Renal Transplant Referral and Criteria

Fig. 39.1

Trends in transplantati on: unadjusted rates, waiting list counts, waiting time, counts of transplants per year, and total functioning transplants. Percent of dialysis patients wait-listed and unadjusted and transplant rates (vol 2 Fig. 6.1)

The important first step to a successful kidney transplant is a timely referral for transplant evaluation. It requires collaboration and effective communication between the primary nephrologist, dialysis unit, and the multidisciplinary transplant team, which includes transplant nephrologists, transplant surgeons, nurse coordinators, pharmacists, dieticians, social workers, and financial counselors. There are a number of barriers to early referral for kidney transplant evaluation. These include a lack of complete understanding of the process and the advantages and disadvantages of kidney transplantation as a therapy for CKD and ESRD by both patients and physicians [6, 7].

Late referrals can lead to missed opportunities for pre‐emptive transplantation [8]. Kidney transplantation performed prior to initiation of dialysis is associated with better outcomes of graft and patient survival [9]. Other advantages are the avoidance of morbidity associated with dialysis and dialysis access procedures. A large portion of preemptive transplants are performed using living donor kidneys. Recipients of preemptive kidney transplants tend to be white and of higher socioeconomic status. Late referrals are known to occur with ethnic minorities, patients with lower socioeconomic status, and geographically disadvantaged patients with limited access to specialized care [10].

Kidney Donors

Kidney transplantation can be from either deceased or living donors. Living kidney transplantation could be from related or unrelated living donors. Living donors constitute a very significant source of the best quality organs. Living kidney transplants have a better graft survival, despite poor HLA matching when compared to well-matched deceased donor kidneys [11, 12].

In the United States, most kidney transplants come from deceased kidney donors (Fig. 39.2). The average waiting time for a kidney is at least 3–7 years depending on blood type and the region of residence [5]. Deceased donors could be either brain-dead donors or donors after circulatory death (DCD). Kidney transplantation from DCD donors have similar allograft and patient survival compared with kidney from donation after brain death; however, DCD transplantation has higher incidence of the delayed graft function (need for at least one dialysis treatment during the first week after transplantation) when compared to the brain-dead donor kidneys [13].

Fig. 39.2

Trends in transplantation (vol 2 Fig. 6.1), Counts of Transplants

There exists variability in the quality of deceased donor kidneys that are used for transplantation. The use of kidneys from older donors with multiple comorbidities previously known as expanded criteria donors (ECDs) is a way to address the shortage of organs. Although organs from such donors produce suboptimal results compared with standard donors, these results are still better than remaining on dialysis [14]. At the present time, the quality of the donor kidneys is defined by the kidney donor profile index (KDPI). KDPI combines ten donor factors – age, height, weight, ethnicity, history of hypertension, history of diabetes, cause of death, serum creatinine, hepatitis C virus (HCV) status, and donation after circulatory death (DCD) status – into a single number and summarizes the risk of graft failure after a kidney transplant. Lower KDPIs are associated with better donor quality when compared to higher KDPI kidneys [15].

The Process of Transplant Referral

The referral to a transplant center is done by the treating primary nephrologist. Most centers require a substantial level of involvement by the patient who will demonstrate good understanding of the transplant process, understand the importance of effective communication, and have good social support. The decision to be considered for transplantation is based on the complete evaluation by the transplant team. Patients with ESRD tend to have significant comorbid conditions. With advances in transplantation, some of these candidates can be considered for transplantation after careful evaluation. This is more likely with living donor transplantation as it allows for optimization of the recipient while planning for the procedure. The following are some of the guidelines and evaluation criteria:

1.

Renal function: Patients with advanced chronic kidney disease (CKD stages 4–5, eGFR < 29 ml/min/1.73 m²) are appropriate for referral for consideration for kidney transplantation. Studies have demonstrated that progressively worsening CKD increases mortality with time [16]. Single center studies have shown that longer waiting times on dialysis have a negative impact on posttransplant graft and patient survival [17]. Consequently, it is ideal for a patient to be transplanted preemptively or within a short time after initiating dialysis in order to achieve better outcomes.
2.

Age: In the past older age was considered a contraindication for transplant, however, now increasing numbers of older patients are being transplanted. Studies have shown that kidney transplantation can improve the longevity of patients over the age of 60 when compared to remaining on dialysis [18]. It has also been shown that it is safe to transplant older individuals with acceptable comorbidities. Using donor kidneys with higher KDPI score (previously known as ECD) has been shown to be beneficial in this age group as it may potentially reduce the time on the wait list [19].
3.

Comorbidities: Patients with ESRD tend to have multiple comorbidities related and unrelated to their kidney disease. In the United States, diabetes mellitus is a number one cause of kidney disease (Fig. 39.3) [20]. Cardiovascular disease is present in 63 % of patients with advanced CKD, compared with 5.8 % of adults without CKD [21]. Significant peripheral vascular disease is a relative contraindication for transplantation. Anemia is very prevalent in patients with kidney disease, and its prevalence increases with worsening kidney function. Patients with anemia before a kidney transplant are known to have more hematologic and cardiovascular complications [22]. During the evaluation of the patient, all comorbidities are carefully considered prior to patient’s approval for transplantation.

