Timing Of Kidney And Pancreas Transplantation

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Due to the current availability of dialysis technology, an increasing number of patients with ESRD are surviving much longer now than they did in the past. Subsequently, a large portion of Medicare's budget is spent in providing dialysis and access for dialysis. Furthermore, dialysis has become an imperfect modality, fraught with problems of poor quality of life, demands of long periods of repeated exhausting therapy, loss of vascular access, complications of access surgery, and decreased sexual function. Transplantation, on the other hand, offers ESRD patients the opportunity to resume a normal lifestyle without the burden of dialysis and its associated complications. Economically, the cost of transplantation, medications, and follow-up is still less than the cost of the procedure for access and a dialysis regimen.

Transplantation, though the best therapeutic option for ESRD patients, is not always a viable one for several reasons. First, the number of cadaveric kidney transplantations has remained at a constant level despite the growing number of ESRD patients waiting on the list. This has resulted in the death of a growing number of patients waiting for a kidney transplant. Despite this, the demand continues increasingly to outstrip supply. Second, not every patient is a candidate for kidney transplantation. Cardiac disease, infectious processes, malignancies, chronic debilitating illnesses, and contraindications to general anesthesia all can preclude a patient's receiving a transplant. Third, once listed, the waiting time for a kidney is also excessive. Patients can wait on average 3 to 5 years on the kidney transplant list. Depending on the region in the country, this wait can be even longer. Finally, compliance issues can also preclude successful transplantation. Although compliance with dialysis regimens can be somewhat an indicator, accurately predicting patient compliance with medications at home and follow-up continues to be difficult.

ESRD patients have options. Once transplantation has been decided on and viability of the patient is determined, the option of living related and living unrelated donors can be presented to the patient and, possibly, to the patient's family. This alternative has multiple advantages over cadaveric kidney transplantation. First and foremost, the waiting period for transplantation can be eliminated. This means it is possible to transplant patients prior to their ever needing dialysis, thus avoiding the need for multiple access surgeries and the subsequent complications associated with the procedures. An added benefit of receiving a living related or living unrelated graft is that the donor is well known to the physician and can be thoroughly screened. The case can also be scheduled electively. Living related and living unrelated grafts have very low rates of acute tubular necrosis and graft nonfunction, and graft survival is superior to cadaveric graft survival. With the advent of laparoscopic donor nephrectomies and refinements of open techniques, the procedure is well tolerated, with low morbidity and mortality. Given these advantages, patients have realized this is the best option to avoid dialysis and resume their regular lifestyle. Transplant centers have also come to the conclusion that this option allows for the best possible result and provides a means for correcting the deficiencies associated with cadaveric kidney transplantation.

To allow the best possible outcome for ESRD, and allow for transplantation prior to initiating dialysis, proper timing of referral to the transplant center is crucial. The current dogma in management of ESRD is to begin the process of hemodialysis automatically. The change to a mentality of proper patient referral for transplantation rather than dialysis needs to be made. Proper monitoring of glomerular filtration rates (GFRs) in a nondiabetic patient with a GFR of 15 ml/ min, and in a diabetic with 20 ml/min, is the key to correct timing of referrals for transplantation. This is the typical GFR at which patients are usually thought to require dialysis eventually and are referred to surgeons for access. Referral for transplantation at this time allows for appropriate preoperative workup and discussion for living related or living unrelated transplantation.

If transplantation is not feasible or available, the standard of care is dialysis. The two main modes of dialysis are hemodialysis and peritoneal dialysis. Indications for beginning dialysis include (1) GFR of 5-15 ml/min, (2) severe hyperkalemia, (3) metabolic acidosis refractory to medical therapy, (4) fluid overload, (5) uremic pericarditis, (6) neurological manifestations (e.g., lethargy, myoclonus, seizures), and (7) blood urea nitrogen (BUN) > 100 (not absolute—decreases morbidity and mortality). The timing of placement of access depends on the form of dialysis and type of access. Peritoneal dialysis via peritoneal dialysis catheter needs 2 weeks to mature prior to use. This form of dialysis, which requires an intact peritoneal membrane, has certain pros and cons. The major benefit to this access is independent lifestyle and shift of control of the therapy back to the patient. A major drawback to this form of dialysis is the inefficiency inherent in peritoneal dialysis. Persistent hyperkalemia and elevated BUN and creatinine levels leave patients uremic. Catheter infections can be frequent, depending on the hygienic practices of the patient, and may require removal of the catheter. Contraindications to peritoneal dialysis include multiple abdominal surgeries without an intact peritoneal membrane, abdominal aortic grafts, compliance issues of the patient, as well as the patient's lack of motivation.

In hemodialysis, the most common form of dialysis, there are many options when choosing forms of access for hemodialysis, such as temporary or permanent catheters, arteriovenous (AV) fistulas, AV grafts, and basilic vein interposition grafts. The superior form of access is an AV fistula, the varieties of which include the cephalic vein-radial artery fistula and upper-arm basilic vein-brachial artery fistula. The advantages to a fistula, once matured, are duration of patency lasting the life expectancy of a dialysis patient, with an extremely low incidence of thrombosis, as well as low infection rates. The disadvantages include time to mature (6-8 weeks) and requirement of a vein that is of sufficient diameter as well as superficial. The fistula also has the disadvantage of giving the patient a deformed appearance and requiring special training for the dialysis technician to access the fistula. With all these disadvantages, it is no surprise that only approximately 15% of all dialysis patients have AV fistulas.

AV grafts are the most widely utilized forms of access for hemodialysis. The material for the grafts is usually polytetrafluoroethylene (PHI,). Advantages to AV grafts include rapid time to maturity (2 weeks), easy access by dialysis technicians, and ease of placement. The disadvantages include low patency rates (6 months to 1 year), with frequent thrombosis, high rate of infection, higher incidence of steal syndrome, venous hypertension, and upper-extremity edema. The surgeon has many sites for placement of an AV graft. The preferred site is the nondominant forearm, followed by the nondominant upper arm, and then the dominant arm in similar fashion. AV grafts can also be placed in the lower-extremity, but this is not a preferred site due to patient comfort, higher incidence of lower extremity ischemia, and poor inflow due to secondary atherosclerosis. Therefore, these are usually sites of last resort.

The various forms of access for hemodialysis for a particular patient are dependent on multiple factors, such as life expectancy of the patient and comor-bidities. Obesity or body habitus is a major determinant of the feasible form for a patient. The urgency of the need for dialysis also plays a role in the decision-making process. If a patient is in immediate need for hemodialysis, this might sway the surgeon to place an AV graft rather than a fistula. Patients with short-term life expectancy are better served with a temporary catheter (Permacath) placement than a formal AV access. Despite all of these factors that play a major role in determining form of access, the most important factor is still the size and status of the artery and vein. For example, the criteria for the size of a viable vein is 4 mm or larger for an AV fistula.

The timing of pancreas transplantation is covered in another chapter. Suffice to say that it is a function of whether the pancreas will be transplanted synchronously or metachronously to a kidney transplant, or whether it will be transplanted alone. Of course, the main indication for pancreas transplantation is intractable DM with associated ESRD.

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