Recipient Evaluation

Currently, kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD) as it improves both patient survival and quality of life when compared to dialysis. It must be noted, however, that although the risk of death in the first year after transplantation is less than 5%, not all patients qualify for the surgery due to their unacceptably high risk for complications. The transplant evaluation process requires a comprehensive assessment of each patient’s medical, surgical, and psychosocial history. A systematic approach should be used in the evaluation of potential renal transplant candidates.

The Initial Evaluation Process

Prior to the formal evaluation process, all potential transplant candidates are encouraged to attend a “patient education” session. At the meeting, patients are informed about the medical and surgical risks and benefits of renal transplantation, the necessity for frequent outpatient visits in the early postoperative period, the potential adverse effects of immunosuppression, and the importance of compliance with immunosuppressive therapy. The potential advantages and disadvantages of deceased versus living donor renal transplantation are discussed with the patients and, when possible, with their family members, significant others, and/or friends. Other issues that are addressed include the prolonged waiting time for a deceased donor transplant due to the critical shortage of donor organs and the adverse effects of waiting time on patient and graft survival. In addition, patients are forewarned that various medical and psychosocial conditions may preclude a patient from being a transplant candidate. Absolute and relative contraindications to kidney transplantation are outlined in Table 53–1.

General Assessment

The routine assessment of a renal transplant candidate includes a detailed history and a thorough physical examination. In particular, it is important to determine the cause of the original kidney disease as it can help in predicting the transplant course and outcome and the risk for disease recurrence. When available, the kidney biopsy report should be reviewed. Patients with ESRD secondary to congenital or genitourinary abnormalities should undergo a voiding cystourethrogram (VCUG) and appropriate urologic evaluation, preferably by the kidney transplant surgeon. Documentation of the patient’s residual urine volume from the native kidneys is invaluable in the assessment of graft function in the posttransplant period. A history of familial or hereditary renal disease must be obtained if living related kidney donation is an option. The patients’s surgical history should be elicited with special emphasis on previous abdominal operations. A complete physical examination should include a careful assessment for the presence of carotid and peripheral vascular disease. Patients should preferably have a body mass index below 30–35 as obesity is associated with a higher incidence of postoperative complications. In addition to a thorough history and physical examination, patients should also undergo a number of routine laboratory testings and imaging studies as outlined in Table 53–2. Specific risk factors need to be addressed during the transplant evaluation process.

Evaluation of Risk Factors by Specific Organ System Disease

Cardiovascular Disease and Peripheral Vascular Disease

Cardiovascular disease (CVD) is the leading cause of death after renal transplantation. Deaths with a functioning graft occurring within 30 days after transplantation are due to ischemic heart disease in nearly 50% of cases. A detailed cardiovascular history not only predicts the operative risk but also helps in postoperative cardiac management to improve short-term and long-term cardiac outcomes. Although the determinants of CVD risk in ESRD patients have not been well defined, all patients with CKD should be considered increased cardiac risk candidates. Major conventional risk factors include diabetes mellitus, hypertension, dyslipidemia, obesity, a history of angina pectoris, congestive heart failure, previous cardiac events, older age, smoking, and family history. Other suggested risk factors include preexisting left ventricular hypertrophy, dialysis for a prolonged period, coronary artery vascular calcification, abnormal electrocardiogram, and hyperhomocysteinemia. Exercise tolerance should be assessed along with cardiac-related symptoms as many patients on dialysis lead sedentary lifestyles and are symptom free. Noninvasive cardiac screening such as nuclear stress test or dobutamine stress echocardiogram is probably adequate for low-risk candidates. However, for those with multiple risk factors, particularly diabetes mellitus and/or previous cardiac events, coronary angiography is warranted. If necessary, coronary angioplasty/stenting or coronary bypass surgery and cardiac rehabilitation should be performed prior to transplantation. In general, high-risk candidates should undergo a formal evaluation by cardiology.

Patients with a history of transient ischemic attacks or cerebrovascular accidents should undergo carotid Doppler studies. When carotid bruits are detected on physical examination in an asymptomatic patient, further diagnostic imaging should be performed at the discretion of the clinician. Evidence of significant stenosis requires vascular surgery consultation. If necessary, carotid endarterectomy should be performed prior to transplantation and patients should be symptom free for at least 6 months prior to transplantation. For those with milder carotid disease, a neurologic consultation and optimal medical management may be sufficient.

Peripheral vascular disease is present in a significant number of renal transplant recipients and is associated with increased morbidity and mortality. Vascular imaging with either a Doppler ultrasound or a noncontrast abdominal/pelvis CT scan is indicated in patients with a history of claudication and/or signs of diminished peripheral arterial pulses (particularly in diabetics) on physical examination. An angiogram should be considered if noninvasive studies suggest the presence of large-vessel disease. Significant aortoiliac disease requires evaluation by the surgical transplant team and may preclude transplantation.

