The Interdisciplinary Clinic for Chronic Kidney Disease

C H A P T E R

56 The Interdisciplinary Clinic for Chronic Kidney Disease Roberto Pisonia, Carolyn A. Bauerb, Jerry Yeec, Ruth C. Campbella a

Medical University of South Carolina, Division of Nephrology, Charleston, SC, United States; bDivision of Nephrology, Bronx, NY, United States; cHenry Ford Hospital, Division of Nephrology and Hypertension, Detroit, MI, United States

Abstract The chronic kidney disease (CKD) clinic has emerged as an interdisciplinary care (IDC) model that encompasses patient education, medical management of CKD complications and CKD risk factors, and quality improvement. The CKD clinic team may include physicians, advanced practice providers, nurses, dieticians, pharmacists, and social workers. Team structure and clinic goals should be tailored to local practice needs. Common goals include CKD education, renal replacement therapy (RRT) planning, and treatment of complications of CKD based on national/international guidelines. Data suggest that CKD clinics slow CKD progression, improve CKD and RRT education, and lead to greater rates of home dialysis and permanent access placement. Financing of CKD clinics remains problematic as many insurers do not pay for IDC services. The long-term viability of the CKD clinic model may ultimately depend on demonstrating effectiveness and a reduction in overall patient care costs.

BACKGROUND Chronic kidney disease (CKD) is a global health problem.1 Approximately 15% of the US and Canadian populations have CKD.2,3 The prevalence of CKD has been rising due to increased prevalence of hypertension, obesity, and diabetes mellitus.4 This is mainly driven by the elderly with significant comorbidities.5 Individuals with CKD have high morbidity and mortality and increased health care utilization.6 High poverty rates and low health literacy contribute to the poor outcomes of the CKD population.7e10 As a result, CKD presents an increasing substantial burden to health services. In 2013, the cost of end-stage renal disease (ESRD) care was $32.8 billion, accounting for more than 7% of US Medicare

Chronic Renal Disease, Second Edition https://doi.org/10.1016/B978-0-12-815876-0.00056-5

spending, and was estimated to be over $1 trillion worldwide.11,12 The care of individuals with CKD is complex and requires many interactions by nephrologists with patients, their family, other providers, and inpatient services. This occurs despite an increasing physician workload, the pressure to improve outcomes and limit costs, and a shrinking workforce with fewer US nephrology fellowship applicants.13 These issues have led to a critical evaluation of how CKD care is delivered and what outcomes should be targeted in health care systems. Which individuals would benefit most from intensive management from an interdisciplinary care (IDC) clinic? What should be the CKD goals of care? Slowing CKD progression, decreasing cardiovascular morbidity and mortality, improving perception of quality of life, management of CKD complications, preparation for ESRD care, or all of these? How will this care be delivered in the most cost-effective way and by whom? The IDC clinic has emerged as an alternative to the traditional model of care for individuals with CKD as a way to address many of these pressing issues. In particular, such a clinic may address patient education, quality improvement, management of CKD risk factors and complications, and timely patient preparation for renal replacement therapy (RRT).

DEFINITION OF THE CKD IDC CLINIC There is no single definition of IDC for CKD. IDC requires that health care providers of different disciplines, including physicians, advanced practice providers

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FIGURE 56.1 Interdisciplinary chronic kidney disease clinical aspects of care. Quality improvement, interdisciplinary care, risk factor management, and education of CKD patients require balanced integration.

(APPs: nurse practitioners or physician assistants), nurse specialists, pharmacists, dieticians, and social workers work collaboratively, cohesively, and synergistically and communicate together as a team to provide care for patients. The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines specify that interdisciplinary nephrology care should encompass dietary counseling, education regarding different RRT modalities, transplantation options, vascular access surgery, and ethical, psychological, and social care (Figure 56.1).14 This approach to CKD care often entails collaboration of health care providers to implement evidence-based, guideline-driven protocols in CKD care within the confines of the patient’s (or the patient’s health care proxy’s) expressed wishes. Financial restraints of the provider(s) and/or patient(s) may limit the ability to offer all of these services to patients. Additionally, not all insurance providers will provide reimbursement for some or all of the disciplines included in IDC-based CKD care in the US. Thus, nephrology practices should identify which aspects of patient care (such as education regarding management of ESRD) or clinical outcomes (such as arteriovenous fistula [AVF] placement) are needed urgently by their patient population and use the available components of IDC to construct an intervention. To do this, the IDC CKD team needs to monitor changes in outcomes for quality improvement processes to maximize patients’ benefits. Based on local needs and resources, IDC clinics often have different staffing models and configurations. Many include APPs who do a large part of the patient education and coordination and follow protocols to achieve guideline benchmarks with the collaboration of a

nephrologist. Of APPs associated with nephrology practices in the US, 83% report working in CKD or anemia management clinics.15 IDC CKD clinic teams may include members similar to the make-up of dialysis units, with dieticians, nurses, and social workers to provide resources and patient support. When patients are deemed likely to progress to ESRD, coordination with transplant surgeons, vascular surgeons, and interventional radiologists is important to ensure timely access placement and a smooth transition to dialytic management of ESRD. Given the increasingly elderly CKD population, geriatricians and palliative care physicians can aid with prognostication, advanced care planning, and symptom management. Although there is always a focus on patient education and management of comorbidities and complications, how an IDC clinic may achieve these goals may differ. The degree of renal dysfunction required to participate in an IDC clinic may vary. Some IDC clinics standardize the number of visits that a patient will receive from each provider based on CKD stage, others base interventions on individual risk factors and patient preferences. A common IDC CKD clinic structure has the nephrology practice provide interdisciplinary services. Some IDC clinics alternate patients between IDC visits and general nephrology visits. Other IDC clinics may incorporate a nephrology evaluation as part of their services and take referrals directly from primary care physicians (PCPs) instead of accepting patients only from a participating nephrologist.16 This illustrates the importance of clearly defining the role of the IDC team in relation to both nephrology and primary care. Different types of nephrology practices and multiple health care delivery models lead to vast differences in IDC in CKD. In the US, these centers range from private practices that include an APP to large integrated managed care consortiums, such as Kaiser Permanente, and to governmental health care agencies, like the Veterans Affairs (VA) System. Although IDC clinics for CKD are prevalent in Canada and Taiwan, the number of patients who receive IDC for CKD in the US is difficult to measure. The US Renal Data System (USRDS) states that of approximately 120,000 patients who progressed to ESRD in 2015, only 8% had dietary care.2 In addition to IDC clinics started by nephrologists and hospital systems, dialysis providers and start-up companies are contracting with health systems, health plans, nephrologists, and governmental agencies to help manage pre-ESRD patients. These companies employ proprietary risk stratification algorithms, management protocols, technology platforms,

