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Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient

Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient
Literature review current through: Jan 2024.
This topic last updated: Jan 17, 2024.

INTRODUCTION — Kidney transplantation is the treatment of choice for most patients with end-stage kidney disease (ESKD). A successful kidney transplant improves quality of life, reduces the mortality risk, and is less costly for the majority of patients when compared with maintenance dialysis.

Patients with ESKD often have significant comorbidities. It is important that kidney transplant candidates are carefully evaluated in order to detect and treat coexisting illnesses, which may affect perioperative risk and survival after transplantation as well as transplant candidacy. The evaluation should be as efficient and cost effective as possible.

This topic will review the evaluation of the potential kidney transplant recipient. The evaluation of the living kidney donor is discussed separately. (See "Kidney transplantation in adults: Evaluation of the living kidney donor candidate".)

TIMING OF REFERRAL — Transplantation should be discussed with all patients with irreversible and progressive chronic kidney disease (CKD).

Patients who are interested in transplantation and who have no known contraindications should be referred to a transplantation program when the estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m2 [1]. Although no form of kidney replacement is indicated at this level of kidney function, this early referral allows sufficient time for a complete evaluation and for interventions that may be required to address relative contraindications prior to transplantation, both of which can be time consuming. It also allows an opportunity for the candidate to explore their potential living-donor options in a timely manner, which may facilitate a transplant before needing dialysis.

Ideally, the transplant should take place before dialysis is required. Studies have reported improved patient and graft survival when patients receive their first transplant before the need for maintenance dialysis. (See "Kidney transplantation in adults: Timing of transplantation and issues related to dialysis", section on 'Timing of transplantation'.)

CONTRAINDICATIONS

Absolute contraindications – Absolute contraindications to kidney transplantation include the following:

Active infections

Active malignancy (excluding non-melanoma skin cancers)

Active substance use disorder (with center-specific policies on marijuana use)

Reversible kidney failure

Uncontrolled psychiatric disease

Documented active and ongoing treatment nonadherence

A significantly shortened life expectancy is generally a contraindication to transplantation. There is no universally accepted life expectancy below which an individual is ineligible for kidney transplantation, although a life expectancy of less than one year posttransplant precludes the possibility of transplantation at virtually all centers. Some centers are hesitant to transplant an individual with a life expectancy of less than five to seven years since that approximates the expected half-life of the allograft [2]. However, in other centers, individuals with much shorter life expectancy may be eligible for transplantation, depending upon the nature of the chronic illness.

Recipient age alone is not a contraindication to transplantation. Many patients >60 years of age and selected patients >70 years have been transplanted safely and with an acceptable rate of long-term graft function [3,4]. Based on the Organ Procurement and Transplantation Network National Data, in the year 2020, recipients ≥65 years of age comprised 23 percent of deceased-donor recipients and 19 percent of living-donor recipients [5]. However, in order to be evaluated for transplantation, patients should have an estimated life expectancy exceeding the anticipated waiting time for a kidney, and kidney transplantation should not be pursued in cases where limited life expectancy minimizes the potential benefit of transplantation.

Relative contraindications – Many relative contraindications are identified by the pretransplant evaluation and by the additional evaluation of identified comorbid conditions. These are discussed below. (See 'Targeted evaluation of comorbid conditions' below.)

In addition to the potential contraindications that are discussed in individual sections below, certain systemic conditions are relative contraindications to transplantation and require careful evaluation and, if possible, intervention. These include malnutrition, primary oxalosis, and active systemic diseases that may limit the longevity of the transplant allograft (such as uncontrolled antineutrophil cytoplasmic antibody-associated vasculitides, systemic lupus erythematosus, or monoclonal gammopathy of renal significance). Some centers exclude patients with severe hyperparathyroidism although some clinical guidelines recommend not refusing a recipient on the basis of uncontrolled hyperparathyroidism [6].

Patients with severe hyperparathyroidism may be referred for subtotal parathyroidectomy prior to transplantation. Issues associated with transplantation in patients with severe hyperparathyroidism are discussed elsewhere. (See "Refractory hyperparathyroidism and indications for parathyroidectomy in adult patients on dialysis", section on 'Patients awaiting transplantation'.)

Patients with primary oxalosis should be evaluated for combined kidney-liver transplantation. (See "Primary hyperoxaluria", section on 'Transplantation'.)

Patients with systemic amyloidosis, particularly those with cardiac involvement, may not be candidates for kidney transplant due to high mortality. This should be evaluated on an individual basis. (See "Renal amyloidosis", section on 'Dialysis and kidney transplantation'.)

INITIAL EVALUATION — The goal of the pretransplant evaluation is to identify comorbidities that could affect candidate survival after transplantation. The evaluation also determines whether transplantation is technically feasible and may guide posttransplant immunosuppression. Comorbidities that significantly shorten survival may render a candidate ineligible for transplantation because of the decrease in the absolute survival benefit conferred by transplantation.

History and physical examination — The initial evaluation begins with a thorough medical and surgical history, with an emphasis on the following [7]:

Etiology of the original kidney disease and the risk of recurrence in the transplanted kidney. The native kidney biopsy report should be reviewed, if available, in order to assess the risk of recurrent disease after transplantation. Current disease activity should also be assessed.

History of familial or hereditary kidney disease, particularly if living, related donation is an option.

Potential sensitization risks, including history of blood or platelet transfusion, pregnancies, and previous transplants.

History of prior immunosuppressive therapy.

Medical comorbidities, including the following (see 'Targeted evaluation of comorbid conditions' below):

Cardiovascular disease, cerebrovascular disease, or peripheral vascular disease.

Diabetes mellitus.

Prior or active cancer.

Prior or active infection.

Pulmonary disease or pulmonary hypertension.

Peptic ulcer disease, cholelithiasis, or diseases of the colon or liver.

Hypercoagulable state, as suggested by a history of recurrent miscarriage, arterial/venous thrombosis, hemodialysis graft or fistula thrombosis, systemic lupus erythematosus, or prior unexplained graft thrombosis.

