Long-Term Posttransplantation Care: The Expanding Role of Community Nephrologists

Long-Term Posttransplantation Care: The Expanding Role of Community Nephrologists Andrew D. Howard, MD, FACP ● Improvements in transplantation practices, immunosuppressive agents, and management of comorbid conditions have led to better outcomes for kidney transplant recipients. Transplantation has become the treatment of choice for patients with end-stage renal disease (ESRD). This has resulted in continued growth in the number of patients living with a functioning kidney allograft as a percentage of the total ESRD population. These patients require long-term follow-up care, which already is straining the limited resources of transplant centers. Community nephrologists are the logical choice to assume responsibility for the posttransplantation care of these patients after discharge from transplant centers when they are stabilized. Optimal management of kidney transplant recipients depends on regular interactive communication between the patient’s community nephrologist and the transplant center. Open communication will not only facilitate the initial transition of care, it also will decrease the frequency of referrals back to the transplant center. In an ideal situation, the transplant center and community nephrologist would develop and discuss plans for discharge and transition of care for the individual patient before the actual kidney transplantation. Important issues for effective communication include changes in laboratory results and kidney function; pretransplantation and posttransplantation comorbid conditions, surgical complications, or adverse effects of medications; modifications to immunosuppressive therapy or other medications; recurrent hospitalizations or emergency care; and changes in biopsy results. Am J Kidney Dis 47(S2):S111-S124. © 2006 by the National Kidney Foundation, Inc. INDEX WORDS: Long-term transplant; communications; protocols; community nephrologist; transplant center; transplant nephrologist; transplant surgeon; transfer of care.

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INCE THE FIRST successful kidney transplantation in 1954, transplantation has evolved into the treatment of choice for patients with endstage renal disease (ESRD). Improvements in transplantation practices, an ever-increasing armamentarium of immunosuppressive agents, and management of comorbid conditions have substantially changed clinical outcomes. The number of successful long-term kidney transplants has been increasing steadily.1 As of 2002, the US Renal Data System reported that 122,374 patients currently were alive with a functioning kidney allograft.2 Unfortunately, the number of patients with ESRD on the waiting list for a kidney transplant also has continued to increase at a steady rate. As of October 7, 2005, a total of 63,481 patients were on the United Network for Organ Sharing Organ Procurement and Transplantation Network waiting list for a kidney transplant.3 By the year 2010, the number of patients on the waiting list is projected to reach 95,550 ⫾ 5,478 patients, and the number of transplant recipients living with a functioning kidney allograft is projected to reach 178,806 ⫾ 4,349 patients.4 Increased life expectancy has led to a significant increase in the number of individuals aged 50 years and older. This has led to a shift in the US population toward an increasing percentage of older individuals (ie, ⱖ60 years)—a trend that is projected to continue through 2030.5 As a

result, the incidence and prevalence of chronic diseases that are related to aging (including cardiovascular disease [CVD], hypertension, diabetes mellitus, and chronic kidney disease [CKD]) will continue to increase.2,6 It is expected that an increasing percentage of patients aged 50 years and older will continue to receive kidney transplants and require more intensive care.7 As of 2002, a total of 28% of patients with ESRD (122,374 patients) had received a kidney transplant that was still functioning.8 Of the remaining patients with ESRD, 65% were being treated with hemodialysis and 6% were being treated with peritoneal dialysis.8 Patients who receive kidney transplants have a survival advan-

From Metropolitan Nephrology Associates, Alexandria, VA. Received November 4, 2005; accepted in revised form December 14, 2005. This article was published as part of a supplement supported by an educational grant from Astellas Pharma US, Inc. Honoraria: Astellas Pharma US, Inc, Ortho Biotech Products, LP. Consultant: Astellas Pharma US, Inc. Acknowledgement of research support: Shire, Amgen Inc. Address reprint requests to Andrew D. Howard, MD, FACP, Metropolitan Nephrology Associates, 2616 Sherwood Hall Lane, Ste 209, Alexandria, VA 22306. E-mail: [email protected] © 2006 by the National Kidney Foundation, Inc. 0272-6386/06/4704-0109$32.00/0 doi:10.1053/j.ajkd.2005.12.040

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tage over patients who remain on dialysis therapy; 72% of kidney transplant recipients survive at least 5 years compared with 33% to 34% of patients who are treated with dialysis.2 This survival advantage has made transplantation the treatment of choice for patients with ESRD. In addition to increasing survival, kidney transplantation is a preferred choice of treatment because it frees the patient from the limitations of dialysis therapy and improves quality of life. The expected remaining years of life for transplant recipients are 52% to 69% as long as the expected remaining lifetime of the general population.9 However, improved patient and graft survival have led to steadily increasing numbers of successful long-term recipients of kidney transplants. Kidney transplant recipients require lifelong administration of maintenance immunosuppressive therapy.7 These patients have a high risk for comorbid conditions (eg, CVD) and metabolic abnormalities (eg, hypertension, diabetes mellitus, and dyslipidemia) that may be causes and/or consequences of CKD. In general, they need frequent monitoring and a relatively high degree of ongoing long-term care. Stable transplant recipients should have routine checkups by their physicians and have laboratory tests performed every 1 to 2 months up to 2 years posttransplantation.7 Organ transplantations generally are performed at specialized centers that serve patients from extended geographic areas. It can be difficult for patients to regularly travel long distances for follow-up care.7 Other potential obstacles to receiving long-term care include the constraints imposed by managed care and other medical insurance coverage, issues related to patient nonadherence, lack of home support, and patient preferences. Health care resources provided by transplant centers are crucial for the initial care and stabilization of transplant recipients. However, it is not feasible for centers to accommodate all recipients long term. Community nephrologists represent an alternative and often more convenient option to provide long-term follow-up care for these patients. To facilitate and enhance the specialized care of these patients, it is crucial that community nephrologists understand immunosuppressive therapy, including the adverse effects and potential drug interactions of

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these medications that have a pivotal role in the long-term monitoring, evaluation, and management required by kidney transplant recipients.7 MANAGEMENT ISSUES FOR KIDNEY TRANSPLANT RECIPIENTS

