Kidney and Pancreas Transplantation

Indications

Kidney transplantation offers patients a chance to be free from dialysis. Patients state that their quality of life is improved and transplant is the preferred modality of renal replacement rather than remaining on dialysis. The largest study to date showed that kidney transplant is clearly lifesaving, and over 25 years, 1,373,272 life years have been saved (4.4 life-years per recipient). The kidney waiting list continues to grow, and, currently, over 95,000 patients are awaiting kidney transplants ( https://optn.transplant.hrsa.gov/data/view-data-reports , accessed January 2, 2019). There continues to be a trend of patients who are removed from the waitlist due to deteriorating health status. The waitlist is increasingly comprised of patients in an older demographic (222,681 patients older than 65 years old waiting), and ethnicity has remained stable. With the implementation of a new allocation system in 2014 that used years on dialysis as a metric for waiting time points, the number of patients listed in an inactive status has decreased.

The most common causes of renal disease in patients on the transplant waiting list continue to be hypertension and diabetes. Overall, the percentage of patients with diabetes has increased to 36% from 28%. An increasing percentage of the waitlisted patients have had end-stage renal disease (ESRD) requiring dialysis for more than 10 years. Older patients with longer times on dialysis are a surgical challenge. Given that more than 600,000 patients in the United States have kidney disease and 468,000 are on dialysis ( https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease ), transplant remains a sought-after therapy for renal replacement.

Patient Selection

The evaluation of patients as appropriate candidates for transplantation is an arduous process for both the patient and the transplant center professionals. Patients with ESRD have significant comorbidities, and these must be taken into account in evaluating for transplantation. Guidelines for evaluation of these patients have been established. Emphasis should be placed on obtaining the original cause of renal disease so the patient can be given reasonable expectations for dialysis-free survival. Recurrence of native kidney disease can occur in up to 20% of patients and may be the cause of graft failure. Depending on the cause for recurrence, changes in immunosuppression may be warranted. Table 27.1 shows common diseases that recur after transplant and the percentage of loss if disease recurs. Mortality rates are above 20% per year with dialysis. Long-term follow-up of kidney transplant recipients has shown a clear survival advantage over remaining on dialysis. The most important consideration in addressing patients who seek transplant is the improvements gained in quality of life and participation measures.

Recipients must be carefully evaluated for surgical technical risk as well as for their ability to tolerate long-term immunosuppression. The absolute and relative contraindications for transplant candidacy are shown in Box 27.2 . Patients do not need to be on dialysis to be listed for kidney transplant, and those patients whose glomerular filtration rate (GFR) falls below 20 mL/min/1.72 m ² should be evaluated for possible transplant if they do not have an absolute contraindication.

Human immunodeficiency virus (HIV) infection was once a contraindication to transplantation; however, select patients with appropriate cell counts (CD4+ above 400 cells/mm ³ ) and an undetectable viral load have good results with transplantation as a treatment modality for HIV-associated nephropathy. There has been an increase in transplantation as a treatment modality for HIV-associated nephropathy and currently 300 patients on the waiting list have HIV-associated nephropathy ( https://optn.transplant.hrsa.gov/data/view-data-reports , accessed 1/2/2019). The HIV Organ Policy Equity (HOPE) Act passed by Congress in 2015 has allowed organs from HIV-positive donors to be transplanted to HIV-positive recipients.

Screening of potential recipients should begin with a detailed history and careful physical exam. The length of time on dialysis has been noted to be an independent risk factor for poorer outcomes; however, the death rate is highest in the first year after transplant and survival benefit is gained by 2 years after transplant. In addition to queries about chronic illnesses and the etiology of kidney failure, it is important to gather information about exposures to infectious diseases (especially tuberculosis, cytomegalovirus [CMV], Epstein-Barr virus, hepatitis), recent travel history, and any history of malignancy. Cardiac risk factors should be evaluated. Family history of renal disease or other systemic illnesses should be documented. Routine age-appropriate screening examinations, such as Papanicolaou smears, mammograms, colonoscopy, prostate specific antigen, dental prophylaxis, and bone density, should be obtained as recommended by clinical practice guidelines. In addition, the patient should be questioned about thrombotic events, such as miscarriages, multiple dialysis access thrombectomies, deep venous thrombosis, and pulmonary embolism, so a hypercoagulable profile can be obtained. The ability of the patient to tolerate immunosuppression should be evaluated. This involves consideration not only of the medical conditions but also of the ability to comply with a complex medical regimen and the financial ability to obtain lifelong immunosuppression.