Monoclonal gammopathy of undetermined significance (MGUS).

Bladder dysfunction, augmentation, or substitution; recurrent urinary tract infection; or pyelonephritis or reflux.

Psychiatric disorders including depression, anxiety, and bipolar disorder.

History of prior surgery, especially abdominal procedures.

Review of medications, particularly looking for drugs metabolized by the cytochrome P450 system that may potentially interact with immunosuppressive agents administered posttransplant.

Immunization history. (See 'Infections' below.)

Physical activity history, including frequency, intensity, and type of activity, to assess functional status. (See 'Frailty' below.)

In retransplantation candidates, prior transplantation courses and cause of graft loss, medication adherence, and previous transplantation complications.

A detailed physical examination should be performed; important features include the following:

Assessment of body mass index (BMI) and central adiposity. (See 'Obesity' below.)

Oral examination looking for advanced dental decay and signs of infection. (See 'Infections' below.)

Auscultation for carotid bruits. (See 'Cerebrovascular disease' below.)

Assessment of bilateral femoral and pedal pulses and lower extremity integrity. (See 'Peripheral vascular disease' below.)

Palpation for abdominal masses (eg, polycystic kidneys) and assessment of prior abdominal procedures (eg, peritoneal dialysis catheter placement) that may affect placement of the kidney transplant.

Dialysis access location (in patients on dialysis).

Psychosocial assessment — All potential transplant recipients should undergo a psychosocial evaluation to identify behavioral, social, and/or financial issues that may influence adherence and outcomes after transplant [1,8,9]. The psychosocial assessment is typically performed by a social worker or psychologist trained in the evaluation of transplant candidates, with referral for neuropsychiatric assessment if needed. Important elements of the assessment include the following:

Understanding of the transplant process – Patients must be able to demonstrate understanding of the potential risks and benefits of transplantation, the need for lifelong immunosuppressive therapy, and the need for adherence to medication and follow-up [10].

Cognitive evaluation – A cognitive evaluation is performed to assess the patient's decision-making capacity and ability to provide informed consent for transplantation. Patients with severe cognitive impairment may be acceptable candidates for transplantation, provided that adequate caregiver support and supervised medication administration are guaranteed.

Psychiatric disorders – Patients with mood, anxiety, or personality disorders should be referred to psychiatry for treatment in order to improve access to and success after transplantation.

Alcohol and/or substance use – Alcohol and/or substance use disorders must be addressed prior to transplantation. We require that patients with alcohol and/or substance use disorder enroll in a rehabilitation program and remain drug or alcohol free, confirmed by random drug testing. Policies on marijuana use vary by center. Some centers consider marijuana use a contraindication to transplant due to the risk of fatal pulmonary aspergillosis when inhaled; increased risk of hypotension, cardiovascular disease, and peripheral vascular disease; and potential drug interactions with calcineurin inhibitors. If a center accepts marijuana use, patients should be counselled to switch to edible marijuana at the time of transplant.

Some centers require patients to abstain from tobacco. We require candidates with known end-organ disease (cardiovascular, pulmonary, or peripheral vascular disease) and those at high cardiovascular risk (eg, patients with diabetes) to quit smoking for six months. Some programs will require proof of tobacco cessation by checking blood nicotine levels.

Adherence – The patient's prior and current adherence to medications and other recommended therapies (eg, dialysis) should be assessed. Proven habitual medication nonadherence or insurmountable psychosocial barriers to posttransplant adherence are a relative contraindication to transplantation.

Social support – Patients should ideally have an available and stable social support system in place throughout the transplant process. Lack of a support system is considered a contraindication to transplantation at most centers.

Financial support – Given the high costs of immunosuppressive therapy, financial resources and insurance coverage for each transplant candidate should be reviewed. Potential financial barriers should be addressed prior to transplant, with determination of whether transplant is feasible.

Laboratory and imaging tests — Laboratory and imaging tests that are routinely obtained during the kidney transplant evaluation are provided in the table (table 1). Specific tests may vary depending upon the patient's age and medical history, geographic location, and the practice of the individual transplant center.

TARGETED EVALUATION OF COMORBID CONDITIONS — Further evaluation is directed to comorbidities and risk profiles of individual patients.

Cardiovascular disease — Patients with known heart disease, or who are at high risk for heart disease, are eligible for transplantation but require careful evaluation. Cardiovascular disease is the leading cause of death after kidney transplantation [11,12] and is also a major cause of morbidity and mortality in patients on the waiting list [13-15].

The cardiac evaluation begins with a history, physical examination, and electrocardiogram (ECG) [1,12]. In addition, transthoracic echocardiography is routinely performed at many centers to assess for left ventricular dysfunction, valvular heart disease, and pulmonary hypertension [1,9,12]. Further evaluation depends upon the patient's risk profile, as discussed below.

Coronary artery disease — Cardiovascular events are a leading cause of mortality among kidney transplant recipients. (See "Risk factors for cardiovascular disease in the kidney transplant recipient", section on 'Overview of cardiovascular risk'.)

Eligibility for transplantation – We agree with the 2005 Canadian Society for Transplantation guidelines, which suggested that the following patients with known coronary artery disease (CAD) may be eligible for kidney transplantation (table 2) [9]:

Asymptomatic low-risk patients

Asymptomatic patients in whom noninvasive testing is negative

Patients on appropriate, guideline-directed medical therapy with angiographic results showing acceptable burden of disease

Patients in whom successful revascularization interventions have been performed

Many centers consider the following as relative contraindications to transplantation:

Progressive symptoms of angina that are not amenable to angioplasty or bypass surgery

History of myocardial infarction within the past three to six months

Known severe CAD that is not amenable to intervention

Irreversible ischemic cardiomyopathy with severe systolic dysfunction

Evaluation for CAD – Evaluating asymptomatic transplant candidates for CAD is commonly performed at transplant centers with the goal of diagnosing occult CAD, reducing perioperative cardiac events and mortality, and improving long-term outcomes after transplantation. However, it is uncertain whether evaluating asymptomatic candidates provides any benefit [12,16,17]. The optimal approach to evaluation is not known, and clinical practice varies significantly among transplant centers. Some centers evaluate only patients with significant risk factors, while other centers evaluate all candidates. Clinical practice guidelines also vary considerably [1,6,8,9,12,18].

