The Patient with Chronic Kidney Disease
The insidious nature of progressive uremia deludes many patients with chronic kidney disease (CKD) into failing to take the opportunity to understand their disease; learn about their dialysis, transplant, and palliative care options; and plan their future. Relatively asymptomatic decline in renal function may explain why many ignore the early warnings of disease and fail to optimize their medical care until they are in a hospital emergency department, hyperkalemic, acidotic, and confused. The physician’s primary aims in patients with CKD are to prevent progression of disease and to ensure that the patient and their family understand the prognosis and their need to make longer term decisions. Intelligent, well researched, and financially stable members of the community tend to prepare better for the onset of end-stage kidney disease, whereas at the other extreme the poorly advised, badly educated, frightened, or noncompliant tread a hazardous course to dialysis and all too often, to an earlier death.
It is not surprising that those who plan their treatment well and receive a living donor transplant preemptively before the requirement for dialysis tend to have the best outcomes. It should also not be surprising that access to preemptive living donor transplantation is better for patients with higher socioeconomic status ( Fig. 4.1 ). Most people are, however, treated by hemodialysis or peritoneal dialysis for weeks, months, or years before finally being transplanted. There are some benefits to pretransplant dialysis, especially if the patient is chronically debilitated by their CKD, or if time is needed to enable a family member to understand the benefits of offering a kidney. For some people, the experience of dialysis provides an important demonstration of life without a renal transplant, which usually strengthens their resolve both to undergo the operation and accept the long-term consequences of immunosuppression. This chapter attempts to identify the issues that the patient, his or her family, and the community must consider before deciding to have a renal transplant.
Fitness to Transplant
The patient has, in principle, only one simple question to consider: will the quality and quantity of life be better after a transplant than on dialysis? For many people the answer is clear and unequivocal—either because the alternative of long-term dialysis treatment is not available or unaffordable, or because transplantation is the obvious solution because they are young and otherwise fit. For some people, however, the answer is clouded in uncertainty because of the relative unavailability of organs for transplantation, or because they have comorbid conditions that will be exacerbated by the operation or the ensuing immunosuppression.
Quality of life is perhaps the single most important issue for most people and yet the field has found the social sciences difficult to grasp, and there are few studies comparing quality of life on dialysis and after transplantation. Most clinicians find it hard to identify living individuals with a lower quality of life after a successful transplant than they had or would have had on dialysis, and thus find it easy to advocate for transplantation. This approach ignores the patient deaths and graft failures, and the diminished quality of life for those who struggle with the consequences of immune deficiency, infections, and malignancies. Both governments and transplant programs tend to substitute graft survival data for true quality of life data and use it as a surrogate, but objective, measure of the success that each individual might expect instead of a measured comparison of quantity of life.
In countries without sufficient access to dialysis, the decision to receive a renal transplant is obvious for almost all patients, because transplantation is the only alternative to a slow death from uremia. This does assume access both to lifelong immunosuppressant drugs and specialist medical follow-up, either of which may not be available or affordable and without which transplantation becomes a futile delusion. Understanding by a patient and their family of the lifelong commitment needed for a successful transplant is critical because patient and graft survival rates are substantially affected by compliance with follow-up and adherence to medication protocols. Transplantation has been promoted as a cure, when it is actually a complicated treatment requiring regular follow-up by specialists working in sophisticated medical centers using expensive drugs. If the patient and his of her family fail to understand the costs, level of follow-up, and the adherence that will be required of them, then it is likely that the published statistics of average survival will not apply to them.
Predicting the success rate after transplantation relies on characteristics of both the recipient and the donor. Probably the most comprehensive studies comparing transplant recipients with those remaining on dialysis come from the US where it has been possible to track the outcomes of all individuals entered onto the transplant waiting list and compare those who were transplanted with those who remained on dialysis. These studies show that transplantation carries the greater risk of death for the first 3 months or so, and reverses after that point in time so that the risk of death is equal by 6 to 9 months, thereafter favoring the transplant recipient dependent on donor and patient risk factors. Similar analyses show that the patient who is transplanted preemptively carries an advantage compared with one who has needed a period of time on dialysis; furthermore, the longer the period of dialysis the worse the outcome.
