Pancreas Transplantation: An Alarming Crisis in Confidence.

In the past decade, the annual number of pancreas transplantations performed in the United States has steadily declined. From 2004 to 2011, the overall number of simultaneous pancreas-kidney (SPK) transplantations in the United States declined by 10%, whereas the decreases in pancreas after kidney (PAK) and pancreas transplant alone (PTA) procedures were 55% and 34%, respectively. Paradoxically, this has occurred in the setting of improvements in graft and patient survival outcomes and transplanting higher-risk patients. Only 11 centers in the United States currently perform ≥20 pancreas transplantations per year, and most centers perform <5 pancreas transplantations annually; many do not perform PAKs or PTAs. This national trend in decreasing numbers of pancreas transplantations is related to a number of factors including lack of a primary referral source, improvements in diabetes care and management, changing donor and recipient considerations, inadequate training opportunities, and increasing risk aversion because of regulatory scrutiny. A national initiative is needed to "reinvigorate" SPK and PAK procedures as preferred transplantation options for appropriately selected uremic patients taking insulin regardless of C-peptide levels or "type" of diabetes. Moreover, many patients may benefit from PTAs because all categories of pancreas transplantation are not only life enhancing but also life extending procedures.

Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes.

The APOL1 gene and allograft survival after kidney transplantation.

Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with nephropathy in African Americans (AAs). The effect of transplanting kidneys from AA donors with two APOL1 nephropathy risk variants is unknown. APOL1 risk variants were genotyped in 106 AA deceased organ donors and graft survival assessed in 136 resultant kidney transplants. Cox-proportional hazard models tested for association between time to graft failure and donor APOL1 genotypes. The mean follow-up was 26.4 ± 21.8 months. Twenty-two of 136 transplanted kidneys (16%) were from donors with two APOL1 nephropathy risk variants. Twenty-five grafts failed; eight (32%) had two APOL1 risk variants. A multivariate model accounting for donor APOL1 genotype, overall African ancestry, expanded criteria donation, recipient age and gender, HLA mismatch, CIT and PRA revealed that graft survival was significantly shorter in donor kidneys with two APOL1 risk variants (hazard ratio [HR] 3.84; p = 0.008) and higher HLA mismatch (HR 1.52; p = 0.03), but not for overall African ancestry excluding APOL1. Kidneys from AA deceased donors harboring two APOL1 risk variants failed more rapidly after renal transplantation than those with zero or one risk variants. If replicated, APOL1 genotyping could improve the donor selection process and maximize long-term renal allograft survival.

Guidelines for the diagnosis of antibody-mediated rejection in pancreas allografts-updated Banff grading schema.

The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.

Donor-recipient relationships in African American vs. Caucasian live kidney donors.

PURPOSE: The purpose of the study was to characterize differences in donor and recipient relationships between African American (AA) and Caucasian living kidney donors. METHODS: Data from all successful living kidney donors at a single institution between 1991 and 2009 were reviewed. Relationships between donor and recipient were categorized and between-group comparisons performed. RESULTS: The study sample consisted of 73 (18%) AA and 324 Caucasian living kidney donors. The distribution of donor-recipient relationships differed significantly between AA and Caucasians. AA donors were more likely to be related to the recipient (88% vs. 74%, p = 0.007) than Caucasians. AA donors were more likely to participate in child to parent donation and were less likely to participate in parent to child donation or to donate to unrelated individuals. Sibling and spousal donations were similar in both groups. Caucasian donors were more likely to be unrelated to the recipient than AA donors. CONCLUSIONS: Differences exist in donor-recipient relationships between AA and Caucasian living kidney donors. Future studies exploring cultural differences and family dynamics may provide targeted recruitment strategies for AA and Caucasian living kidney donors. Living unrelated kidney transplantation appears to be a potential growth area for living kidney donation in AA.

Short-term renal outcomes in African American and Caucasian donors following live kidney donation.