Overview of Managing a Kidney Transplant Recipient The medical management of kidney transplant recipients is unique and complex, requiring lifelong medical care.7 Many of the clinical objectives for managing a transplant recipient are similar to those related to delivering care for patients with CKD. The key management issues for long-term follow-up care for kidney transplant recipients are listed next. Table 1 lists comorbid conditions common in kidney transplant recipients.7 ●

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Monitor and treat medical problems present before transplantation, complications of transplantation surgery, and posttransplantation comorbid conditions Monitor kidney graft function (eg, serum creatinine [SCr] level, glomerular filtration rate) Monitor, coordinate, and adjust many medications (eg, immunosuppressive agents and such concomitant medications as antihypertensive, lipid-lowering, and hypoglycemic agents) Assess patient adherence with medication Monitor body mass index and assess ongoing fitness and diet regimens Perform other appropriate laboratory testing (eg, lipids, urinalysis [including proteinuria and hematuria], glucose, hemoglobin A1c, liver enzymes, electrolytes, blood urea nitrogen, uric acid, calcium, and phosphorus) Screen for malignancy Screen for selected infections (eg, cytomegalovirus, hepatitis B and C, and BK virus) Discuss pregnancy with age-appropriate female patients Ensure ongoing dental care

All medications should be reviewed and monitored at all visits. This should include appropriate dosage adjustments to immunosuppressive therapy, assessment of medications prescribed for comorbid conditions, and monitoring for potential adverse effects of medications or drugdrug interactions. Familiarity with immunosup-

POSTTRANSPLANTATION CARE BY COMMUNITY NEPHROLOGISTS Table 1. Common Comorbid Conditions in Kidney Transplant Recipients CVD (eg, coronary artery disease, heart failure, and arrhythmias) Peripheral vascular disease Metabolic disorders (ongoing or de novo) Hypertension Dyslipidemia Diabetes mellitus Weight gain or obesity Gout Proteinuria Late kidney allograft dysfunction Chronic allograft nephropathy Infection (eg, cytomegalovirus, urinary tract infection, chronic hepatitis B or C, or BK virus) De novo renal disease Posttransplantation recurrent renal disease Drug toxicity Late acute rejection Malignancy (eg, posttransplantation lymphoproliferative disorders and skin, breast, cervical, prostate, and colorectal cancers) Hematologic complications Anemia Erythrocytosis Metabolic bone disease (including osteoporosis, osteonecrosis, and residual hyperparathyroidism) Pregnancy Adapted from Cohen D, Galbraith C: General health management and long-term care of the renal transplant recipient. Am J Kidney Dis 38:S10-S24, 2001 (suppl 6).7

pressive agents and their potential adverse effects is a critical component of patient management. Continued monitoring of immunosuppressive therapy is necessary to ensure adequate immunosuppression while preventing unwanted adverse effects and complications. Currently Available Immunosuppressive Agents Kidney transplant recipients may receive one of several combinations of immunosuppressive agents in varied protocols. Transplant centers may have specific differences in initial dosages and dose adjustments over time after transplantation. Immunosuppressive regimens usually are based on calcineurin inhibitors—the mainstay of modern immunosuppressive therapy (either cyclosporine [CsA] or tacrolimus [TAC]). More than 90% of kidney transplant recipients are discharged on therapy with 1 of these agents.10 Other agents that may be included in the regimen are prednisone and/or an adjunctive agent, such

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as the purine synthesis inhibitors mycophenolate mofetil, mycophenolate sodium, or azathioprine and/or sirolimus, which inhibits the target of rapamycin.11 The adverse effects of corticosteroids are well known, including opportunistic infections, decreased wound healing, aseptic necrosis, enhanced risk factors associated with CVD (ie, hypertension, dyslipidemia, diabetes mellitus, and weight gain), bone loss, osteopenia, osteoporosis, cataracts, and cushingoid disfigurement.12,13 With the introduction of many new immunosuppressive drugs, some transplant centers have attempted to withdraw prednisone therapy as early as possible posttransplantation. Prednisone also may be avoided completely by using a variety of protocols with induction agents, such as rabbit antithymocyte globulin, monoclonal anti-interleukin 2 receptor antagonists (eg, daclizumab and basiliximab), and alemtuzumab (a humanized antiCD52 monoclonal antibody).14 Managing Immunosuppressive Therapy The transplant center will determine the initial immunosuppressive regimen and adjust it as necessary to stabilize the kidney transplant recipient immediately posttransplantation, based on pretransplantation donor and recipient factors and whether there is delayed allograft function. The goal of managing immunosuppressive therapy is to prevent acute rejection, as well as increase both graft and patient survival.11 This is accomplished by reaching and maintaining optimal dosages and blood levels of immunosuppressive agents, which will balance efficacy and safety. Overimmunosuppression can lead to toxicity and infection, whereas underimmunosuppression can lead to acute rejection. Therapeutic Drug Monitoring Monitoring blood levels of immunosuppressive agents clearly is important for physicians in making decisions about dosage adjustments for patients. A clinically relevant therapeutic drugmonitoring parameter must reliably reflect total drug exposure and should define a range of therapeutic values associated with efficacy, as well as toxicity. The area under the curve reliably reflects total exposure to drugs.15 Minimum concentration (Cmin), which measures whole-blood trough lev-

