timely manner, with early identification of contraindications to a particular modality. A perspective on the relative amount of time required to prepare for each of the options, including transplantation, should be provided. The option of conservative care should also be discussed with patients, particularly those who wish to focus on quality of life rather than extending life expectancy.
Vascular Access Creation
For most patients considering hemodialysis, the preferred vascular access option is an AVF, due to longer patency, lower infectious complications, improved quality of life, improved cost effectiveness, and lower all-cause mortality compared with AVGs and CVCs. Timely referral is recommended to ensure sufficient time for creation and maturation, particularly as more than one procedure may be required to establish functionality. If creation of an AVF is delayed, it may not mature in time for dialysis initiation and subsequently a CVC may be required. The patient should be reassured that the presence of a functioning AVF does not signify that dialysis must be initiated; rather, it reduces the chance that additional procedures, such as placement of a temporary dialysis catheter, might be needed at the actual time of dialysis initiation. Creating an AVF too early has been associated with a small increase in complications and potential utilization of the limited lifespan before hemodialysis is needed. The process for access creation begins with timely referral to the CKD clinic and patient education, followed by appropriate investigations and interventions in preparation for the desired access, including venous mapping and surgical referral where appropriate. After access creation, the multidisciplinary team should coordinate surveillance of the dialysis access.
Although traditionally a fistula-first approach has been adopted, recent studies suggest that not all patients may benefit from AVF compared with AVGs and CVCs. When considering options for vascular access, clinicians should consider the patient’s risk of death before reaching ESKD, their anticipated life expectancy after initiating dialysis, expected duration of therapy, and risk of complications with each type of access. Elderly patients are more likely to have limited life expectancy and lower likelihood of AVF maturation, necessitating multiple procedures, which may mitigate the relative benefits of AVFs over AVGs and CVCs. Furthermore, recent data suggest that for patients with an estimated life expectancy of 2 years, AVFs are no more cost effective than AVGs, and neither form of vascular access is more cost effective than CVCs for patients with a life expectancy of 6 months. Therefore AVG placement and, in some cases, continued CVC use after dialysis initiation may be reasonable vascular access options for older adults with reduced life expectancy. For patients requiring a temporary period of hemodialysis, either as a bridge to living donor kidney transplantation or while awaiting transition to peritoneal dialysis, a CVC may also be acceptable vascular access option due to the anticipated short duration of therapy.
Planning for vascular access creation should begin at least 6 months in advance of the anticipated need to start. According to most published guidelines, vascular access should be created when the eGFR is approximately 15 to 20 mL/min/1.73 m 2 in those who are anticipated to progress and who do not have a reasonable chance for a preemptive transplant. The timing of AVF creation in any individual patient should also take into account the rate of CKD progression. Reasons for lack of permanent access at the start of dialysis may include patient factors such as denial of inevitable dialysis, being too unwell to undergo permanent access procedures, failure of AVF maturation, acute deterioration of kidney function in a previously stable patient, or late decision to undertake chronic dialysis. However, this may also reflect the multidisciplinary team’s inability to predict the start of dialysis, lack of resources, or poor planning. Late recognition of CKD and late referral to nephrology contribute to the problem. In consultation with the patients and the clinic team, optimal timing around education, decision making, and access creation should be undertaken.
Timely Initiation
When to initiate dialysis is a complex decision that involves the consideration of many variables. Although there are some easily identified absolute indications for initiation, debate exists with respect to “timely” dialysis when these indicators are not so apparent. Indeed, since the 1970s some have advocated for initiation of dialysis before clinically significant markers of uremia appear. These studies suggested a positive association between residual kidney function at dialysis initiation and clinical outcomes. Unfortunately, lead-time bias, patient selection, or referral bias may favor outcomes in the population of patients starting “timely” dialysis.
According to USRDS data, there has been a trend toward early dialysis initiation in the United States since 1996, with the fraction of patients transitioning to dialysis with eGFR of 10 to 14 mL/min/m 2 rising from 20% to 52% and from 4% to 17% for patients with eGFR of ≥15 mL/min/m 2 . The appropriate timing for initiating hemodialysis in patients with advanced CKD in terms of optimal patient outcomes and cost effectiveness remains unclear. Recent randomized controlled trial data, together with large registry-based studies corrected for confounding, show no survival advantage to early-start dialysis. The Initiating Dialysis Early and Late (IDEAL) study examined whether early initiation of dialysis influenced survival among 828 patients with progressive CKD. They found no difference in survival or clinical outcomes (cardiovascular events, infectious events, and complications of dialysis) between early (MDRD eGFR 9 mL/min/1.73 m 2 versus late eGFR 7.2 mL/min/1.73 m 2 ) start dialysis. Furthermore, several recent studies have reported reduced comorbidity-adjusted survival rates for early-start hemodialysis, raising the possibility that dialysis may be incurring more harm than benefit. A further observational study found that planned early initiation of dialysis has also been shown to be more costly and was not associated with an improvement in quality of life. The failure to find benefit of early hemodialysis by the IDEAL study and the potential harm of early initiation of hemodialysis reported in recent studies raises questions relating to the trend to early start of hemodialysis.
Given the risks and benefits of kidney replacement therapy, the decision to start dialysis should be individualized and based on symptoms rather than relying solely on a laboratory estimate of kidney function, which is subject to imprecision unless this measure is accompanied by definitive ESKD-related indications for dialysis. The 2012 KDIGO guidelines recommend considering initiation of dialysis for the treatment of progressive CKD if one or more of the following are present: symptoms or signs attributable to kidney failure (serositis, acid base or electrolyte abnormalities, pruritus); inability to control volume status or blood pressure; a progressive deterioration in nutritional status refractory to dietary intervention; or cognitive impairment. Invariably, most patients will experience these with eGFR 5 to 10 mL/min/1.73 m 2 . Earlier initiation may be required in patients with certain complications of CKD.