INTRODUCTION: Although African Americans (AA) are considered higher risk kidney donors than Caucasians, limited data are available regarding outcomes of AA donors. METHODS: We performed a single-center retrospective review of all kidney donors from 1993 to 2007 and evaluated race/ethnic differences in post-donation changes in renal function, incident proteinuria, and systolic blood pressure (SBP) using linear mixed models. RESULTS: A total of 336 kidney donors (63 AA, 263 Caucasian, 10 other) were evaluated. Before donation, AA had higher serum creatinine concentrations, estimated glomerular filtration rate (GFR) values, and SBP levels than Caucasians. No significant changes in SBP or renal function were observed between the two groups within the first year after donation, although results were limited by incomplete follow-up. CONCLUSION: AA had higher pre-donation serum creatinine, GFR, and SBP values compared to Caucasians; however, the degree of change in renal function and blood pressure did not differ between groups following kidney donation. Although long-term studies are needed, our study suggests that AA and Caucasians experience similar short-term consequences after donation. The incomplete data available on donor outcomes in our center and in prior publications also indicates a global need to implement systems for structured follow-up of live kidney donors.

Renal allograft failure due to emphysematous pyelonephritis: successful non-operative management and proposed new classification scheme based on literature review.

Emphysematous pyelonephritis (EPN) is a rare necrotizing infection of the kidney caused by gas-forming organisms, usually occurs in diabetic patients, and often requires nephrectomy for effective therapy. EPN is rarely reported in renal allografts, with only 20 cases found in the English literature. We report herein a case of EPN in a transplanted kidney resulting in acute renal failure and sepsis. The patient was managed non-operatively with subsequent recovery of renal allograft function. Based on this experience and a review of the literature, we suggest an amended classification system for EPN in kidney transplantation to plan and guide treatment options accordingly. However, the scarcity of this disease process, coupled with the lack of prospective validation of the new classification scheme, prevents drawing definitive conclusions regarding optimal management strategies including the role and timing of allograft nephrectomy.

Potential donor-recipient MYH9 genotype interactions in posttransplant nephrotic syndrome after pediatric kidney transplantation.

Recurrence of focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome is relatively common after kidney transplantation in young recipients whose predialysis course consists of heavy proteinuria, hypertension and subacute loss of kidney function. The gene(s) mediating this effect remain unknown. We report an unusual circumstance where kidneys recovered from a deceased African American male donor with MYH9-related occult FSGS (risk variants in seven of eight MYH9 E1 haplotype single nucleotide polymorphisms) were transplanted into an African American male child with risk variants in four MYH9 E1 risk variants and a European American female teenager with two MYH9 E1 risk variants. Fulminant nephrotic syndrome rapidly developed in the African American recipient, whereas the European American had an uneventful posttransplant course. The kidney donor lacked significant proteinuria at the time of organ procurement. This scenario suggests that donor-recipient interactions in MYH9, as well as other gene-gene and gene-environment interactions, may lead to recurrent nephrotic syndrome after renal transplantation. The impact of transplanting kidneys from donors with multiple MYH9 risk alleles into recipients with similar genetic background at high risk for recurrent kidney disease needs to be determined.

Impact of race and gender on live kidney donation.

BACKGROUND: African Americans (AA) and women are less likely to receive a live kidney donor (LKD) transplant than Caucasians or men. Reasons for non-donation are poorly understood. METHODS: A retrospective review of 541 unsuccessful LKD was performed to explore reasons for non-donation and to assess for racial and/or gender differences. RESULTS: We identified 138 AA and 385 Caucasian subjects who volunteered but did not successfully donate. Females (58.2%) were more likely to be excluded than males due to reduced renal function (glomerular filtration rate < 85 mL/min, 7.9% vs. 0.9%, p < 0.0001) or failure to complete the evaluation (6.4% vs. 1.8%, p = 0.01). AA were more commonly excluded due to obesity (body mass index >or= 32 kg/m(2); 30.4% AA vs. 16.6% Caucasian, p = 0.0005) or failure to complete the evaluation (12.3% AA vs. 1.8% Caucasian, p < 0.0001) whereas Caucasians were more often excluded due to kidney stones (1.5% AA vs. 7.3% Caucasian, p = 0.01). CONCLUSIONS: Significantly different reasons for exclusion of LKD exist between potential Caucasian and AA LKD, particularly among women. Among the differences that we observed are potentially modifiable barriers to donation including obesity and failure to complete the donor evaluation. A further understanding of these barriers may help point to strategies for more effective recruitment and successful LKD.