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els, is a clinically relevant monitoring parameter that correlates well with and may be used as a surrogate for TAC area under the curve in kidney transplant recipients.16 This has been more problematic with CsA.17 Although a proven range of Cmin values associated with efficacy and toxicity has been clearly defined for TAC (5 to 15 ng/ mL),16 a clear range that defines CsA toxicity has not been established.18 The use of a 2-hour peak level was proposed as a more suitable alternative to Cmin, although patient compliance in obtaining this level can be problematic.15 Therapeutic drug monitoring of the newer microemulsion formulation of CsA is more predictable.19 Cmin for sirolimus has been accepted, and therapeutic drug monitoring for mycophenolate mofetil is evolving.15 Patient Participation and Adherence to Therapy Patient self-management is an important aspect of care that needs to be incorporated into the long-term management of kidney transplant recipients. The patient should be counseled about the importance of adhering to prescribed medication regimens, schedules of follow-up visits, diet and nutrition, maintaining a healthy lifestyle (ie, no smoking and limited alcohol consumption), and regular exercise. Patient adherence to the self-management program should be assessed at every visit. Reports of the prevalence of nonadherence to immunosuppressive medications and methods for assessing nonadherence vary widely.20 Methods for assessing nonadherence include self-reporting by the patient, reports by health care providers or family members, monitoring pill counts and filled prescriptions, monitoring medication blood levels, and assessing medication adverse effects.20 To measure perceptions about patient nonadherence, the Medication Compliance Survey was mailed electronically to 767 members of the International Transplant Nursing Society.20 Results of the survey showed that overall nonadherence and nonadherence to immunosuppressive medications in particular are very significant problems in the care of kidney transplant recipients. Proper diet (29%) and exercise (27%) were perceived by the respondents to be the most prevalent areas of nonadherence, followed by nonadherence to immunosuppressive medications

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(17%), other medications (12%), smoking (19%), keeping appointments (10%), and exceeding guidelines for alcohol use (3%). In addition, nonadherence to immunosuppressive medications was perceived to be frequently or always associated with other forms of posttransplantation nonadherence, such as nonadherence to concomitant medications (88%), failure to keep appointments (72%), diet nonadherence (59%), exceeding guidelines for alcohol use (42%), smoking (39%), and use of illicit drugs (34%).20 COMMUNICATION ISSUES BETWEEN TRANSPLANT CENTERS AND COMMUNITY NEPHROLOGISTS

Optimal management of kidney transplant recipients depends on regular interactive communication between the patient’s community nephrologist and the transplant center. Open communication facilitates the transition of care and decreases the frequency of patient referral back to the transplant center. Ideally, the transplant center and community nephrologist should develop and discuss plans for discharge and transition of care for the individual patient before the kidney transplantation is performed. The initial transfer of care from the transplant center to the community nephrologist often represents a critical opportunity for establishing effective communication and interaction. Suboptimal communication at this point in time can influence the future relationship between the transplant center and nephrologist and can be detrimental to the patient’s care. Appropriate documentation in the form of a discharge summary containing key elements of the patient’s hospitalization and early posttransplantation management is crucial for transition of care. The community nephrologist can manage the majority of the transplant recipient’s medical needs locally.21 Major changes or adjustments in immunosuppressive therapy also can be accomplished locally. However, the community nephrologist should always consult with the transplant center to tailor the schedule of medication adjustments. In general, referral back to the transplant center may not be needed unless acute rejection occurs or is suspected or other serious complications or serious adverse events occur. These events should result in immediate consultation with the transplant center. For example,

POSTTRANSPLANTATION CARE BY COMMUNITY NEPHROLOGISTS Table 2. Situations When the Transplant Center Should Be Consulted Major alterations in the immunosuppressive regimen Patient nonadherence Suspicion of acute or chronic allograft rejection Unexplained reproducible change in SCr level of 0.3 mg/dL or greater Malignancy suspected or reported Unremitting febrile illness Swelling or pain at the allograft site Thrombocytopenia or hematuria Hospitalization Patient returns to dialysis therapy or is considered for relisting for transplantation Patient is enrolled in clinical trial (although this probably will be done by the transplant center before referring the patient back to the community nephrologist, rather than the reverse) NOTE. To convert SCr in mg/dL to ␮mol/L, multiply by 88.4. Adapted from Howard AD: Long-term management of the renal transplant recipient: Optimizing the relationship between the transplant center and the community nephrologist. Am J Kidney Dis 38:S5-S57, 2001 (suppl 6).21

contact with the transplant center is essential if posttransplantation malignancy develops or is suspected so that a plan for coordinated care can be formulated.21 Table 2 lists common, challenging, or important issues that represent opportunities for communication between the community nephrologist and the transplant center. It is desirable for the community nephrologist to remain involved in the management of these conditions. Obstacles to Communication Although communication between community nephrologists and transplant centers is crucial for the management of kidney transplant recipients, several factors can hinder communication. These obstacles must be addressed to optimize patient care. What the transplant center can do to enhance communication. When a transplant recipient is referred or returned to a community nephrology practice, the transplant center must provide a comprehensive summary of the patient’s medical records. Insufficient information may interfere with the community nephrologist’s ability to manage the patient. There also must be a designated contact or point person at the transplant center (eg, physician assistant, nurse practitioner,

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or transplant coordinator). Difficulty reaching an appropriate member of the transplant team can prevent the community nephrologist from obtaining important information about the patient or communicating complications or changes in patient care to the transplant care team in a timely manner. Transplant centers have variable protocols for the care of transplant recipients. The number and variety of available immunosuppressive agents and regimens now are much greater than what was available 10 years ago (eg, new and more potent immunosuppressive agents, various protocols for minimizing corticosteroid therapy, and a variety of induction protocols). In addition, there are a variety of approaches to monitor and treat polyomavirus nephropathy. Each transplant center has preferred protocols for immunosuppressive therapy, reducing the risk for adverse events, schedules for visits and laboratory testing, and other aspects of care for transplant recipients. In the absence of standardized protocols for posttransplantation monitoring, communication and coordination of care between transplant centers and community nephrologists become even more important. Therefore, transplant centers should make their protocols available to community nephrologists and designate personnel to manage patient transfers and facilitate consultations. A member of the transplant team should be immediately available by telephone to consult with the community nephrologist whenever needed. These procedures will strengthen the relationship between the community nephrologist and transplant center, facilitate communication, and enhance patient care. What the community nephrologist can do to enhance communication. The most common reason for the community nephrologist to consult the transplant center is if a patient’s SCr level changes significantly. The community nephrologist should contact the transplant center if SCr level increases by 0.3 mg/dL or greater (ⱖ26.52 ␮mol/L) or fails to return to baseline after volume expansion or discontinuation of diuretic therapy (and there is no obvious cause for the increase, such as volume depletion, high calcineurin inhibitor levels, or obstruction). Under most circumstances, the transplant center should perform a biopsy of the kidney allograft and prescribe treatment for acute rejection, if needed.21