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and telephone management to decrease hospitalization and defray health care costs. The VA has started using telehealth to expand their CKD outreach.17

TARGET POPULATION OF THE CKD IDC CLINIC Individuals at the highest risk of progression to ESRD and those who have CKD complications that need specialized management (e.g. anemia, mineral and bone disease, metabolic acidosis, hyperkalemia) are logical populations to target for IDC. The 2012 KDIGO CKD guidelines suggest that patients with progressive CKD be treated in an IDC setting, but no glomerular filtration rate (GFR) cutoff is specified.14 An accurate identification of this population is necessary. Models are available to estimate the risk of progression to ESRD.18 An internationally validated risk prediction model of ESRD, called Kidney Failure Risk Equation (KFRE), is available as a web-based calculator and smartphone app.19e21 Its four-variable version incorporates an individual’s age, sex, estimated GFR (eGFR), and urine albumin:creatinine ratio (UACR), whereas the eight-variable equation additionally incorporates serum calcium (S[Ca]), phosphorus, bicarbonate, and albumin (S[Alb]) levels and is incrementally more accurate than the four-variable version. In Ontario, Canada, KFRE is used in the clinical setting to triage nephrology referrals and determine the need of IDC and the time for AVF creation.22,23 The rate of GFR change over time, the degree of proteinuria, and advanced age are key predictors of fast progression of CKD and may help identify the potential target population for IDC. The 2012 KDIGO guidelines define rapid CKD progression as loss of eGFR >5 mL/min/ 1.73 m2 per year.14 Of more than 36,000 adults with eGFR 30e59 mL/min/1.73 m2 within a large integrated health care delivery system in northern California, 23% of individuals with diabetes and 15% of those without were recently identified as fast CKD progressors over a 2-year period.24 Within this population, proteinuria, age >80 years, elevated systolic blood pressure, and heart failure were independent predictors of fast CKD progression regardless of the presence of diabetes. Individuals with these risk factors may warrant more aggressive modification of risk factors and education for RRT. The 2012 KDIGO guidelines recommend referral for access planning when the anticipated risk of starting RRT is >10% within 1 year.14 Proteinuria is the strongest modifiable predictor of progression to ESRD in both diabetic and nondiabetic CKD patients.24,25 Proteinuria is also an independent predictor of cardiovascular disease (CVD) and death.26e29 Both the relative reduction in proteinuria

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and the level of achieved proteinuria after initiation of renoprotective treatment are predictors of the subsequent rate of GFR decline over time.30e32 The degree/ category of albuminuria is now included in the KDIGO classification of CKD. The 2012 KDIGO guidelines recommend individuals with UACR >300 mg/g or protein:creatinine ratio >500 mg/g be referred to a nephrologist.14 A standardized, multimodal intervention targeting urinary protein excretion has been shown to be effective to slow CKD progression in subjects with nondiabetic CKD at high risk of progression to ESRD.33 Although elderly patients with CKD are more likely to die than progress to ESRD, they represent the fastest growing group to develop ESRD in several countries. Approximately 25% of incident ESRD individuals were over 75 years of age in 2010.34 Elderly individuals benefit from starting dialysis with a permanent access.35 However, there is small survival benefit, and quality of life may actually decrease from starting dialysis in individuals older than age 80 years and with a high burden of comorbidities and/or living in a nursing facility.36,37 Thus, a thoughtful discussion of RRT modalities, including the option of supportive, nondialytic care, is extremely important. Screening for sensory deficits (e.g. vision, hearing, and reaction), anxiety, depression, and cognitive impairment and involving individuals’ family/caregivers is important in this population as these conditions may affect individuals’ ability to communicate effectively, retain the information provided, and adhere to treatment recommendations. Individuals with advanced CKD are at high risk of progression to ESRD and have higher rates of CKD complications such as anemia, bone and mineral disease, and CVD that need specialized management. Treating these complications is associated with decreased morbidity and improved quality of life.14

GOALS OF THE CKD IDC CLINIC The ultimate goals of a CKD IDC clinic are to improve morbidity and mortality of patients with kidney disease. The IDC team has the challenging task of using evidence-based guidelines and information from recent studies to decrease the high risk of cardiovascular events and death in the CKD population, decrease the rate of progression to ESRD, treat known complications of CKD, and prepare patients at the highest risk of ESRD for dialysis and when possible renal transplantation (Table 56.1). All of these interventions must be done with the patient’s, and often families’, understanding and must be consistent with the patient’s wishes and values. To accomplish these goals effectively, members of the IDC team must focus on patient education and

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TABLE 56.1 Principal Goals of an Interdisciplinary Care Chronic Kidney Disease Clinic Goal

Comment

Coordination of CKD care

Collaborative engagement/partnership with primary care physicians and specialists

Determination of CKD progression risk and rate

Estimation of GFR decline; proteinuria determination(s)

Mitigation of CKD complications and cardiovascular risk

Blood pressure; mineral and bone disorders; metabolic acidosis; anemia; lipids

CKD education

Multiple component/personnel utilization; MIPPA

Transition to RRT for ESRD

Discussion for prognosis; RRT modality/option planning; transplant and vascular access evaluations