Outcomes of extended donors in pancreatic transplantation with portal-enteric drainage.

OBJECTIVE: Limited data are available on extended (EX) donor criteria in pancreatic transplantation (PTX). METHODS: This retrospective study from February 2007 through April 2007 compared 2 cohorts of simultaneous kidney-pancreas transplantations (SKPT): the first from EX donors, which were defined as age <10 years or > or =45 years, or donation after cardiac death [DCD]), and the second from conventional (CONV) donors. RESULTS: Among 79 SKPT, 19 (24%) were from EX donors (12 older than age 45 [mean age, 50.2 years], 3 pediatric donors <10, and 4 DCD donors) and the remaining 60 SKPT from CONV donors. The mean donor age was higher in EX than CONV donors (38 vs 25 years, P < .05). There were no other differences between the 2 cohorts. With a similar median follow-up of 29 months, patient, kidney and pancreatic graft survival rates were 89%, 89%, and 79%, for the EX, whereas corresponding outcomes for CONV donors were 93%, 87%, and 80%, respectively (all P = NS). The incidences were similar for delayed kidney graft function (5% in each group), early pancreatic graft loss due to thrombosis (5% EX vs 8% CONV donors), acute rejection (16% EX vs 18% CONV donors), surgical complications, and infections. There were no significant differences in 1-year mean serum creatinine (1.4 mg/dL in each group) or glycohemoglobin (5.2% vs 5.5%) levels between the EX and CONV donor groups, respectively. CONCLUSION: Short-term outcomes among SKPT from selected EX donors were comparable to CONV donors. Donors at the extremes of age and DCD donors may represent underused resources in SKPT.

Analysis of bacteremia after pancreatic transplantation with enteric drainage.

OBJECTIVE: The objective of this study was to review the incidence, risk factors, and impact of bacteremia after pancreas transplantation (PTX). METHODS: We performed a retrospective analysis of consecutive simultaneous kidney-pancreas transplantations (SKPTs) and solitary PTXs from January 2002 through April 2007. Positive blood cultures were correlated with other coexisting infections and parameters. RESULTS: One hundred ten PTXs with enteric drainage included 80 SKPTs and 30 solitary PTXs. Mean follow-up was 32 months. Bacteremia occurred in 29 (26%) patients with 5 (17%) being recurrent; it was seen during the first month after transplantation in 13 (12%), between 1 and 3 months in 12 (11%), between 3 and 12 months in 3 (3%), and after the first year in 3 cases (3%). Typical organisms were as follows: MRSE, MSSE, Klebsiella, Escherichia coli, vancomycin-resistant enterococci (VRE), and Acinetobacteri. Bacteremia was associated with coexisting site infection in 20 cases (69%): deep abdominal wound (31%); line (31%); urinary tract (34%); and pulmonary (7%). Similar bacterial species in blood and a coexisting site occurred in 15 cases (52%). No correlation was seen with cytomegalovirus (CMV) infections. In the first year, bacteremia was associated with more acute rejection episodes (32% vs 17%; P = .09), surgical complications (54% vs 42%; P = .267), mortality (11% vs 4%; P = .15), and death-censored pancreatic (14% vs 9%; P = .39) and kidney (4% vs 0; P = .08) graft loss. Fewer patients with bacteremia received alemtuzumab compared with rATG induction (14% vs 39%; P = .04). CONCLUSIONS: Bacteremias were common within 3 months of PTX. A significant number (39%) were multidrug resistant. The majority were accompanied by abdominal, urinary, or line infections. Bacteremias were associated with slightly higher incidences of rejection, mortality, and graft loss.

Do pretransplant C-peptide levels influence outcomes in simultaneous kidney-pancreas transplantation?