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The availability of a nephropathologist who is comfortable with the interpretation of a transplant biopsy is essential. Some community nephrologists are less comfortable than others about making adjustments in the medical care of kidney transplant recipients.21 This may delay referral of the patient from the transplant center and make follow-up care more difficult. Obstacles to communication occur if the community nephrologist does not contact or consult with the transplant center, which hinders the coordination of care. If it becomes necessary to refer the patient back to the transplant center, the transplant care team will not have all the information needed for patient management. Advantages of Posttransplantation Care by Community Nephrologists The kidney transplant recipient should be referred by the transplant center to the community nephrologist as soon as the patient is stabilized. The long-term relationships that community nephrologists establish with their patients before transplantation can be useful for providing optimal posttransplantation care. As levels of comfort and trust between the transplant center and community nephrologist increase, transfer of the transplant recipient to the community nephrologist can be made earlier. This can facilitate access to care, minimize travel time, and make follow-up care easier for the patient, which will enhance the continuity of care. Patients likely will be reassured in the knowledge that the community nephrologist is familiar with their medical history and conditions. The convenience of follow-up with a community physician can reassure patients that appropriate medical care is close, rather than hours away, especially during an emergency. Adherence with appointments should increase if patients do not have to travel long distances. In addition, the community nephrologist often has an ongoing working relationship with other physicians in the community, many of whom already have seen the patient and will continue to be involved in the patient’s posttransplantation care. TRANSITION OF CARE

Knowledgeable community nephrologists should be comfortable with monitoring and adjusting immunosuppressive medications after the

early posttransplantation period, with input from the transplant center. They can assess patients for adverse effects or failure of immunosuppressive medications, as well as for interactions with concomitant medications. If allograft function deteriorates or adverse effects occur, an adjustment in dosage or conversion from one immunosuppressive agent to another might become necessary. Community nephrologists have varying levels of comfort about altering immunosuppressive therapy (eg, minimizing or withdrawing corticosteroid therapy or adjusting immunosuppressive drug levels). Some may be comfortable monitoring and changing immunosuppressive therapy, but others may prefer that the transplant center be responsible for managing immunosuppressive regimens. Open communication will increase the likelihood that community nephrologists will be willing to take more responsibility for their patients’ immunosuppressive therapy. Clearly, this can facilitate and enhance transition of care and reduce the need to refer patients back to the transplant center. Recommended Schedule of Visits There are few scientific data for basing decisions about optimal schedules and types of follow-up patient visits to transplant centers. Therefore, the Clinical Practice Guidelines Committee of the American Society of Transplantation developed a set of evidence-based guidelines for outpatient screening and prevention of diseases and complications that commonly occur after transplantation.22 The guidelines are not intended to address the diagnosis and treatment of such posttransplantation conditions and do not address the pretransplantation evaluation of candidates, initial choice of immunosuppressive medications, or treatment of allograft rejection. Initial posttransplantation care usually consists of frequent visits of the patient to the transplant center and close observation by the transplant team.7 Long-term care of kidney transplant recipients is less structured and is not well defined, but it still is essential to the successful outcomes of kidney transplantation and patient well-being. Most acute rejection episodes and allograft losses occur during the first 3 months posttransplantation.22 During the remainder of the first year, rejection, allograft loss, opportunistic infection, and toxicity of immunosuppressive agents still are major

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Table 3. Suggested Schedule of Follow-Up Visits During the First Year Posttransplantation

Posttransplantation Period (mo)

No. of Visits

1 1-3 4-12 ⬎12

2-3/wk 1 every 1-3 wk 1 every 4-8 wk 1 every 2-4 mo 1 every 3 to 6 mo 1/mo

% of Surveyed Transplant Centers*22

80 86 75* 62 25

Health Care Provider

Transplant center Transplant center Transplant center or community nephrologist Transplant center or community nephrologist Transplant center or community nephrologist

NOTE. Transplant center indicates transplant physician or surgeon. *Care remains at transplant center. Adapted from Cohen D, Galbraith C: General health management and long-term care of the renal transplant recipient. Am J Kidney Dis 38:S10-S24, 2001 (suppl 6)7; Howard AD: Long-term management of the renal transplant recipient: Optimizing the relationship between the transplant center and the community nephrologist. Am J Kidney Dis 38:S5-S57, 2001 (suppl 6)21; and Kasiske BI, Vasquez MA, Harmon WE, et al, for the American Society of Transplantation: Recommendations for the outpatient surveillance of renal transplant recipients. J Am Soc Nephrol 11:S1-S86, 2000 (suppl 15).22

concerns, although they diminish in frequency after this time.22 The schedule of follow-up visits for the first year is based on the major risk factors during specific periods posttransplantation (Table 3).7,21,22 The transplant center most commonly will refer a patient to a community nephrologist any time after the third month, depending on the stability of the individual patient.7,22 Patient monitoring after the first 3 months posttransplantation varies greatly among transplant centers.22 The amount of care provided by transplant surgeons decreases during this time. At some transplant centers, transplant nephrologists become the primary health care providers, but other centers typically refer patients to community nephrologists. During months 4 through 12 posttransplantation, transplant recipients are examined at least monthly, with a significant percentage of outpatient visits still made at the transplant center.22 After the first 12 months posttransplantation, the risk for acute rejection greatly decreases; therefore, immunosuppressive therapy should require less frequent monitoring and adjustment.22 The focus of outpatient visits after the first 12 months posttransplantation is to screen for allograft dysfunction, CVD risk, malignancy, adverse effects of immunosuppressive medications, general health maintenance, and patient adherence. Most patients will be examined no less than every 3 to 4 months, at either the transplant center or by a community nephrologist (approximately half are examined at transplant centers).22 Laboratory

