Chapter 28 – Kidney and Pancreas Transplantation

666 CHAPTER 28 HISTORICAL PERSPECTIVE Interest in transplanting organs into humans dates back to the early 1900s. Floresco described anastomosis of the renal graft to the iliac fossa in 1905. In 1906, Jaboulay attempted to use a pig kidney to cure a patient with acute nephritis. He anasto- mosed the renal xenograft to the brachial arteries of the patient and urine was noted for 1 hour postreperfusion. Alexis Carrel was developing techniques of triangulation of vascular anasto- moses by performing various organ transplants in animals and received the Nobel Prize in 1912. However, organ function was minimal and further attempts at organ transplantation were abandoned. However, in the early 1950s, Medawar and col- leagues described the prevention of rejection in mice and human organ transplantation was again attempted. The first successful renal transplantation was performed by Murray in 1954 between identical twins. Other major milestones in trans- plantation have included the discovery of cyclosporine and other effective immunosuppressive medications, description of the histocompatibility antigens, and perfecting of preservation solutions (Table 28-1). The history of the discovery of diabetes and insulin is fas- cinating and well-documented. Pancreas transplantation has also developed as a durable way to provide constant insulin to the type 1 diabetic. The first pancreas transplantation in an animal was performed by Hedon in 1913, who attempted placement of a pancreas allograft in the neck of pancreatectomized dogs. The first successful human pancreas transplantation was performed by William Kelly and Richard Lillehei at the University of Min- nesota. They transplanted a duct-ligated segmental pancreas graft simultaneously with a kidney graft from the same deceased donor. The pancreas was placed into the left iliac fossa but, unfortunately, had to be removed on the seventh postoperative day. Management of the exocrine pancreas secretions remained problematic, with many revisions over the years from using a donor duodenal button technique, bladder drainage, duct abla- tion via injection, and finally enteric drainage. This chapter describes aspects of kidney and pancreas transplantation. Patient selection for transplantation with a kidney or pancreas is con- sidered first. Organ procurement, preservation, transplant technique, and outcomes of kidney and pancreas transplantation are discussed independently. KIDNEY TRANSPLANTATION Indications Kidney transplantation offers patients better long-term out- comes than dialysis. The quality of life is improved and survival is projected to be 10 years longer than if the patient remains on dialysis.1 During the past decade, the kidney waiting list has grown and the death of candidates who die while waiting has doubled. This reflects a change in demographics in the recipient waiting list, with patients listed at older ages and an increasing number of patients being inactive on the waiting list.2 The most common causes of renal disease have evolved over the last 10 years. Overall, the percentage of patients with diabetes and hypertension as the cause of failure has increased from 24% to 28% and the percentage of glomerular disease has declined from 42% to 21%.2 In addition, the incidence of chronic kidney disease has also rapidly increased, from 209,000 patients in 1991 to 472,000 in 2004. Coresh and associates3 have noted that the higher prevalence of diabetes, hypertension, and higher body mass index (BMI) explains this trend. Simi- larly, the waiting list for kidney transplantation continues to grow every year. Potential recipients are also older than in past decades, with the group aged 50 to 64 years seeing the greatest increase (Fig. 28-1) This change in demographics has certainly presented challenges in preparation of these patients for trans- plantation and immunosuppression. It is also estimated that by 2015, the annual incidence of end-stage renal disease will be 136,000 patients/year and the prevalence will be 712,000 patients/year. Patient Selection The evaluation of patients as appropriate candidates for trans- plantation can be an arduous process. Patients with end-stage kidney disease have significant comorbidities and these must be taken into account when evaluating for transplantation. Guide- lines for evaluation of these patients have been established.4 Emphasis should be placed on determining the original cause of renal disease so that the patient can be given reasonable expecta- tions for graft survival. A graded association has been reported between reduced glomerular filtration rate (GFR) and risk of death and cardiovascular events.5 Mortality rates are more than 20%/year with dialysis. Long-term follow-up of kidney trans- plant recipients has shown a clear survival advantage over historical perspective kidney transplantation pancreas transplantation islet transplantation KIDNEY AND PANCREAS TRANSPLANTATION Yolanda Becker Kidney and Pancreas TransPlanTaTion  Chapter 28  667 SECTIO N IV Tr an sPlan TaTio n an d iM M U n o lo G y guidelines, patients with a GFR of 30 mL/min/1.72 m2 or less, and/or chronic kidney disease (CKD), stage 3 or 4, should be referred to a nephrologist (http://www.kidney.org/professionals/ kdoqi/index.cfm). Patients whose GFR falls below 20 should be evaluated as possible kidney transplant recipients if they do not have an absolute contraindication. Common causes of renal failure leading to the need for replacement therapy include diabetes, hypertension, glomerular disease, interstitial disease, cystic disease, and chronic allograft nephropathy, with subsequent failure of a transplanted kidney. Kidney disease can recur in the allograft with varying frequency. Some diseases may lead to transplant failure with an inability to retransplant, such as aggressive focal sclerosing glomerulone- phritis. Common primary renal diseases and their probability of recurrence are listed in Table 28-2.10–15 Screening of potential recipients should begin with a detailed history, paying particular attention to the original cause of disease. The length of time on dialysis has been noted to be an independent risk factor for poorer outcomes.16 The past medical history should include exposures to infectious diseases (especially tuberculosis, cytomegalovirus, Epstein-Barr virus, FIGURE 28-1 additions to the Unos-oPTn (organ Procurement and Transplantation network) waiting list by age. (oPTn/Unos ethics committee report: Waiting list patient characteristics at end of year; kidney waiting list; active waitlist patients, 1999 to 2008 [http:// www.ustransplant.org/annual_reports/current/501a_age_ki.htm]). 