Malignancy

Transplant recipients are at greater risk of developing both de novo and recurrent malignancy due to the use of immunosuppressants. As the incidence of malignancy increases with the intensity and duration of immunosuppression, a history of immunosuppressive therapy for the native kidneys represents an added risk for posttransplant malignancy. For patients with a history of malignancy, consultation with an oncologist is advisable. Table 53–3 provides general guidelines for minimum tumor-free waiting periods for common malignancies.

Infections

All patients should be assessed for common latent or active infections and questioned for a history of infectious exposures. Active infections including diabetic foot ulcers and osteomyelitis must be fully treated prior to transplantation. A prior history of tuberculosis or untreated tuberculosis exposure requires appropriate posttransplant prophylactic therapy. Patients with an established history of systemic coccidioidomycosis or histoplasmosis or those from an endemic area should undergo appropriate antibody testing. In addition, these patients should be informed of possible disease reactivation with immunosuppressive therapy and indefinite posttransplant azole prophylactic therapy.

A history of immunization should also be obtained to ensure adequate immunizations for common infections prior to transplantation (eg, hepatitis B, pneumovax, and other standard immunizations appropriate for age). An immunization update is mandatory for those who have undergone surgical splenectomy. Infections with the human immunodeficiency virus (HIV) was once considered a contraindication to transplantation due to early reports of serious infectious complications and death following HIV infection transmitted from a transplanted organ or inadvertent transplantation of HIV-infected patients. However, with the advent of effective highly active antiretroviral therapy (HAART) regimens, there have been changing views regarding transplantation in HIV-positive patients. Currently, a number of transplant centers would consider transplantation in stable HIV patients, defined as those with an undetectable HIV viral load, CD4 lymphocyte count >300/mm3, and absence of opportunistic infections in the previous year. Specific recommendations may vary from center to center and a formal consultation with an infectious disease specialist is recommended.

Specific Gastrointestinal Disease Evaluation

There has been no consensus on whether all asymptomatic renal transplant candidates should be screened for cholelithiasis. Screening is warranted, however, in diabetics and patients with a history of cholecystitis. Pretransplant cholecystectomy is recommended for these patients if there is evidence of cholelithiasis due to the increased risk of life-threatening cholecystitis after transplantation.

Urologic Evaluation

All renal transplant candidates on dialysis should be imaged with a renal ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) to evaluate for acquired cystic kidney disease and associated renal cell carcinoma if no imaging study has been performed within the previous 3 years. Urinalysis and urine cultures should be performed in all patients with significant residual urine volume. Transplant candidates with a history of recurrent urinary tract infections, voiding symptoms, or ESRD secondary to congenital or genitourinary abnormalities should undergo a VCUG. Persistent hematuria or sterile pyuria may warrant endoscopic evaluation and/or retrograde pyelography. Urodynamic studies may be helpful in patients with a history of lower urinary tract dysfunction and/or urinary incontinence. Patients with bladder dysfunction secondary to neurogenic bladder or chronic infections can often be managed without urinary diversion. In continent patients with lower urinary tract dysfunction, intermittent self-catheterization is a safe and effective alternative to urinary diversion. However, a formal urologic evaluation and patient education during the initial transplant evaluation process are mandatory. Augmentation cystoplasty or urinary diversion procedures may be necessary in patients in whom simple reimplantation into a dysfunctional bladder is not an option. Male transplant candidates with sufficient urine volume and symptoms of outflow tract obstruction due to benign prostatic hypertrophy should undergo prostate resection before transplantation, whereas in anuric patients, the procedure should be postponed until after a successful renal transplant.

Special Urologic Considerations: Pretransplant Native Nephrectomy

For most patients with autosomal dominant polycystic kidney disease (ADPKD) pretransplant nephrectomy is not routinely recommended. However, unilateral or bilateral pretransplant nephrectomy(ies) may be necessary for those with massively enlarged kidneys, recurrent infection, bleeding, and/or intractable pain. Table 53–4 lists the special indications for pretransplant native nephrectomy. Generally, a minimum of 6 weeks after nephrectomy is recommended prior to transplantation. For transplant candidates who undergo preemptive transplantation from a living donor, simultaneous native nephrectomy and transplantation may be performed.

Evaluation of Risk Factors Related to Specific Patient’s Characteristics

Advanced Age

There is no arbitrary age limit for transplantation. The United Network for Organ Sharing organ procurement and transplant network (UNOS OPTN) database reveals that the number of kidney transplants performed in patients >65 years old has more than tripled over the past 10 years. Similar to the younger population, transplantation in the older age group of 60–74 years has been shown to improve survival compared to their wait-listed counterparts. Graft loss from rejection is lower in older compared to younger recipients presumably due to the decreased immune responsiveness in the aged population. It must be noted, however, that older transplant recipients are at increased risk for infectious complications, malignancy related to immunosuppression, and deaths in the early posttransplant period, most often as a consequence of cardiovascular disease. Screening for covert cardiovascular disease and occult malignancy in older potential recipients is, therefore, crucial and mandatory.