OBJECTIVE: To analyze outcomes in simultaneous kidney-pancreas transplantation (SKPT) recipients who retain C-peptide production at the time of SKPT. METHODS: This retrospective analysis of SKPTs from January 2002 through January 2007 compared outcomes between patients with absent or low C-peptide levels (<2.0 ng/mL, group A) with those having levels > or =2.0 ng/mL (group B). RESULTS: Among 74 SKPTs, 67 were in group A and seven in group B (mean C-peptide level 5.7 ng/mL). During transplantation, group B subjects were older (mean age 51 vs 41 years, P = .006); showed a later age of onset of diabetes (median 35 vs 13 years, P = .0001); weighed more (median 77 vs 66 kg, P = .24); had a greater proportion of African-Americans (57% vs 13%, P = .004); and had a longer pretransplant duration of dialysis (median 40 vs 14 months, P = .14). With similar median follow-up of 40 months, death-censored kidney (95% group A vs 100% group B, P = NS) and pancreas (87% group A vs 100% group B, P = NS) graft survival rates were similar, but patient survival (94% group A vs 71% group B, P = .03) was greater in group A. At 1-year follow-up, there were no significant differences in rejection episodes, surgical complications, infections, readmissions, hemoglobin A1C or C-peptide levels, serum creatinine, or MDRD GFR levels. CONCLUSIONS: Diabetic patients with measurable C-peptide levels before transplant were older, overweight, more frequently African-American and had a later age of onset of diabetes, longer duration of pretransplant dialysis, and reduced patient survival compared to insulinopenic patients undergoing SKPT. The other outcomes were similar.

Early detection of rejection in pancreas transplantation.

A major dilemma in pancreas transplantation is the lack of reliable methods for the early detection of allograft rejection. Over a 26-mo period, 70 rejection episodes occurred in 36 patients (13 isolated-pancreas, 23 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 300 radionuclide pancreas examinations were performed (mean 8.3/patient) utilizing 99mTc-labeled DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft (technetium index, TI). Rejection episodes were defined as isolated pancreas, isolated kidney, or combined pancreas-kidney. Mean urinary amylase (UA) levels and TI during normal allograft function were 30,256 U/L and 0.57%, respectively, whereas levels heralding rejection were 6873 U/L and 0.39% (P less than .05). The treatment of rejection based on kidney dysfunction or combined pancreas-kidney dysfunction resulted in significantly higher graft salvage and a lower incidence of hyperglycemia compared with isolated-pancreas-allograft rejection. After therapy, a TI greater than 0.3% was associated with 95.9% graft survival, whereas levels less than 0.3% resulted in a 72.7% rate of graft loss (P less than .001). Similarly, pancreas allografts with a UA greater than 10,000 U/L had 92.2% functional survival, whereas levels less than 10,000 U/L resulted in a 53.3% rate of graft loss (P less than 0.001). Overall, reversal of rejection occurred in 80% of cases, with 10 pancreas and 2 kidney allografts lost due to rejection. Monitoring pancreas-allograft function by UA, TI, and renal function in simultaneous transplants allows for the timely diagnosis and successful treatment of pancreas-allograft rejection.

Use of UW solution in pancreas transplantation.

We have recently reported successful 72-h preservation of the canine pancreas with a new cold-storage solution developed at the University of Wisconsin (UW solution). Over 10 mo, we performed 11 combined pancreas-kidney and 4 isolated-pancreas transplants with this solution. In situ cooling of the donor pancreas was performed with 1000 ml of UW solution followed by ex vivo perfusion with an additional 250-500 ml. Graft preservation times ranged from 3 to 19 h (mean 10.2 h). Pancreas transplants were vascularized whole-organ grafts with pancreaticoduodenocystostomy. Early graft function was excellent as assessed by immediate insulin independence, high urinary amylase and low serum amylase levels, and a technetium perfusion index indicating good pancreatic blood flow. There were no episodes of primary nonfunction, graft pancreatitis, or vascular thrombosis. Actuarial patient and graft survival at 1 mo was 92.9%. We conclude that UW solution provides excellent early graft function for up to 19 h of cold storage. Based on previously reported data on its efficacy in liver and kidney preservation, UW solution seems ideally suited as a universal intra-aortic flush and cold-storage solution.

OKT3 rescue therapy in pancreas-allograft rejection.