Abbreviations: CKD, chronic kidney disease; ESRD, end-stage renal disease; GFR, glomerular filtration rate; MIPPA, Medicare Improvement of Patients and Providers Act; RRT, renal replacement therapy.

protocol-driven care based on national and international guidelines, such as the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) and the KDIGO guidelines.14,38 Treatment protocols should also include findings of large randomized controlled trials (RCTs) that have not yet been integrated into published guidelines to provide the best practices for this high-risk population. To slow progression of kidney disease and improve cardiovascular factors, control of underlying causes of CKD such as diabetes and hypertension needs to be addressed. Complications of CKD including metabolic bone derangements, anemia, electrolyte disturbances, and fluid imbalance must be diagnosed and treated. Given the immunosuppressive nature of advancing CKD and the possible need for kidney transplantation, vaccines to prevent influenza viruses, streptococcal pneumonia (including both the pneumococcal polysaccharide and the 13-valent conjugate pneumococcal vaccinations), herpes zoster, and hepatitis B should be administered in the recommended settings.39e42

Patient Education Despite the awareness of the importance of patient education in improving health outcomes in CKD, almost 80% of newly initiated dialysis patients started hemodialysis (HD) using a catheter.34,43e47 CKD IDC allows multiple disciplines to facilitate and optimize patient education and has been shown to lead to increased selection of home dialysis modalities, improved permanent

access placement, and decreased mortality.43,45,46 Educational interventions offered for only one day have significant benefits.43,48 In 2010, under the Medicare Improvement of Patients and Providers Act (MIPPA), Medicare started to reimburse for CKD education provided by a physician, APP, or clinical nurse specialist for Medicare recipients with CKD stage 4 or 5. Up to six sessions of education are reimbursed and can be delivered either as a class or on an individual basis in the outpatient setting.49 The classes must cover management of comorbidities, prevention of uremic complications, and options for RRT (including HD, peritoneal dialysis [PD], home therapies, access options, and transplantation). A recent survey of US nephrology practices found that 60% offered a CKD education class and that an APP delivered 87% of the classes.50 The educational materials for these classes were either developed locally, originated from the NKF CKD education series “Your Treatment, Your Choice,” or represented a hybrid of local and NKF materials. An important consideration in CKD education programs is the impact of health literacy. Low health literacy, or how well a patient understands and assimilates information to make decisions regarding his or her health, is common among CKD patients and is associated with increased mortality on dialysis and with lower referral rates for transplantation.10,51,52 Cognitive impairment is also common in individuals with CKD. A recent study found that 19% of patients with eGFR <20 mL/min/1.73 m2 had cognitive impairment, which was associated with an increased rate of using a dialysis catheter for dialysis initiation and a lower rate of PD as a first modality.53 These data support the need to assess patients’ understanding of the education that they have been given. An advantage of the NKF “Your Treatment, Your Choice” program is that it provides outcome assessment tools to help determine whether class participants found the information understandable and helpful. IDC may allow for more time and resources to identify barriers to learning.

Cardiovascular Risk Management Patients with CKD have an extremely high burden of CVD. In addition to delaying and preparing for ESRD, the goal of CKD IDC is to improve patients’ cardiovascular health and decrease the incidence of heart attacks, strokes, and congestive heart failure (CHF). The higher risk of death compared with the progression to ESRD becomes even more pronounced in the expanding elderly stage 3 and 4 CKD population, mostly due to CVD.2,6,54 Traditional risk factors for CVD such as increasing age, hypertension, diabetes, and hyperlipidemia are highly prevalent in the CKD population. In addition, other

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nontraditional risk factors for CVD have been identified in patients with CKD, including anemia, fluid overload, vascular calcifications, inflammation, malnutrition, and increased oxidative stress.55e58 Albuminuria, even when not associated with diabetes, is associated with higher incidence of cardiovascular events.59,60 Patients frequently have CHF and CKD that need to be comanaged. Treatment with diuretics and angiotensinconverting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are mainstays of therapy in both conditions. Having CHF and CKD increases a patient’s mortality risk and may require earlier dialysis initiation.61,62 CKD IDC should focus on interventions that modify CVD risk factors. Guideline-driven care for CKD can improve cardiovascular risk, and CKD IDC has been shown to improve mortality both before and after starting dialysis.44,63e66 Interventions to decrease cardiovascular events in CKD have had varied results. Smoking is associated with CVD, and observational data suggest that smoking may influence the progression of renal disease. Therefore, smoking cessation should be addressed with each patient.67,68 Conversely, it is unclear if aspirin therapy confers cardiovascular protection in this high-risk population. A post hoc analysis of the large RCT, the Hypertension Optimal Treatment (HOT) study, demonstrated that aspirin decreased mortality and major cardiac events in patients with diastolic hypertension and eGFR <45 mL/min/1.73 m2.69 However, a recent meta-analysis including HOT and two other randomized trials did not show any benefit of aspirin in the primary prevention of CVD in the CKD population, and its use was associated with increased bleeding risk.70 In addition, a meta-analysis evaluating the use of aspirin for secondary prevention in CKD patients with acute coronary syndromes undergoing revascularization procedures revealed only a nonsignificant improvement in cardiovascular outcomes, but an increased bleeding risk.71 Despite the recommendation of aspirin therapy by the KDIGO 2012 guidelines, more data are likely required to determine the role of aspirin in this population.14 Lifestyle modification and lipid lowering can also benefit patients with CKD. Aggressive lipid lowering therapy in pre-ESRD CKD patients has been shown to improve cardiovascular outcomes in RCTs.72,73 International treatment guidelines now recommend that all pre-ESRD CKD patients over 50 years old be started on a statin, as well as those patients younger than age 50 who are at high risk for coronary artery disease or stroke.74 In addition to medications, CKD patients should be educated about healthy lifestyle modifications. Dieticians and other members of the IDC team encourage adherence with individualized diets, weight loss when necessary, and appropriate exercise programs.