testing often is performed on a more frequent basis (ie, every 1 to 2 months) for the duration of posttransplantation care. Although some patients can be transitioned in 4 to 12 weeks, a longer transition is preferable in most cases to allow sufficient time for the patient to stabilize.21 In addition to increased risk for acute rejection, many laboratory values continue to fluctuate for several months posttransplantation. In ideal circumstances, transition probably should occur between 3 and 6 months posttransplantation. Most kidney transplant recipients are transferred to community nephrologists by the end of the first 12 months posttransplantation. However, several factors can delay the transition of care. The American Society of Transplantation Survey found 5 main reasons for delaying referral to the community nephrologist and 4 reasons that can interfere with transfer back to the referral nephrologist (ie, the transplant center; Table 4).21,22 Table 5 provides a checklist of donor and recipient information that should be included with the patient’s medical records when care is transferred from the transplant center to the community nephrologist. Follow-Up Protocols Although there are no universal standards for the timing of posttransplantation laboratory tests and follow-up office visits,21,22 many transplant centers have their own protocols.21 Therefore, a similar follow-up protocol can be established between the transplant center and community

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Table 4. Reasons for Delays in the Transfer of Care Reasons that can hinder the transfer of care from transplant center to community nephrologist Patient prefers to remain under care of the transplant center Patient has experienced a significant number of acute rejection episodes Patient has concomitant disease(s), complications, or urological issues Lack of trained or willing community nephrologists to manage kidney transplant recipients Transplant center protocol Reasons that can hinder the transfer of care from community nephrologist to transplant center Travel distance to transplant center Insurance coverage issues Limited transplant center resources Patient prefers to remain under care of the community nephrologist

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Data from Howard21 and Kasiske et al.22

nephrologist after the transfer of care. This will enhance the relationship and communication between the community nephrologist and transplant center. Office visits are scheduled more frequently during the first 3 to 6 months posttransplantation because of the increased risk for acute rejection during this period.21,22 Tables 67,21,22 and 721 outline sample schedules for office visits and laboratory tests. The schedule of visits can vary, based on the continuing stability of the patient or the occurrence of complications, abnormal laboratory test results, or adverse effects. Stable patients can be assessed less frequently, but should be monitored at least every 1 to 2 months during the first 2 years posttransplantation.7,21,22 CLINICAL AND CLERICAL CAPABILITIES NEEDED FOR A COMMUNITY PRACTICE

Role of the Clinical Staff The community nephrologist and his or her staff must be capable of delivering optimal care to kidney transplant recipients. The number of clinical staff should be based on the size of the practice and include at least 1 registered nurse, nurse practitioner, or transplant coordinator. Optimal care requires the following factors: ●

Working knowledge of immunosuppressive therapy and the management of adverse effects

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Recognition and appropriate treatment of the complex medical comorbidities and risk factors involved in posttransplantation care that often will impact on patient and allograft survival An efficient tracking system for laboratory data Registered nurses who have experience or interest in the long-term care and management of kidney transplant recipients Flexible office hours, which may be in conflict with: — Care provided at outpatient dialysis centers — Volume of inpatient consultations Access to a community hospital that is clinically equipped to offer services for kidney transplant recipients Laboratories that report test results in a timely manner

Expanded Role of the Registered Nurse or Nurse Practitioner In general, registered nurses can expedite communication between the community nephrologist and the patient, laboratory, transplant center, and other medical specialists. For example, they can alert community nephrologists of critical laboratory results (eg, changes in SCr or immunosuppressive medication levels or the occurrence of Table 5. Checklist for Transferring the Care of Kidney Transplant Recipients From Transplant Center to Community Nephrologist □

Donor type (living or deceased) HLA antigen matching □ Donor and recipient serological test results □ Patient demographics (age, race, sex, state/territory) □ Warm ischemia time (minutes) □ Cold ischemia time (hours) □ No. of rejection episodes (timing, severity, resolution) □ Urinalysis or urinary protein-creatinine ratios □ Delayed allograft function and duration □ SCr levels (1, 6, and 12 mo posttransplantation) □ Glomerular filtration rate □ Lipid levels □ Hepatitis B and C status □ Cytomegalovirus status □ Pretransplantation and 6-mo posttransplantation bone densitometry □ Immunosuppressive agent protocol and target levels □ Changes in therapy that can be expected (both immunosuppression and concomitant medications) □

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Table 6. Suggested Protocol for Posttransplantation Laboratory Tests and Office Visits

Time Posttransplantation

Laboratory Testing Schedule*

Time Posttransplantation

Office Visit Schedule†

1 mo 1-3 mo 3-6 mo 6 mo-1 y Up to 2 y ⬎2 y

2-3 times/wk Weekly Every 2 wk Monthly Every 1-2 mo Every 2-3 mo

Up to 6 wk 6 wk-3 mo 4 mo-1 y ⬎1 y ⬎2 y

Weekly Every 2 wk Monthly Every 2 mo Every 3-4 mo

*Tests performed at each visit will vary, depending on patient medical condition and recommended scheduling of individual laboratory tests (see Table 7). †With or without laboratory testing (ie, separate schedules for laboratory testing and office visits, which may overlap at times). Adapted from Cohen D, Galbraith C: General health management and long-term care of the renal transplant recipient. Am J Kidney Dis 38:S10-S24, 2001 (suppl 6)7; Howard AD: Long-term management of the renal transplant recipient: Optimizing the relationship between the transplant center and the community nephrologist. Am J Kidney Dis 38:S5-S57, 2001 (suppl 6)21; and Kasiske BI, Vasquez MA, Harmon WE, et al, for the American Society of Transplantation: Recommendations for the outpatient surveillance of renal transplant recipients. J Am Soc Nephrol 11:S1-S86, 2000 (suppl 15).22

anemia). They also can educate patients and inform them about changes to ongoing care, such as adjustments to medications or the need for additional testing, and help patients locate and enroll in prescription-assistance and social services programs. Registered nurses can write orders for laboratory and radiology testing. In addition, nurse practitioners and physician assistants can write prescriptions for medications.