At our centers, we take the following approach to evaluating asymptomatic transplant candidates (algorithm 1):

In patients who have evidence of cardiomyopathy with a low ejection fraction (<30 percent), we refer for cardiology evaluation and angiography. For those on dialysis, some clinicians would first review the patient's dialysis records to make sure that the patient has been adequately dialyzed to their dry weight with acceptable interdialytic weight gain. Patients with a low ejection fraction are considered to be at high risk for CAD. The decision to proceed with angiography and possible angioplasty or surgery is made in conjunction with the patient's cardiologist.

In patients who do not have evidence of cardiomyopathy with low ejection fraction, we obtain noninvasive stress testing if the patient is ≥45 years old, has diabetes mellitus, or has a prior history of CAD. We do not routinely obtain noninvasive stress testing in transplant candidates <45 years old who do not have diabetes or a prior history of CAD, although some contributors to this topic would obtain stress testing for such patients if they have a prolonged duration of chronic kidney disease (CKD), dialysis vintage >1 year, a history of uncontrolled hypertension, or family history of heart disease [19,20]. Noninvasive testing can be performed with a stress echocardiogram (exercise or dobutamine), myocardial perfusion study, or coronary computed tomography (CT) angiography [21]. The optimal choice is generally based upon the expertise of the particular medical center and clinical patient characteristics [22].

-Patients with an abnormal noninvasive stress test should be referred for cardiology evaluation and possible angiography.

-In patients with a negative noninvasive stress test who are waitlisted for transplantation, we repeat noninvasive stress testing every one to two years in those who have diabetes and every two years in those who do not have diabetes. Other transplant programs may elect to defer testing in patients without a living donor until they have sufficient priority on the deceased donor waitlist for kidney transplantation [23]. There is no evidence to support periodic stress testing of asymptomatic candidates while they are on the waiting list [12]. A randomized trial (Canadian-Australasian Randomised Trial of Screening Kidney Transplant Candidates for Coronary Artery Disease) evaluating the benefit of periodic testing for CAD among waitlisted transplant candidates is in progress (NCT03674307).

A Cochrane systematic review of 11 studies (690 patients) found that dobutamine stress echocardiography and myocardial perfusion scan both have moderate sensitivity and specificity in detecting severe CAD among kidney transplant candidates [24]. Dobutamine stress echocardiography appeared to have a higher sensitivity and specificity than myocardial perfusion scan, but this difference was not statistically significant. In another systematic review of 52 studies (7401 patients), both dobutamine stress echocardiogram and myocardial perfusion scan were as good as coronary angiography at predicting cardiovascular mortality and major adverse cardiac events [25].

Whether detecting and intervening on CAD prior to transplantation leads to improved outcomes is uncertain. One randomized trial found similar rates of death or nonfatal myocardial infarction at a median of 2.2 years between waitlisted transplant candidates who underwent preemptive angiography and revascularization and those who were treated with optimal medical therapy [26,27]. Data from observational studies have been mixed, with some, but not all, studies showing improved survival with revascularization compared with no revascularization [28-31]. Some experts believe that evaluating candidates for CAD may help to exclude high-risk patients from transplantation. However, even patients at high risk for major cardiac events have better survival and quality of life compared with those who remain on dialysis, and, therefore, excluding patients on the basis of CAD alone may not be in their best interest. (See "Kidney transplantation in adults: Patient survival after kidney transplantation", section on 'Survival compared with dialysis'.)

Heart failure — Severe ischemic cardiomyopathy (ejection fraction <30 percent) is a relative contraindication to kidney transplantation. Combined kidney-heart transplantation may be considered in select patients who require transplantation of both organs. Among potential recipients, it is extremely important to exclude the presence of reversible impairment of either organ. (See "Heart transplantation in adults: Indications and contraindications".)

Patients with nonischemic cardiomyopathy and no other significant comorbidities may be candidates for kidney transplantation alone after consultation with a heart failure specialist. Cardiomyopathy may reverse or improve after kidney transplantation.

Left ventricular diastolic dysfunction and left atrial enlargement have been associated with worse outcomes after transplantation [32,33]. These risk factors are potentially modifiable by strategies that improve left ventricular compliance, such as more aggressive ultrafiltration on dialysis. As such, it is important to perform cardiac echocardiography when the patient is at their dry weight in order to avoid false positive results and to repeat echocardiography after dry weight reduction and after load control have been attempted. There are insufficient data to determine that patients with diastolic dysfunction are not suitable transplant candidates.

Valvular heart disease — Patients who have significant valvular heart disease may not be eligible for kidney transplantation and should be referred to cardiology for further evaluation and management prior to transplantation [34-37].

Pulmonary hypertension — Patients with irreversible moderate to severe pulmonary hypertension may not be eligible for kidney transplantation [1]. Other factors that should be considered when determining transplant candidacy in such patients include overall cardiac status (especially the extent of right ventricular systolic dysfunction), donor source, and degree of sensitization. Severe pulmonary hypertension has been associated with decreased posttransplant survival [38] and, among recipients of a deceased-donor kidney, an increased risk of early kidney allograft dysfunction [39]. (See "Pulmonary hypertension in patients with end-stage kidney disease".)

We evaluate all kidney transplant candidates for pulmonary hypertension by echocardiography [40]. Among patients who have pulmonary hypertension suggested by echocardiogram, we generally reassess after challenging the estimated dry weight by either diuresis or ultrafiltration during dialysis. If testing remains abnormal, further evaluation, including right heart catheterization, should be performed to confirm the diagnosis and to elucidate the underlying cause. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Initial diagnostic evaluation (noninvasive testing)'.)