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Hypertension Control Control of hypertension by CKD IDCs is essential given that it both slows progression of renal disease and decreases the incidence of cardiovascular events.75e79 New guidelines, including the 2017 American College of Cardiology/American Heart Association and the 2018 European Society of Cardiology/ European Society of Hypertension, have altered the blood pressure target to initiate and treat hypertension based on cardiovascular risk.80,81 These guidelines suggest targets of <130/80 mm Hg in high-risk individuals, which include CKD patients, based on newer studies especially the large randomized Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT excluded patients with diabetes, but 28% of more than 9000 participants had CKD with eGFRs of 20e59 mL/min/ 1.73 m2.82 These newer guidelines are more consistent with the 2012 KDIGO blood pressure guidelines for patients with CKD, which recommended a blood pressure target <130/80 mm Hg for those patients with albuminuria based on renal outcome trials.83e85 Points of controversy in the guidelines include BP targets in the elderly, those without albuminuria, and those with wide pulse pressures. Controlling BP in CKD patients takes many visits and interventions, including low salt diet, home BP monitoring, and adherence to medication. A patientfocused, interdisciplinary team providing patient education is recommended to improve hypertension control. CKD IDCs have been shown to improve hypertension control.86 Management of BP in CKD is particularly difficult because hypertension often worsens as CKD progresses, requires multiple drug combinations, and may be complicated by fluid overload, acute kidney injury, and hyperkalemia. ACEIs or ARBs are used as first-line medications in CKD and are most beneficial in the setting of proteinuria, which is a risk factor both for the development of CVD and advancing CKD.14 Second-line medications include calcium channel blockers or diuretics followed by beta blockade.14

Management of CKD Complications The CKD IDC team must address complications that arise as CKD progresses. Complications include anemia, metabolic derangements, and metabolic bone disease. Individual dietary counseling is an important part of CKD IDC to decrease complications and engage the patients. Nutritional counseling is paramount as CKD patients are often asked to follow multiple diets including low sugar, low protein, low salt, low potassium, low phosphorus, and fluid restriction, while avoiding malnutrition. CKD clinics educate patients to avoid nephrotoxins, particularly nonsteroidal

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antiinflammatory drugs, and ensure that all medications are appropriately dosed based on a patient’s eGFR. Anemia of CKD As CKD advances, many patients develop anemia of CKD due to ineffective iron use, inflammation, and decreased production of erythropoietin.87 Previously, CKD clinics were often centered on administration of erythropoiesis-stimulating agents (ESAs) for treatment of anemia. However, the use and insurance coverage of these drugs have greatly decreased because the Trial to Reduce Cardiovascular Events with Aranesp Therapy, the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta trial, and the Correction of Hemoglobin and Outcomes in Renal Insufficiency trial did not demonstrate benefits of hemoglobin normalization and demonstrated potential harm.88e90 The Food and Drug Administration (FDA) issued a “black box” warning concerning thrombosis and cancer growth associated with these drugs and required that providers distribute a medication guide (risk evaluation and mitigation strategies) to every patient receiving a new prescription.91 Presently, treatment of anemia with ESAs should be individualized to limit blood transfusions. When CKD programs initiate ESAs, they need to carefully monitor patients monthly to ensure their hemoglobin levels do not rise too rapidly or exceed 11 g/ dL. All anemic patients must be screened for iron deficiency, which should be treated with intravenous or oral iron compounds. Supplementing iron may also decrease the amount of ESA necessary.92 In addition, appropriate evaluations for occult blood loss must be performed before ESA administration. Metabolic Bone Disease CKD is often complicated by metabolic bone disease. CKD patients may have deranged circulating calcium levels, elevated circulating phosphate and intact parathyroid hormone levels, and vitamin D deficiency. The KDIGO working group recently published updated mineral and bone disorder guidelines in 2017, which stated that activated vitamin D analogs, such as calcitriol, are no longer routinely recommended to treat hyperparathyroidism but may be considered in severe and progressive cases.93 Activated vitamin D therapy was associated with hypercalcemia and did not improve cardiovascular outcomes.94,95 Dieticians and clinicians should encourage low phosphorus diets, adequate 25hydroxyvitamin D repletion, and avoidance of high doses of calcium-based phosphate binders. Hyperkalemia and Acidosis Hyperkalemia and acidosis are complications of CKD that need to be evaluated and treated. Improving acidosis has been shown to decrease progression to

ESRD, mitigate bone buffering, and improve nutritional status and lean body mass.96e98 Hyperkalemia may occur as CKD progresses, which requires dietary management and can hasten the need for RRT. In addition, hyperkalemia limits the use of ACEIs or ARBs. Potassium-binding resins (patiromer and sodium zirconium cyclosilicate) were recently approved by the US FDA and can be used in the setting of chronic ACEI and ARB use.99e101

Management of Underlying Disorders CKD clinic staff must coordinate with primary care providers to ensure that the underlying causes of CKD, such as diabetes and hypertension, are addressed. Diabetes, which is a risk factor for both CVD and CKD, must be controlled by diet and usually by medications. Coordination with the IDC team including the dietician, PCP, and nephrologist is important to control diabetes and prevent hypoglycemia. Comanagement with PCPs and cardiology is also necessary when treating both CKD and CHF, as many therapies impact both disorders. Effective communication with PCPs and other involved physicians is essential to ensure that all providers recognize their specific responsibilities when treating these diseases.