Obesity

Obesity is considered a contraindication to transplantation by some centers as it is associated with increased risk of posttransplant complications including delayed graft function, surgical wound infection, and death, particularly from cardiovascular disease. Although there has been no consensus on an acceptable upper limit body mass index (BMI), weight reduction to a BMI of 30–35 kg/m2 or less prior to transplantation is recommended. Morbidly obese candidates may benefit from surgery referral for gastric bypass surgery or gastric banding procedure. Data on patient and graft survival in obese versus nonobese transplant recipients are variable and contradictory. Determination of transplant candidacy in obese patients should, therefore, be assessed on an individual basis rather than reliance on an absolute BMI index. Obese candidates with comorbid conditions such as known coronary artery disease and advanced age are at particularly high risk and may fare better receiving dialysis.

Donor Evaluation

This section focuses primarily on the evaluation of the living donor candidate.

Evaluation of the Living Donor

Over the past decade, the number of living donors has steadily increased whereas the number of deceased donor kidneys has remained relatively unchanged. The increased rates of living donation are in part due to excellent patient and graft survival rates achieved with living donor transplant, the advent of laparoscopic donor nephrectomy, and improved patient and public awareness and education. Living donor transplantation offers survival advantages over deceased donor transplantation and permits the prospective recipient to undergo preemptive or elective transplantation at the time of optimal medical health. General guidelines for evaluating a potential donor candidate are described.

General Assessment

Similar to the evaluation process of the potential recipient, living donor evaluation requires a complete history, physical examination, and psychosocial assessment. A formal psychiatric evaluation by the transplant center is recommended to evaluate for any significant psychiatric problem and any possibility of coercion. The presence of either of these would preclude donation. The mandatory preliminary evaluation of a potential living donor includes determination of ABO blood group compatibility, HLA typing, and cross-matching against the potential recipient. In cases in which more than one donor is available, selection of the best donor depends on the degree of HLA matching and donor age. In addition, biologically related donors are generally preferred over unrelated donors. A suggested routine evaluation and optional testing are listed in Table 53–5.

Medical Assessment of the Potential Donor

There are significant variations among transplant centers regarding the medical evaluation of living donors, but the universal goals are to ensure that the potential donor (1) is sufficiently healthy to undergo the operation, (2) has normal kidney function with minimal future risk of kidney disease, and (3) represents no risk to the recipient in terms of infection or transmission of malignancy. Absolute and relative contraindications to living kidney donation are listed in Table 53–6.

Measurement of creatinine clearance based on a 24-hour urine collection is generally adequate, although some centers prefer iothalamate or diethylenetriaminepentaacetic acid (DTPA) clearance for a more accurate estimation of the glomerular filtration rate (GFR). A minimum GFR of 80 mL/minute/1.73 m2 is required by most centers, considering that unilateral nephrectomy reduces overall renal function by about 20% at long-term follow-up. Renal imaging studies are mandatory to assess the anatomic features of the kidneys, to delineate renal vessels to select one kidney for donation, to determine the most appropriate nephrectomy technique, and to exclude potential donors with incidental masses or fibromuscular dysplasia.

The medical evaluation should specifically probe for possible hereditary renal disease, diabetes, and hypertension. The most commonly encountered hereditary renal disease is ADPKD. For potential donors over the age of 30 years, it is safe to proceed with donor nephrectomy if ultrasound or CT imaging reveals no evidence of cysts. For potential donors between the age of 20 and 30 years, genetic studies such as linkage analysis or direct deoxyribonucleic acid (DNA) sequencing can reliably exclude the presence of ADPKD. These tests, however, are not routinely available. Potential donors with a family history of Alport’s syndrome should be screened for hematuria and hypertension and should undergo special hearing and ocular testing. Alport’s syndrome is predominantly transmitted as X-linked and less commonly as autosomal recessive or autosomal dominant. The absence of hematuria in an adult male 20 years of age or older essentially excludes the presence of the genetic defect. Adult female siblings with normal urinalysis have a low risk of being carriers and can safely donate. However, female relatives with persistent hematuria are most likely carriers of the mutation and donation is not advisable. Although genetic testing is possible it is not readily available and generally is not performed.

