Recipient selection for kidney transplantation Candidate has to meet medical, social, lifestyle and psychosocial criteria for new organ Dr. Javier González Dept. of Urology Renal Transplant Unit General University Hospital Gregorio Marañón Madrid (ES) fjgg1975@yahoo.com
Prof. Enrique Lledó Dept. of Urology Renal Transplant Unit General University Hospital Gregorio Marañón, Madrid (ES) enrique.lledo@ salud.madrid.org Kidney transplantation (KT) is an elective procedure. Unlike for other solid organ transplants, there are different alternatives such as renal replacement therapy (RRT), representing an option for the treatment of patients with end-stage chronic kidney disease (CKD). Most patients suffering from this condition will benefit from these options. However, providing the patient with sufficient counselling is a prerequisite before including a candidate in the waiting list. Whether or not to include a candidate remains a complex decision that should balance the expected benefits (sometimes detriment) of KT, patient equitability and social responsibilities of the professionals involved in order to allocate the limited supply of donor organs wisely. [1] This article aims to outline and discuss the commonly used selection criteria to help potential recipient screening in an individual fashion. Selection criteria There are many factors that may render a candidate ineligible for KT. Criteria to put a candidate on the waiting list for KT should take into account the potential risks for surgical complications and issues related to immunosuppression. These criteria, when adequately applied, should limit patient perioperative mortality and screen for conditions that would be exacerbated by immunosuppression. Overall, practice guidelines always include broad cardiovascular contraindications. However, differences in age cut-offs, estimated life expectancy and glomerular filtration rate do exist among different practice guidelines. In addition, inconsistencies occur in cancer-free intervals, human immunodeficiency virus (HIV) thresholds and adherence to antiretroviral therapy, psychological screening or clinical assessment tools. Nevertheless, the following four major criteria are quite consistent among the different practices guidelines available: i) ii) iii) iv)
recipient age; life expectancy; medical criteria social, lifestyle, and psychosocial circumstances.
Expected Post-transplant Survival The Scientific Registry of Transplant Recipients Review Committee of the United Network of Organ Sharing (UNOS) has analysed these four factors and their potential role in life expectancy after KT. This analysis led to the Expected Post-transplant Survival (EPTS) score. [2] The score includes the following elements: time on dialysis, current diagnosis of diabetes, prior solid organ transplants, candidate age. The EPTS score is currently used in the UNOS allocation policies and intents to optimise longevity-matching in an effort to maximise the utility of KT.
and psychosocial history and detailed physical examination aimed at detecting such comorbid conditions. Infection screening Screening for infections is mandatory in the initial evaluation of a potential KT recipient. The presence of hepatitis B and C, syphilis, HIV and tuberculosis viruses should be excluded in advance. Evidence of active infection warrants treatment prior to immunosuppression initiation. Cytomegalovirus (CMV) serostatus guides further post-transplant prophylaxis and should be determined in all candidates. Immunisation prior to KT should be administered to those candidates who are seronegative for Varicellazoster virus, given that in immunocompromised patients, infection can be devastating. Finally, it is advisable to screen for Epstein-Barr virus serostatus because an increased risk for lymphoproliferative disease is carried by seronegative candidates. In fact, it is also unsafe for these patients to receive betalacept in the post-transplantation period. Viral hepatitis Active viral hepatitis increases the risk of upregulation of virus replication and favours ongoing liver damage. In these cases, a transjugular liver biopsy is indicated to assess its underlying severity. The information provided by the liver biopsy may also help in identifying patients at a special risk of liver failure, which facilitates the decision in the case of a dual organ transplantation. Although chronic hepatitis B infection may not be considered an absolute contraindication to KT, candidates affected should undergo a test for virus hepatitis B e-antigen and DNA titers as an additional evaluation to predict the risk of reactivation.
"... in immunocompromised patients, infection can be devastating." Hepatitis C treatment before KT remains controversial in the light of newer highly effective antiviral agents. Active hepatitis C patients without advanced liver disease may opt to receive grafts from hepatitis C positive donors. Accepting these grafts may result in earlier transplantation, thus decreasing dialysis time frames and improving transplantation outcomes. Actually, the treatment of hepatitis C is so successful that the Ethics Committee of UNOS has suggested that it is justifiable to transplant hepatitis C positive kidneys into hepatitis C negative recipients. A wise approach to this issue would be to defer treatment of hepatitis C in patients with stage 0-2 liver fibrosis under proper consent, to treat hepatitis C before KT in patients with liver fibrosis stage 3 to decrease the patient´s risk of cirrhosis, and to refer patients with stage 4 liver fibrosis for combined kidney-liver transplantation. Cardiovascular screening Cardiovascular comorbid conditions are extremely common in patients with end-stage CKD, particularly asymptomatic coronary artery disease (37-53% for at least one coronary artery stenosis of 50% or greater). Without a doubt, cardiovascular conditions remain an important source of morbidity and mortality, representing the first cause of death in the immediate postoperative period. In fact, cardiovascular complications account for 30% of deaths with a functioning renal allograft.
