Pancreas Transplant Alone Research Articles

Recent Trends and Results for Organ Donation and Transplantation in the United States, 2005

Recent Trends and Results for Organ Donation and Transplantation in the United States, 2005

Pancreas Retransplantation: Ideal Timing and Early and Late Results

Surgical complications are the leading cause of pancreatic graft loss among diabetic patients who undergo pancreas transplantation alone (PTA), or combined with kidney transplantations (PK) or after kidney transplantations (PAK). Therapeutic effects on secondary complications of diabetes justify pancreas retransplantation (re-PT) when the first graft is lost. However, the appropriate timing for retransplant and related problems is not known. We present our initial experience on re-PT performed on seven diabetic patients who lost their first pancreas grafts (PK) due to surgical complications (venous thrombosis in five and enteric fistula in two). Five re-PT were performed a few days after the first PT without a second course of induction therapy, while two patients received re-PT some months later with reinduction therapy. In the early re-PT group, one patient died some hours after the second surgical procedure due to pulmonary embolism, while four patients lost their second grafts due to accelerated rejection within 2 years from re-PT. In the late re-PT group, both patients have good graft function without signs of rejection. Our initial experience showed discouraging results in the group of early re-PT, due to accelerated rejection episodes leading to a high incidence of graft loss. Late re-PT accompanied by reinduction therapy seemed to have better results.

Immunosuppression: Evolution in Practice and Trends, 1994–2004

Over the last 10 years, there have been important changes in immunosuppression management and strategies for solid-organ transplantation, characterized by the use of new immunosuppressive agents and regimens. An organ-by-organ review of OPTN/SRTR data showed several important trends in immunosuppression practice. There is an increasing trend toward the use of induction therapy with antibodies, which was used for most kidney, pancreas after kidney (PAK), simultaneous pancreas-kidney (SPK) and pancreas transplant alone (PTA) recipients in 2004 (72-81%) and for approximately half of all intestine, heart and lung recipients. The highest usage of the tacrolimus/mycophenolate mofetil combination as discharge regimen was reported for SPK (72%) and PAK (64%) recipients. Maintenance of the original discharge regimen through the first 3 years following transplantation varied significantly by organ and drug. The usage of calcineurin inhibitors for maintenance therapy was characterized by a clear transition from cyclosporine to tacrolimus. Corticosteroids were administered to the majority of patients; however, steroid-avoidance and steroid-withdrawal protocols have become increasingly common. The percentage of patients treated for acute rejection during the first year following transplantation has continued to decline, reaching 13% for those who received a kidney in 2003, 48% of which cases were treated with antibodies.

Disappearance of Nephrotic Syndrome in Type 1 Diabetic Patients Following Pancreas Transplant Alone