As discussed, the Medication Compliance Survey identified nurses’ perceptions about the prevalence and importance of patient nonadherence and how to manage this problem.20 The respondents perceived that various communication issues that are discussed in this article were major impediments to assessing patient adherence, including absence of notes in medical records, inability to access pharmacy prescription records, and prob-

Table 7. Suggested Schedule for Monitoring and Timing of Posttransplantation Laboratory Tests Test

Monitors for

Glucose

Established or new-onset diabetes mellitus

Hemoglobin A1c Blood urea nitrogen, SCr Electrolytes Urinalysis

Adequacy of blood glucose control Kidney allograft function Hyperkalemia, acidosis, hyponatremia Glucosuria, proteinuria, hematuria, casts, bacteria Resolution of hyperparathyroidism, complications of osteoporosis therapy Expected posttransplantation hypophosphatemia Possible gout Hyperlipidemia

Calcium Phosphorus Uric acid Low-density lipoprotein cholesterol/triglycerides Aspartate and alanine aminotransferase Intact parathyroid hormone

Hepatotoxicity Hyperparathyroidism, hypercalcemia

Timing*

Year 1: monthly Year 2: every other month Year 3⫹: every 3 mo Every 3 mo See glucose See glucose See glucose See glucose Year 1: monthly Year 2⫹: every 6-12 mo As needed Year 1: every 3 mo Year 2⫹: annually See glucose Year 1: every 3 mo, if needed

*The suggested schedule for monitoring and timing of laboratory tests in this table applies to patients who are 6 months or more posttransplantation. Before 6 months posttransplantation, patients are tested more frequently. Adapted from Howard AD: Long-term management of the renal transplant recipient: Optimizing the relationship between the transplant center and the community nephrologist. Am J Kidney Dis 38:S51-S57, 2001 (suppl 6).21

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lems integrating information from multidisciplinary team members. Examples of interventions used frequently by respondents to enhance patient adherence included20: ● ● ● ● ● ● ● ● ● ● ●

Reading materials, videos, and educational classes about transplant care Assessment of the patient’s ability to adhere to prior interventions Reminders during clinic visits Family or support persons involved in education and behavioral interventions Questioning the patient about adherence during long-term follow-up visits Reducing the complexity of the medication regimen Tailoring the regimen to the patient’s lifestyle Patient sees the same clinical staff at each visit More frequent visits or calls to the patient’s home Support group directed at adherence Cueing (use of special alarms or pagers)

Role of the Clerical Staff In addition to having competent and knowledgeable clinical staff, optimal long-term management of kidney transplant recipients in the community setting also requires skilled clerical assistance. One individual should be designated as an office traffic coordinator to orchestrate all the information that passes back and forth among physicians, the laboratory, the transplant center, and the patient. The number of office staff should be based on the size of the practice. Support staff can include clerical assistants to manage medical records. In larger practices, these individuals also manage financial and social services. Hiring and maintaining office staff can be challenging. The following tips for hiring and keeping qualified staff may be helpful: ●

Review hiring processes — Interview candidates more than once — Check references ● Offer competitive salaries and benefits to improve the chances for attracting and keeping skilled and talented staff23 ● Be creative with benefits ● Let employees offer input—listen to them and let their opinions count

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Show appreciation and praise staff members regularly—do not assume that they know you appreciate them INSURANCE BILLING AND REIMBURSEMENT ISSUES

Overview of Nephrology Coding Coding requirements can vary greatly among insurance carriers. Medicare requires that claims indicate a diagnosis or diagnoses by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes24 and Current Procedural Terminology (CPT) codes.25 Proper coding is necessary for appropriate reimbursement, and medical necessity for the service(s) provided must be documented in the patient’s medical records. Undercoding often is a problem and represents a loss of revenue to the practice. A knowledgeable staff with experience in coding and medical record audits is a vital part of a community medical practice. Table 8 lists a selection of nephrologyrelated coding reminders.24,25 Aids for Recording Patient Information and Physician Services A “superbill” can be designed with preprinted ICD-9-CM and CPT codes. Regular internal audits of medical records and an annual review of CPT codes will help ensure proper coding and reimbursement for services performed and will ensure appropriate documentation. In certain states (Arizona, California, Florida, New York, Oregon, Texas, and Washington), billing is outside the national norm (higher levels of CPT codes than per national averages are used). It should be noted that new ICD-9-CM codes for CKD are to be implemented in 2006. Preprinted office notes can be a useful tool for recording patient information, progress notes, treatment protocols, and services performed for coding. Costs for transcription of dictation range from approximately 13¢ to 23¢ per line of 65 characters, with or without spaces, or approximately $5 to $10 per note. Possible options include the use of conventional or digital voice recorders, as well as voice-activated transcription. There are several advantages to the use of digital recorders, including infinite storage capacity, easy data transfer to a Health Insurance

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Table 8. Reminders for Coding Nephrology-Related Services ICD-9-CM for coding diagnoses (ie, “Why”)24 ICD-9-CM presumes a relationship between renal disease and hypertension when both conditions are present Code the primary reason for the visit, not the symptoms, if the underlying disease is established Code only the disease that is known to the highest level of specificity and certainty It is not possible to code suspected conditions per ICD-9-CM Codes for chronic renal failure/ESRD: 585.1 (stage 1), 585.2 (stage 2), 585.3 (stage 3), 585.4 (stage 4), and 585.5 (stage 5); 585.6 (ESRD with transplant or failed graft), effective October 1, 2005 Renal Physicians Association nephrology ICD-9 quick reference pocket guide is useful CPT for coding services (ie, “What”)25 Code for proper complexity of the patient visit Code ranges 99213-99215 for evaluation and management services (99214 is most common) Code 99214 includes detailed history, detailed medical examination, medical decision making of moderate complexity (25 min of physician time spent with patient) Code 99215 includes 40 min of physician time spent with patient and at least 2 of these 3: detailed history, detailed examination, and medical decision making of high complexity NOTE. ICD-9-CM indicates International Classification of Diseases, Ninth Revision, Clinical Modification; ESRD indicates end-stage renal disease; ICD-9 indicates International Classification of Diseases, Ninth Revision; CPT indicates Current Procedural Terminology.