The patients’ expectations from a successful transplant may be that they will die in old age with a perfectly functioning kidney. The reality is that they will die much earlier than an age- and sex-matched individual without renal disease, and more than half will have lost their graft before they die.
Analysis of patient perspectives of the most feared risks after a transplant are a little at odds with physician views because graft loss is feared more than death.
Appropriateness to Transplant
The patient with access to both dialysis and transplantation can compare their prognosis using simple outcome statistics of dialysis and transplant patients, as seen in Fig. 4.2 . Even elderly people who have been accepted for transplantation and received a transplant survive better than those remaining on dialysis. The presumption, from the recipient’s perspective, should thus be to be assessed for fitness to be transplanted.
The next issue, for those fit enough for the procedures, is the source of a donated kidney. In many countries this will be restricted to a living donor kidney from a relative or an altruistic friend ( Fig. 4.3 ). Where the luxury of deceased donation exists, organ allocation policies become critical to the options. Careful counseling and education is needed to arrive at a decision. Consider an elderly father or mother in their late 60s without any comorbid conditions, deciding whether or not to accept a donation from a 30-year-old son or daughter. The son or daughter may consider it appropriate to offer a kidney to their parent, acknowledging the small but real immediate and possible long-term risks to themselves. The parent may consider it highly inappropriate to place their offspring at even the slightest risk to provide a few years of better quality of life for them. In the reverse situation it may be considered obvious for a 20-year-old recipient to be transplanted, but not to accept a donor offer from an elderly parent, both because of the increased risk of donation by an older person and because of the worse outcome predicted from an older kidney. It is the responsibility of the transplant unit to provide independent medical advice to ensure that both the donor and the recipient can arrive at a considered and individual decision.
Waitlisting and Allocation of Deceased Donor Organs
In those countries with deceased organ donor programs the community must decide how to manage the allocation of deceased donor kidney offers. In most countries national, regional, or local waiting lists provide access to the offer, although in some places where deceased donors are rare, selection may be ad hoc. The percentage of dialysis patients actively listed for transplantation varies quite surprisingly. There are not only barriers because of age and comorbidities but also from demographic, geographic, and socioeconomic factors. The community—when asked—almost always regards “equity of access” as the most dominant factor, but the reality is a complex balance of medical utility and sometimes conflicting notions of equity. Healthcare professionals are far from agreed on what should constitute the criteria for medical eligibility and whether or not it is appropriate to include consideration of social and lifestyle factors, ability to understand and adhere to treatment, and medical estimates of prognosis.
There are many published guidelines on assessment for transplant waiting lists. The stated aim of almost all of these guidelines is to provide objective and explicit advice to the clinician assessing an individual patient. Most achieve a comprehensive perspective, but there are substantial differences over the methodology behind each recommendation. There is a largely consistent approach to the required level of renal impairment and medical comorbidities, with most also providing broad statements on age criteria, life expectancy, and both psychological and social factors. The effect of high body mass index (BMI) is interpreted as both a criterion for surgical acceptability and a medical criterion predicting cardiovascular and other morbidity and mortality; however, advice is based on expert opinion rather than hard evidence. There is as yet little effect of formal assessment of frailty for which the data are developing. Shortage of donor organs in most environments leaves a tension between maximizing utility on the one hand and equity on the other. In resolving this tension, most guidelines attempt to promote a transparent decision-making process in the absence of a robust formula that is universally applicable to each individual.
Considerable statistical effort has been expended on predicting patient outcomes based on pretransplant factors in both the donor and the recipient. The donor element is assessed using the kidney donor profile index (KDPI), which uses only data derived from the donor before donation. The recipient element is derived by the Scientific Registry of Transplant Recipients (SRTR) from age, dialysis duration, prior transplant, and diabetes to create an expected posttransplant survival (EPTS). Using these elements it was possible to derive a new kidney allocation system in the US—the early results of which are becoming evident.
