Simultaneous pancreas-kidney transplantation

Simultaneous pancreas-kidney transplantation: an overview of indications, complications, and outcomes.

Pancreas-Kidney Transplantation

Simultaneous pancreas-kidney transplantation (SPK) has become an accepted therapy for the treatment of patients with insulin-dependent diabetes mellitus and renal failure from diabetic nephropathy. The procedure has evolved over the last twenty years, and refinements in technique, better organ preservation solutions, and more potent immunosuppressive therapies have improved one-year graft-survival rates to 81% for the pancreas and 88% for the kidney (International Pancreas Transplant Registry Data-1996). Proper patient selection is important, given the increased complexity of the procedure, the increased need for immunosuppression, and the need for compliance with postoperative medications and monitoring. The benefits of a successful SPK include more physiologic glucose metabolism and freedom from dialysis. This review will describe the indications and selection process for potential candidates, outline the procedure and postoperative care, and discuss the potential impact on secondary complications of diabetes mellitus. It will then discuss results and complications from the use of current protocols and immunosuppression at the University of California at San Francisco. Canadian Pharmacy

Introduction
Diabetes mellitus is prevalent in about five percent of the general population. Complications of diabetes, includ¬ing retinopathy, microvascular disease, and renal disease, cause significant morbidity and mortality in this group of patients. Diabetes and its complications are the eighth leading cause of death in the United States, the leading cause of renal failure and blindness in adults, and the most frequent, underlying disease leading to amputations.

Approximately 30% of patients with diabetes require daily insulin injections. The administration of insulin in this fashion prevents the serious, metabolic derangements that can occur with hyperglycemia, and tight control of serum glucose may slow or prevent the secondary complications of diabetes. No exogenous insulin administration, however, can compare to the physiologic delivery of insulin by an intact pancreas. For this reason, whole-organ, pancreas transplantation was first attempted in humans in 1966. The development of the surgical techniques for successful transplantation, the use of newer immunosuppressionants, and an understanding of the pitfalls and complications following pan creas transplantation have enabled graft- and patient-survival rates to reach levels far superior to early results. These results justify offering the procedure to carefully selected patients, for whom earlier intervention in the course of the disease will possibly result in better prevention of secondary complications.

The University of California at San Francisco (UCSF) initiated a program of simultaneous pancreas-kidney transplantation (SPK) in 1989. Since that time, over 140 patients have undergone the procedure at our institution. This review will outline our indications and approach to patient selection, describe the surgical procedure and its complications, and comment on current results and effects on secondary complications.

Indications and Patient Selection
Simultaneous pancreas-kidney transplantation is typically offered to patients who have insulin-dependent diabetes mellitus and in whom diabetic nephropathy and renal insufficiency have developed. Many of these potential recipients have other manifestations of diabetes, including retinopathy, neuropathy and gastropathy. Patients who may benefit from the SPK procedure must be selected carefully in order to best use scarce organs. buy abilify online

Potential recipients are identified by their nephrolo-gists or endocrinologists and referred to a transplant surgeon for evaluation. Other team members, including transplant nephrologists, nurse coordinators, social workers, and financial counselors, also participate in the initial evaluation. Absolute contraindications to an SPK include active infection, recent or current history of malignancy, and human immunodeficiency virus (HIV) infection. Morbid obesity, advanced cardiovascular or peripheral vascular disease, advanced age, and a history of poor compliance or substance abuse are relative contraindications. Although some centers have reported favorable, SPK results in patients with coronary artery disease who have undergone revascularization, we typically recommend solitary kidney transplant in this patient group. Furthermore, patients must demonstrate a high degree of motivation and an ability to cooperate with the complex protocols for postoperative monitoring and medication. buy cheap levitra

After a suitable candidate has been identified, we perform an immunologic evaluation, cytomegalovirus, HTV, rapid plasma reagin, human T-lymphotrophic virus I/П and hepatitis serologies, HLA and ABO typing, and panel reactive antibody screening, as well as basic blood chemistries, complete blood count, electrocardiogram (EKG), chest x-ray and coagulation studies. Cardiac evaluation consists of the above EKG, an echocardiogram, and a non-invasive assessment for coronary artery disease. If ischemic heart disease is identified, we request coronary catheterization. Further gastrointestinal evaluation is indicated in patients with a history of peptic ulcer disease or poor gastric emptying. Patients with frequent foot infections or non-healing ulcers warrent a more accurate, non-invasive assessment of the degree of peripheral vascular disease. Patients may also undergo urologic evaluation consisting of a cystourethro-gram or possible cystoscopy, depending on their history, and further evaluation by a neurologist is necessary in patients with a history of cerebrovascular disease. Given the long waiting time for transplant, patients must be reevaluated annually to determine any change in their medical status and need for repeat studies. canadian generic viagra