OKT3 has emerged as a highly effective antirejection therapy, but its efficacy in pancreas transplantation remains to be determined. During a 26-mo period, 46 vascularized pancreas transplants were performed with pancreaticoduodenocystostomy. Twenty-one patients (45.7%) were treated with OKT3. Indications for OKT3 use included steroid- and/or antilymphoblast globulin-resistant rejection in isolated-pancreas transplant (n = 8) or simultaneous pancreas-kidney-transplant (n = 13) recipients. A total of 46 rejection episodes occurred (mean 2.2). OKT3 was administered for a 14-day course concomitant with pulsed corticosteroids, azathioprine, and cyclosporin. OKT3 rescue therapy was successful in 13 cases (61.9%). The mean time to rejection reversal was 8.8 days (range 5-14 days). In isolated-pancreas transplants, OKT3 reversed only 1 episode of rejection (12.5%). In contrast, 12 episodes (92.3%) of allograft rejection were responsive to OKT3 in simultaneous pancreas-kidney recipients (P less than .05). Graft loss from rejection occurred at a mean 5.5 mo posttransplantation. OKT3 therapy was more successful in the setting of early rejection, rejection in combined pancreas-kidney transplants, and rejection not associated with hyperglycemia. No graft loss due to infection or patient death has occurred after OKT3 therapy. After a mean follow-up of 17.3 mo, patient survival was 89.1%, and allograft survival was 26.3% in isolated-pancreas and 85.2% in simultaneous pancreas-kidney transplants (P less than .05). Salvage therapy with OKT3 is a safe and effective means of reversing rejection in pancreas-allograft recipients. OKT3 is more effective in simultaneous pancreas-kidney recipients due to the earlier diagnosis of rejection.

Surgical nuances in pancreas transplantation.

The modern surgical era of vascularized pancreas transplantation (PTX) began with the systemic-bladder drainage technique. According to International Pancreas Transplant Registry (IPTR) data, most PTX procedures are performed with systemic venous delivery of insulin and either bladder (systemic bladder) or enteric (systemic-enteric) drainage of the exocrine secretions. Since 1995 the number of PTX procedures performed with primary enteric drainage has increased dramatically, accounting for more than 70% of cases since 2001. Despite an evolution in exocrine drainage, the proportion of enteric drained PTXs with portal venous delivery of insulin (portal enteric drainage) has remained low, representing about 20% of cases. In recent IPTR analyses no differences were reported in short-term outcomes according to surgical technique. Coincident with more physiologic implantation techniques, the surgical complication rate has decreased to 10% to 20%. Experience with donor and recipient selection can reduce morbidity, inasmuch as risk factors for surgical complications include prolonged pre-transplantation peritoneal dialysis, donor or recipient BMI body mass index >28 kg/m2, donor or recipient age older than 45 years, cerebrovascular cause of donor brain death, prolonged preservation, and prior abdominal surgery in the recipient. New techniques include simultaneous living donor kidney and deceased donor PTX, gastroduodenal artery revascularization, laparoscopic living donor nephrectomy and distal pancreatectomy, en bloc kidney and pancreas transplantation, P-E drainage with venting jejunostomy, retroperitoneal PTX with P-E drainage, and unusual vascular grafts. In the future the emphasis will shift from short-term surgical to long-term medical outcomes as the ultimate measure of success.

Multivariate analysis of the influence of donor and recipient cytomegalovirus sero-pairing on outcomes in simultaneous kidney-pancreas transplantation: the South-Eastern Organ Procurement Foundation Experience.