In association with new evidence-based reviews, there is now detailed advice on specific issues in recipient assessment. The EPTS and KDPI can be calculated for an individual using a published calculator. Different countries have assessed local adaptations of these formulae with varying reproducibility, demonstrating the principles are widely applicable but the detail has to be adjusted to the demographics of each environment.
What the Patient Needs to Know
The transplant unit has the responsibility to provide each patient with advice based on his or her own medical conditions and education about the options for long-term treatment ( Box 4.1 ). The starting point for such education is thus a comprehensive evaluation of the suitability, availability, and financial cost of dialysis options. The quality of physical and emotional well-being provided by dialysis therapy usually becomes abundantly clear to most patients, either through meeting other patients already on dialysis, or through dialysis education programs and finally, definitively, through direct personal experience, except in that small minority able to undergo preemptive transplantation.
General cardiorespiratory fitness for operation
Effect of obesity
Vascular system suitability for operation
Risks of recurrent renal disease
Fitness for lifelong immunosuppression
Malignancies, especially skin cancers
Cardiovascular risk factors
Histocompatibility and organ donor source; effect on outcomes
Waiting times and allocations systems on the deceased organ donor waiting list
Availability and donor outcomes of living donor procedures
Financial costs and specific risks of the donor and transplant procedures including disease transmission from the donor
Financial and adverse event costs of prophylactic immunosuppressive and antiinfective drugs
Long-term follow-up protocol
Short- and long-term risks of graft failure and death after transplantation
Consideration of acceptance of extended criteria donor organs
Patient specific issues (e.g., options for pancreas transplantation in diabetics and liver/kidney in primary oxalosis)
A comprehensive evaluation needs to be provided by the transplant unit of each individual’s medical risks if he or she were to undergo a renal transplant. Much of the rest of this chapter details the medical assessment, but a checklist is provided in Table 4.1 . This list includes those issues that affect the individual patient’s technical transplantability in addition to the short- and long-term factors that influence such outcomes as graft and patient survival. In assessing the patient’s suitability for a transplant operation the physician will be focused on the heart and lungs, the surgeon on the blood vessels and bladder. The surgeon will need to discuss the various complications and risks of the surgical procedure, whereas the physician discussion should revolve around the drugs, long-term risks, and follow-up protocols. Providing the patient with sufficient knowledge on organ allocation processes, the pros and cons of particular donor kidney offers, and on the financial costs that he or she will be expected to bear, are easily left out of a traditional medical consultation. Most established transplant programs thus have additional formal education sessions provided by a range of specialized coordinators, social workers, and pharmacists. The Internet and social media increasingly provide a wide range of both good and bad information, which patients will certainly access extensively. A guide to the better material and warnings against the bad sources of information should also play a part in the advice provided by the transplant program.
|General History and Physical Examination|
|Diagnosis of Cause of Renal Disease, with Specific Tests as Required|
|HIV antibody||HIV 1 and HIV 2|
|Hepatitis B||HBsAg, HBcAb, HBsAb|
|Hepatitis C||HCVAb, (HCV RNA if HCVAb positive)|
|Herpes virus||Herpes simplex IgG, Herpes varicella zoster IgG, HHV6, and HHV7 IgG|
|Epstein–Barr virus||EBV IgG|
|OTHER INFECTIOUS DISEASE|
|In endemic areas:||PPD skin testing|
|Trypanosoma cruzi serology|
|West Nile Virus serology|
|HTLV I and II serology|
|Toxoplasma screening |
Chest x-ray with follow-up tests as required if abnormal
Echocardiogram/stressed cardiac test—with follow-up tests as required if abnormal
Abdominal ultrasound (kidneys, gall bladder, liver, spleen)
Vascular duplex ultrasound (femoral/carotid)
It is, of course, normal practice to seek written informed consent just before undergoing any surgical procedure and all transplant operations are preceded by such a ritual signing of a legalistically phrased document. Somewhere among this scant and hastily signed documentation will be the expectation that the individual has accepted all the risks of transplantation, from transmission of serious disease from the donor, through to the side effects of every drug that they will be given. Many patients will also be presented with a dazzling array of research protocols to sign up for, with patient information sheets of many pages of closely typed and densely constructed language more designed to protect the researcher, hospital, and pharmaceutical company than inform the patient. This documentation of “consent” often takes place under pressure of time and in the middle of the night, sometimes even via the telephone. It is hard to see how anything provided by the patient in the haste of the anesthetic workup, no matter what it is written on, can be argued to be informed consent. Legal opinions have been given that suggest that no reliance can be placed on a patient’s decision taken under the duress of an immediate pretransplant consent, unless backed by extensive prior education and information. In constructing education programs, it would be wise for the transplant unit to consider the traditional “operation consent form” a legally valueless protection.