The main goal of cardiovascular screening should be to detect the subpopulation of recipients who will probably develop a cardiac event after transplantation and would benefit from a pre-transplant strategy. However, the appropriate cardiac risk assessment strategy for patients with end-stage CKD is still at contention. The American Society of Transplantation (AST) recommends stress echocardiography or scintigraphy as a part of the screening process. Depending on these test outcomes, the patient may have to undergo an angiogram (with or without revascularisation) before the KT is attempted. Conversely, the American Heart Association (AHA) do Although suitability of KT is a topic for debate, most not recommend pre-transplantation cardiac would agree that there are some absolute evaluation since KT can be considered a procedure of contraindications. Active infection or malignancy, substance abuse, reversible renal failure, uncontrolled intermediate risk under adequate functional status. psychiatric disease, documented treatment nonLack of meaningful consensus adherence, and a significantly shortened life expectancy are factors to consider in the suitability of The lack of meaningful consensus leads to difficulty in determining which patients require no testing, KT. Therefore, the initial assessment of a potential recipient should include a thorough medical, surgical non-invasive cardiac testing or invasive interventions. Screening all patients on the waiting list may turn out to be expensive, time consuming, and impractical. For EAU Section of Transplantation Urology (ESTU) these reasons, many transplant programmes support 44
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the guidelines of the AST. In fact, there is great emphasis on focused screening for patients at a higher risk of coronary artery disease among the group with end-stage CKD. The AST advocates non-invasive cardiac stress imaging for patients with diabetes, prior ischemic heart disease or two of the following criteria: i) men older than 45 years ii) women older than 55 years iii) ischemic disease in a first-degree relative iv) smoking v) hypertension vi) cholesterol level > 200 mg/dL vii) HDL > 35 mg/dL viii) left ventricular hypertrophy [3] The most commonly used non-invasive screening tests for heart disease include exercise electrocardiogram and myocardial perfusion study (Thallium/Sestamibi scintigraphy and echocardiography under exercise/dobutamine). The physical basal condition of the patient under dialysis often does not allow an exercise test due to reduced reserve capacity, making perfusion studies the usual choice. However, the ideal perfusion test remains under debate. Every centre is encouraged to choose the myocardial perfusion test under the consensus of a multidisciplinary team. It seems clear that patients harbouring critical coronary artery lesions should be referred for angioplasty, stent placement or coronary artery bypass graft surgery. Non-ischemic cardiac conditions There are other non-ischemic cardiac conditions that may impact patient morbidity and mortality after KT including systolic/diastolic cardiac dysfunction, pulmonary hypertension and valvular heart disease. Structural and functional myocardial impairment is rather frequent among patients with CKD. The term “uremic cardiomyopathy” describes the alterations that explain the diastolic dysfunction that worsens with CKD progression. Abnormalities that arise on echocardiogram in this context, particularly left atrial volume, have emerged as a risk marker of death in patients suffering from end-stage CKD after transplantation. Myocardial dysfunction is directly related to the number of cardiovascular events that occur after transplantation. Conversely, the abnormalities leading to myocardial dysfunction may be counterbalanced (thus returning to normal) in many occasions after KT. If myocardial dysfunction has any point of reversibility, KT should be encouraged. Otherwise, if the screening of myocardial dysfunction does not show any point of reversibility, the patient should be referred for combined dual heart-kidney transplantation.
treatment are a matter of debate and vary among institutions and cancer types. In situ or superficial cancers may not require any interval until safe transplantation. Conversely, extensive cancer situations may require longer free-intervals. The AST advise in favour of at least a 2-year disease-free interval for most cancers and a 5-year interval for stage II breast cancer, extensive cervical cancer, stage C colorectal cancer, melanoma other than in situ, and locally advanced renal cell carcinoma. A valuable source to be used in ambiguous cases is the American Cancer Society routine cancer screening recommendation for the general population for patients prior to transplantation. [5] An intense screening for renal cell carcinoma is advisable in patients suffering from Balkan nephropathy, analgesic induced nephropathy and Chinese herb-induced nephropathy. Although there is no convincing evidence to support a recommendation, patients with prior exposition to cyclophosphamide may require more intense screening for bladder cancer.