Slowing CKD Progression The IDC team should address interventions to slow the decline of kidney function. Unfortunately, few interventions delay progression to ESRD. Control of hypertension, especially with ACEIs or ARBs in diabetic and nondiabetic patients with proteinuria, retards progression of CKD and decreases the incidence of cardiovascular events.75,76,78,79,102e104 Dietary sodium restriction and diuretic therapy can further increase the efficacy of hypertension and proteinuria reduction by ACEIs or ARBs.105,106 Other interventions that may slow progression of kidney disease include treatment of metabolic acidosis, avoiding nephrotoxins (e.g. nonsteroidal antiinflammatory drugs and exposure to contrast agents) and volume depletion, quitting smoking, and effective education.96,107,108 Dieticians and pharmacists in an IDC clinic may work in concert with nephrologists to ensure patient adherence to diet and medications and to determine medications that should be discontinued or whose dose/frequency should be adjusted according to the level of kidney function. A randomized study of individuals with advanced CKD showed that a single educational session with the provision of a printed summary booklet and supportive telephone calls delayed initiation of RRT by approximately 3 months.43

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GOALS OF THE CKD IDC CLINIC

Transitioning from CKD to ESRD IDC should safely and effectively transition individuals with advanced CKD to ESRD with the goal to lower the high morbidity and mortality associated with starting dialysis.34,109 Ultimately, this should result in reduced costs. The pathways for transitions from CKD to RRT should be well defined, along with the role of the various IDC team members involved. The IDC team should provide patient-centered action plans for initiating dialysis, coordinate listing for kidney transplantation, and define goals of care for individuals who may not desire or benefit from these modalities. Education, in individual and/or group sessions, regarding RRTs is fundamental to this process. Patients and their relatives need to understand the different RRT options (PD, in-center or home HD, and transplantation) to facilitate informed decision-making that best accommodates their desires and circumstances. A discussion of each patient’s prognosis and the risks and benefits of each RRT modality should be provided to each individual. The modality of RRT should be established at least 6 months to 1 year before the development of ESRD to allow for timely AVF placement in appropriate patients and to perform the work-up required before transplantation. Individuals who are independent, enjoy travel, are working, and have adequate supply space may opt for PD or home HD. Preparation for dialysis should occur simultaneously with evaluation for transplantation. Individuals must prepare for RRT before the onset of uremia. Patients should be educated to avoid venipuncture, intravenous lines, and BP measurements in the nondominant arm to protect the veins for the potential creation of an AVF and after this is created. Hemodialysis Data from the Dialysis Outcomes and Practice Patterns Study show consistent higher mortality rate in the first 120 days after starting HD. However, this mortality rate is significantly higher in the US compared with other countries.34,109 Risk factors associated with early mortality in HD are older age, hypoalbuminemia, heart failure, use of HD catheter, and lack of predialysis care.110,111 Individuals beginning HD using a catheter have significantly increased mortality and morbidity compared with those who begin HD using an AVF.112,113 Pre-ESRD nephrology care and presence of permanent AV access provided most of the 1-year survival advantage shown in patients who started dialysis while receiving care through the Military Health System (MHS) compared with those who initiated dialysis outside the MHS.114 Pre-ESRD nephrology care for more than 12 months had a comparable survival impact to that of a functioning AVF in this population. Current guidelines recommend consideration of AVF creation

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when the risk of ESRD is estimated to be greater than 10% within 1 year.14 Collaborative partnership with a surgeon with high-expertise in AVF and AV graft construction ensures consistent establishment of wellfunctioning permanent HD accesses in suitable candidates. IDC teams should aim to facilitate the initiation of dialysis in the outpatient setting in appropriate individuals, therefore limiting the need of hospitalization and related high costs. IDC dieticians should work with individuals to prevent, diagnose, and treat malnutrition. Individuals with CHF should be closely monitored and treated for volume overload. Peritoneal Dialysis Individuals interested in PD should meet with a PD nurse to receive further education before deciding which RRT modality to pursue. The IDC team should determine whether the patient’s living environment has adequate space to perform the mandatory sterile procedures and store supplies. Individuals should also be closely monitored for symptoms, signs, and laboratory studies suggestive of uremia to coordinate the timing of PD catheter placement with an experienced surgeon. Individuals should then be smoothly transitioned into a PD unit to initiate PD training following catheter insertion. Family members should be encouraged to learn about PD and assist the patient. Kidney Transplantation Transplantation offers the best survival advantage among the RRT modalities. Transplantation before starting dialysis is associated with improved mortality and allograft survival.115e117 The IDC team should educate individuals and their families about transplantation, ensure timely referrals for transplant evaluation, and facilitate discussions about living kidney donations between individuals and their families. Individuals should be wait-listed when eGFR <20 mL/min/1.73 m2 to accrue time on the deceased-donor waiting list before starting dialysis and potentially decrease the duration of dialytic care. Advanced Care Planning ESRD in the elderly is associated with a high risk of mortality and decreased functional status and therefore warrants advanced care planning. In the US, 20% of patients who died in the initial 120 days after starting dialysis had discontinued treatment.109 Predictive tools available to risk stratify a patient’s outcomes can aid a clinician’s understanding of an individual’s prognosis. Clarifying patients’ wishes before ESRD may decrease aggressive and costly measures that patients may not want at the end of their lives. If progression to ESRD is likely, the risks and benefits of dialysis and transplantation should be provided to patients to ensure informed

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decision-making. In addition, patients should clarify circumstances under which they would want to withdraw from dialysis. Allowing a patient to make these decisions before the onset of an emergency setting benefits the patients’ families who will understand their loved ones’ wishes before they reach kidney failure. For patients who decide on medical management at stage 5 CKDdthe “no dialysis” optiondIDC programs should continue to provide services that facilitate the patients’ overall wellness and comfort.