At the time of admission for transplant, we do a thorough history and physical examination and repeat the laboratories, chest x-ray, and EKG. Any new medical problems or EKG changes may eliminate the patient as a candidate for that particular set of organs. Because we have limited time, once patients are admitted to prepare them for transplant, it is often difficult to do many extra tests to address new medical problems. For this reason, a backup set of patients is often screened for compatibility with any given donor and can be brought in quickly, if the top, potential recipient is deemed unsuitable.

The Surgical Procedure
The first clinically successful SPK transplants were performed at the University of Minnesota in 1966 by Lillihei and Kelly. The first patient developed a pancre atic fistula and rejection, which led to early graft removal and eventual death. The second patient became normoglycemic by the sixth postoperative day and remained so for six months, until she developed a fatal pulmonary infection. This initial report demonstrated the feasibility of pancreas transplantation. There were, however, less than 100 pancreas transplants performed in the next decade, and further advancement in the field was only possible after the improvement of surgical techniques, the introduction of newer immunosuppressants, and the development of a better understanding of pancreas-allograft rejection. canadian pharmacy topamax

Early technical issues that needed to be resolved included the management of exocrine drainage of the pancreas allograft, the placement of the venous drainage of the allograft, the prevention of graft thrombosis, and the optimum timing of the pancreas transplant in relation to the renal transplant. The management of exocrine drainage was initially accomplished by anastomosing the donor duodenum to a loop of recipient bowel. The use of this technique resulted in a high incidence of anastomotic breakdown with abscess formation and subsequent graft loss. Another technique, the occlusion of the pancreatic duct with injected neoprene, often led to early graft fibrosis. Bladder drainage, whereby the donor’s duodenum is anastomosed at the Vater’s ampulla directly to the recipient’s bladder, has become the most widely accepted technique. This approach permits exocrine secretions to be expelled with the urine and allows for the monitoring of urinary amylase, which is helpful in detecting rejection early in its course. This technique, however, is accompanied by its own set of problems, including fluid and electrolyte, especially bicarbonate, losses; urinary tract complications; and the development of leaks, if the bladder becomes over-distended. Thus, some centers have returned recently to using the technique of enteric drainage and have had more favorable results than before. cialis professional

The pancreas allograft is now commonly placed in the right iliac fossa with anastomosis of the donor portal vein to the recipient external iliac vein for venous outflow. Arterial inflow is established from the recipient external iliac artery to the superior mesenteric artery and splenic artery of the donor pancreas via an extension graft of donor iliac artery. This results in insulin delivery to the systemic circulation. Careful studies of postprandial glucose metabolism indicate that carbohydrate metabolism remains relatively unaffected, but that a state of hyperinsulinemia is created. This effect appears to be secondary to decreased insulin clearance, because C-peptide levels are not increased. A few groups have questioned this route of insulin delivery and have devised a procedure to allow for anastomosis of the donor portal vein to the recipient portal circulation via the superior mesenteric vein. The benefit of this more physiologic positioning of the graft remains to be seen. Canadian Pharmacy prednisone

The pancreas graft is a low-flow organ compared to the kidney or liver allograft. Therefore, thrombosis of either the arterial supply or the splenic/portal vein occurred at a significant rate in most centers’ early experience. Initial attempts to decrease rates of graft thrombosis focused on anticoagulation in the early postoperative period. Many programs continue to use aspirin and dipyridamole immediately after surgery. A graft thrombosis rate of less than 5% in most current series has resulted from improvements in preservation solution and organ-recovery techniques, the proper selection of donors and recipients, and better attention to the vascular anastomoses, with proper orientation of the arterial bifurcation graft and shortening of the portal vein to eliminate kinking.