Diabetic nephropathy affects approximately 40% of diabetic patients and is the leading cause of kidney disease in patients starting renal replacement therapy (1, 2). It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion in the absence of other renal diseases (1, 2). Nephrotic syndrome, characterized by massive proteinuria (≥2.5–3.0 g/24h), dysproteinemia/hypoalbuminemia, hyperlipidemia and edema, may be a devastating clinical manifestation of diabetic nephropathy (3). Pancreas transplant alone (PTA) can be effective in significantly improving the quality of life of type 1 diabetic patients, and can also eliminate diabetes acute complications, such as hypoglycemic and/or hyperglycemic episodes (4). In addition, evidence is growing to show that pancreas transplantation alone may have positive effects on chronic diabetes complications (4). We have recently observed that this procedure reduced urinary protein excretion in a group of type 1 diabetic patients (5). Here we describe the effects of pancreas transplant alone on the course of nephrotic syndrome in six type 1 diabetic patients (four females and two males, aged 35.3±3.7 years at the time of transplantation, with a diabetes duration of 24.1±7.5 years) with histologically documented diabetic nephropathy. Patients were evaluated before and after successful PTA (28.0±6.9 months of follow-up, with a range of 3–36 months), and results were compared with those obtained from a group of five matched type 1 diabetic patients (four females and one male, aged 26±5 years, with a diabetes duration of 18±3 years, and 28.0±5.6 months of follow-up, with a range of 3–36 months), who were evaluated for pancreas transplantation but did not accept to undergo the procedure. All the transplanted patients received portal drainage of endocrine pancreas secretions. Induction immunosuppression therapy consisted of basiliximab and steroids, and maintainance therapy consisted of tacrolimus (given at doses to achieve blood through levels of 10–15 ng/ml during the first month posttransplant, and 8–12 ng/ml thereafter), mycophenolate mophetil and steroids (tapered to 5 mg per day after 3 months) (6). Pancreas transplantation restored sustained normoglycemia, without exogenous insulin administration (plasma glucose levels: from 238±123 to 98±1.5 mg/dl; A1c values: from 9.52±2.26% to 5.6±0.41%, both P<0.01 of last posttransplant control vs. pretransplant measurements). Under these conditions, edema disappeared in all the patients, and urinary protein excretion decreased (Fig. 1A), with values from 6.3±3.5 before transplantation to 0.50±0.18 g/24h at the end of follow-up (P<0.01). Conversely, no significant change occurred in non-transplanted patients (Fig. 1B). As shown in Table 1, serum protein levels normalized in transplanted patients, whereas, again, no major change was observed in the control group (Table 1). Furthermore, in PTA patients serum total and LDL cholesterol decreased significantly (Table 1) in the absence of antidyslipidemic therapy modifications. These improvements occurred without any significant change of creatinine clearance values (from 84±19 ml/min pretransplantation to 78±28 ml/min posttransplantation, P=0.47).FIGURE 1.: Course of proteinuria in transplanted (A) and nontransplanted (B) patients.TABLE 1: Some biochemical parameters of transplanted and nontransplanted patientsThis study demonstrates for the first time that in type 1 diabetic patients, successful pancreas transplant alone determines the disappearance of nephrotic syndrome, as documented by disappearance or significant improvement of the clinical signs of this condition. These effects were accompanied by no change of creatinine clearance. Routine native kidney biopsies of pancreas transplant alone recipients are not performed in our centre for ethical reasons. Nevertheless, the beneficial actions of PTA that we observed are unlikely to be due to anatomical changes in the kidneys, because it has been previously demonstrated that reversal of diabetic renal lesions occurred many years after pancreas grafting (7). Rather, diabetes “curing” by PTA is likely to have played the major role, by normalization of circulating glucose levels and restoration of endogenous insulin and C-peptide secretion. These data suggest that the beneficial effects of PTA may be more evident than currently appreciated. Alberto Coppelli Rosa Giannarelli Ugo Boggi Stefano Del Prato Gabriella Amorese Fabio Vistoli Franco Mosca Piero Marchetti Department of Endocrinology and Metabolism University of Pisa Pisa, Italy

Remodeling of renal interstitial and tubular lesions in pancreas transplant recipients

Tubular atrophy and interstitial fibrosis, important in progression of renal diseases, including diabetic (D) and cyclosporine-induced (CSA) nephropathy, have been considered irreversible. Normoglycemia for 10 years following pancreas transplantation alone (PTA) reversed D glomerulopathy lesions. This study quantified tubular, interstitial, and arteriolar parameters in PTA recipients. Kidney function studies and biopsies were performed in eight non-uremic type I D patients (pts) at 5 and 10 years after PTA. Renal biopsies were analyzed by morphometric analysis. All pts were normoglycemic and insulin independent and received CSA during the study. Cortical interstitial volume fraction was increased at 5 years (0.31+/-0.07 vs normal 0.15+/-0.02, P<0.01) and decreased at 10 years post-PTA (0.23+/-0.03, P<0.02 vs 5 years). There was a reduction in the volume fraction of interstitial collagen and cells per cortical tissue, measured using electron microscopy, from 5 (0.126+/-0.061 and 0.103+/-0.026, respectively) to 10 years (0.079+/-0.031, P<0.05, and 0.074+/-0.018, P<0.05, respectively). The volume fraction of tubules which were atrophic (AT) was abnormal at 5 years (0.160+/-0.090) and decreased from 5 to 10 years (0.044+/-0.034, P<0.02), apparently due to AT reabsorption. The index of arteriolar hyalinosis did not change during the study (1.30+/-0.22 and 1.34+/-0.33 at 5 and 10 years, respectively, nonsignificant). This study demonstrates, for the first time in humans, that interstitial expansion is reversible and that atrophic tubules can be reabsorbed. In contrast, there was no improvement in the arteriolar lesions. Whether this is due to long-term normoglycemia, reduction of CSA dose or other mechanisms is unclear.