What the Potential Living Donor Needs to Know
A potential living donor usually needs to be provided information on both the recipient outcomes and the donor operation with its attendant risks to decide on whether or not to proceed. There has been considerable recent data analysis of the risks of donating a kidney (see Chapter 7 ).
A donor who expects only a successful outcome from his or her donation has a chance of being badly disappointed. It is thus essential that the best estimates of the risks of recipient death and graft failure are clearly laid before the donor. It is also important for most donors to appreciate the dialysis alternatives available to the patient and the deceased donor waiting list times. In countries with substantial waiting lists and long waiting times, living donation clearly offers huge advantages that are not so clearly apparent where deceased donor waiting times are short. In countries with high deceased donor rates, the advantages of providing a better kidney with better long-term survival may be less obvious, but just as real.
A living donor must provide fully informed consent to a surgeon with no conflicts of interest through his or her care of the potential recipient. In addition it is relevant for the donor to appreciate his or her blood group and histocompatibility match with the recipient and any concerns that there might be about the crossmatching data. A general overview of the risks that the recipient faces will help ensure that the small percentages of procedures that end in disaster are not followed by endless recrimination and litigation. More importantly, a well prepared donor is better able psychologically to face the future after a failed transplant or even death of the recipient.
What the Family Needs to Know
The families of pediatric patients are best regarded as if they were the patient, with respect to the information and counseling that they require, though there are special considerations that young age brings to bear on the decision making in renal transplantation. The family of the adult patient is in a special situation compared with other areas of medicine, because the family represent a potential source of organ donation and cannot simply be thought of as emotionally involved onlookers and supporters for the patient. Transplant units vary in the way in which information is provided about the potential to donate a kidney, with some distributing information packets directly to all known family members or encouraging attendance at education sessions covering the issue, whereas others await specific individual approaches before providing information on living related donation. In countries with low deceased organ donation rates, the increasing attention being placed upon living donation creates the ambience for routine dissemination of information to family members and friends. Accurate provision of specific relevant information is of course dependent on the consent of the recipient to release his or her private medical details. Asking the question: Is there anyone in the family who would donate you a kidney? elicits some interesting insights into the dynamics of families with members with serious chronic illness. Some patients refuse to consider a discussion of their illness with their families, whereas others are glad that an independent person is prepared to raise awareness in their family regarding the seriousness of their illness.
Lack of information is almost always the starting point for a breakdown in trust and communication between patients, their families, and their medical attendants. For this reason it is important that even the most distant of families are aware of the possibility of a poor outcome from transplantation and the importance of compliance with medication and follow-up to the long-term success of the transplant.
Specific Medical Considerations
The first consideration of any CKD patient undergoing a major operation is the state of their heart. Dialysis patients and especially diabetic dialysis patients have high incidences of both symptomatic and asymptomatic ischemic heart disease and thus a careful evaluation of the heart is essential as summarized in the recent American Heart Association guidelines. The diversity of evidence and opinion leaves open the alternative approaches as identified in the European Best Practice Guidelines.