Patients with pulmonary hypertension should be treated, if possible, prior to transplantation. Select patients that are otherwise acceptable transplant candidates may become eligible if pulmonary hypertension is successfully controlled with hemodynamic optimization or pulmonary vasodilator therapy. (See "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)".)

Cerebrovascular disease — Older patients with risk factors such as hypertension, cigarette smoking, and hypercholesterolemia should be carefully examined for evidence of carotid stenosis (eg, carotid bruits), which should be evaluated by carotid Doppler studies and addressed prior to transplantation. Patients with a history of stroke or transient ischemic attacks (TIA) should be evaluated by a neurologist and receive carotid Doppler studies. If carotid surgery is indicated, it should be done prior to transplantation. The indications for carotid surgery are the same for transplant candidates as for the general population. (See "Carotid endarterectomy", section on 'Carotid atherosclerotic disease' and "Management of symptomatic carotid atherosclerotic disease".)

The optimal timing of transplantation after a stroke or TIA is uncertain, and there are no data to guide clinical decisions. Guidelines based upon expert opinion suggest that patients should wait at least six months after a stroke and at least three months after a TIA before being transplanted [1].

We perform a screening magnetic resonance angiogram (MRA) in all transplant candidates with autosomal dominant polycystic kidney disease (ADPKD) who have a history of headaches or a family history of aneurysm. However, some centers perform MRA in all ADPKD transplant candidates irrespective of symptoms or family history. Those found to have aneurysms >7 to 10 mm in diameter warrant neurosurgical evaluation prior to transplant. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations", section on 'Screening' and "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations", section on 'Indications for intervention'.)

Diabetes mellitus — Several issues of particular concern should be addressed in the pretransplant setting among transplant candidates with diabetes:

In all transplant candidates with diabetes, we assess the duration of diabetes and insulin use, daily insulin requirements, and the presence and severity of diabetes-related complications. In addition to a hemoglobin A1c level (see 'Laboratory and imaging tests' above), obtaining a fasting C-peptide and simultaneous glucose level may be useful to assess endogenous insulin production.

Patients with insulin-requiring diabetes mellitus, low endogenous insulin production, and advanced CKD or end-stage kidney disease (ESKD) may be potential candidates for combined pancreas-kidney transplantation. The selection and evaluation of such patients for pancreas-kidney transplantation are discussed in detail separately. (See "Pancreas-kidney transplantation in diabetes mellitus: Patient selection and pretransplant evaluation".)

All transplant candidates with diabetes should be screened for CAD in order to identify modifiable cardiac conditions and potentially reduce morbidity and/or mortality while on the waitlist and following transplantation. (See 'Coronary artery disease' above.)

All transplant candidates with diabetes should be routinely screened for peripheral vascular disease (PVD). PVD is common among patients with ESKD who have diabetes and may prevent a successful anastomosis to the kidney allograft. (See 'Peripheral vascular disease' below.)

Other issues related to kidney transplantation in patients with diabetic kidney disease are discussed elsewhere. (See "Kidney transplantation in diabetic kidney disease".)

Frailty — Frailty is characterized by a physiologic decline, including features such as weight loss, fatigue, weakness, slow gait, and low activity, that exceeds what might be expected based on age alone (see "Frailty"). Frailty in kidney transplant recipients has been associated with an increased risk of delayed graft function [41], early hospital readmission [42], longer length of hospital stay [43], and death [44,45]. Despite this strong association, there is no consensus on whether and how to perform a functional assessment of the potential transplant recipient [46,47].

Given the increasing age of kidney transplant recipients, we believe that a comprehensive functional assessment including functional status, physical performance, and frailty score should be performed in candidates older than 60 years of age and those with apparent frailty during the transplant evaluation and waitlist management process. The best instrument to assess physical performance remains to be determined. We use the six-minute walk test (table 3). Other tests include the gait-speed test, get up and go test, grip strength, and frailty score [44,48]. (See "Frailty", section on 'Instruments developed to identify frailty' and "Kidney transplantation in adults: Physical activity in kidney transplant recipients", section on 'Assessment of physical performance' and "Kidney transplantation and the older adult patient", section on 'Pretransplant evaluation'.)

Prehabilitation should be considered for those transplant candidates who are found to have low physical performance and activity levels. (See "Kidney transplantation in adults: Physical activity in kidney transplant recipients", section on 'Pretransplantation physical activity interventions'.)

Gastrointestinal disease — The presence of peptic ulcer disease, cholelithiasis, and diseases of the colon and liver may place patients at increased risk posttransplantation.

Relative contraindications to transplantation include the following:

Active peptic ulcer disease – Active peptic ulcer disease is a relative contraindication to transplantation. Patients with active peptic ulcer disease should be adequately treated, with resolution of lesions confirmed by endoscopy prior to transplantation [49]. Patients with symptoms or prior peptic ulcer disease may require endoscopy in order to exclude active disease.

Active hepatitis and chronic liver disease – Active hepatitis and chronic liver disease are relative contraindications for transplantation. Patients with suspected liver disease and patients with hepatitis B and C should be referred to a hepatologist for pretransplant evaluation. Patients with bridging fibrosis or cirrhosis and elevated portal pressure may not be suitable candidates for kidney transplant alone and should be considered for combined liver-kidney transplant. (See "Kidney transplantation in adults: Hepatitis B virus infection in kidney transplant recipients" and "Hepatitis C infection in kidney transplant candidates and recipients" and "Kidney function and non-kidney solid organ transplantation", section on 'Eligibility criteria for SLK'.)

While they are not contraindications to transplantation, symptoms of cholecystitis and known diseases of the colon (or family history of colon cancer) require special evaluation:

Patients with symptoms of cholecystitis are screened for cholelithiasis. Transplant recipients with diabetes have a high incidence of cholelithiasis. In one study, 30 percent of pancreas transplant recipients, 27 percent of kidney transplant recipients with diabetes, and only 12 percent of kidney transplant recipients without diabetes had gallstones at a mean interval of 13 months [50]. Prophylactic cholecystectomy is not routinely performed, however [51,52].