Pancreas transplantation: advantages of both enteric and bladder drainage combined in a two‐step approach

Although there is a tendency to perform enteric drainage of pancreas transplants in simultaneous pancreas-kidney (SPK) transplantation, bladder drainage is still preferable in pancreas transplantation alone (PTA) or after a previous kidney transplantation (PAK). Our hypothesis was that enteric conversion of a bladder drained pancreas is an effective and safe procedure. We studied the complication rate and physiological effects of enteric conversion in patients with primary bladder-drained SPK transplantation. We performed 51 enteric conversions in bladder-drained SPK transplant recipients. As we observed a low complication rate, with time enteric conversions were also performed for less strict and severe indications. The main indications for conversion were urological problems, metabolic complications and reflux-pancreatitis. The median transplantation-conversion interval was 12 months (range 2-40 months). Post-operative complications consisted of seven urinary tract infections, two low-grade superficial wound infections, one minor bleeding, one phlebitis and one paralytic ileus. In two patients, a relaparotomy was necessary. No graft rejection following enteric conversion was found. Long-term renal and pancreatic function were not affected by the enteric conversion. Three-year patient, kidney and pancreas survival rates after enteric conversion were 93, 97 and 93%, respectively (censored data). Enteric conversion after pancreas transplantation is an effective and safe procedure. Therefore, we suggest a policy of a two-step approach of primary bladder drainage followed by an enteric conversion of the pancreas in a selected group of SPK patients.

Early morbidity after pancreas transplantation

This study aims to evaluate and compare the early outcome of both pancreas-alone transplantation (PTA) and simultaneous kidney-pancreas transplantation (SPKT) focusing on the complications affecting the first month after the procedures. The records of all patients who underwent PTA or SPKT were reviewed. We considered the length of ICU stay, the need for postoperative ventilatory support, hemodynamic and metabolic data (arterial pH, serum glucose, need for exogenous insulin), infectious diseases incidence, microbiological colonization rate and any kind of postoperative complication arising during the first month after the transplantation. PTA recipients underwent a quicker surgery (P < 0.01) with shorter ICU stay (P < 0.05) and a lower need for postoperative mechanical ventilation (P < 0.05). They also had a higher hemodynamic stability (P < 0.05) with less cardiological complications (P < 0.05) in the intra- and postoperative phases; bacterial colonisation was also less frequent in PTA recipients (P < 0.05). On the contrary, no significant difference was noted with regard to postoperative nausea/vomiting, sudden myocardial death, ICU re-admissions, graft function, rate of rejection, grafts explantation and re-transplantation. PTA could be considered as preemptive for severe diabetic complications in patients with long-lasting severe type I diabetes. However, establishing the correct timing of PTA is of paramount importance in order not to expose the patients early to risks arising from a major surgery and heavy immunosuppressive treatments.