Patients with chronic kidney disease (CKD) are 10 to 20 times more likely to have significant cardiovascular disease compared to the general population. Hence, a careful preoperative cardiac screening must be completed. There is little consensus as to the optimal screening algorithm; however, dobutamine stress echocardiography has been shown to have superiority in accuracy and predictability for perioperative cardiac events. Patients should have a baseline electrocardiogram, recognizing that nearly 75% will have evidence of left ventricular hypertrophy. The patient’s risk profile should be assessed to determine whether any risk factors can be modified (diet, weight management). Low-risk patients include those who have good functional capacity and no cardiac disease previously identified. These are typically patients with isolated renal disease, such as immunoglobulin A nephropathy or polycystic kidney disease, and have little comorbidity. Moderate-risk patients should undergo stress testing. It is important to ensure that the stress test is diagnostic and a reasonable heart rate was achieved. Moderate-risk patients include those without cardiac symptoms but who have diabetes, a prior history of heart disease, or two or more other risk factors for coronary disease (smoking, strong family history, hyperlipidemia, hypercholesterolemia). High-risk patients include those with a positive result on noninvasive testing, long-standing diabetes, or history of severe congestive heart failure. These patients require cardiac catheterization before being accepted for the transplant list. Cardiac revascularization should occur before transplantation. Fig. 27.1 shows our current algorithm for cardiac evaluation. Patients who are awaiting deceased donor transplant may be listed for many years and will undergo reevaluation. At any reevaluation, the cardiac status should be routinely reviewed and updated.

Renal failure patients are at increased risk for cerebrovascular events, and the stroke risk is 10 times higher than that of the general population. If carotid bruits are discovered, patients should be screened for significant carotid stenosis. Atrial fibrillation can also be discovered on physical examination. The femoral, dorsalis pedis, and posterior tibial arteries should be palpated and any bruits documented. If the pulses are abnormal or the patient has undergone previous amputation for vascular disease, further diagnostic vascular evaluation should be obtained to assess the level of peripheral vascular disease. It may be that iliac inflow is significantly compromised, which would prevent the patient from having a successful outcome. If inflow is compromised, one can consider whether a revascularization with conduits is warranted before or at the time of transplantation.

Kidney organs can be obtained from living or deceased donors. The demand for kidney transplant and appropriate organs has continually increased, given the increase in the burden of ESRD. The number of living donor transplant has remained flat for several years. A worrisome trend is the increase in discard rate in donors over age 65 or donors with diabetes. In 2014, a new allocation system was adopted in which donor kidneys receive a kidney donor profile index (KDPI) score. This score is derived using 10 clinical parameters shown in Table 27.2 . A KDPI score of greater than 85% is associated with decreased graft survival and increases in delayed graft function. This may lead to surgeons hesitating to accept these high-score kidneys for transplant.

Deceased donation occurs after the patient has been declared brain dead or the family has given permission for donation after circulatory (cardiac) death (DCD). In DCD, the care team has determined that the patient is unlikely to make a reasonable recovery and the patient is being maintained on mechanical ventilation but has not met the criteria for brain death ( Box 27.3 ). If the family consents for DCD, the ventilator is disconnected in either the operating room or intensive care unit. If the heart stops within a designated time frame (usually 60–90 minutes), the team waits several minutes to ensure cardiac standstill. The patient is then declared dead by the care team (not a member of the organ recovery team), and the organs are procured en bloc.

Living Donor Selection

The first successful living kidney donation was performed in 1954. Since that time, data continue to show that living kidney donation provides the best graft and patient survival results in recipients. Donors may or may not be genetically related to their intended recipient. In some cases, living donors are anonymous. There are several reports of extended altruistic donor chains. In these cases, an initial donor-recipient pair cannot go forward with transplantation, usually because of ABO incompatibility or sensitization of the recipient. A reciprocal exchange with another incompatible pair allows a “domino transplant” with multiple exchanges, with centers across the country participating. There has been no difference in outcomes of kidneys requiring shipping in paired donation versus traditional living kidney donation. The 5-year survival of an unrelated kidney transplant is the same as that of a kidney transplant from a related donor. The underlying premise of living donation is that the donor will not suffer any medical consequences from the donation and has minimal surgical risk.