Patients with known colonic polyps, diverticular disease, or inflammatory bowel disease or those at high risk for colon cancer (ie, family history of colon cancer or familial adenomatous polyposis) should be evaluated with a barium enema and/or colonoscopy if not performed according to gastrointestinal guidelines. Partial resection should be considered in those with extensive and/or recurrent symptomatic diverticular disease. Indications for resection are the same for transplant candidates as for the general population. (See "Overview of colon resection", section on 'Indications for colon resection'.)

Hematologic disorders — Additional evaluation of hematologic disorders and transplant eligibility are guided by the specific disorder or abnormality:

Hypercoagulability – Patients with a history of recurrent miscarriage, arterial/venous thrombosis, hemodialysis graft or fistula thrombosis, systemic lupus erythematosus, prior unexplained graft thrombosis, or abnormal prothrombin time or partial thromboplastin time in the absence of medications that interfere with these tests should be evaluated for an underlying hypercoagulable state. Such patients may require anticoagulation therapy in the perioperative period. (See "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors", section on 'Evaluation for hypercoagulable disorders'.)

Bleeding disorders – Patients with bleeding or coagulopathic tendencies should have detailed coagulation studies with hematology consultation as indicated. (See "Approach to the adult with a suspected bleeding disorder".)

Cytopenias – Patients with significant cytopenias should be evaluated to determine the underlying cause, if not already known. Pretransplant cytopenias may be exacerbated by induction and maintenance immunosuppressive therapy. Cytopenia may be a relative contraindication to transplant depending upon its cause and severity.

Monoclonal gammopathy – Patients with monoclonal gammopathy of undetermined significance (MGUS) should be carefully evaluated by a hematologist to exclude a plasma or B cell clonal disorder prior to transplantation [7]. If a malignant clonal disorder has been excluded, patients with MGUS can be considered for kidney transplantation. In one study that compared long-term outcomes between kidney transplant recipients with MGUS at the time of transplant and matched controls without MGUS, rates of graft and patient survival as well as rejection were comparable between the groups [53].

Patients with monoclonal gammopathy of renal significance or multiple myeloma who are in hematologic remission on maintenance therapy may be considered for kidney transplantation [54]. A multidisciplinary approach with a team familiar with kidney transplantation in this high-risk population is recommended.

Thrombotic microangiopathy – Patients with unexplained ESKD in conjunction with hemolytic anemia, thrombocytopenia, or biopsy-proven thrombotic microangiopathy (TMA) of unclear etiology should be evaluated for complement-mediated TMA prior to transplantation. Pretransplant diagnosis of this rare entity is fundamental, as eculizumab, a monoclonal antibody to C5, has been demonstrated to improve graft survival in this population [55,56]. (See "Thrombotic microangiopathy after kidney transplantation".)

Myelodysplastic syndrome – Myelodysplastic syndrome is a relative contraindication to transplantation since these disorders may be at risk for accelerated progression or transformation after transplant. Decisions about transplantation should be made in collaboration with the patient's hematologist.

Infections — The patient should be free of all untreated, active infection before transplantation. The patient identified from the initial evaluation to have a positive chest radiograph, tuberculin skin test, or interferon-gamma release assay should be evaluated and treated adequately for tuberculosis before undergoing transplantation. Dental infections should be treated prior to transplantation.

Certain infections require special considerations and may be relative contraindications to transplantation:

Controlled human immunodeficiency virus (HIV) infection is not a contraindication to kidney transplantation, and these patients can be successfully transplanted with careful management. This is discussed in detail separately. (See "Kidney transplantation in adults: Kidney transplantation in patients with HIV".)

Serologic testing is performed for cytomegalovirus (CMV), Epstein-Barr virus, and hepatitis B and C viruses. Issues surrounding infection and malignancy associated with these viruses and kidney transplantation are presented separately:

(See "Clinical manifestations, diagnosis, and management of cytomegalovirus disease in kidney transplant patients".)

(See "Kidney transplantation in adults: Hepatitis B virus infection in kidney transplant recipients".)

(See "Hepatitis C infection in kidney transplant candidates and recipients".)

(See "Malignancy after solid organ transplantation".)

Retransplantation should be delayed after graft loss due to BK polyomavirus (BKPyV)-associated nephropathy until plasma viral replication is absent; there is no consensus regarding the need for transplant nephrectomy in this scenario. (See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy", section on 'Kidney retransplantation'.)

In areas with known endemic infections, especially fungal infections (eg, coccidiomycosis in the southwestern United States, histoplasmosis in the Mississippi River Valley), serologic testing for these infections should be performed and treatment administered as appropriate.

For candidates with origins outside the United States, some centers refer for transplant infectious disease consultation to properly screen for, treat, and administer prophylaxis against endemic infections (eg, Strongyloides, Chagas disease).

In addition to being treated for active infection, high-risk potential recipients should receive prophylaxis for certain infections (see "Evaluation for infection before solid organ transplantation"). High-risk patients are those with prior splenectomy, chemotherapy, or immunosuppressive history or inherited or acquired immunodeficiencies.

Appropriate transplant recipients should be immunized against influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pneumococcus, hepatitis B, and varicella, if antibody negative. Vaccination for Haemophilus influenzae and meningococcus should be considered in asplenic individuals and those who may require therapy with eculizumab. Human papillomavirus (HPV) vaccines should be given to all candidates who meet the age-based indications for vaccination given the higher incidence of HPV-associated cancers in this population. (See "Immunizations in solid organ transplant candidates and recipients".)

Malignancy — Active malignancy (excluding nonmelanoma skin cancers) is an absolute contraindication to transplantation. (See 'Contraindications' above.)

For most patients with a prior history of cancer, we and most clinical guidelines generally suggest a waiting period free of recurrence of two to five years [57-59]. This is to minimize the risk of recurrence due to the enhanced development of micrometastasis by immunosuppressive medications [60]. There is, however, a marked variability in the likelihood of recurrence according to tumor type that determines the recommendations for patients with preexisting tumors [57-59]. Discussion with a multidisciplinary team including an oncologist is recommended.