Outcomes of pancreas transplants for patients with type 2 diabetes mellitus

The objective of this study was to examine how effectively pancreas transplants provide long-term glucose control in patients with type 2 diabetes mellitus (DM). We used guidelines from the American Diabetes Association (ADA) and the World Health Organization (WHO) to appropriately classify recipients with type 2 DM (vs. type 1 DM). From 1994 through 2002, a total of 17 patients with type 2 DM underwent a pancreas transplant at our center. Mean recipient age was 52.5 yr. The mean age at diabetes onset was 35.7 yr; mean duration, 16.8 yr. Most recipients had one or more secondary complications related to their diabetes: retinopathy (94%), neuropathy (76%), or nephropathy (65%). At the time of their transplant, three (18%) were on oral hypoglycemic agents alone and 14 (82%) were on insulin therapy. Of the 17 transplants, seven (41%) were a simultaneous pancreas-kidney transplant (SPK); four (24%), pancreas after kidney transplant (PAK); and six (35%), pancreas transplant alone (PTA). One recipient died during the perioperative period because of aspiration. The other 16 recipients became euglycemic post-transplant and had a functional graft at 1 yr post-transplant (patient and graft survival rates, 94%). Now, with a mean follow-up of 4.3 yr post-transplant, the patient survival rate is 71%. The four additional deaths were because of sepsis (n = 2), suicide (n = 1), and unknown cause (n = 1). All four of these recipients were insulin-independent at the time of death, although one was on an oral hypoglycemic agent. Of the 12 recipients currently alive, 11 remain euglycemic without requiring insulin therapy or oral hypoglycemic agents; one began insulin therapy 1.2 yr post-transplant (current daily dose, 60 units). These findings suggest that pancreas transplants can provide excellent glucose control in recipients with type 2 DM. All 16 (94%) of our recipients whose transplant was technically successful were rendered euglycemic. Long-term results were comparable with those seen in transplant recipients with type 1 DM.

Pancreas transplant outcomes for United States (US) and non‐US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004

As of December 31, 2004, more than 23,000 pancreas transplant had been reported to the IPTR, >17,000 in the US and almost 6000 from outside the US. An analysis of US pancreas transplants performed between 1988 and 2003 showed a progressive improvement in outcome, with pancreas transplant graft survival rates (GSRs) going from 75% at 1 yr for 1988/1989 to 85% for 2002/2003 simultaneous pancreas-kidney (SPK) cases, from 55 to 78% for pancreas after kidney (PAK) cases, and from 45 to 77% for pancreas transplants alone (PTA) cases. The improvements were due both to decreases in technical failure (TF) rates (from 12 to 6% in SPK, 13-8% in PAK, and 24-7% in PTA) and immunological failure rates (going from 7 to 2% for SPK, from 28 to 7% for PAK, and from 38 to 8% for PTA cases). These results are even more impressive under the aspect that during the same time the rate of potential risk factors increased and the duct management techniques changed from bladder to enteric drainage. The improvement in outcome allowed also an increase in the number of solitary pancreas transplants from initially 12% to now 35%. Contemporary primary deceased donor pancreas transplant outcomes were calculated separately for 2000-2004 US and non-US cases. The US patient survival rates at 1 yr were >95% in each recipient category, with 1 yr primary pancreas GSRs of 85% for SPK, 78% for PAK, and 76% for PTA (p < 0.0001). The immunological graft failure rates for 2000-2004 technically successful (TS) SPK, PAK, and PTA cases were 2, 8, and 10% at 1 yr (p = 0.0001). In the majority of all transplants ED was used for duct management (81% of SPK, 67% of PAK, and 56% for PTA cases). Of the ED transplants, venous drainage via the portal system was used for 20% of SPK, 23% of PAK, and 35% of PTA cases. Duct management technique did not have a significant impact on overall pancreas graft function in the univariate or the multivariate model. The outcomes of ED and BD transplants are comparable with 85 vs. 87% at 1 yr for SPK, 77 vs. 80% for PAK, and 72 vs. 79% for PTA. The overall TF rate was higher in ED pancreas transplants but this difference did reach significance only in SPK. In addition, in technically successful PTA the immunological graft loss rate was higher in ED vs. BD transplants (15 vs. 5% at 1 yr). The different vascular management techniques did not seem to have an impact on the outcome of the pancreas transplants. Kidney GSRs were not significantly different for ED vs. BD SPK cases, 93 and 91% at 1 yr (p = 0.24). The overall conversion rate from BD to ED was 9% at 1 yr and 17% at 3 yr post-transplant. The most influential factor for patient survival in SPK and PAK in the multivariate and the univariate models was the status of the transplanted organ. The hazard ratio (HR) for a failed kidney was 14.99 in SPK and 9.17 in PAK (p = 0.0001). The HR for a failed pancreas graft was 3.51 in SPK and 4.17 for PAK (p = 0.0001). In PTA a failed pancreas graft did not have a direct impact on patient survival. SPK and PAK patients older than 44 yr at the time of transplants also showed an increased mortality risk, but at the same time the risk of immunological graft loss was significantly decreased for those patients. TAC&MMF remained the dominant maintenance immunosuppressant for 2000-2004 US cases (approximately two-third) in all three categories and with this regime 1-year GSRs were > or =80% in all three recipient categories. The results were comparable (> or =83% 1-year GSR) for patients (approximately 10%) treated with Sirolimus (SIR) under various protocols. In regard to non-US pancreas transplants, even for 2000-2004 the overwhelming majority continued to be in the SPK category (91%), with 1-year patient, kidney and pancreas survival rates of 94, 92, and 87%. Solitary transplants are still very rarely done outside the US. Non-US PAK GSR at 1 yr was 85%, non-US PTA GSR at 1 yr was 76%. In summary, with the new advancements in immunosuppression and changes in surgical techniques the outcomes in patient survival and pancreas transplant graft function continue to improve even with an increasing proportion of high risk patients in all three categories.