60,000 50,000 40,000 30,000 20,000 10,000 0 65+ 50–64 2000 2002 20082004 2006 35–49 18–34 BOX 28-1  Contraindications for renal transplantation Absolute active malignancy active infection Unreconstructable peripheral vascular disease severe cardiac or pulmonary disease active iV drug abuse Relative life expectancy History of nonadherence to medication regimen History of noncompliance with dialysis Financial barriers Psychiatric issues renal disease with high recurrence rate table  28-1  Major  Milestones  in  the  history  of  transplantation Year MILeStONe 1954 dr. Joseph Murray performs the first successful kidney transplantation between identical twins. 1966 Kelly and lillihei perform the first pancreas transplantation. 1967 First simultaneous kidney and pancreas transplantation. 1970s Borel, stahelin, calne, and White initiate trials of use of cyclosporine in transplantation. 1980s Belzer and southard develop University of Wisconsin solution (Viaspan). 1990 dr. Murray receives the nobel Prize in Medicine. 1990 scharp and lacy report the first successful human clinical islet transplantation. table 28-2  primary renal Diseases and recurrence rates DISeaSe reCUrreNCe rate  (%) GraFt LOSS (%) diabetes 100 low until 10 yrs post-transplant Focal segmental glomerulosclerosis 20–30, first transplant; 80, second transplant 40–50 Membranoproliferative glomerulonephritis (MPGn) type 1 20–30 20–60 MPGn type 2 50–100 10 iga nephropathy 40–50 30 Membranous nephropathy 40 Up to 50 Hemolytic uremic syndrome 30 20–30 systemic lupus 30 rare Polycystic kidney disease 0 0 remaining on dialysis.6 Studies have also shown significant improvements in quality of life measures.7 The first step in the evaluation process is referral to a trans- plantation center. Many factors may affect the ability of the patient to be seen for evaluation. Furth and coworkers8 have shown that lower socioeconomic status, female gender, and lower level of education results in fewer referrals. There has been concern that geographic distance to a transplantation center might negatively influence access to care. However, a study of rural populations has shown that remote or rural residence is not associated with a longer waiting list time. Recipients must be carefully evaluated for surgical risk as well as their ability to tolerate long-term immunosuppression. With improvements in perioperative management, the indica- tions for kidney transplantation have increased. The absolute and relative contraindications for transplantation are shown in Box 28-1. HIV infection was once a contraindication to transplantation, but select patients have good results with trans- plantation as a treatment modality for HIV-associated nephrop- athy.9 According to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) 668  SeCtION IV TransPlanTaTion and iMMUnoloGy unrelated donor (LURD) numbers have increased in recent years, expanding the deceased donor pool is crucial. In 2003, the National Organ Breakthrough Collaborative was launched. The intent of this national effort was to increase the conversion rate (number of families consenting to donation in appropriate potential donors) to 75%. An update in 2005 sought to increase donors organs further by increasing the average organs transplanted/donor to 3.75.20 Deceased donor kidneys are placed in three broad categories: extended-criteria donor (ECD), standard criteria donor (SCD), and donor after cardiac death (DCD). As part of the effort to increase the pool of potential kidney organs, an emphasis was placed on ECD and DCD kidneys. In the past, these donor organs had a high rate of discard and there were no uniform DCD policies across the country. ECD kidneys are obtained from donors older than 60 years or from donors aged 50 to 59 years with at least two of the following criteria: cerebrovascular accident as cause of death, terminal creatinine higher than 1.5 mg/dL, or a history of hypertension. Kidneys from donors meeting the criteria for ECD have a 1.7 relative risk of graft loss when compared with kidneys from other donors.21 However, recipients of ECD kidneys clearly have a survival benefit when compared with those remaining on the waiting list.22 In regard to donation after cardiac death, the health care team determines that the patient is unlikely to make a reasonable recovery and the patient is being maintained on mechanical ventilation. If the family is interested in organ donation, a request is made to consider donation after cardiac death. If the family consents, the ventilator is disconnected in the operating room or intensive care unit. If the heart stops within a desig- nated time frame, which depends on the organ to be procured, the team waits several minutes to ensure cardiac standstill. The patient is then declared dead by the health 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.23 Donors may or may not be genetically related to their intended recipient. In some cases, living donors are anonymous. There are now reports of extended altruistic donor chains. In these cases, an initial donor-recipient pair cannot go forward with transplan- tation usually because of ABO incompatibility or sensitization of the recipient. A reciprocal exchange with another incompat- ible pair allows for a domino transplantation, with multiple exchanges with as many as 10 kidney transplant chains reported.24 The 5-year survival of an unrelated kidney transplant is the same as that from a related donor. Interestingly, the outcome from a completely mismatched donor and one who is haploidentical is also similar. 