The suggested cancer-free interval prior to transplantation should be individualized based upon patient and tumor characteristics. We agree with the waiting period recommendations of the American Society of Transplantation and International Transplant Skin Cancer Collaborative for the following cancers [57-59]:

Breast cancer (table 4)

Colorectal cancer (table 5 and table 6)

Prostate cancer (table 7)

Renal cell carcinoma (table 8)

Bladder cancer (table 9)

Gynecological cancer (table 10)

Lung cancer (table 11)

Nonmelanoma skin cancer (table 12)

Melanoma (table 13)

Hematologic malignancies (table 14 and table 15)

A discussion of malignancy following solid organ transplantation is presented elsewhere. (See "Malignancy after solid organ transplantation".)

Obesity — Obesity is a relative contraindication to kidney transplantation. Although there is no firm body mass index (BMI) cutoff, some transplant centers exclude patients with class 2 (BMI of 35 to <40 kg/m2) or class 3 (BMI ≥40 kg/m2) obesity and refer them for consideration for weight-loss surgery.

Kidney transplant recipients with obesity are at increased risk for adverse outcomes posttransplant. In a meta-analysis including over 209,000 kidney transplant recipients that compared outcomes among recipients with and without obesity, obesity (BMI >30 kg/m2) was associated with an increased risk of death (relative risk [RR] 1.52), delayed graft function (RR 1.52), acute rejection (RR 1.17), wound infection (RR 3.13), wound dehiscence (RR 4.85), and posttransplant diabetes mellitus (RR 2.24) [61]. Another cohort study found that overweight or obesity was associated with an increased risk of graft function deterioration (defined as a decrease in estimated glomerular filtration rate [eGFR] of ≥25 percent within six months to two years after transplant; odds ratio 1.64, 95% CI 1.10-2.44) [62]. However, compared with remaining on dialysis, kidney transplantation is associated with improved survival among patients with obesity [63,64].

In one retrospective study, robotic-assisted kidney transplantation in patients with obesity (median BMI 41 kg/m2) was associated with low surgical complication rates and similar patient and graft survival when compared with those of contemporary patients undergoing open surgery [65].

Peripheral vascular disease — Severe bilateral iliac or lower-extremity arterial disease or large abdominal aneurysms that are not amenable to intervention are relative contraindications to transplantation. High-grade calcific stenosis in the aortoiliac vessels may preclude kidney transplantation in the ipsilateral iliac fossa if there is insufficient length of soft artery to allow safe clamp and anastomosis.

We obtain noninvasive vascular testing in transplant candidates who have a history of known PVD, diabetes, claudication, or poor peripheral pulses on examination. Practice varies among transplant centers; some contributors to this topic routinely obtain an aortoiliac Doppler ultrasound and calculate the ankle-brachial index (ABI), while others screen first with a noncontrast CT of the abdomen/pelvis to examine for iliac calcification and obtain a follow-up Doppler ultrasound if there are concerns about flow. This information may be utilized to determine optimal allograft placement. (See "Noninvasive diagnosis of upper and lower extremity arterial disease".)

PVD is present or develops after surgery in a significant number of kidney transplant recipients, especially among those with diabetes. In one retrospective study, the incidence of severe PVD (defined by requirement for bypass, major amputation, claudication, or angioplasty) was 4 and 6 percent at 5 and 10 years after transplantation, respectively [66]. In another retrospective study of 43,427 transplant recipients, the incidence of PVD (identified by Medicare claims data) was 20 percent among patients with diabetes and 5 percent among those without diabetes [67].

PVD is associated with an increased risk of amputation (particularly in patients with diabetes), allograft ischemia, significant morbidity, and poor patient survival. In the study cited above, PVD was associated with an almost twofold increase in patient mortality following transplantation [67]. Similar findings were reported in a study of 819 patients who had arterial studies within five years prior to kidney transplantation; those with PVD as defined by a low ABI had a twofold higher risk of mortality and threefold higher risk of graft failure [68]. In another report, among 129 prospective kidney allograft recipients (34 and 95 with and without diabetes, respectively), PVD, established by noninvasive Doppler vascular studies at the time of transplantation, was associated with increased risk of proximal foot amputations and increased patient mortality [66,69].

Pulmonary disease — There are little data on the optimal pretransplant evaluation of patients with pulmonary disease. At minimum, the evaluation should be consistent with that for the general population who undergo a preoperative pulmonary assessment [70]. (See "Evaluation of perioperative pulmonary risk", section on 'Preoperative risk assessment'.)

We agree with the 2020 Kidney Disease: Improving Global Outcomes guidelines, which suggest that patients with the following clinical features should not be candidates for kidney transplantation [1]:

Home oxygen therapy requirement.

Uncontrolled asthma.

Severe cor pulmonale.

Irreversible moderate to severe pulmonary hypertension. (See 'Pulmonary hypertension' above.)

Severe chronic obstructive pulmonary disease/pulmonary fibrosis/restrictive disease. This is defined by best forced expiratory volume in one second (FEV1) <25 percent predictive value, PO2 room air <60 mmHg with exercise desaturation SaO2 <90 percent, more than four lower respiratory tract infections in the last 12 months, and/or moderate disease with progression.

All patients should be encouraged to discontinue smoking [9] since it increases the risk of allograft loss and patient death. In one study, patients with a 25-pack-year smoking history at the time of transplantation had a 30 percent higher risk of allograft failure than those who either had never smoked or had smoked less [71]. In addition, patients who had quit cigarette smoking more than five years prior to transplantation had a 34 percent lower relative risk of graft failure. The enhanced risk of graft failure among smokers was largely due to increased patient death.

Urologic abnormalities — An abnormal lower urinary tract may be a barrier to successful transplantation. In addition, among patients who are anuric or oliguric, urologic abnormalities may not become evident until after the patient has been transplanted. Patients with a history of urologic abnormalities are generally referred to a urologist experienced in transplant issues for additional evaluation:

A voiding cystourethrogram with or without urodynamics is often performed for patients with bladder dysfunction, bladder augmentation, or substitution who still produce urine; history of recurrent urinary tract infection; pyelonephritis or reflux; and/or inconclusive findings on baseline ultrasonography. This test should be obtained early in the evaluation while patient still produces urine.