All potential donors should have a fasting plasma glucose to detect diabetes mellitus or undiagnosed impaired glucose tolerance. The presence of diabetes mellitus would preclude living donation. All individuals with impaired fasting glucose and those with risk factors for developing type 2 diabetes mellitus should undergo a 2 hour oral glucose tolerance test (OGTT). The latter includes first-degree relatives of patients with type 2 diabetes mellitus, obesity, gestational diabetes mellitus, and dyslipidemia. If the OGTT test is normal (<140 mg/dL) and no other risk factors are present, it is reasonable to proceed with the donation process. Individuals with impaired glucose tolerance are at risk for the development of diabetes mellitus and risk factor modifications including exercise and weight reduction or avoidance of excessive weight gain should be emphasized. Potential donors with impaired glucose tolerance should be assessed on an individual basis. Those with mild or borderline impaired glucose tolerance and additional risk factors and those with blood sugar levels in the high range should probably not donate since the higher the blood sugar within the range of impaired glucose tolerance (140–199 mg/dL) or impaired fasting glucose (100–125 mg/dL), the greater the tendency for tolerance to deteriorate.

Risks of Donation

Donor nephrectomy is either performed via open nephrectomy or, increasingly more popular, laparoscopic nephrectomy. Acute mortality rates related to open nephrectomy are estimated at 0.03–0.04%. The incidence of postoperative complications including wound infection, pneumonia, ileus, deep vein thrombosis, or pulmonary embolism is approximately 3%. The incidence of testicular pain, paresthesia of L1, and the need for reoperation or conversion from laparoscopic to open donor nephrectomy ranges from 0% to 3% and may vary among centers. The incidence of complications is slightly higher for laparoscopic compared to open nephrectomy. However, with the refinement in surgical techniques and the increasing expertise of the surgeons performing the procedures, comparable postoperative complication rates between the two surgical operations have been reported. The potential advantages of laparoscopic versus open nephrectomy include less donor pain and shorter donor recovery time.

The risk of future development of chronic kidney disease and progression to ESRD in the remaining single kidney has always been a major concern for prospective donors. At long-term follow-up, unilateral nephrectomy reduces renal function by approximately 20%. Similar to the nondonating population, an additional 5 mL/minute loss in GFR per decade occurred after donating. Although data on the effects of nephrectomy on the progression and complications of ESRD are lacking, the UNOS database revealed that of the 48,000 living kidney donors whose donations occurred between 1987 and 2001, 20 (or 0.04%) donors were listed for transplantation. It should also be noted that the baseline lifetime risk of developing ESRD in the general population is about 2–3% for whites and about 7% for African-Americans. Annual medical evaluation of renal function, proteinuria, fasting blood sugar, and blood pressure measurements is warranted after donation.

Evaluation of the Deceased Donor

Whereas the number of patients on the transplant waiting list has steadily increased, the number of deceased donor kidneys has remained far below the growing need, leading to longer waiting times and increased wait-list deaths. One approach to increasing the pool of deceased donor organ supply has been to expand the previously defined criteria for acceptable donor kidneys, such as advanced donor age (>60 years of age), donor comorbid conditions, such as hypertension or diabetes, donor preprocured high serum creatinine level, pediatric donors (<5 years of age), donors after cardiac death (DACD), and donor kidneys with prolonged cold preservation time. Dual kidney transplantation into one recipient from an otherwise nonacceptable donor has also been performed by some centers. More recently, UNOS set forth a new expanded criteria donor (ECD) kidney policy defining donors that meet these criteria. These kidneys are defined by donor characteristics that are associated with a 70% greater risk of kidney graft failure when compared to a reference group of normotensive donors aged of 10–39 years whose cause of death was not a cerebrovascular accident (CVA) and whose terminal serum creatinine was <1.5 mg/dL. The donor factors associated with this increased relative rate of graft failure include age 60 years or older or age 50–59 years with at least one comorbid factor. The latter may include CVA as a cause of death, hypertension, and/or terminal serum creatinine greater than 1.5 mg/dL (Table 53–7). Despite inferior outcomes compared to standard criteria donor kidneys, ECD kidney transplantation offers survival advantages over “wait-listed” continued dialysis. Compared to the younger age group, older recipients (>65 years) had a significant proportional increase in longevity, and compared to patients with nondiabetic nephropathy, more patients with ESRD due to diabetic nephropathy died while awaiting kidney transplantation (4.3% versus 10.8%, respectively, p < 0.001). Acknowledging the potential benefits and risks of ECD kidney transplantation compared to maintenance dialysis has led many centers to liberalize the criteria for accepting deceased donor kidneys.

Table 53–8 lists the absolute and relative contraindications to deceased donor donation. However, it should be noted that the acceptance criteria for deceased donor kidneys may be institution specific.

Complications following renal transplantation vary over time and can be arbitrarily categorized into those occurring early (the first 1–6 months) or late (after 6 months). We concentrate more on the early complications, describe a basic approach to evaluating renal allograft dysfunction in the immediate and early postoperative period, and discuss the urologic and infectious complications commonly encountered in the first 1–6 months following renal transplantation.

Renal Allograft Complications

Delayed Graft Function and Primary Nonfunction