Cardiovascular disease is the leading cause of death for both dialysis and renal transplant patients [6, 7]. Much of the survival benefit of transplantation is likely due to the long-term reduction in cardiac stress resulting from dialysis [2]. However, many patients with chronic kidney disease (CKD) have such severe cardiovascular disease that perioperative mortality precludes transplantation. As a result, cardiovascular disease is the most common reason for disqualifying a patient for transplantation [8]. While assessing the risk, it is important to remember that the presence of renal failure makes the perioperative evaluation and risk stratification of these patients different from general population [9]. The details of cardiovascular testing and therapy are discussed in Chap. 10.

Before proceeding with transplantation on a patient at elevated risk for cardiovascular disease, such as diabetics, smokers, the elderly, and those on dialysis for a long time, noninvasive cardiac testing should be performed. Patients with positive findings usually require coronary angiography to determine the extent of coronary disease and perform therapeutic interventions. While the trend in general cardiology is for decreased invasive testing and percutaneous coronary interventions [10], especially for asymptomatic patients, the approach to pre-transplant cardiac evaluation is often more aggressive. In part, this is due to the high rate of CKD patients who are diabetics and might have silent ischemia, and patients who have minimal physical activity, so may not report symptoms. In patients at particularly high cardiovascular risk, some advocate proceeding with cardiac catheterization as “first-line” screening test [7]. Once treatable causes of cardiac disease have been addressed, patients should be advised about their perioperative risk of heart attack and death. This risk assessment often requires the input of a cardiology consultant [11].

Many CKD patients are also at increased risk for cerebrovascular disease, but no data demonstrates a benefit of routine screening for cerebrovascular disease in asymptomatic transplant candidates. However, patients with a history of stroke or transient ischemic attack (TIA) should have imaging of their carotid arteries and be counseled about the risk of peri-transplant stroke. Peripheral vascular disease (PVD) is also an important part of the pre-transplant evaluation. PVD increases the risk of infections and can cause technical difficulties in the creation of the arterial anastomosis and hypoperfusion of the graft. In addition, a steal syndrome has been described, in which perfusion of the graft reduces distal flow sufficiently to cause or worsen limb ischemia [12]. In those with known PVD, CT scans can demonstrate the location of vascular calcifications, but angiography may be required to accurately delineate the arterial anatomy and flow. Groups at high risk for PVD, including diabetics, smokers, and the elderly, as well as those with symptoms of claudication, should be considered for noninvasive peripheral artery testing and vascular surgery consultation.

Cigarette smoking has been shown to contribute to graft loss and death, so cessation of smoking should be advised and facilitated with available resources [13]. Some programs will deny transplantation to patients who refuse to quit smoking, while others only deny transplantation to smokers with known cardiovascular or lung disease. Smoking cessation is an undeniable benefit to patients, but those who are unable to quit are potentially denied a life-prolonging organ if smoking cessation is required; many programs will strongly encourage cessation, but do not make it an absolute requirement.

Infections are the second most common cause of death for ESRD patients [14] and may worsen with immunosuppression at the time of the transplantation. Pre-transplant evaluation should therefore include the diagnosis and treatment of any ongoing infections. Transplantation may have to be delayed until an acute infection, such as a wound infection, can be fully resolved. Infections that cannot be resolved, such as chronic osteomyelitis, are usually a contraindication to transplantation. In some cases, such an HIV, the infection was previously considered an absolute contraindication to transplantation, but more recent studies [15] demonstrate that with good control of the infection, even without a cure, transplantation can be safely performed.

The pre-transplant evaluation is an important time to ensure completeness of immunizations. Vaccine response rates are significantly reduced by immunosuppression after transplant, and live vaccines are not safe to administer to immunosuppressed patients. Vaccines, which must be administered regularly, such as tetanus and pneumococcus, should be updated. For other vaccinations, immune status can be evaluated so that vaccination can be performed as needed. Required serological screening includes hepatitis B, hepatitis C, HIV, RPR, CMV, and EBV. This testing can detect lack of immune status, which requires vaccination, for example, for hepatitis B. It can also detect infections that may be treatable, such as hepatitis B or C. CMV and EBV screening are mostly relevant for posttransplant management. Consideration should also be given to screening for hepatitis A, measles, mumps, rubella and varicella and vaccinating those who are not immune.

A number of latent infections such as TB are usually asymptomatic in a patient with CKD, but can become severe infections after immunosuppression for transplantation. Although low-risk patients may not need screening, a careful exposure history and CXR should be reviewed, and a low threshold should exist for performing further testing, such as a PPD or interferon release assay (such as Quantiferon Gold). Potential exposure history should also prompt testing and appropriate treatment for parasitic infections such as strongyloides and endemic mycoses such as histoplasmosis and coccidiomycosis [16]. Many insurance companies require a formal dental evaluation in all pre-transplant patients to rule out occult abscess, and certainly patients with possible mouth lesions or no recent dental care should see a dentist before transplantation.

Malignancy is more common in patients with ESRD than the general population, so detection of malignancies and reduction of risk factors for cancer are an important part of the pre-transplant evaluation. In addition, immunosuppression increases the risk of cancers [17] and existing malignancies can follow a more aggressive course. For example, squamous cell carcinoma is 20 times more common in transplant recipients than the general population and is more likely to metastasize [18]. There are two main mechanisms by which immunosuppressive medications increase the risk for and severity of malignancies. The first is that immune surveillance for newly arising tumor antigens is impaired. The second is that infections are more common in immunosuppressed patients, and a number of infections are the direct cause of malignancies, such as Kaposi’s sarcoma and EBV-driven posttransplant lymphomas.

Because of the increased cancer risk from immunosuppression, ongoing malignancy is usually a contraindication to proceeding with transplantation. However, many patients that have been successfully treated for cancer are suitable candidates. Published guidelines [4] provide suggestions as to appropriate time to wait between cancer cure and transplantation. In addition, detailed information about a specific patient can be obtained by querying the Israel Penn International Transplant Tumor Registry (IPITTR) formerly known as Cincinnati Transplant Tumor Registry (CTTR). In making a decision regarding the waiting time, the risk of recurrence must be balanced with overall benefits from the transplant. The goal of this waiting period is to ensure that early recurrence is detected before proceeding with transplantation, but later recurrence is always a possibility. In general, a minimal time of 2 years is recommended for most malignancies, with exception of localized and in situ malignancies, which do not require waiting time. A 5-year wait is often recommended for malignancies with higher later recurrence risk, such as metastatic or large tumors.

Recommendations regarding waiting time after selected malignancies are summarized in Table 3.2.

The evaluation should focus on malignancies relevant to the patient’s gender, age, environmental exposures, and family history. This might include a pelvic exam and Pap smear, breast exam and mammography for women, digital rectal exam and PSA for men, and colorectal screening. Guidelines for cancer screening change over time, and thorough review of evidence-based workup is available elsewhere [19]. In addition, given the dramatically increased incidence of skin cancer after transplantation, we recommend dermatologist evaluation in anyone with questionable skin lesions. The dialysis population has a particularly high risk for cancer of the kidney and urinary tract, especially when ESRD is a result of toxic, infectious, or cystic process [20]. Screening individual patients for renal and urinary tract malignancies with a CT scan should be considered, especially if appropriate history or symptoms are present. Serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) should also be considered, particularly in older patients in whom the cause of kidney disease is unclear, such as those labeled as hypertension. While MGUS is usually not a contraindication to transplantation, multiple myeloma usually is.