The timing of the pancreas transplant in relation to the renal transplant has also improved. Solitary pancreas transplantation before the development of uremia results in a higher graft loss, secondary to thrombosis. Pancreas transplant after a previous kidney transplant has been performed successfully but is also accompanied by a higher thrombosis rate caused by a lack of uremia. Thrombosis rates are clearly lower when a simultaneous kidney-pancreas transplant is done. Additionally, there are immunologic advantages to the simultaneous transplant procedure. Because concurrent rejection of the kidney and pancreas is seen frequently in recipients of SPK transplants and because rejection of the pancreas can be difficult to diagnose, the parameters of kidney rejection are generally used to trigger the initiation of rejection therapy. Therefore, the presence of a simultaneously-transplanted kidney may result in more prompt treatment of rejection. The recipient of an SPK transplant is also exposed to only one set of HLA antigens; this may have implications regarding sensitization, should re-transplant be necessary. The majority of pancreas transplants have been SPK transplants in the last 15 years. With better immunosuppression, however, solitary pancreas transplantation is becoming more popular, because earlier intervention carries with it the obvious advantage of preventing the secondary complications of diabetes. cialis super active

The procedure currently used at the UCSF is a culmination of the work and experience outlined above. A successful SPK begins with appropriate donor selection. In general, potential pancreas-kidney cadaver donors tend to be younger; they also have no underlying history of cardiovascular disease or diabetes and no hemodynamic instability during the pre-recovery phase. Donors are typically less than 50 years old, with no absolute cutoff at the lower age limit, although donors weighing less than 45 kg tend to have arterial anatomy of smaller caliber, which may increase the rate of technical complications. A careful medical and social history is obtained, and the ideal donor has no underlying medical conditions that may contribute to pancreatitis, acute tubular necrosis, or infection in the immediate, post-transplant period. Because of the increased need for immunosuppression in SPK recipients, attention to these donor factors is critical.

The recovery operation for the pancreas is a modification of several described techniques. It involves a minimal amount of in situ dissection, mostly to mobilize the gland and to identify major vessels, followed by a low¬pressure portal and aortic perfusion with University of Wisconsin preservation fluid and subsequent removal of the liver, pancreas and spleen en-bloc. On the back table, in iced solution, the liver and pancreas grafts are carefully separated. The blood supply to each organ is preserved to allow for transplantation. Most arterial anomalies can be handled to accommodate transplantation of both organs, and the meticulous dissection in a cold, bloodless field on the back table allows for identification and preservation of arterial anomalies. cymbalta online

Once the pancreas graft is separated from the liver, the ends of the duodenal segment are trimmed and oversewn. The spleen is removed, and peri-pancreatic tissue is cleared. A culture of the duodenal fluid is obtained to guide postoperative, antibiotic therapy. The splenic artery stump and superior mesenteric artery stump are anastomsed to a Y-graft of donor iliac artery, so that only one arterial anastomosis is necessary in the recipient. The portal vein is mobilized in the donor pancreas to facilitate the venous anastomosis and is kept short to avoid problems with kinks or twists. The time between the cross-clamping of the donor aorta and the implantation of the pancreas graft is kept as short as possible, usually to within 16 hours.

While the recovery team is working on the donor, the recipient will have been selected and brought into the hospital. The preoperative preparation of the recipient consists of several phases. Final cross-matching with current and several earlier recipient serum specimens is completed, using conventional, T-cell cross-matching in non-sensitized patients. Sensitized potential recipients also undergo cross-matching, and in these cases we used fluorescence-activated cell sorter (FACS) cross-matching techniques. The recipient undergoes standard laboratory screening, EKG, and chest x-ray and is given preoperative antibiotics, consisting of vancomycin, fluconazole, and tobramycin, to prevent clinical infections from organisms that frequently reside in the donor duodenum. Enemas are administered until clear, and dialysis is completed if necessary.

Perioperative immunosuppression consists of azathioprine at 4 mg/kg, given in the operating room. One gram of methylprednisolone is also given in the operating room, prior to the administration of the monoclonal antibody Ortho-Clone T-cell 3 (OKT3). Colloid, in the form of albumin, is the preferred intravenous fluid during the procedure, because it appears to minimize graft swelling.