The purpose of this study was to determine if donor (D) and recipient (R) CMV sero-pairing at the time of simultaneous kidney-pancreas transplantation (SKPT) subsequently influenced outcomes in a large cohort of patients with long-term follow-up. Between January 1, 1997 and December 31, 1999 complete data were available on 723 primary SKPTs performed at South-Eastern Organ Procurement Foundation member institutions. For purposes of this study, four groups were defined: D+/R-, n = 203 (28%); D+/R+, n = 206 (28%); D-/R+, n = 156 (22%); and D-/R-, n = 158 (22%). Patient and graft survival rates for the study groups were computed by Kaplan-Meier estimates and tests of equality of survival curves were performed utilizing both the log-rank and Wilcoxon test statistics. A multivariate analysis was performed using a Cox proportional hazards model and logistic regression. A total of 56% of Ds were CMV+ and 50% of Rs were CMV-. D serostatus was not, but R serostatus was, a significant independent risk factor for patient and kidney, but not pancreas, graft survival rates in the uncensored analysis. When examining the CMV D/R groups in both univariate and multivariate fashion, CMV sero-pairing was not an independent risk factor for death, graft loss, or rejection. However, when considering CMV sero-pairing as a binary variable (D-/R- versus all other D/R groups), 6-year patient, kidney, and pancreas graft survival rates were significantly higher in the D-/R- group (P < .05). In conclusion, CMV seronegativity is present in half of diabetic patients at the time of SKPT, and protective CMV seronegative matching confers a long-term survival advantage.

A multicenter analysis of the significance of HLA matching on outcomes after kidney-pancreas transplantation.

The purpose of this study was to determine the influence of HLA matching on outcomes in simultaneous kidney-pancreas transplant (SKPT) recipients in a multicenter trial. From March 1999 to May 2001, a total of 297 SKPT recipients were enrolled in a prospective randomized trial of 2 daclizumab dosing strategies versus no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids in SKPT recipients. Subanalyses using both univariate and multivariate models were performed at 1 year to identify factors associated with acute rejection, graft loss, or death. Potential risk factors evaluated were treatment group, African American ethnicity, HLA-A mismatches (MM), HLA-B MM, HLA-DR MM, total HLA MM, surgical technique, cytomegalovirus status of donor and recipient, and delayed graft function (DGF). Univariate analyses revealed that treatment group, HLA-A MM, HLA-B MM, total HLA MM >3, and DGF were significantly associated with acute rejection. These variables were then entered into logistic and Cox regression analyses. HLA-A MM and DGF were the only variables that remained significantly associated with acute rejection in the multivariate model. The relative risk for acute rejection in recipients with HLA-A MM was 1.56 (P = .02). In conclusion, despite contemporary immunosuppression, the degree of HLA MM, particularly HLA-A, and DGF are associated with an increased risk for acute rejection in SKPT recipients at 1 year. Less rejection was noted in patients with 0 MM at all 3 HLA loci and in patients with total HLA-MM <3. However, none of these factors affected short-term patient or graft survival rates.

Risk factors and outcomes analyses at 36 months of a prospective, randomized, multicenter, trial of daclizumab induction in simultaneous kidney-pancreas transplant recipients.

UNLABELLED: The purpose of this study was to analyze risk factors for acute rejection (AR) and long-term outcomes in simultaneous kidney-pancreas transplant (SKPT) patients enrolled in a prospective, multicenter study of daclizumab (DAC) versus no antibody induction. METHODS: A total of 298 SKPT patients were randomized into three groups and categorized based on an intent to treat analysis, and factors associated with AR and survival were identified using logistic regression and Cox proportional hazards models. RESULTS: There were no differences in patient or allograft survival or rejection rates among the three groups at 36 months follow-up. Delayed (kidney) graft function (DGF) was a risk factor for subsequent kidney AR (odds ratio = 2.79, P = .002). The presence of kidney AR was also a risk factor (hazard ratio [HR] = 3.1, P = .003) for kidney graft loss, whereas risk factors for pancreas graft loss (censored for graft loss within 30 days or death with functioning graft) included pancreas AR (HR = 1.97, P = .012), kidney AR (HR = 1.61, P = .042), CMV serostatus donor +/recipient - (HR = 1.62, P = .026), and HLA-B mismatch (HR = 1.58, P = .01). Kidney graft loss (HR = 5.5, P = .02) was the only predictor of mortality. CONCLUSIONS: At 36 months, no significant differences in outcomes were noted in the three study groups. DGF was the major risk factor for kidney AR, kidney AR was the major risk factor for kidney graft loss, and kidney graft loss was the major determinant of mortality. Prevention of kidney DGF and AR in SKPT recipients may play a pivotal role in optimizing long-term outcomes.