CLINICAL OUTCOMES OF THE CKD IDC CLINIC The prevailing literature suggests that IDC slows CKD progression, decreases hospitalizations, improves mortality rates during transition from CKD to ESRD, and improves AVF placement before initiation of RRT. Snyder and Collins found that a higher number of preventive measures including monitoring of lipids, glucose, and mineral and bone parameters as well as influenza vaccination were associated with a significantly decreased risk of atherosclerotic heart disease in a Medicare CKD cohort.63 Hemmelgarn et al. showed a 50% decreased mortality risk in a predialysis cohort with IDC compared with a propensity-matched control group that had standard nephrology care.64 Decreased mortality was also shown in a cohort of patients who had access to IDC in Taiwan.118 Exposure to IDC decreased mortality rates after dialysis initiation in two other cohort studies.44,65 Data from Fresenius Medical Care North America, a large dialysis organization, showed that individuals who underwent a predialysis educational program were significantly more likely to choose PD as their RRT, begin HD with an AVF or AV graft, and were less likely to die within the first 90 days following onset of dialysis.119 The Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study, a randomized trial of 788 Dutch patients with CKD stages 3 and 4, showed that the implementation of CKD guidelines by nurse practitioners added to standard nephrology care, after an extended median follow-up of almost 6 years, slowed eGFR decline by 0.45 mL/min/1.73 m2 per year, and decreased the incidence of the composite endpoint (death, ESRD, and a 50% increase in S[Cr]) by 20% compared with standard nephrology care.120 The previously published MASTERPLAN trial with median follow-up of 5 years did not show a significant difference in CVD outcomes, but showed that APP supported care significantly decreased CVD risk factors (hypertension, low-density lipoprotein cholesterol, anemia, and proteinuria).86 The latter trial had several limitations

including contamination bias, fewer than expected events likely related to the inclusion of a relatively young and “healthy” CKD population, and being underpowered to demonstrate a significant difference in CVD outcome. Other trials have shown that CKD education and IDC can slow the progression of CKD to ESRD. A randomized trial demonstrated that a single 90-minute education session along with follow-up phone calls significantly delayed dialysis initiation by approximately 3 months in individuals expected to start dialysis English patients with within 6e18 months.43 eGFRs <30 mL/min/1.73 m2 who had access to a nurse, patient education, medication management, and nutrition counseling had a slower eGFR decline over time with the greatest benefit in those patients with rapidly progressive CKD.121 Data are conflicting regarding the efficacy of IDC in early CKD and nonprogressive CKD patients. Slower CKD progression was detected in subjects enrolled in IDC compared with historical controls in a large health maintenance organization population.122 A Canadian RCT found no difference in GFR decline and control of most CKD risk factors by adding a nursecoordinated model in subjects with slowly progressive CKD.123 However, nurse-coordinated care was associated with fewer visits to specialists and hospitalization days. Cohort studies performed in California, Taiwan, and Canada showed that patients exposed to IDC had significantly more AVFs placed and decreased hospitalizations.48,124,125 A single-center study showed that guideline-driven care by APPs was associated with improved functioning, permanent vascular accesses, and decreased hospitalizations 12 months after dialysis initiation.126

ECONOMICS OF CKD IDC CLINICS CKD IDC have different components and funding sources. IDC is funded by the National Health Service in certain countries such as Canada and Taiwan, whereas many fee-for-service insurance providers only reimburse for physicians or APP visits in the US. This may cause IDC clinics not to be available in many locations. Dieticians are reimbursed by Medicare for stage 4 CKD patients but may not be covered by other US insurance companies. The MIPPA benefits include six education classes, if taught by a physician, an APP, or clinical nurse specialist. A social worker can bill insurance companies only if providing counseling for a DSM-V mental disorder diagnosis. Nursing staff can charge for administration of injectable medications and vaccines. Pharmacist services are not reimbursable in

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CONCLUSIONS

the US. In addition, enhanced administrative personnel efforts required to coordinate all the providers and educational services are not reimbursable. Grants, awards, donations, or alternative sources of funding have often been required, which has initially limited CKD IDC clinics to large academic institutions in the US. Data revealing cost savings with implementation of CKD IDC clinics have generated interest by health care organizations that assume responsibility for the quality, cost-effectiveness, and general health care in creating CKD IDC clinics or partnering with other businesses that offer CKD IDC. As mentioned previously, dialysis providers and related companies have developed interdisciplinary models that employ telephone calls and leverage technology to provide care. After such companies enroll a CKD patient, patient profiles may be input into their ESRD facilities as patients progress toward kidney failure. Increased outpatient dialysis starts and greater AVF and PD selection rates can help persuade funders that CKD clinics are cost-effective and sustainable. In 2007, the average inpatient cost for the first month of dialysis in the US was $9846 per Medicare member and $22,841 per employer group health plan member.127 This cost could be greatly reduced by increasing outpatient dialysis starts. Increased AVF rates will also lower the expense associated with ESRD. AVFs were associated with approximately $3000 lower vascular access-related expenses compared with HD catheters.128 IDC may increase the rate of PD as the initial modality for ESRD, which is also cost-effective; according to the USRDS, the total yearly expenditure per patient in 2015 for HD was $89,000 compared with $75,000 for PD.2 Improved advanced care planning may also defray costs. Discussing patients’ wishes and values before ESRD may decrease the number of patients who start dialysis and withdraw within the first 120 days. Studies have assessed the cost-effectiveness of CKD IDC clinics. IDC clinics show greater pre-ESRD costs compared with conventional nephrology care and likely decrease mortality which would also drive up health care costs. Despite the increased costs of an IDC team, a study in Taiwan reported saving $1200 in patients beginning dialysis.125 After Taiwan started a nationwide multidisciplinary pay-for-performance initiative in 2006, enrollees were compared with a cohort of patients not enrolled, finding that pre-ESRD patients who attended IDC had lower hospitalization costs but higher outpatient costs.129 However, once these patients progressed to dialysis, the outpatient, hospitalization, and dialysis costs were less than those of patients who did not receive IDC care.130 A theoretical model evaluating the cost-effectiveness of US Medicare reimbursement for multidisciplinary care revealed a 0.23 quality of life

year (QALY) gain over usual care, with a cost of $51,285 per QALY gained. Although the multidisciplinary care was more costly than standard care, it resulted in a reasonable cost per QALY gained compared with ESRD.131 Because financial restraints limit the ability to offer all possible services to all CKD patients, IDC clinics must prioritize the interventions with the best outcomes. Not all patients may benefit to the same degree from IDC. Choosing the patient population most likely to benefit would decrease costs. Progression of CKD may be a slow, unpredictable process, and several years may be needed to demonstrate a financial benefit, particularly if a patient changes health care systems or insurance providers. The additional time spent seeing different providers in IDC and the costs incurred by patients during travel could adversely impact patient engagement. Overcoming some of these barriers may necessitate intensive case management and is potentially costly.