Currently accepted eligibility criteria include the following: age, 18 to 70 years; body mass index (BMI) below 35; no cancer or active infection; and adequate renal function. ABO compatibility is also a consideration. However, recipients can undergo desensitization protocols, and transplantation can be performed across ABO barriers. The donor should be informed in these circumstances of an increased risk of rejection of the kidney by the recipient. There is some individual variation among transplant centers concerning acceptable GFR or BMI. Relative contraindications include renal stones, impaired glucose tolerance with a family history of type 2 diabetes, GFR of 70 to 80 mL/min/1.72 m ² , hypertension, and BMI above 35. Absolute contraindications are listed in Box 27.4 . For screening, all donors should have a thorough history and physical examination completed. Potential donors should be asked about nonsteroidal use in addition to questions about any medical illnesses. Potential donors should be made aware of the need to be away from work for a time, and their willingness to donate free of coercion should be ascertained. An electrocardiogram and chest radiograph should be obtained. Routine laboratory work should include urinalysis, complete blood count, liver function testing, creatinine concentration (with estimated GFR), chemistries, lipid profile, microalbumin level, and oral glucose tolerance test. All age-appropriate screening examinations should be complete prior to donation. Radiographic evaluation of the anatomy of the renal arteries, veins, and collecting system should be performed and can be done by computed tomography (CT) angiography, magnetic resonance imaging, or arteriography on the basis of local expertise. In addition, all donors must be evaluated by an independent donor advocate. The independent donor advocate is not influenced by a relationship with the intended recipient or the transplant center. The donor and recipient pair must also adhere to the National Organ Transplant Act of 1984, which states, “It is unlawful for any person to knowingly acquire, receive, or otherwise transfer any human organ for valuable consideration for use in human transplantation.” Many transplant centers ask potential donors to undergo a psychological or psychiatric evaluation.

Potential donors should be informed that the risk of perioperative mortality regardless of surgical technique is approximately 0.03%. Lentine and colleagues combined data obtained from the Organ Procurement and Transplant Network (OPTN) and hospital administrative records. They reported that, overall, 16.8% reported a perioperative complication, with the most common being gastrointestinal (4.4%) and bleeding (3%). Risk factors for complications include being male, being African American, or having preexisting conditions (genitourinary, hematologic, or psychiatric disorders).

Donor nephrectomy may be performed by open or laparoscopic techniques. The open technique is performed through a flank incision. There are variations in the technique of laparoscopic donor nephrectomy. Some centers use a hand-assisted approach; others perform the procedure entirely laparoscopically and make a Pfannenstiel incision to retrieve the kidney, and still, others perform the procedure robotically. Some centers perform a single-incision donor nephrectomy and dissect the renal hilum using instruments placed through a GelPort system, which is ultimately the site of kidney retrieval. There is no difference in outcome based on technique so the exact placement of ports and the retrieval incision is best left to the operative surgeon. If unexpected anatomy or bleeding is encountered, it is important to promptly convert to open techniques to prevent any donor complications or prolonged surgery.

Laparoscopic Surgical Technique

Either the right or left kidney can be procured laparoscopically. The left renal anatomy is generally preferred as the renal vein is longer. Many studies have shown that the right kidney can be procured safely. A left kidney dissection is described here as it is far more common. A 5-mm entry site is placed in the left lower quadrant, and a Veress needle is used to insufflate the abdomen to a pressure of 10 to 15 mm Hg. A 12-mm port is placed at the umbilicus. Two additional 5-mm ports are placed, one at the left costal margin and the last in the midaxillary line to retract the kidney.

The left colon and splenic flexure are taken down at the line of Toldt with the harmonic scalpel. The ureter and gonadal vein complex are identified at the pelvic brim and isolated from surrounding tissue. The renal vein is identified by following the gonadal vein to its entry point. The artery is identified, and lymphatic tissue overlying the artery and vein is divided with the harmonic scalpel.

The adrenal gland is visualized at the upper pole of the kidney and divided from the upper pole of the kidney. The adrenal vein is dissected free from surrounding tissue and transected. The kidney is retracted medially, and the posterior and lateral attachments outside of Gerota fascia are divided with the harmonic scalpel. A Pfannenstiel incision is made approximately three fingerbreadths above the pubis. The rectus abdominis muscles are split at the midline, and a purse-string suture with 0 Vicryl suture is made in the peritoneum. Electrocautery is used to enter the peritoneum, and an Endo Catch bag is introduced for retrieval of the kidney. The ureter and gonadal vein are transected with the linear Endo gastrointestinal anastomosis (GIA) white load stapler at the pelvic brim. The artery is isolated and divided with an Endo GIA white load linear cutting stapler. The vein is also divided with the Endo GIA stapler. The kidney is placed in the Endo Catch bag and brought out through the Pfannenstiel incision and given to the recipient surgeon for flushing.