Portability and Accountability Act of 1996– compliant Web site, and allowing simple encryption and decryption for transfer back and forth between the transcriptionist and the office. REIMBURSEMENT FOR IMMUNOSUPPRESSIVE MEDICATIONS: MEDICARE

Medicare is the most common payer for ESRD medical care services. However, Medicare, Medicare plus Medicaid, or a Medicare health maintenance organization alone cover fewer patients who receive a kidney transplant than patients who receive dialysis because many health insurance plans choose not to participate in the Medicare⫹Choice managed care payment system. Currently, Medicare and Medicaid cover almost one third of hemodialysis patients, with health maintenance organizations covering an additional 5.5% and private insurance covering 62%.8 However, there is still a substantial number of kidney transplant recipients who are or will be dependent, at least in part, on Medicare coverage.8 Currently, Medicare will pay up to 80% of costs charged for immunosuppressive medications for 36 months posttransplantation if the patient’s disability was granted based on a diagnosis of ESRD. This assumes that the medications will be obtained through a pharmacy that will bill Medicare directly. For transplant recipients who are receiving Medicare benefits for causes of disability other than ESRD, all immu-

nosuppressive medications furnished after December 31, 2000, are covered at 80% of the cost, without any time limit. Many pharmaceutical companies now offer programs to provide low-cost medications to patients in need of assistance. State-sponsored medication programs and supplemental Medicare policies also are available. Patients must meet specific criteria to be eligible for these programs (eg, they do not have prescription drug insurance or have limited incomes). Beginning on January 1, 2006, Medicare beneficiaries will be able to enroll in the Medicare Part D prescription drug plan.26 Tables 9 and 10 outline the extremely complicated features of this plan.26 Individuals with incomes less than 135% of the poverty level will pay no monthly premium, no deductible, and have no “gap” in coverage. In 2006, beneficiaries will pay $35 a month for the coverage ($420 annual premium; Table 9).26 The beneficiary then pays a $250 deductible and 25% of the next $2,000 in drug expenses. After $2,250 in drug costs, the beneficiary pays 100% of the next $2,850 in drug expenses. After $5,100 in total drug expenses, the beneficiary then pays 5% of the cost. Unfortunately, for the majority of the population with incomes above the poverty level, the plan has substantial built-in escalators (resulting in steadily increasing out-of-pocket costs) that will seriously erode the benefit by the year 2013 (Table 10).26

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ANDREW D. HOWARD Table 9. Medicare Part D Prescription Drug Plan Effective January 1, 2006 Patient’s Annual Drug Costs ($)

Patient Pays Out of Pocket (%)

Up to a Maximum Out of Pocket ($)

Total Costs to Patient ($420 annual premium ⫹ $)

0-250 251-2,250 2,251-5,100 ⬎5,100

100 25 100 5

250 500 2,850 No limit

250 750 3,600 3,600 plus 5% of drug costs ⬎5,100

Adapted from Medicare Prescription Drug Coverage (as of August 19, 2005): Available at: http://www.egyptianaaa.org/ MedicareDrugBill.htm. Accessed August 22, 2005.26

The costs for immunosuppressive medications can be substantial, often averaging $1,000 to $2,500 per month.27 It is not surprising that these high costs often result in patient nonadherence, which increases the risks for allograft failure and death in kidney transplant recipients who have inadequate insurance coverage for immunosuppressive medications.28 Despite the cost of immunosuppressive therapy, medical care for dialysis patients is considerably more expensive than that for patients with functioning kidney allografts.28 It is important that every transplant recipient meet with the social worker at the transplant center before transplantation to ensure that appropriate drug coverage will be available to meet the patient’s needs posttransplantation. CONCLUSION

Medical management of kidney transplant recipients is unique and complex and requires lifelong medical care, monitoring, and patient commitment. There is remarkable overlap between the clinical objectives of managing the comorbid conditions of a kidney transplant recipient and those of a patient with CKD. Familiarity with immunosuppressive agents and their potential adverse effects is criti-

cal. Care during the initial 3 months posttransplantation generally is provided by the transplant center. After the kidney transplant recipient is stabilized, transfer of care to the community nephrologist may occur as soon as possible. Knowledgeable community nephrologists are well equipped to assume responsibility for these patients. Ongoing communication before and after the transition of care is crucial for optimal longterm patient management. Important issues for communication include changes in laboratory results; pretransplantation and posttransplantation comorbid conditions, complications, or adverse effects of medications; alterations in immunosuppressive therapy or other medications; and hospitalization, changes in renal function, and transplant biopsy results. Community nephrologists should maintain communication with the transplant centers. Consultation is essential if modifications are made to the immunosuppressive regimen and nonadherence of the patient to the regimen should be reported. The transplant center also should be contacted if the patient has any unexplained reproducible changes in SCr levels of 0.3 mg/dL or greater (ⱖ26.52 ␮mol/L), acute rejection or

Table 10. Annual Escalators in Medicare Part D Prescription Drug Plan Through 2013

Year

Estimated Annual Premium ($)

Annual Deductible ($)

Main Benefit Limit ($)

Catastrophic Coverage Begins at ($)

Gap in Coverage ($)

2007 2008 2009 2010 2011 2012 2013

444 492 516 564 588 648 696

275 300 325 350 380 410 445

2,470 2,710 2,920 3,170 3,400 3,690 4,000

5,596 6,158 6,596 7,165 7,715 8,360 9,068

3,126 3,448 3,676 3,995 4,315 4,670 5,066

Adapted from Medicare Prescription Drug Coverage (as of August 19, 2005): Available at: http://www.egyptianaaa.org/ MedicareDrugBill.htm. Accessed August 22, 2005. 26