Ninety-Five Percent Insulin Independence Rate 3 Years After Pancreas Transplantation Alone With Portal-Enteric Drainage

Aims Portal-enteric drainage (PED) might be particularly suitable for pancreas transplantation alone (PTA), since it has been associated with an immunologic advantage and achieves excellent metabolic results. We describe our experience with a consecutive series of 40 PTAs with PED. Methods Between April 2001 and March 2004, 40 consecutive PTAs were performed with PED. Recipients were selected according to the American Diabetic Association recommendations. Donors were selected according to standard criteria irrespective of HLA match, although matching for A and B loci was considered at the time of graft allocation. Immunosuppression consisted of induction treatment with basiliximab (n = 34) or thymoglobulin (n = 6), and maintenance therapy with steroids, mycophenolate mofetil, and tacrolimus. Results After a mean cold ischemia time of 690 minutes (range, 517–965 min) all pancreases functioned immediately. Three grafts were lost due to hyperacute or accelerated rejection. No graft was lost to vascular thrombosis, although 5 (12.5%) nonocclusive thromboses were identified and the grafts were rescued with intravenous heparin infusion. A repeat laparotomy was required in 7 recipients (17.5%) No patient required multiple repeat laparotomies, and none died. After a mean follow-up of 16.4 months (range, 1–36 mo), 2 recipients were diagnosed with rejection episodes, which were reversed with steroid boluses. Actuarial 3-year patient, and graft survival rates were 100% and 94.9%, respectively. The following parameters showed significant improvement compared with pretransplantation evaluation: hemoglobin A 1C concentration, total and high-density lipoprotein cholesterol levels, arterial blood pressure, cardiac performance, retinopathy, proteinuria, and neuropathy. Conclusions Pancreas transplantation alone with PED provides high rates of long-term insulin-independence.

Anesthesia for pancreas transplantation alone or simultaneous with kidney

Improvements in perioperative care, namely, organ preservation solutions, immunosuppression, and increased experience of surgical, anesthetic, and intensive care teams, have contributed to the success of pancreas transplantation. The objective of this study was to present data on anesthesia for pancreas transplantation alone (PTA) or simultaneous with kidney (SPKT), evaluating crystalloid, albumin and blood component infusions, graft ischemic times, and weights and ages of recipient. We evaluated patients undergoing SPKT ( n = 73), PTA ( n = 49), or SPKT with kidney living donor ( n = 8). Agressive monitoring and therapy were used to avoid hypoperfusion, optimized with intravenous fluids, vasoative drugs, and correction of metabolic disturbances. Three SPKT patients were not extubated at the end of surgery. There were no other complications related to anesthesia in any patient. Although it is a high-risk surgery, PTA or SPKT is routine in our practice. Adequate perioperative care is important not only for the safety of the procedure but also for graft viability, contributing to a promising long-term treatment of insulin-dependent diabetic patients.