A loopogram may be performed for patients with an ileal conduit to document the length and course of conduit [72].

Uroflowmetry, postvoid residual measurement, and cystoscopy may be performed for patients with obstructive symptoms; however, intervention for etiologies such as benign prostatic hypertrophy and urethral stricture may be deferred until posttransplant in the oliguric patient due to high rates of restricture [73]. A plan for intermittent straight catheterization or extended foley placement should be in place prior to proceeding with transplantation.

RE-EVALUATION — Potential kidney transplant recipients must be periodically reassessed, given the prolonged wait time for a donor kidney and the significant number of comorbid conditions among this patient population. This is discussed in detail separately. (See "Kidney transplantation in adults: The kidney transplant waiting list in the United States", section on 'Health care of transplant candidates'.)

SPECIAL CONSIDERATIONS

Cause of ESKD — The etiology of end-stage kidney disease (ESKD) should be documented as part of the initial evaluation, if possible, since the risk of recurrence of the primary kidney disease in the transplanted kidney varies depending upon the specific disease. (See 'History and physical examination' above.)

Although the type of original kidney disease is not a contraindication to transplantation, the clinician should be aware that many diseases can recur in the allograft and, in some cases, are more likely to lead to graft failure [74,75]. Early failure of a prior kidney transplant due to recurrent disease is generally deemed to be a relative contraindication to retransplantation unless novel therapeutics are available to mitigate risk. There is, however, no disease in which recurrence in the transplant is so common and so predictive of graft failure that transplantation should not be performed.

Examples of diseases that more commonly recur include the following:

Primary and genetic focal segmental glomerulosclerosis (FSGS) (see "Kidney transplantation in adults: Focal segmental glomerulosclerosis in the transplanted kidney")

Membranous nephropathy (see "Membranous nephropathy and kidney transplantation")

Immune complex-mediated membranoproliferative glomerulonephritis (see "Membranoproliferative glomerulonephritis: Recurrence of idiopathic disease after transplantation")

C3 glomerulopathy (see "C3 glomerulopathies: Recurrence after transplantation")

Immunoglobulin A (IgA) nephropathy (see "IgA nephropathy: Recurrence after transplantation")

Diabetic kidney disease (see "Kidney transplantation in diabetic kidney disease", section on 'Recurrent diabetic kidney disease')

Monoclonal gammopathies of renal significance (see "Diagnosis and treatment of monoclonal gammopathy of renal significance", section on 'Patients with end-stage kidney disease')

Lupus nephritis (see "Kidney transplantation in adults: Issues related to lupus nephritis", section on 'Recurrent lupus nephritis posttransplantation')

In addition, optimal timing of transplant may depend upon the cause of ESKD. This issue is discussed for individual disorders:

Anti-glomerular basement membrane (GBM) disease (see "Anti-GBM (Goodpasture) disease: Treatment and prognosis", section on 'Kidney transplantation')

Lupus nephritis (see "Kidney transplantation in adults: Issues related to lupus nephritis", section on 'Timing and type of transplantation')

Granulomatosis with polyangiitis and microscopic polyangiitis (see "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Kidney transplantation')

Antiphospholipid antibody syndrome (see "Antiphospholipid syndrome and the kidney", section on 'Kidney transplantation')

Patients with scleroderma may be transplant candidates if disease is quiescent and limited extrarenal involvement is present. (See "Kidney disease in systemic sclerosis (scleroderma), including scleroderma renal crisis", section on 'Kidney transplantation'.)

Patients with von Hippel-Lindau disease (VHL) and ESKD due to treatment of localized renal cell carcinoma (nephrectomy) should be considered for transplant. A study of 32 patients with VHL compared with 32 matched transplant recipients without VHL showed no difference in graft or patient survival between the groups [76]. (See "Clinical features, diagnosis, and management of von Hippel-Lindau disease", section on 'Renal cell carcinomas'.)

Patients with Fabry disease may also be eligible for kidney transplant, ideally maintained on enzyme replacement therapy posttransplant. (See "Fabry disease: Treatment and prognosis".)

Retransplantation — Prior transplantation and specific kidney diagnosis are not contraindications to transplantation. The prior transplant course (including complications), cause of graft loss, and any history of nonadherence should be obtained. Most centers retransplant suitable candidates although second and later transplants are associated with a higher rate of graft failure [77].

The majority of centers do not require a minimum waiting time prior to the second or third transplant. Those patients who are highly sensitized may have to wait longer to find a compatible deceased-donor kidney; however, the current kidney allocation system favors highly sensitized recipients with a panel reactive antibody ≥98 percent. If retransplantation is anticipated to be relatively soon after graft failure, immunosuppression may be continued in order to avoid further sensitization. (See "Kidney transplantation in adults: Management of the patient with a failed kidney transplant", section on 'Management of immunosuppression'.)

Recurrent disease, particularly if rapid, may influence whether to use a living donor in retransplant attempts. As an example, among patients with primary FSGS, recipients who develop recurrent disease in the first transplant are at very high risk (up to 75 percent) for recurrence in subsequent allografts [78,79]. If the first graft is lost to recurrent FSGS, the chance of recurrence in subsequent transplant attempts markedly increases. Among such patients, both the potential donor and recipient should be advised of the increased risk of recurrent disease. (See "Kidney transplantation in adults: Focal segmental glomerulosclerosis in the transplanted kidney", section on 'Retransplantation'.)

Although a history of prior graft loss from BK polyomavirus (BKPyV) poses a particular concern because of the risk of recurrence, retransplant may be performed in selected patients. The absence of viral replication should be confirmed prior to retransplant although successful cases of retransplant during active viremia have been reported [80]. (See 'Infections' above and "Kidney transplantation in adults: BK polyomavirus-associated nephropathy".)