Once the patient is anesthetized, a large-bore Foley catheter, an arterial line, and a central venous catheter are placed. The procedure is performed through a generous mid-line incision. A careful abdominal exploration is done to rule out pathology and assess the status of the iliac vessels. The external iliac artery and vein are mobilized on the left for eventual implantation of the kidney. The right iliac artery and vein are extensively mobilized from the inguinal ligament to the vena cava bifurcation, allowing the vein to be positioned laterally to the artery at the completion of the dissection.

The pancreas graft is implanted first. After completion of the vascular anastomoses, blood sugars are carefully monitored on an hourly basis, because serum-glucose levels typically drop 50 mg/dl each hour and dextrose infusion may be necessary. After the duodenal segment has been anastomosed to the dome of the bladder, allowing exocrine secretions to drain with the urine, the kidney is implanted on the left side with an extra-vesicular bladder anastomosis, using standard techniques (Figure 1). Because SPK donors are carefully selected, the rate of delayed, kidney graft function is less than 5%, and the majority of patients leave the operating room producing urine. Peripancreatic drains are placed prior to closure, which is done in multiple layers. This approach has led to a low level of deep-and superficial-wound infection. female pink viagra

completed-pancreas-transplaFigure 1.—Schematic diagram of completed pancreas transplant. The pancreas is anastomosed to the external iliac vessels on the right side with the kidney implanted on the left. The exocrine drainage of the pancreas is controlled by anastomosis to the bladder. Alternatively, this anastomosis could be done to the small bowel.

Postoperative patients are monitored in the intensive care unit for 24 hours. A nasogastric tube is left in place until there is evidence of bowel function, and a diet is typically started by postoperative day five. Dipyridamole and aspirin are administered for two to three weeks to reduce the risk of graft thrombosis. After a diet is started, serum glucoses are carefully monitored four times a day. With the exception of one patient, who was subsequently able to discontinue daily insulin injections three months after transplant, patients have not required the perioperative administration of insulin described at some other centers. Once the patient is tolerating a liquid diet, oral immunosuppressive agents are introduced, and thereafter, other medications are converted from intravenous to oral administration. Prophylactic antibiotics are continued for five postoperative days, unless a specific organism is cultured from the donor duodenal segment or from a drain culture. In that case, appropriate antibiotics are continued for two weeks. Drains are typically removed when the drain amylase values have dropped to low levels. Lastly, serum and urine amylase values are monitored daily to detect any evidence of graft pancreatitis, rejection, or other technical problems.

Postoperative immunosuppression consists of methyl-prednisolone administered in a protocol taper. We administer 5 mg of OKT3 (Orthoclone, Ortho Biotech, New Jersey) daily, until an adequate level of either cyclosporine or tacrolimus is achieved. Azathioprine is continued intravenously at 2 mg/kg until the patient is able to tolerate oral intake, at which time mycophenalate mofetil (MMF) is started at 1.5 grams, twice daily. Either cyclosporine (Neoral, Novartis, New Jersey), or tacrolimus (Prograf, Fujisawa, Japan), is initiated when the patient is tolerating oral intake, and daily levels are followed. Adequate levels are usually achieved by postoperative day ten, and the OKT3 is discontinued. Tacrolimus, MMF (Cellcept, Roche Laboratories, New Jersey) and prednisone have been used more commonly in recent transplants at our center, because we have become more proficient in drug monitoring and the use of this immunosuppressive combination. Several centers have reported a lower rejection rate with this regimen.

The bladder catheter is left in place for two weeks post-transplant. If patients remain otherwise stable, they can be sent home, once the OKT3 is stopped, and re-admitted for Foley removal. Owing to sodium, bicarbonate, and water loss, hydration status is critical in bladder-drained pancreas patients. Thus, they are typically discharged with an intravenous line in place for at-home saline-administration during the first one to four weeks. Postoperative patients should take in between three and four liters of fluid per day. This goal is more easily met with the at-home use of intravenous (IV) fluid, which has further resulted in fewer early re-admissions for dehydration. The IV is discontinued when the patient can demonstrate a consistent daily oral intake of the required amount of fluid. cheap levitra

Outpatient management consists of frequent clinic visits in the first month after surgery. Laboratory indicators of renal and pancreatic function, including a urinary amylase, are initally followed three times a week. The dosage of prednisone is gradually tapered over the first 6 to 12 months to 10 mg a day, as the patient tolerates. We have recently begun using percutaneous ultrasound-guided biopsies of the pancreas graft to guide rejection therapy, and a system for grading the severity of rejection has been developed.