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malignancy is suspected or reported, unremitting febrile illness occurs, or the patient goes to the emergency department, is hospitalized, or returns to dialysis therapy. Optimal management of kidney transplant recipients depends on regular interactive communication between the patient’s community nephrologist and transplant center. Open communication will not only facilitate the initial transition of care, but also decrease the frequency of referrals back to the transplant center. In an ideal situation, the transplant center and community nephrologist would develop and discuss plans for discharge and transition of care before the actual kidney transplantation. Important issues for effective communication include changes in laboratory results and kidney function; pretransplantation and posttransplantation comorbid conditions, surgical complications, or adverse effects of medications; modifications to immunosuppressive therapy or other medications; recurrent hospitalizations or emergency care; and changes in biopsy results. The community nephrologist’s staff must be capable of assisting in the delivery of optimal care to these patients. REFERENCES 1. US Renal Data System: Chapter 7, Transplantation, in USRDS 2004 Annual Data Report. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2004. Available at: http:// www.usrds.org/atlas.htm. Accessed August 5, 2005 2. US Renal Data System: Precis, background on the US ESRD Program, in USRDS 2004 Annual Data Report. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2004. Available at: http://www.usrds.org/atlas.htm. Accessed August 24, 2005 3. United Network for Organ Sharing: Organ Donation and Transplantation. US Transplantation Data. Available at: http://www.unos.org/data. Accessed October 7, 2005 4. Xue JL, Ma JZ, Louis TA, Collins AJ: Forecast of the number of patients with end-stage renal disease in the United States to the year 2010. J Am Soc Nephrol 12:27532758, 2001 5. United Nations Population Division: World Population Prospects: The 2004 Revision Population Database. Available at: http://esa.un.org/unpp. Accessed October 25, 2005 6. Hansberry MR, Whittier WL, Krause MW: The elderly patient with chronic kidney disease. Adv Chronic Kidney Dis 12:71-77, 2005

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7. Cohen D, Galbraith C: General health management and long-term care of the renal transplant recipient. Am J Kidney Dis 38:S10-S24, 2001 (suppl 6) 8. US Renal Data System: Chapter 4, Treatment modalities, in USRDS 2004 Annual Data Report. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2004. Available at: http://www.usrds.org/atlas.htm. Accessed August 5, 2005 9. US Renal Data System: Chapter 6, Outcomes: Hospitalization and mortality, in USRDS 2004 Annual Data Report. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2004. Available at: http://www.usrds.org/atlas.htm. Accessed October 26, 2005 10. Shapiro R, Young JB, Milford EL, et al: Immunosuppression: evolution in practice and trends, 1993-2003. Am J Transplant 5(part 2):874-886, 2005 11. Halloran PF: Immunosuppressive drugs for kidney transplantation. N Engl J Med 351:2715-2729, 2004 12. Woodle ES, Vincenti F, Lorber MI, et al: A multicenter pilot study of early (4-day) steroid cessation in renal transplant recipients under simulect, tacrolimus, and sirolimus. Am J Transplant 5:157-166, 2005 13. Vanrenterghem Y: Strategies to reduce or replace steroid dosing. Transplant Proc 31:S7-S10, 1999 (suppl 8A) 14. Khwaja K, Asolati M, Harmon J, et al: Outcome at 3 years with a prednisone-free maintenance regimen: A singlecenter experience with 349 kidney transplant recipients. Am J Transplant 4:980-987, 2004 15. Chiaramonte S, Dissegna D, Ronco C: Monitoring of immunosuppressive therapy in renal transplanted patients, in Ronco C, Chiaramonte S, Remuzzi G (eds): Kidney Transplantation: Strategies to Prevent Organ Rejection. Contrib Nephrol Basel, Switzerland: Karger, 146:73-86, 2005 16. Ihara H, Shinkuma D, Ichikawa Y, Nojima M, Nagano S, Ikoma F: Intra- and interindividual variation in the pharmacokinetics of tacrolimus (FK506) in kidney transplant recipients—Importance of trough level as a practical indicator. Int J Urol 2:151-155, 1995 17. Barone G, Chang CT, Choc MG Jr, et al, for the Neoral Study Group: The pharmacokinetics of a microemulsion formulation of cyclosporine in primary renal allograft recipients. Transplantation 61:875-880, 1996 18. Laskow DA, Vincenti F, Neylan JF, Mendez R, Matas AJ: An open-label, concentration-ranging trial of FK506 in primary kidney transplantation. A report of the United States Multicenter FK506 Kidney Transplant Group. Transplantation 62:900-905, 1996 19. Holt DW: Therapeutic drug monitoring of immunosuppressive drugs in kidney transplantation. Curr Opin Nephrol Hypertens 11:657-663, 2002 20. Russell CL: Medication noncompliance: Perceptions of transplant healthcare providers. Dial Transplant 34:301307, 2005 21. Howard AD: Long-term management of the renal transplant recipient: Optimizing the relationship between the transplant center and the community nephrologist. Am J Kidney Dis 38:S5-S57, 2001 (suppl 6) 22. Kasiske BI, Vazquez MA, Harmon WE, et al, for the American Society of Transplantation: Recommendations for

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the outpatient surveillance of renal transplant recipients. J Am Soc Nephrol 11:S1-S86, 2000 (suppl 15) 23. Rice B: How do your staff salaries compare? Medical Economics, August 5, 2005. Available at: http://www.memag. com/memag/. Accessed October 17, 2005 24. International Classification of Diseases, Ninth Revision, Clinical Modification (ed 6). Available at: http:// www.cdc.gov/nchs/data/icd9/icdguide.pdf. Accessed October 17, 2005 25. Current Procedural Terminology 2006 Professional. Chicago, IL, American Medical Association, 2006

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26. Medicare Prescription Drug Coverage (as of August 19, 2005): Available at: http://www.egyptianaaa.org/ MedicareDrugBill.htm. Accessed August 22, 2005 27. Chisholm MA, Marshall J, Smith KE, Garrett CJ, Turner JC: Medicare-approved drug discount cards and renal transplant patients: How much can these cards reduce prescription costs? Clin Transplant 19:357-363, 2005 28. Yen EF, Hardinger K, Brennan DC, et al: Costeffectiveness of extending Medicare coverage of immunosuppressive medications to the life of a kidney transplant. Am J Transplant 4:1703-1708, 2004