There is agreement that all patients need a careful clinical history and examination, including an electrocardiogram and chest x-ray. In addition, most units will perform an echocardiogram to assess left ventricular function and a stressed ECG, echocardiogram, or myocardial perfusion study to exclude significant ischemic heart disease in asymptomatic high-risk patients. Whereas CKD itself is the strongest risk factor for coronary artery disease, it is also important to assess obesity, family history, lipid profile, blood pressure, smoking history, and diabetes to define risk. Attitudes to smoking history vary among transplant units from outright refusal to transplant those patients that continue to smoke, through to more liberal approaches.
Some transplant programs require routine coronary angiography before acceptance onto a waiting list. There is certainly a rationale for such an approach given the high levels of coronary disease uncovered by such a strategy. The only randomized trial of surgical or medical intervention in this situation (diabetics with CKD) was so unequivocal about the value of intervention that the trial was halted and the nonintervention arm offered surgery or angioplasty. The weaknesses of this study (it only assessed diabetics and the optimum medical therapy would not be considered optimum today) and the lack of alternative randomized studies leave the field with uncertainties, but also a very clear view that diabetic patients need comprehensive cardiac evaluation.
A lesser strategy is to use a noninvasive test such as a stressed dopamine echocardiogram, or stressed nuclear study, or more recently, CT coronary angiography as a screening method for asymptomatic and low-risk patients, thus reserving coronary angiography for those with symptoms, significant risk factors, or a positive screening test. A systematic review of the predictive value of the screening tests suggested a dobutamine stress echocardiogram had the best accuracy. Despite careful screening close to the time of the transplant, patients with disease in minor coronary branches will be operated on, sometimes leading to postoperative chest pain, troponin leakage into the blood, and cardiovascular instability.
Proceeding to transplantation in patients with normal left ventricular function and normal coronary vasculature is the easy decision. The more complex issue is deciding who to transplant despite known cardiac disease, which needs to be considered not only on its own merits, but also because of the implications that it carries for widespread vascular disease. There is no evidence-based answer to this question as yet, and clinicians must thus rely on local opinion based decisions, guided by some general principles:
Treatable coronary and valvular disease is almost always worth treating before transplantation rather than afterward, both because of the risks posed by the cardiac disease during the transplant procedure and because of the risks that cardiac interventional procedures carry in the presence of immunosuppression and a functioning transplant.
It is usually wiser to avoid transplantation if, despite treatment of coronary artery and/or valvular disease, there remains a substantial risk of infarction of a large area of myocardium, or there is substantial left ventricular dysfunction. Cardiac disease is the single largest cause of mortality in both the dialysis and transplant populations and there is little evidence that transplantation will beneficially alter the outcome of ischemic heart disease. There is less certainty with respect to congestive cardiac failure, where poorly dialyzed patients may recover significant function when uremia and chronic fluid overload are corrected by transplantation.
In patients with severe and irreversible cardiac dysfunction, the remaining consideration is the option of combined heart and kidney transplantation, available to a limited number of young and otherwise healthy individuals transplanted in highly specialized centers.
There is an absolute requirement for an available recipient artery for anastomosis of the transplant renal artery. Atheromatous iliac arteries that have been ossified through years of CKD management must thus be carefully assessed by the surgeon planning to perform the transplant. Absence of intermittent claudication and presence of palpable femoral and pedal pulses may be sufficient to confirm that renal transplantation is technically feasible. There are, however, many potential recipients with a high risk of severe vascular disease, where duplex ultrasound scanning of the femoral and carotid vessels will identify those at significant risk of peripheral or cerebrovascular events either during or after transplantation.
Selection of patients with known preexisting peripheral vascular disease must include a general assessment of their prognosis and specific assessment of the vascular supply needed for the transplant operation. The largest numbers of patients commencing dialysis in most developed countries are elderly obese type 2 diabetics, and many have severe peripheral vascular disease. Only a very small proportion of such patients prove to be suitable for transplantation because of the combined effects of obesity, cardiac, and vascular disease on their operative mortality and 3- to 5-year survival rates. Two-thirds of dialysis patients requiring lower limb amputations are dead within 2 years, implying that this group of patients have such a poor prognosis that only few, very highly selected patients should be accepted for transplantation.