TABLE 1 Reasons for graft and patient loss*
Patient loss Kidney Loss Pancreas Loss
suicide patient death (2) patient death (3)
sudden death (2) rejection rejection
sepsis microsporidia infection microsporidia infection
malignancy HUS thrombus
microangiopathy infection
PTLD
*For 49 patients receiving simultaneous kidney pancreas transplants from 1 /95 to 12/96. Overall patient survival was 94% at one year, with kidney and pancreas graft survival of 90% at one year. HUS = hemolytic uremic syndrome, PTLD = Post-transplant lymphoproliferative disorder. Number in parentheses = number of patients. If number not noted = one patient.

Results at UCSF
Since 1989, over 140 SPK transplants have been performed at UCSF, using the above described surgical techniques and perioperative protocols. The biggest changes over the last eight years have involved the types of immunosuppressants used. Induction therapy with OKT3 remains mainstay of our protocol, with MMF and tacrolimus having come into greater use over the last two years. We have reviewed extensively our results in a subset of 49 patients who have received transplants that use these newer immunosuppressive agents. In our review of this subset, we have paid attention to patient and graft outcome, rejection rates, and complication rates.

From January 1995 to December 1996, these 49 patients underwent SPK transplantation at UCSF. The median age of recipients was 38 years, with a range of 24 to 51 years. There were 22 women and 27 men in this subset of patients. All patients had at least 6 months of detailed follow-up. order cialis professional

The overall, one-year patient survival rate was 94%. After one year, the rate of pancreas graft survival, defined as insulin independence, was 90%. There was one loss in the first two weeks due to a graft thrombosis. The rate of kidney graft survival, defined as freedom from dialysis, was also 90%, after one year. The mean creatinine value for patients with one year of followup was 1.5 mg/dl and 1.4 mg/dl at two years. Table 1 shows the reasons for patient and graft losses during the entire, follow-up period.

All patients received OKT3 induction, maintenance prednisone, and various combinations of azathioprine or MMF and cyclosporine or tacrolimus. Rejection of the pancreas was diagnosed by any combination of clinical parameters and laboratory abnormalities, for we have only recently used pancreas biopsies. We considered the following symptoms as potential indicators of pancreas rejection: graft tenderness, fever, sustained fall in urinary amylase to less than half of baseline, rise in serum amylase, or rise in urine eosinophils. Kidney rejection was documented by biopsy in the majority of cases. After 6 months of follow-up, results indicated that 34.7% of these 49 patients were free of rejection, 14.3% had isolated kidney rejection, 12.2% were treated for isolated pancreas rejection, and 28.6% were considered to have had simultaneous pancreatic and renal allograft rejection. Multiple rejections of one or both allografts occurred in 10.2% of these patients. Without biopsy results to confirm pancreas rejection, it is possible that many of the patients classified as having kidney-only rejection may have had concurrent pancreas rejection, but had not yet developed clinical or laboratory signs. Indeed, other centers have reported a much higher rate of concurrent rejection of the two organs. In patients who experienced rejection of either organ in the first six months post-transplant, the mean time to the rejection was 34 days, plus or minus 5.1 days. Rejection treatment consisted of a course of OKT3 for 7 to 10 days in 68.3% of the patients with rejection; the rest received pulsed steroids. Most patients received only a single course of OKT3 for rejection, and more recently, patients undergoing rejection treatment have been given tacrolimus for maintenance immunosuppression. canada pharmacy mall

Complications in the post-transplant period can be divided into technical complications, which usually appear early, and complications of immunosuppression, which often appear later. Only one pancreas graft was lost to thrombosis on postoperative-day 10. During the follow-up period, re-operation for surgical problems directly related to the pancreas and kidney transplant occurred 22 times in 18 patients. Reasons included the repair of leaks at the duodenal segment in 3 patients, conversion to enteric drainage of pancreatic exocrine secretions in 3 patients, lymphocoele drainage in 4 patients, transplant nephrectomy in 3 patients, transplant pancreatectomy in 2 patients, and removal of both grafts in 1 patient. Drainage of an intra-abdominal abscess, repair of a ureteral obstruction, re-exploration for bleeding, and repair of a wound dehiscence each occurred once, and two patients required re-exploration for small bowel obstruction.