PATIENT SATISFACTION WITH CKD IDC CLINICS There is lack of data examining patient satisfaction with IDC clinics for CKD. A recent cross-sectional study from Australia, involving adult subjects with CKD, not on dialysis, who attended nurse-led CKD clinics, showed high satisfaction with the quality of care provided in the majority of those who responded to a survey questionnaire.132 Limited waiting time about access to services, adequate coordination of care, in-depth specialty knowledge, and listening to and understanding individual patient needs were factors contributing to patient satisfaction.

CONCLUSIONS The CKD clinic has emerged as an IDC model that encompasses patient education, medical management of CKD complications and risk factors, RRT planning, and quality improvement. The CKD IDC clinic team may include physicians, APPs, nurses, dieticians, pharmacists, and social workers. CKD IDC clinics are associated with greater patient preparedness and improved health outcomes during the transition from CKD to ESRD, especially among individuals at increased risk for CKD progression. Different models for IDC in CKD exist. Team structure and clinic goals should be tailored to local practice needs and resources. Funding for IDC services may be challenging as many insurers do not pay for these services despite the potential cost savings

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of such clinics. Although CKD IDC appears promising, studies with longer follow-up and higher-risk patients are required to better understand the quality and utility of IDC teams in the management of patients with CKD.

Acknowledgments The authors express their gratitude to Ms. Sarah Whitehouse for expert proofreading and editing of the manuscript.

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102. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345(12):861e9. 103. Solomon SD, Rice MM, Jablonski AK, Jose P, Domanski M, Sabatine M, et al. Renal function and effectiveness of angiotensinconverting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial. Circulation 2006;114(1):26e31. 104. Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL, et al. Effects of intensive BP control in CKD. J Am Soc Nephrol 2017;28(9):2812e23. 105. Esnault VL, Ekhlas A, Delcroix C, Moutel MG, Nguyen JM. Diuretic and enhanced sodium restriction results in improved antiproteinuric response to RAS blocking agents. J Am Soc Nephrol 2005;16(2):474e81. 106. Vogt L, Waanders F, Boomsma F, de Zeeuw D, Navis G. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan. J Am Soc Nephrol 2008;19(5):999e1007. 107. Gadola L, Noboa O, Marquez MN, Rodriguez MJ, Nin N, Boggia J, et al. Calcium citrate ameliorates the progression of chronic renal injury. Kidney Int 2004;65(4):1224e30. 108. Susantitaphong P, Sewaralthahab K, Balk EM, Jaber BL, Madias NE. Short- and long-term effects of alkali therapy in chronic kidney disease: a systematic review. Am J Nephrol 2012; 35(6):540e7. 109. Robinson BM, Zhang J, Morgenstern H, Bradbury BD, Ng LJ, McCullough KP, et al. Worldwide, mortality risk is high soon after initiation of hemodialysis. Kidney Int 2014;85(1):158e65. 110. Bradbury BD, Fissell RB, Albert JM, Anthony MS, Critchlow CW, Pisoni RL, et al. Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Clin J Am Soc Nephrol 2007;2(1):89e99. 111. McQuillan R, Trpeski L, Fenton S, Lok CE. Modifiable risk factors for early mortality on hemodialysis. Int J Nephrol 2012;2012:435736. 112. Astor BC, Eustace JA, Powe NR, Klag MJ, Fink NE, Coresh J, et al. Type of vascular access and survival among incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study. J Am Soc Nephrol 2005;16(5):1449e55. 113. Xue JL, Dahl D, Ebben JP, Collins AJ. The association of initial hemodialysis access type with mortality outcomes in elderly Medicare ESRD patients. Am J Kidney Dis 2003;42(5):1013e9. 114. Nee R, Fisher E, Yuan CM, Agodoa LY, Abbott KC. Pre-end-stage renal disease care and early survival among incident dialysis patients in the US Military health system. Am J Nephrol 2017;45(6): 464e72. 115. Liem YS, Weimar W. Early living-donor kidney transplantation: a review of the associated survival benefit. Transplantation 2009; 87(3):317e8. 116. Meier-Kriesche HU, Kaplan B. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation 2002;74(10):1377e81. 117. Mange KC, Joffe MM, Feldman HI. Effect of the use or nonuse of long-term dialysis on the subsequent survival of renal transplants from living donors. N Engl J Med 2001;344(10):726e31. 118. Wu IW, Wang SY, Hsu KH, Lee CC, Sun CY, Tsai CJ, et al. Multidisciplinary predialysis education decreases the incidence of dialysis and reduces mortality–a controlled cohort study based on the NKF/DOQI guidelines. Nephrol Dial Transplant 2009;24(11): 3426e33. 119. Lacson Jr E, Wang W, DeVries C, Leste K, Hakim RM, Lazarus M, et al. Effects of a nationwide predialysis educational program on modality choice, vascular access, and patient outcomes. Am J Kidney Dis 2011;58(2):235e42. 120. Peeters MJ, van Zuilen AD, van den Brand JA, Bots ML, van Buren M, Ten Dam MA, et al. Nurse practitioner care improves

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56. THE INTERDISCIPLINARY CLINIC FOR CHRONIC KIDNEY DISEASE

QUESTIONS AND ANSWERS Question 1 A 48-year-old man with a medical history of obesity, hypertension, diabetes, and hyperlipidemia presents to an IDC CKD clinic. He is a current smoker and drinks four glasses of wine per day. His laboratory results are significant for an eGFR 29 mL/min/1.73 m2, urinary protein-to-creatinine 2 g/g, an LDL-C 130 mL/dL, and hemoglobin 9.1 mg/dL. Which one of the following agents may increase cardiovascular risk in this patient? A. B. C. D.