Symptomatic cerebrovascular disease presents a separate problem in selection for transplantation. A history of transient ischemic attacks obviously promotes a search for a cardiac or carotid vascular cause, which if diagnosed and resolved or treated, need not contraindicate subsequent transplantation.
One group of patients that need particular attention are those with adult polycystic kidney disease, especially if they have a personal or family history of cerebral aneurysm. Evaluation of such high-risk patients requires cerebral vascular imaging such as cerebral computed tomography (CT) angiography or a magnetic resonance image angiogram to exclude berry aneurysms before proceeding to transplantation.
Assessment of respiratory disease in the potential transplant candidate has two purposes: to identify patients at risk from the anesthetic and to identify patients who will be at risk of life-threatening infection in the long term as the result of immunosuppression. The former is based around assessment of smoking and both acute reversible and chronic obstructive airway disease. It is no different from the assessment that must be made before any elective operation. The latter is a more complex decision and remains largely subjective. The diseases of importance are bronchiectasis, tuberculosis, and prior fungal infections, all of which may quickly become uncontrollable under the influence of immunosuppression. Formal evaluation of the degree of respiratory compromise and the frequency and severity of infective exacerbations will determine the advisability of transplantation of the patient with bronchiectasis.
Active pulmonary tuberculosis must be identified from routine chest x-ray and effectively treated before consideration of transplantation. Patients at high risk of reactivation of tuberculosis after transplantation include those from areas with high endemic rates, a history of exposure, calcified lesions on chest x-ray or elsewhere, and a positive QuantiFERON Gold test. Transplant units in endemic areas tend to advise high-risk patients to have a full treatment course for tuberculosis after transplantation. In developed countries, based on slender evidence, management usually involves adding a prophylactic course of isoniazid for 6 months.
The majority of dialysis patients with past or current hepatitis B will have been identified through routine testing of serum for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core and surface antigens. Many dialysis programs have a routine hepatitis vaccination policy to improve protection from cross infection, even though vaccination is much more effective if administered before the need for dialysis. Thus most patients being assessed for transplantation have been screened for prior exposure to hepatitis B.
Data from transplantation of chronically infected HBsAg-positive patients, predominantly gained in the 1980s and 1990s, demonstrate worse outcomes than for HBsAg-negative patients.
Knowledge of the status of the liver histology is important in predicting outcomes after renal transplantation, with mortality correlating with preexisting chronic hepatic inflammation grades. It is now clear that use of posttransplant lamivudine therapy has not carried the survival benefits hoped for but entecavir was associated with reduced mortality. Choice of immunosuppression after transplantation may influence the progression of hepatitis with concern expressed about steroids, azathioprine, and cyclosporine reactivating hepatitis B in the chronic carrier. Hepatitis B is not a contraindication to renal transplantation, but established cirrhosis raises the option of combined liver and renal transplantation. Data at present indicates that survival advantage is conferred by combined renal and liver transplantation only in those patients with a low model for end-stage liver disease (MELD) score of 16 to 20.
Hepatitis C represents different challenges to transplant programs in different countries, with high prevalence in dialysis programs where there is reuse of dialysis consumables and in patients transfused in the 1980s. The natural history of hepatitis C infection leading to high proportions of patients eventually developing significant liver disease has now been transformed by the advent of the new direct-acting antiviral agents (DAAs).
Limitations to treatment of patients with CKD stages 4 and 5D have been compounded by the responsiveness of different hepatitis C genotypes to the first wave of DAAs. At this moment there are no ribavirin-free and interferon-free treatments available for genotypes 2, 3, 5, and 6. Sofosbuvir regimens cannot be used safely in patients with severe renal impairment or on dialysis because of renal excretion of active metabolites though treatment after transplantation is both safe and effective. Recent advances in DAAs have, however, resolved both these problems with a combination of glecaprevir and pibrentasvir providing a 98% sustained virologic response after 12 weeks of treatment in patients with all genotypes of hepatitis C and severe renal impairment.