"... cardiovascular complications account for 30% of deaths with a functioning renal allograft." Psychosocial screening The main purpose of the psychosocial screening is to identify barriers that may impact adherence to a complex medical schedule. These barriers may include behavioural, social and financial issues that most programmes address through a multidisciplinary team including social workers/ mental health professionals with enough experience and expertise in the field. Patients with end-stage CKD are at substantial risk of psychiatric conditions that may negatively impact adherence to a tight treatment schedule. Depression and anxiety are especially prevalent with incidences reported of 2-16% and up to 39%, respectively. However, evidence on how these conditions impact morbidity/mortality after transplantation are inconsistent. Patients suffering from alcohol abuse and other dependencies pose a special challenge. Every effort aimed at treating substances abuse prior to transplantation is advisable. These patients should undergo extensive counselling, and a documented drug-free period may be required.
High cost Financial issues should be evaluated before transplantation. The high cost of medications and the requirements regarding postoperative follow-up may pose a hard-to-afford task for many families, especially if the recipient is the primary source of Pulmonary hypertension Pulmonary hypertension is detected in almost 50% of income. Financial risks may lead to medication discontinuation, miss of follow-up appointments, and patients with end-stage CKD on haemodialysis and has been highlighted as an independent risk factor for thus renal allograft rejection. early graft dysfunction after deceased donor KT. Finally, an intense scrutiny regarding behavioural However, this condition may improve after patterns of adherence to pre-transplantation transplantation. Aggressive diuresis or ultrafiltration medication is advisable since this behaviour predicts on dialysis may favour a substantial decrease in the pattern of adherence to medication in the pulmonary artery pressures. If these measures are postoperative period. Non-adherence to proved unsuccessful, right heart catheterisation may be required to better define the perioperative risk and immunosuppression remains a leading cause of graft failure post-transplantation. This situation can be potential reversibility, making those patients with predicted based on the behaviour the patient shows uncorrected severe pulmonary hypertension poor candidates for transplantation. Valvular heart disease with dietary, medication and treatment compliance in is also rather frequent in patients with end-stage CKD. the dialysis period or the willingness and ability to follow through with transplant screening Although there are no specific guidelines on how to recommendations in a timely manner. proceed with these patients, it seems clear that moderate/severe aortic stenosis should be considered References for valvular replacement in order to increase the 1. Rodríguez-Faba O, Boissier R, Budde K, et al. European chance for better outcomes. [4] Cancer screening The risk of developing cancer in the patient harbouring a kidney allograft has been estimated 2-3 fold higher than that of the general population. Active malignancy remains a major contraindication for two reasons: i) the shortage of organs in the donor pool makes providing an organ to individuals with limited life expectancy unjustifiable ii) the immunosuppression required after KT to ensure optimal graft function may accelerate the progression of an underlying malignancy However, in cancer survivors with end-stage CKD requiring RRT, transplantation may represent an excellent choice. The optimum time free-intervals regarding curation or relapse possibility after cancer
Association of Urology Guidelines on Renal Transplantation: Update 2018. Eur Urol Focus 2018; 4: 208-215. doi: 10.1016/j.euf.2018.07.014. 2. Organ Procurement and Transplantation Network (U.S. Department of Health & Human Services). A Guide to Calculating and Interpreting the Estimated PostTransplant Survival (EPTS) Score Used in the Kidney Allocation System (KAS). https://optn.transplant.hrsa.gov/ media/1511/guide_to_calculating_interpreting_epts.pdf 3. Gill JS. Screening Transplant Waitlist Candidates for Coronary Artery Disease CJASN 2019; 14: 112-114. doi: 10.2215/CJN.10510918 4. Delos Santos RB, Gmurczyk A, Obhrai JS, Watnick SG. Cardiac Evaluation prior to Kidney Transplantation. Semin Dial. 2010 May-Jun; 23(3): 324–329. doi: 10.1111/j.1525-139X.2010.00725.x 5. http://www.cancer.org/healthy/findcancerearly/ cancerscreeningguidelines/american-cancer-societyguidelines-for-the-early-detection-of-cancer
August/September 2021