Mortality Assessment for Pancreas Transplants

We determined and compared the mortality of pancreas transplant recipients and of patients on the pancreas waiting lists by using United Network for Organ Sharing (UNOS) and International Pancreas Transplant Registry (IPTR) data. From January 1, 1995, through May 31, 2003, a total of 12,478 patients were listed for a simultaneous pancreas-kidney (SPK) transplant; 2942 for a pancreas after (previous) kidney transplant (PAK); and 1207 for a pancreas transplant alone (PTA). In this retrospective observational cohort study, patients with multiple listings at different transplant centers and patients who changed transplant centers were counted only once. The Social Security Death Master File (SSDMF) and the UNOS kidney transplant database were used to update mortality information. By univariate analyses, 4-year patient survival rates on the waiting lists (vs. post-transplant), in the SPK category, were 58.7% (vs. 90.3%); in the PAK category, 81.7% (vs. 88.3%); and in the PTA category, 87.3% (vs. 90.5%). Up to one-third of recipient deaths after post-transplant day 90 were not related to the transplant procedure itself. Multivariate analyses showed that the overall mortality in all three categories was not increased after transplantation (for SPK recipients only, it was significantly decreased). In summary, the mortality for solitary pancreas transplant recipients is not higher than for wait-listed patients.

Technical Failures after Pancreas Transplants: Why Grafts Fail and the Risk Factors—A Multivariate Analysis

Technical failure (TF) rates remain high after pancreas transplants; while rates have decreased over the last decade, more than 10% of all pancreas grafts continue to be lost due to technical reasons. We performed a multivariate analysis to determine causes and risk factors for TF of pancreas grafts. Between 1994 and 2003, 937 pancreas transplants were performed at our center in the following transplant categories: simultaneous pancreas-kidney (SPK) (n=327), pancreas after kidney (PAK) (n=399), and pancreas transplant alone (PTA) (n=211). Of these, 123 (13.1%) grafts were lost due to technical reasons (thrombosis, leaks, infections). TF rates were higher for SPK (15.3%) versus PAK (12.2%) or PTA (11.4%), though this was not statistically significant. Thrombosis accounted for 52.0% of all TFs. Other causes were infections (18.7%), pancreatitis (20.3%), leaks (6.5%), and bleeding (2.4%). Thrombosis was the most common cause for TF in all three transplant categories. By multivariate analysis, the following were significant risk factors for TF of the graft: recipient body mass index (BMI) >30 kg/m (relative risk [RR]=2.42, P=0.0003), preservation time >24 hr (1.87, P=0.04), cause of donor death other than trauma (RR=1.58, P=0.04), enteric versus bladder drainage (1.68, P=0.06), and donor BMI >30 kg/m (1.66, P=0.06). Not significant were donor or recipient age, a retransplant, and the category of transplant. TFs remain significant after pancreas transplants. In SPK recipients, TF represents the most common cause of pancreas graft loss. For isolated pancreas transplants, TF is second only to rejection as a cause of graft loss. Increased preservation times and donor or recipient obesity seem to be risk factors. Minimizing these risks factors would be important to try to decrease TF.