The decision should be individualized with a careful assessment of the benefits and risks each patient may incur with each therapy option. Overall, the key factor is to avoid commencing dialysis when the patient is so ill that education opportunities and the chances for maintaining independence are missed.
Independent Therapies
Home Hemodialysis
Time taken for home hemodialysis training can vary widely according to patient characteristics, vascular access, machine selection, and delivery method of the training program. CKD patients electing for home hemodialysis normally require initial hemodialysis sessions in-center to assess for early complications, such as a dialyzer reaction, before transitioning to home hemodialysis training. The role of the CKD clinic is to ensure that patients are referred in a timely manner for assessment for home hemodialysis and vascular access creation. Coordination between the clinic and dialysis unit is vital to ensure smooth transition for the patient through these various initiation steps.
Peritoneal Dialysis
Patients should be oriented to the peritoneal dialysis unit and staff. The role of the CKD clinic in organizing peritoneal dialysis catheter placement will vary according to the center. However, the timing, placement, and preliminary education should be done in concert with the peritoneal dialysis team. As in hemodialysis, specific orders and transfer summaries should be sent to the peritoneal dialysis unit and the training/initiating schedule coordinated with appropriate team members, family members, and other health professionals.
In-Center Hemodialysis
The goal is a smooth transition to hemodialysis care, and the CKD clinic staff should ensure the appropriate commencement of dialysis with a functional vascular access. Patients should be oriented to the hemodialysis unit in advance and schedules coordinated with appropriate team members in the hemodialysis unit, family members, and other medical professionals. The CKD clinic should send initial dialysis orders and transfer summaries to the hemodialysis unit.
Transplant
As part of the educational process early in the course of CKD, the concepts of transplantation, including living donation, should be explored with patients and families. Conversations with individuals about RRT and transplantation are individualized, but given that most centers require a 3 to 12 month period for living transplantation processes, education should likely commence in potentially living donor–eligible patients, when GFR trajectory is steep, or at GFR values around 25 mL/min with evidence of progression over time. The 2012 KDIGO guidelines suggest that preemptive transplantation should be considered when the GFR is less than 20 mL/min/1.73 m 2 along with evidence of irreversible progression of their CKD over the previous 6 to 12 months. However, education and discussions regarding transplantation should ideally take place earlier in the patients’ CKD course, given potential complex barriers to transplantation. The CKD clinic, working closely with the transplant assessment team, can help determine eligibility for a kidney transplant and assist with the identification of living donors, which may facilitate preemptive transplantation.
Maximum Conservative Management
Maximum conservative management (MCM) has been proposed as an alternative care pathway for some patients with progressive CKD for whom dialysis is unlikely to confer improved survival or quality of life. Elderly patients with advanced CKD often have a higher burden of comorbidity and frailty that may influence their treatment choices and outcomes. Furthermore, advancing age, increased comorbidities, and higher level of dependency at initiation of dialysis have been associated with adverse survival. Clinical tools such as the Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS) have been shown to be independent predictors of mortality in patients with CKD and may serve as useful adjuncts to identify patients appropriate for a conservative pathway.
Observational data have shown that dialysis may extend survival of patients with ESKD and comorbidities by up to 2 years compared with MCM; however, patients choosing MCM may achieve a similar number of hospital-free days and are more likely to die at home or in a hospice. When discussing treatment options with patients, establishing patient-centered goals of care are important to ascertain what is important to the patient. Often patients are willing to accept shorter life expectancy in return for improved quality of life.
Patients considering conservative management often have many anxieties related to life expectancy, anticipated symptoms, and family expectations. If appropriate, consultation with psychiatric practitioner may be warranted to ensure the patient has the capacity to make a decision regarding their care. A conservative care pathway for patients choosing not to undergo dialysis should focus on symptom control, management of anemia and other complications, social support, and palliative care. Patients may require varying levels of specialist palliative care support, with the option to intensify services in the event of clinical deterioration.
Once the decision to decline kidney replacement therapy is made, end-of-life wishes should be formalized, in particular resuscitation status, with appropriate consent and documentation. The patient should have referrals for home care and for palliative care when appropriate.
Advanced Care Planning
Advance care planning (ACP) for patients with CKD helps identify life goals and can be a useful guide for discussions among patients, their families, and their healthcare providers. ACP should be a dynamic process with the ability to adapt to the changing healthcare needs of the patient with CKD and allow for intervention as necessary. Early initiation of ACP provides time for thoughtful and deliberate consideration of the options available for kidney replacement therapy, their potential effect on a patient’s day-to-day life, and time to contemplate and discuss the choices and preferences that best reflect a patient’s values and life goals. The results of such discussions are typically recorded as an advance care directive.
Patients often enter dialysis programs unaware that ESKD confers such a poor prognosis, with patients considerably overestimating even their 2-year survival rates. The CKD clinic should facilitate timely, consistent, and detailed discussions regarding ACP for all CKD patients as part of a patient-centered approach to nephrology care, including guidance on relevant and timely prognostic data.
Planning ahead for care is preparatory to making decisions about kidney replacement therapy and can facilitate a smooth transition to dialysis as well as optimize the chance that dialysis is not initiated solely because symptoms prompt an urgent decision. To emphasize the role of ACP and prognosis sharing with CKD and ESKD patients and their families, the Renal Physicians Association issued guidelines in 2010. They encourage nephrology practitioners to address ACP within the first 90 days of providing care and to review these care plans at least annually or more frequently if a change in patient status arises.
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