Combined organ transplantation — In general, the evaluation of potential recipients of a simultaneous liver-kidney or heart-kidney transplant is primarily performed by liver and heart transplant centers, respectively. Issues related to combined liver-kidney and heart-kidney transplantation are discussed elsewhere:

(See "Kidney function and non-kidney solid organ transplantation", section on 'Approach in liver transplant candidates'.)

(See "Kidney function and non-kidney solid organ transplantation", section on 'Approach in heart transplant candidates'.)

The evaluation of potential candidates for simultaneous pancreas-kidney transplantation is presented separately. (See "Pancreas-kidney transplantation in diabetes mellitus: Patient selection and pretransplant evaluation".)

Nephrectomy prior to transplantation — Pretransplant recipient nephrectomy is not routinely performed. However, there are conditions in which the procedure may be considered. Such conditions include autosomal dominant polycystic kidney disease (ADPKD), recurrent infection with nephrolithiasis, concern for kidney malignancies, and massive proteinuria in children.

ADPKD – There are conflicting data concerning the benefits of nephrectomy in patients with ADPKD [81-83]. In general, pretransplant nephrectomy is reserved for those with recurrent, symptomatic, cyst-related complications or kidney size that would make the transplant surgery difficult. (See "Autosomal dominant polycystic kidney disease (ADPKD): Treatment".)

Recurrent infection – Given the requirement for immunosuppression, pretransplant nephrectomies may be a reasonable therapeutic option for patients with recurrent infection occurring in association with nephrolithiasis. However, the benefit of nephrectomy among such patients is unclear.

The presence of recurrent pyelonephritis with vesicoureteral reflux has traditionally been considered an indication for pretransplant nephrectomy. However, there is a paucity of evidence to suggest that bilateral nephrectomy lowers the incidence of posttransplant infection [84].

Massive proteinuria in children – Children with massive proteinuria, as observed in congenital nephrotic syndrome of the Finnish type, may benefit from pretransplant nephrectomy. In this setting, nephrectomy decreases mortality, allows for growth, and markedly reduces the risk of kidney transplant thrombosis [85,86]. It is unknown whether pretransplant nephrectomy also reduces the risk of thrombosis in adults with massive proteinuria.

Additional indications for nephrectomy in children prior to transplantation are discussed separately. Preemptive nephrectomy should be considered in congenital syndromes associated with increased risk of Wilms tumor. (See "Kidney transplantation in children: General principles".)

A postnephrectomy waiting time of six weeks is usually recommended to ensure that the wound is not infected and that the patient has adequately healed prior to the transplant surgery. However, some surgeons prefer to perform both operations at the same time.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney transplantation".)

SUMMARY AND RECOMMENDATIONS

Timing of referral – Kidney transplantation should be discussed with all patients with irreversible and progressive chronic kidney disease. Patients interested in transplantation who have no known contraindications should be referred to a transplantation program when the estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m2. (See 'Timing of referral' above.)

Contraindications – Absolute contraindications to transplantation include active infection, active malignancy, active substance use disorder, reversible kidney failure, uncontrolled psychiatric disease, and documented active and ongoing treatment nonadherence. Recipient age alone is not a contraindication to transplant. In addition, there are numerous relative indications that require careful evaluation. (See 'Contraindications' above.)

Initial evaluation – Initial evaluation of the potential recipient should include a thorough history and physical examination, a psychosocial assessment, and laboratory and imaging tests (table 1). Potential sensitization risks should be evaluated, including history of blood or platelet transfusion, pregnancies, and previous transplants. (See 'Initial evaluation' above.)

Evaluation of comorbid conditions – Once the initial evaluation is complete, further evaluation is directed to comorbidities and risk profiles of individual patients (see 'Targeted evaluation of comorbid conditions' above):

Cardiovascular disease – Patients with known heart disease, or who are at high risk for heart disease, are eligible for transplantation but require careful evaluation. The cardiac evaluation begins with a history, physical examination, and electrocardiogram (ECG); in addition, many centers routinely obtain transthoracic echocardiography to assess for left ventricular dysfunction, valvular heart disease, and pulmonary hypertension. Further evaluation for coronary artery disease depends upon the patient's risk profile (algorithm 1). (See 'Cardiovascular disease' above.)

Infections – Patients should be free of all untreated, active infection before transplant. Certain infections (such as HIV, cytomegalovirus (CMV), Epstein-Barr virus, and hepatitis B and C viruses) require special considerations and may be relative contraindications to transplantation. (See 'Infections' above.)

Malignancy – Most patients with a prior history of cancer should undergo a waiting period, free of recurrence, of two to five years. The suggested cancer-free interval prior to transplantation should be individualized based upon patient and tumor characteristics. (See 'Malignancy' above.)

Obesity – Obesity is a relative contraindication to kidney transplantation. Although there is no firm body mass index (BMI) cutoff, some transplant centers exclude patients with class 2 (BMI of 35 to <40 kg/m2) or class 3 (BMI ≥40 kg/m2) obesity and refer them for consideration for weight-loss surgery. (See 'Obesity' above.)

Peripheral vascular disease – Severe bilateral iliac or lower-extremity arterial disease or large abdominal aneurysms that are not amenable to intervention are relative contraindications to transplantation. We obtain noninvasive vascular testing in transplant candidates who have a history of known peripheral vascular disease (PVD), diabetes, claudication, or poor peripheral pulses on examination. (See 'Peripheral vascular disease' above.)

Pulmonary disease – For patients with pulmonary disease, the pretransplant pulmonary evaluation should be consistent with the preoperative pulmonary assessment for the general population. Patients with a home oxygen therapy requirement, uncontrolled asthma, severe cor pulmonale, irreversible moderate to severe pulmonary hypertension, or severe chronic obstructive pulmonary disease/pulmonary fibrosis/restrictive disease are not candidates for transplantation. (See 'Pulmonary disease' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Christina Klein, MD, who contributed to earlier versions of this topic review.

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Topic 7309 Version 32.0

References

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