Angiotensin-converting enzyme inhibitor Aspirin ESA 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor

Answer: C Aspirin, 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, smoking cessation, and blood pressure control may reduce cardiovascular risk in CKD patients. ESAs have been associated with a small increase in the risk of stroke.69,73,90,133

Question 2 A 78-year-old man with a history of hypertension, diabetes, and hyperlipidemia presents to an IDC CKD clinic for evaluation. His laboratory results are significant for an eGFR of 16 mL/min/1.73 m2, UACR 30 mg/g, S[Ca] 8.9 mg/dL, S[Alb] 4.5 g/dL, serum phosphorus 4.6 mg/dL, and venous total carbon dioxide 20 mmol/L. Which one of the following statements regarding this patient’s CKD care is correct? A. Education for this patient could delay the start of dialysis B. The patient’s nephrologist should have referred him to an IDC CKD clinic when his eGFR was greater than 30 mL/min/1.73 m2 C. An IDC CKD clinic is required to have a social worker and pharmacist on staff D. The patient no longer needs to see his primary physician now that he has enrolled in the CKD clinic. Answer: A Patient education has been shown to delay the start of dialysis by approximately 3 months. A randomized study in advanced CKD found a 3month delay to the start of dialysis in patients who received a single education intervention with nurse follow-up. There is conflicting evidence regarding the

efficacy of CKD clinics in early CKD. In a large health maintenance organization cohort, IDC care was found to retard CKD progression. However, in a randomized trial of Canadian patients with slowly progressive early CKD, the CKD program did not improve outcomes. IDC clinics have different staffing models. Economic constraints often limit the ability of an IDC program to hire ancillary providers who cannot bill in a fee-for-service model. The IDC does not replace the need for primary care. The IDC teams needs to coordinate care with the primary care provider to ensure understanding of each provider’s role.123,134,135

Question 3 A 64-year-old woman presents to an IDC CKD clinic with an eGFR of 20 mL/min/1.73 m2 and a hemoglobin of 9.1 g/dL. Which one of the following statements regarding the use of ESAs in CKD is correct? A. ESAs should CKD B. ESAs should hemoglobin C. ESAs should D. ESAs should

be used to delay the progression of be used to normalize the patient’s be used to prevent stroke be used to avoid blood transfusions

Answer: D The FDA recommends that ESAs be used in CKD to avoid blood transfusions to mitigate risk for allosensitization of potential kidney allograft recipients. Normalization of hemoglobin did not improve outcomes and was associated in some studies with increased risk. ESAs did not retard the progression of CKD.88,90,136

Question 4 A 71-year-old woman with CKD due to diabetic nephropathy presents to her nephrologist for a routine visit. Her laboratory testing reveals an eGFR 32 mL/ min/1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula), UACR 40 mg/g, S [Ca] 9 mg/dL, S[Alb] 4 g/dL, serum phosphorus 4.5 mg/dL, and serum bicarbonate concentration 21 mmol/L. Her eGFR has been stable from her last visit 6 months ago. Which one of the following statements describing her 2-year risk of progression to ESRD is correct? A. B. C. D.

3% 5% 7% 21% Answer: A

VIII. THERAPEUTIC CONSIDERATIONS

QUESTIONS AND ANSWERS

Using the ESRD calculator developed by Tangri et al., the estimated risk of progression to ESRD requiring dialysis or transplantation is 3%. The equation is also available as a smartphone app.19,20

Question 5 A 49-year-old man with type 2 diabetes presents to his nephrologist for routine follow-up. He had a renal biopsy 2 years ago for nephrotic range proteinuria that showed focal segmental glomerulosclerosis. His laboratory results show an eGFR of 35 mL/min/1.73 m2 by the CKD-EPI equation, UACR 2800 mg/g, S[Ca] 8.7 mg/dL, S[Alb] 2.8 g/dL, serum phosphorus 4.0 mg/dL, and serum bicarbonate 22 mmol/L. His eGFR 1 year ago was 41 mL/min/1.73 m2 and 55 mL/min/1.73 m2 at the time of the biopsy. Using the 2012 KDIGO guidelines, which one of the following statements best describes the rate of loss of GFR? A. B. C. D.

Slow progression Nonprogression Rapid progression Regressive progression

Answer: C Rapid progression, per 2012 KDIGO guidelines, is defined as a sustained decline in eGFR of >5 mL/ min/1.73 m2 per year. The ability to identify patients with rapid progression allows for earlier referral to CKD and RRT education, rather than simply identifying CKD stage.14

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Question 6 A nephrology practice would like to start an Interdisciplinary Chronic Kidney Disease Clinic that focuses on education and has decided to use NKF materials: “Your Treatment, Your Choice.” The practice is involved in the process of writing a business plan to support the personnel who will be involved in the education. Which one of the following statements regarding the MIPPA benefit for CKD education is correct? A. Patients with eGFRs >30 mL/min/1.73 m2 are eligible for the CKD education benefit B. Patients with an albumin:creatinine ratio >2000 mg/ g are eligible for the CKD education benefit C. Eligible patients may receive up to 10 sessions of CKD education D. CKD education must be delivered by a physician, APP (nurse practitioner/physician assistant), or clinical nurse specialist Answer: D The MIPPA establishes Medicare coverage for six educational sessions for Medicare beneficiaries with stage 4 CKD (precursor to kidney failure, defined as an eGFR of 15e29 mL/min/1.73 m2). Educational sessions must cover management of CKD (management of comorbid conditions, reducing progression to ESRD and prevention of complications) and RRT options. Both individual and group sessions are eligible for coverage. Each session should be 1 hour, with at least 31 documented minutes of time for billing purposes. The educational sessions must be delivered by a physician, APP (nurse practitioner/physician assistant), or clinical nurse specialist.49

VIII. THERAPEUTIC CONSIDERATIONS