Fig. 39.3

Trends in ESRD incident cases, in thousands by primary cause of ESRD, in the US population, 1980–2012 (vol 2 Fig. 1.7)
4.

Active chronic infection: There is a risk of reactivation of chronic infection in recipients of kidney transplant, and thus thorough screening and testing of the recipient is important. It is also important to recognize and treat infections that can be exacerbated or reactivated after immunosuppression; examples of these are tuberculosis, coccidioidomycosis and histoplasmosis, or strongyloidiasis [23].

HIV-positive individuals now have a longer survival due to highly effective antiretroviral therapy. HIV infection and the antiviral medications increase the risk of developing chronic kidney disease [24, 25]. While in the past HIV infection used to be viewed as a contraindication to transplantation, now kidney transplantations in patients infected with HIV have resulted in good outcomes. The legalization of the use of the organs from HIV infected donors in November 2013 by the HOPE Act will increase the number of organs available for transplantation [26, 27].

While there is no consensus on how hepatitis B and C infections affect graft and patient survival, many studies seem to suggest that the graft survival is lower in patients with these infections. To understand the effects of newer anti-hepatitis C, treatments on kidney graft survival will require time [28].

5.

Alcohol and substance abuse: Both are known to cause and progressively worsen renal disease [29]. A strong personal history of ongoing substance abuse can be a harbinger of medication noncompliance, causing an increased risk of early graft failure [30]. Ascertaining this history during the initial evaluation is very important. If identified, these patients must be directed toward rehabilitation. Patients have to demonstrate adequate recovery and sobriety, stable social support, and adequate coping skills in order to proceed with the transplant process.
6.

Psychological factors: Transplantation is a very involved process, and it can be very emotionally and psychologically demanding. There are studies that show that kidney transplant is better than dialysis for patients with anxiety and depression, but there are also studies that show the process of transplantation to be stressful and anxiety provoking. It is vital to screen patients who are being evaluated for transplant for preexisting mental health issues to ensure adequate and continued support [31]. Immunosuppressive therapy can further worsen psychological symptoms. It is also important to assess for drug interactions with the psychiatric medications and immunosuppressants.
7.

Obesity: A high BMI is considered an exclusion criterion in the majority of transplant centers. Although the exact cutoff may vary from center to center, people with BMIs over 35 are generally cautiously approached. Many studies have shown an increase in posttransplant complications in obese patients compared to nonobese patients. These include wound complications such as wound infections, dehiscence, and hematomas as well as urologic complications such as urine leaks and strictures [32, 33]. Patients with high BMI have increased incidence of delayed graft function and a higher mortality rate [34, 35].
8.

Malignancy: Patients with active malignancies are strictly not considered for transplantation due to the concerns of progression of the existing malignancy with immunosuppression. The patients are required to be disease-free prior to transplantation for various periods of waiting time after definitive therapy. The waiting time depends on the type of cancer, stage of the disease, and curative nature of treatment received. It is for the same reason that patients are required to have completed age-appropriate cancer screening. The identification of previous malignancy is important in deciding the choice of immunosuppressant as mTOR inhibitors which have been shown to be beneficial in certain types of cancers [36].
9.

Previous transplant: While patients with a previous failed transplant could be complex, retransplants are routinely done after careful consideration of the risk of recurrence of the primary disease, reason for graft failure, and long-term risks of immunosuppressive therapy [37].

Transplant Evaluation

The candidates referred for kidney transplantation undergo a comprehensive evaluation by the transplant nephrologists, transplant surgeons, nurse coordinators, pharmacists, nutritionist, social workers, and financial coordinators. The process includes patient education, medical evaluation, surgical evaluation, and social evaluation.

The medical and surgical risks and benefits of renal transplantation, the potential adverse effects of immunosuppression, and the importance of compliance with immunosuppressive therapy are discussed with the potential candidates. The advantages and disadvantages of deceased versus living donor renal transplantation are discussed in detail.

The transplant nurse coordinator provides education regarding the transplant evaluation process, listing for transplant, the waiting time, and patient responsibilities before and after transplant and serves as a primary link between the patient and the rest of the transplant team.

Medical evaluation is done by the transplant nephrologists, who perform a thorough review of the history, physical examination, review of medications, and tests. It is important to identify the etiology of the kidney disease as it can predict the outcome and the risk for disease recurrence. A number of laboratory tests and imaging studies are performed to help in the process of assessing the candidacy. The patients are also evaluated by the transplant surgeons who review the history and perform the physical examination while focusing on recognizing any potential surgical issues. History of peripheral vascular disease and bladder dysfunction should be elicited.

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