Enteric conversion after bladder drained pancreas transplantation experience of 14 cases

The method of exocrine diversion in pancreas allograft continues to be controversial due to the advantages versus disadvantages of bladder versus enteric techniques. Bladder drainage (BD) exposes the patient to urological and metabolic problems that may require conversion to enteric drainage (ED). The purpose of this study was to review our initial experience of conversion from BD to ED for patients who underwent pancreas transplantation originally with bladder diversion. Among 114 pancreas transplantation performed with BD, from January 1996 to April 2003, 60 were simultaneous pancreas-kidney transplantation (SPKT), 35 were pancreas transplantation alone (PA), and 19 were pancreas after kidney transplantations (PAK). Twenty-three (20.2%) cases were excluded due to early death of the patient or the graft, yielding an analyses of 91 patients. Enteric conversion (EC) was performed in 14 (15.4%) patients with a mean follow-up of 15.7 months (range, 3–51 months) after transplantation including 8 (8.8%) SPKT, 4 (4.4%) PAK, and 2 (2.2%) PA. No surgical morbidity or mortality was observed related to EC. All patients had complete resolution of the initial problem with preservation of pancreatic function. EC represents an easy, safe procedure with low morbidity and mortality rates, representing the option of choice for patients with persistent urological or metabolic disturbances.

Pancreas transplant alone

Pancreas transplant alone (PTA) represents a growing proportion of overall pancreas transplantations, with 1-year patient and graft survivals of almost 100% and higher than 80%, respectively. PTA can restore normoglycemia without exogenous insulin administration and eliminate acute diabetic complications. In our series of 28 PTA, performed with portal-enteric drainage, 2-year patient and pancreas survivals were 100% and 87%, respectively. In patients with successful transplantation, rapid normalization of blood glucose level and HbA1c concentration was observed, due to restored endogenous insulin secretion. Several classical cardiovascular risk factors were measured before and after transplant, with significant improvements shortly after transplantation. Diabetic retinopathy improved in 58.8% of examined eyes, stabilized in 35.3%, and worsened in 5.9%. In conclusion, PTA represents a clinically relevant option for patients with type 1 diabetes without advanced renal disease. It restores normoglycemia in the vast majority of patients and seems to have a positive impact on late diabetic complications.

Immunosuppression: practice and trends

Over the past decade, immunosuppression therapy has undergone striking changes in the scale and pace by which new immunosuppressive molecules and antibodies have become incorporated into daily transplant medicine. An organ-by-organ review of data reveals several trends. The highest use of induction therapy (over 70% of patients) was reported for simultaneous pancreas kidney (SPK) and pancreas after kidney (PAK) transplants in 2002; use of induction therapy was less common in liver transplants (only 18%). Corticosteroids served as discharge maintenance immunosuppression in over 87% of the recipients of kidney, SPK, PAK and thoracic transplants, and in over 70% of pancreas transplant alone (PTA) recipients. Corticosteroid use in intestine transplants was reported in 64% of recipients in 2002. A shift in the calcineurin inhibitor used for maintenance immunosuppression from cyclosporine to tacrolimus for the majority of patients had occurred for kidney, PAK, SPK, PTA, liver, lung, and heart-lung by 2001. For heart transplants, cyclosporine remained the calcineurin inhibitor of choice; tacrolimus remained the predominant calcineurin inhibitor agent for intestine (since 1994). Use of antibody treatment for rejection during the first post-transplant year for most organs declined. Short-term outcomes have improved, based on the observation that rates of rejection within the first year post-transplant have diminished.

Organ donation and transplantation trends in the USA, 2003

This summary provides an overview of solid organ transplantation in the USA, produced as part of the 2003 OPTN/SRTR Annual Report. The Annual Report is prepared by the Scientific Registry of Transplant Recipients (SRTR) in collaboration with the Organ Procurement and Transplantation Network (OPTN) under contract with the Health Resources and Services Administration (HRSA). A wide range of activities related to solid organ transplantation in the USA are thoughtfully addressed in this publication with the intention of providing useful information to patients, the transplant community, the public, and the Federal Government.

Decline in native renal function early after bladder-drained pancreas transplantation alone.