The best strategy for the future will be to treat patients before transplantation, but excellent results can be achieved by posttransplantation treatment if either the recipient or the donor or both have been infected with hepatitis C. This has transformed the effect of hepatitis C and relegated it to an expensive irritant rather than a major threat to patients’ lives.
Other Liver Disease
Potential renal transplant recipients may suffer from other causes of significant liver disease (see Chapter 32 ), such as alcoholic liver disease, polycystic liver in association with polycystic kidney disease, or cholelithiasis. It is thus important and relatively simple to assess both liver function and appearance of the liver on ultrasound. Fatty infiltration of the liver is the commonest finding of such screening protocols and may be associated with diabetes but is not in itself a contraindication to transplantation. Severe liver disease, no matter what the cause, inhibits acceptance for renal transplantation of most patients. There is diversity of opinion on the role of prophylactic cholecystectomy in dialysis patients with known gallstones, with the larger studies not supporting this approach, but some advocate routine pretransplant screening and surgery for known gallstones.
Infectious Disease (See also Chapter 31 )
General community protection from infectious disease will, in most countries, have led to routine childhood vaccination against measles, mumps, polio, rubella, diphtheria, tetanus, pertussis, Haemophilus influenzae B, varicella-zoster, and more recently, human papilloma virus has been added to the list. Pneumococcal and hepatitis B vaccination programs, though widespread, are far from universal. It is especially important in pediatric practice to ensure that vaccination has not been forgotten among the problems of pediatric renal failure. In adult practice it is also important to understand each patient’s vaccination history and to remedy deficiencies as soon as possible because the responses to vaccines are generally impaired in the dialysis population. Vaccination for meningococcus is especially important in patients for whom eculizumab may be considered.
Vaccination of patients after transplantation is either contraindicated with live vaccines, or may fail with killed antigen vaccines, because the medication used to prevent allograft rejection is well designed to suppress production of an antibody response to a viral antigen. Mycophenolate mofetil, for example, is especially capable of preventing antibody production after vaccination. Live vaccines are absolutely contraindicated after transplantation, with the commonest errors being the use of yellow fever vaccination in travelers to South America and chicken pox vaccination with attenuated virus, leading to life-threatening disseminated pox virus infection in transplant recipients.
Human Immunodeficiency Virus
The advent of highly active antiretroviral therapy (HAART) in the mid 1990s both transformed the outcome of patients infected with human immunodeficiency virus (HIV) and challenged the renal community to treat CKD with both dialysis and transplantation. The outcomes of HIV-positive (HIV+) patients after transplantation are acceptable in the short- and mid-term. It has been demonstrated that use of HIV+ donors is acceptable for HIV+ patients and has been pioneered in countries with high prevalence of HIV.
The accepted criteria for listing HIV+ patients include stable CD4+ T cell levels >200/μL and compliant on HAART with HIV RNA undetectable and without opportunistic infection. The main posttransplant complexity is the extremely potent pharmacokinetic interaction between HAART drugs and immunosuppressive drugs via cytochrome p450, requiring careful planning and close monitoring by both transplant and infectious disease teams. Despite the advances, it is now clear that there are potential long-term consequences of HIV infection of the transplanted kidney, which have yet to be resolved.
Other Viral Infections—CMV, EBV, HHV6/7, HHV8
Knowledge of a recipient’s status with respect to all herpes viruses has become increasingly relevant because of their potential effect after transplantation.
Chemoprophylaxis for CMV, which also protects recipients for HHV6 and HHV7, is usually based upon knowledge of the donor and recipient CMV serologic status. Transplantation of an EBV-positive organ into an EBV-negative recipient carries an increased risk of active EBV infection after transplantation and also of development of posttransplant lymphoproliferative disease (PTLD). All patients should thus be tested for antibody status with respect to each of the herpes viruses. The Transplantation Society guidelines on CMV provide a useful basis for understanding the alternative testing and therapeutic options available. HHV8 remains a potent risk factor for development of Kaposi’s sarcoma posttransplant.