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, BMI less than 35, no cancer or active infec- tion, 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. and hepatitis) as well as malignancy. Cardiac risk factors should be evaluated. A family history of renal disease or other systemic illnesses should be documented. Routine screening examina- tions such as Pap smear, mammography, colonoscopy, dental prophylaxis, and bone density scanning should be carried out as recommended by clinical practice guidelines. Prostate-specific antigen levels should be checked in men older than 50 years. In addition, the patient should be questioned about thrombotic events such as miscarriages, multiple dialysis access events, deep venous thrombosis, or pulmonary embolus so that a hyperco- agulable profile can be obtained. The ability of the patient to tolerate immunosuppression should be evaluated. This not only involves consideration of the medical conditions, but also the ability to comply with a complex medical regimen and the financial ability to obtain the medications. As noted, end-stage kidney disease patients are at increased risk for cardiovascular disease.5 Hence, a careful preoperative cardiac screening must be completed. However, there is little consensus about the optimal screening algorithm. Patients should have a baseline electrocardiogam (ECG) obtained, rec- ognizing that almost 75% will have evidence of left ventricular hypertrophy. The patient’s risk profile should be assessed to see whether any risk factors can be modified (e.g., diet, weight management). Low-risk patients include those who have good functional capacity and no previously identified cardiac disease. These are typically patients with isolated renal disease such as immunoglobulin A (IgA) nephropathy or polycystic kidney disease, and with little comorbidity. Moderate-risk patients should undergo stress testing. It is important to ensure that the stress is diagnostic and a reasonable heart rate is achieved. Moderate-risk patients include those without cardiac symptoms but who have diabetes, prior history of heart disease, or two or more other risk factors for coronary disease (e.g., smoking, strong family history, hyperlipidemia, hypercholesterolemia). High-risk patients include those with a positive noninvasive test result, long-standing diabetes, or a history of severe congestive heart failure. These patients require cardiac catheterization prior to being accepted for the transplant list. Cardiac revasculariza- tion should occur prior to transplantation. If the patient requires lifelong clopidogrel (Plavix), there will be an increased risk of bleeding.17 Patients are required by federal guidelines to be reevaluated on a yearly basis. At any reevaluation, the patient’s cardiac status should be routinely reviewed and updated. A full physical examination should be completed. Renal patients are at increased risk for cerebrovascular events18; there- fore, 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, noncon- trast abdominal and pelvic CT scans should be obtained to assess the level of peripheral vascular disease. Iliac inflow might be significantly compromised, which would prevent the patient from having a successful outcome. If inflow is compromised, then one can consider whether a revascularization is warranted prior to or at the time of transplantation.19 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. Although living related donor (LRD) and living Kidney and Pancreas TransPlanTaTion  Chapter 28  669 SECTIO N IV Tr an sPlan TaTio n an d iM M U n o lo G y others perform the procedure entirely laparoscopically and make a Pfannenstiel incision to retrieve the kidney. Some centers perform a single-incision donor nephrectomy and dissect the renal hilum using instruments placed through a GelPort, which is ultimately the site of kidney retrieval. If unexpected anatomy or bleeding is encountered, it is important to convert to open techniques promptly to prevent any donor complications or prolonged surgery. Laparoscopic Surgical Technique The right or left kidney can be procured laparoscopically. The left renal anatomy is generally preferred because the renal vein is longer. Many studies have shown that the right kidney can be procured safely.23 A left kidney dissection is described here because it is more commonly done. 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 midaxil- lary 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 using the harmonic scalpel. The adrenal gland is visualized at the upper pole of the kidney and divided from that site. 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’s fascia are divided with the harmonic scalpel. A Pfannenstiel incision is made approximately three finger- breadths above the pubis. The rectus abdominis muscles are split at the midline and a purse-string 0 Vicryl suture is sewn 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 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 using the endo GIA stapler. The kidney is placed in the Endo Catch bag, brought out through the Pfan- nenstiel incision, and given to the recipient surgeon for flushing. Open Surgical Technique The patient is placed in the lateral decubitus position. A subcos- tal incision is made from t