Pancreas transplant alone (PTA) has become accepted therapy for select nonuremic patients with type 1 diabetes mellitus. However, PTA may lead to significant complications including a decline in native renal function. This study examines trends in native renal function during the first posttransplant year in PTA recipients with a spectrum of pretransplant glomerular filtration rates (GFR). Renal function was studied in 23 recipients of bladder-drained PTA who underwent transplantation from April 1998 through September 2001. GFR was measured by corrected iothalamate clearance at the time of transplant evaluation and 1 year posttransplant and also calculated using the Cockcroft-Gault method at the transplant evaluation; at the day of transplantation; and at 1, 6, and 12 months posttransplant. Iothalamate clearance decreased in the first year in 96% of patients (22 of 23). The mean measured GFR decreased from 84 +/- 33 mL/min/1.73 m2 pretransplant to 52 +/- 26 mL/min/1.73 m2 at 1 year (P <0.001). Calculated creatinine clearance declined in the majority of patients at both 1 and 12 months after PTA, but some patients, including a few with low GFR, maintained stable renal function. Calculated GFR generally correlated well with measured GFR in most patients, with a few notable exceptions. One patient (baseline GFR, 42 mL/min/1.73 m2) developed renal failure in the first year after transplant and required kidney transplantation. Bladder-drained PTA results in a decline in native renal function in the majority of patients regardless of the pretransplant GFR. These data suggest the need for strategies to prevent or minimize the decline in renal function after PTA.

Incidence, timing and site of infections among pancreas transplant recipients

The incidence, timing and site of infections among the different categories of pancreas transplant recipients were investigated. Patients were divided into three groups: pancreas transplant alone (PTA), pancreas after kidney transplant (PAK), or simultaneous pancreas and kidney (SPK) transplants. Length of follow-up, time to death, pancreas graft survival, incidence, timing and site of bacterial infections were noted. Our study showed that at least 75% of pancreas transplant recipients experienced at least one infection (range from 77.8% in the PTA group to 86.7% in the PAK group). The SPK group presented the highest rate of infections with 35.1 infections per 1000/patient-days. Symptomatic urinary tract infections were the most common cause of infection in all patients. The incidence of infections was higher during the first month after transplantation, except for the SPK transplant group, where infections occurred over a longer time period.

Chronic rejection: the next major challenge for pancreas transplant recipients.

With newer immunosuppressive agents, acute rejection and graft loss resulting from acute rejection have become less common for pancreas transplant recipients. As long-term graft survival rates have improved, an increasing number of grafts are being lost to chronic rejection (CR). We studied the incidence of CR and identified risk factors. We retrospectively analyzed all cadaver pancreas transplants performed at the University of Minnesota between June 19, 1994, and December 31, 2002. We determined the causes of graft loss, the incidence of graft loss to CR and, using multivariate techniques, the major risk factors for CR. A total of 914 cadaver pancreas transplants were performed in the following three categories: simultaneous pancreas-kidney (SPK) (n=321), pancreas after kidney (PAK) (n=389), and pancreas transplant alone (PTA) (n=204). The mean recipient age was 41.3 years and the mean donor age was 30.1 years. Of the 914 pancreas grafts, 643 (70.3%) continue to function (mean length of follow-up, 39 months). The most common cause of graft loss was technical failure, accounting for 118 (12.9%) of the failed grafts. The second most common cause was CR, accounting for 80 (8.8%) of the failed grafts. The incidence of graft loss to CR was highest for PTA (n=23 [11.3%]) and PAK (n=45 [11.6%]) recipients and lowest for SPK recipients (n=12 [3.7%]) (P=0.002). By multivariate analysis, the most significant risk factors for graft loss to CR were a previous episode of acute rejection (relative risk [RR]=4.41, P<0.0001), an isolated (vs. simultaneous) transplant (PAK or PTA [vs. SPK], RR=3.02, P=0.002), cytomegalovirus infection posttransplant (RR=2.41, P=0.001), a retransplant (versus primary transplant) (RR=2.27, P=0.004), and one or two (vs. zero) antigen mismatches at the B loci (RR=1.68, P=0.04). As short-term pancreas transplant results improve and as isolated (PAK or PTA) pancreas transplants gain in popularity, CR will become increasingly common as a cause of pancreas graft loss.