The traditional approach to evaluation of the transplant recipient includes ensuring adequate dental hygiene and review of dentition before acceptance for transplantation. It is certainly true that gingival hypertrophy was a consequence of higher doses of cyclosporine, especially when combined with nifedipine, and that infected dentition may cause problems after transplantation. This has been ameliorated with use of tacrolimus and alternative antihypertensives and it would now be an unusual candidate in whom the dentition provides a risk of transplantation sufficient to outweigh the risk of continued dialysis compared with transplantation, though bacterial endocarditis is certainly important to avoid through prophylactic antibiotics at the time of dental interventions.
Miscellaneous Infections—Syphilis, Strongyloides , Toxoplasmosis, Trypanosoma
Transplant programs must pay heed to the particular infectious risks that are both endemic and prevalent in their geographic region, to properly evaluate the posttransplant risks for their transplant recipients. Trypanosoma cruzi , the causative organism of Chagas’ disease, is for example prevalent in South and Central America. It may be transmitted by donation and reactivated by immunosuppression, requiring serology and blood polymerase chain reaction (PCR) surveillance and early treatment.
Syphilis, Strongyloides , and toxoplasmosis have all been reported as opportunistic reactivations after transplantation. In most areas of the world transplant programs require a heightened awareness and lower threshold for suspicion of these diseases, rather than specific strategies for these uncommon problems. Testing for syphilis serology is still practiced by many programs, but is not seen as essential in recipients from most developed countries. It is good practice routinely to check the patient’s eosinophil count and pursue a diagnosis of infection in anyone with a raised count.
Malignancy (See also Chapter 35 )
There is a clear and defined additional risk of malignancy in patients with CKD, especially after transplantation. This increased risk is assumed to be a result of an effect of immunosuppression either on normal mechanisms for control of neoplastic cells or more likely the effect on viral carcinogenesis. This knowledge has been translated to a reluctance to transplant patients who have had a prior cancer for fear that immunosuppression will allow recurrence that might otherwise not happen.
Recent data question this set of assumptions. First, a number of cancers are increased in CKD patients, in patients on dialysis, and in patients after transplantation. Second, the cancers with substantially increased risk are restricted to skin and lip cancers, renal tract cancers, and those for which a viral etiology is either established or suspected. The implication for the potential transplant recipient is that cancers that are now understood to occur at the same rate as in the normal population should probably be considered differently to those where the risk is increased.
It has been standard advice not to transplant a patient within 2 to 5 years of diagnosis and definitive treatment of cancer, depending on which cancer is under consideration. Most guidelines suggest careful screening for cancers in patients on the transplant waiting list. Unfortunately such blanket rules, though easy to apply, do not take into consideration the variability of the biology of the different cancers and especially do not consider the individual risks of recurrence. Table 4.1 gives a list of cancer types that are known to be increased in dialysis and transplant patients and should thus be viewed with considerable caution in patients being assessed for transplantation. Melanoma, for example, is known to respond to T cell immunotherapy and has a substantially increased risk after transplantation. It is known to recur in normal individuals and to metastasize aggressively. Melanoma has also been observed to recur after transplantation with long disease-free intervals pretransplantation and must thus be approached very conservatively despite the advent of checkpoint inhibitors. Breast and prostate cancer, on the other hand, are not increased in most studies of dialysis and transplant populations but have substantial metastatic potential. To avoid transplanting a patient who will succumb to metastatic cancer soon after transplantation, it is thus prudent to advise a waiting period of at least 2 years, depending to a certain extent on the predicted risk of spread in any given individual.
Common cancers occur frequently in dialysis and transplant patients. It is important not to shift the clinical emphasis from common cancers to rare cancers, such as Kaposi’s sarcoma, just because these rare cancers occur with a greatly increased risk compared with the general population. The common cancers in the Australian CKD population include kidney, bladder, colon, lung, melanoma, breast, and prostate ( Table 4.2 ). There is no specific guideline for cancer screening before listing a dialysis patient for transplantation. It would, however, be reasonable to at least ensure that patients are aware of cancer risks and advise that screening guidelines recommended in the general population for cervical, breast, and bowel screening have been undertaken.