Well-recognized complications of immunosuppression include infections and malignancies. During the follow-up period, 26.5% of patients had positive blood or intravenous-line cultures, which required antibiotic treatment. Most of these cultures tested positive for staphylococcus epidermidis, and infection had occurred during the initial hospitalization. Frequent urinary tract infections were very common, and 69.4% of patients had at least one positive culture requiring treatment. Most were treated on an outpatient basis with a ten-day course of oral antibiotics. Four patients, however, required hospitalization for urosepsis and treatment with intravenous antibiotics. Recurrent urinary tract infections require both an evaluation with cystoscopy to rule out foreign bodies or stones in the bladder and a determination of the ability of the bladder to empty. Patients with poor bladder function and recurrent urinary infections have been considered for enteric conversion, a procedure whereby the duodenal segment is disconnected from the bladder and anastomosed to the small bowel. viagra canadian pharmacy

Severe pulmonary infections, one caused by aspergillus, developed in two patients, and in one patient a deep infection developed around the pancreas, with serratia that initially responded to drainage, but ultimately led to graft loss. No superficial-wound infections developed in this series of patients. One patient eventually died with cardiac involvement, as a result of systemic microsporidia infection.

Viral infections continue to be a significant problem in these heavily immunosuppressed patients. Biopsies provided evidence of cytomegaloviral (CMV) infection in the gastrointestinal tract in 8.2% of patients. Blood cultures for CMV were positive in 18.4% of patients, and one patient had evidence of CMV on a kidney biopsy. These CMV infections were typically treated with a three-week course of intravenous ganciclovir. We are greatly concerned about the recent identification of three patients with renal damage, secondary to polyoma viral infections. These patients all presented with a rise in creatinine, which led to biopsy. Histology revealed the characteristic findings of polyoma. There is, unfortunately, no treatment for this virus, and the lowering of immunosuppression has not resolved the infection in these cases.

Malignancies have been relatively unusual in this patient group. One patient developed a post-transplant, lymphoproliferative disorder, which led to kidney loss. This patient was managed with continued, low-dose immunosuppression, consisting of prednisone alone, and has retained pancreas function. A second patient died of metastatic squamous-cell carcinoma of the lung, which had not been identified preoperatively, despite an aggressive work-up of a pleural effusion. We will not know more about the real effect of these newer, more potent immunosuppressants on malignancies until long-term follow-up is available. Viagra 400 mg

We know the readmission rate for SPK recipients to be much greater than that for kidney recipients. This relates to dehydration, metabolic derangements related to the bladder drainage of the duodenal segment, an increased rate of rejection, and an increased rate of infections. During the follow-up period, 96% of patients required readmission. The average number of readmis-sions was 3.8 per patient, with an average rehospitaliza-tion of 19.7 days per patient. These figures emphasize the complex nature of the management of these patients and the need for close, outpatient follow-up.

We further analyzed the last 15 transplants of 1997. Of these patients, 13 received prednisone, MMF, and tacrolimus as maintenance immunosuppression after OKT3 induction. Follow-up time ranges from three to nine months. There have been no patient deaths, no kidney losses, and two pancreas losses due to thrombosis. Rejection occurred in just 4 patients (27%), only 3 of whom required OKT3 therapy. Mean length of stay for the transplant admission was 12.3 days. Readmission was necessary in 73% of these patients, but was generally of a short duration, averaging 11.2 days per patient that required readmission. This drug combination appears to have favorable, early results in terms of graft and patient survival. The long-term effects, as they relate to malignancies and infections, need to be determined.

Effect of SPK on Secondary Complications of Diabetes
The greatest potential benefit of pancreas transplantation is the prevention of secondary complications associated with diabetes. By definition, most patients who undergo SPK transplant have already progressed to end-stage renal disease, owing to diabetic nephropathy. These patients often display features of neuropathy, retinopathy, gastropathy, and diabetic microangiopathy, with a myriad of vascular diseases. The effect of optimal glucose control following pancreas transplantation has been evaluated for its ability either to halt the progression of or reverse some of these complications. Viagra Professional 100 mg