Open Surgical Technique

The patient is placed in the lateral decubitus position. A subcostal incision is made from the tip of the 12th rib anteriorly extending approximately 10 to 12 cm. The latissimus dorsi and posterior serratus are divided. The external and internal oblique muscles are divided starting at the posterior border. The retroperitoneal space is exposed, and Gerota fascia is identified and incised. The 12th rib may need to be resected to allow better exposure. The ureter is identified and dissected down to the iliac vessels, at which point it is clipped and divided, preserving an appropriate length for subsequent transplantation. Tissue overlying the renal artery and vein is identified and divided. At this point, the kidney is isolated on its vascular pedicle. When the recipient team is ready, a right-angle clamp is placed on the renal artery and the artery is divided. A Satinsky clamp is placed around the inferior vena cava for a right nephrectomy or on the renal vein for a left nephrectomy. The renal vein is divided, and the kidney is given to the recipient team. The renal artery stump is then suture ligated. The renal vein stump is oversewn with a 5-0 Prolene suture in a running fashion.

Postoperative Care and Follow-up of Living Donors

Postoperatively, the patient should be kept well hydrated and careful attention paid to urine output. The diet can be advanced quickly in either open or laparoscopic cases. The most common complications are urinary retention and ileus. Other less common complications are bleeding, deep venous thrombosis or pulmonary embolism, rhabdomyolysis, injury to the bowel or bladder, and injury to the spleen. Patients who undergo laparoscopic donor nephrectomy tend to have shorter hospital stays (2–4 days) compared with patients who undergo open nephrectomy (3–7 days). The group at Duke implemented a protocol for enhanced recovery after surgery that safely allows the patient to be discharged on postoperative day 1 (see Table 27.3 ). Patients report great satisfaction with pain control and early discharge. The OPTN requires that data be submitted for all living kidney donors at 6 months and 1 and 2 years after surgery. Survival and the development of ESRD do not appear to be affected by living donation. In a study of 3698 kidney donors from 1963 to 2007 at a single center, it was shown that ESRD developed in 180 cases per million persons per year in donors compared with 268 cases per million persons per year in the general population. Scores of physical and mental health in the living kidney donor population were significantly better than those of the general US population.

The long-term consequences of kidney donation have been of concern to the transplant community for many years. However, a long-term donor registry is still not a reality. The long-term consequences of decreased GFR seen in living kidney donors and the risk of subsequent renal failure were studied by the group at Johns Hopkins. At issue has been whether original control groups were appropriate in comparing living donors with an unscreened population. In the current study, the authors compared donors to the third National Health and Nutrition Examination Survey (NHANES III). They found that kidney donors had a higher risk for development of ESRD throughout their life (90 per 10,000) compared with a healthy population (14 per 10,000), but the risk was still much lower than in the general population (326 per 10,000). There was increased risk noted in African American, older, and related donors. However, a recent metaanalysis of 53 recent studies revealed that the relative risk of development of ESRD is quite small, with an incidence of 0.5 events per 1000 patient years. Previous living donors who develop ESRD are granted 4 points in the kidney allocation system, thus they have a shorter waiting time.

Deceased Donor Surgical Technique

The criteria for establishing brain death were published in the New England Journal of Medicine in 2001. A complete neurologic examination must first be completed when the patient has a core temperature above 32°C and there is no evidence of drug intoxication, poisoning, or neuromuscular blocking agents. There can be no other medical conditions that can confound the clinical assessment, such as severe electrolyte, acid-base, or endocrine disturbances or hypotension. A complete clinical neurologic examination includes documentation of coma, the absence of brainstem reflexes, and apnea. Confirmatory testing is also completed as outlined in Box 27.3 .

A careful medical and social history is obtained from the medical record and the family. Potential donors are excluded if there is active infection or malignant disease. Renal function and urine output are assessed. If a donor has increased risk behavior as defined by the Centers for Disease Control and Prevention (CDC) for transmission of HIV infection or hepatitis C, the intended recipient must be informed that the donor is high risk, and a written consent for transplantation with an increased-risk CDC donor must be obtained ( Box 27.5 ). In managing a donor, it is important to monitor urine output carefully. Vasopressin may need to be given if diabetes insipidus develops. Many organ procurement specialists administer hormonal therapy to stabilize the donor after the catecholamine release that is common in acute brain death. This catecholamine release can result in significant decreases in thyroid hormone, cortisol, and insulin levels.

Usually, kidney procurement takes place after the thoracic and liver procurements are complete. The retroperitoneum is fully exposed. The ureters are identified and divided as close to the bladder as possible. In procuring the right kidney, it is important to preserve the vena cava cuff so that the renal vein can be lengthened if needed to facilitate the recipient operation.

On the back table, Gerota fascia is removed. The renal artery and vein are identified. The ureter is identified, and the periureteric tissue as well as the tissue along the lower pole of the kidney is preserved to prevent ureter ischemia. If any lower pole renal arteries are identified, these must be reconstructed to ensure adequate blood supply to the ureter.