The recurrence of diabetic nephropathy in the transplanted kidneys of patients that did not receive a pancreas transplant has been documented in many series. An increase in the mesangial matrix density is seen in diabetic recipients of isolated kidney transplants, and this lesion is prevented when a pancreas is transplanted simultaneously. Initial reports indicated that a successful, solitary pancreas transplant was unable to reverse the established lesions of diabetic nephropathy in native kidneys. A recent report, however, has documented histologic improvement in the lesions of diabetic nephropathy after a successful, isolated pancreas transplant and resultant normoglycemia of more than five years. In addition, long-term kidney survival rates in SPK recipients tend to be higher than those for diabetic patients receiving only kidneys, perhaps because the quality of the donor kidneys and the underlying health of SPK recipients are often better. The long-term, graft-survival rate has improved, despite a higher, acute rejection rate and higher requirements for increased doses of immunosuppressants.

Retinopathy is often far advanced by the time patients undergo pancreas transplantation. One series, which compared the degree of retinopathy in patients with successful, versus failed, pancreas transplants, reported that there was no difference in visual symptoms over the first three years. After that time, retinopathy stabilized in patients with successful grafts, and patients with failed grafts had further deterioration in their vision. It appears that by the time nephropathy has developed, retinopathy has advanced far enough for the stabilization of retinal lesions to be the best outcome that we can anticipate.

Several studies have evaluated the effect of successful pancreas transplantation on diabetic polyneuropathy. Symptomatic improvement and measurable increases in both nerve conduction velocities and sensory action potentials have followed successful pancreas transplantation. Symptoms of gastroparesis often improve as well. It must be remembered, however, that improvement of uremia alone can have an effect on both gastropathy and neuropathy. The degree of autonomic dysfunction has a negative effect on long-term survival. Survival rates are improving, however, in patients with autonomic dysfunction quantitated by cardiorespiratory reflexes, who have functioning pancreas grafts. buy generic altace

Potential recipients of pancreas-kidney transplants are carefully screened for evidence of cardiovascular disease. It has been shown clearly that there is a high morbidity and mortality rate in patients who have underlying cardiac disease and receive a pancreas transplant. A successful pancreas-kidney transplant may affect the progression of cardiovascular lesions in patients who undergo the procedure and do not have far-advanced, baseline disease. Levels of serum sialic acid, a risk factor for cardiac disease, have been shown to fall more extensively in patients who have receive a successful kidney-pancreas transplant, as opposed to a kidney alone. Carotid lesions were compared in patients following SPK versus isolated kidney transplant. There was a progression of lesions in both groups, but it was less pronounced in the kidney-pancreas recipients. In general, it is difficult to compare these two groups, because many potential kidney-pancreas recipients with advanced cardiac or vascular disease are typically advised to undergo only a kidney transplant. In addition, differences in the progression of disease may be diluted by the adverse effects of increased steroids and hyperinsulinemia in the pancreas-kidney groups.

Pancreas-kidney transplantation alters lipid profiles; there is an increase in HDL cholesterol and a decrease in plasma concentrations of cholesterol and triglycerides. The use of immunosuppressive agents such as cyclo-sporine and tacrolimus has been associated with worsening lipid profiles in recipients of kidney or liver transplants. It is interesting, however, that lipid profiles improve markedly in SPK patients receiving tacrolimus.
Another advantage of this surgery is the enhanced quality of life enjoyed by patients who receive a successful pancreas-kidney transplant. In a self-reporting questionnaire, patients with a successful transplant reported a more positive health perception, less pain, and greater ability to function socially. In addition, there is a strong willingness on the part of patients with failed grafts to repeat the procedure.

Summary
Simultaneous pancreas-kidney transplantation has evolved over the last 15 years and is now a viable therapeutic option for carefully selected patients. As better drugs become available, both long-term graft- and patient-survival continue to improve, with less rejection and fewer immunosuppressive complications. Overall, the procedure is more complex, has more complications and re-hospitalizations, and a higher incidence of rejection and immunosuppression requirement than renal transplant alone, although these increased risks are diminishing with better patient selection and improvements in technique and postoperative management. The physiologic advantages of near-perfect glucose metabolism and its potential effect on the progression of dia betic complications, as well as overwhelming patient satisfaction, appear to justify these increased risks. Further developments in solitary pancreas transplantation will, we hope, allow for earlier intervention in the natural history of diabetes. In the meantime, all physicians in the field of pancreas transplantation await a practical and successful technique for transplanting islet tissue alone, although this goal remains out of reach.

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