Successful pregnancy and delivery after simultaneous islet-kidney transplantation.

Allogeneic islet of Langerhans transplantation is a recognized beta-cell replacement therapy for patients affected by type 1 diabetes mellitus. Type 1 diabetes mellitus is a condition associated with an increased risk of adverse outcomes for pregnant women and fetuses. We report the case of a 29-year-old woman with type 1 diabetes mellitus, who underwent successful allogeneic islet transplantation with simultaneous kidney transplantation. She achieved durable insulin independence after 2 islet infusions. Pregnancy was desired and planned 2 years after the last islet infusion. Multidisciplinary monitoring of pregnancy was carried out and the immunosuppressive regimen was adapted. Euglycemia was maintained throughout pregnancy without the need for exogenous insulin. After an uneventful pregnancy, she delivered on term an otherwise healthy male child with imperforate anus that was immediately surgically corrected. In conclusion, allogeneic islet transplantation is a suitable treatment for women of childbearing age with complicated type 1 diabetes mellitus, allowing physiologic glycemic control during pregnancy with a low risk of graft loss. This target can be achieved only by a tight multidisciplinary follow-up, including immunosuppressive therapy adaptation and adequate diabetes and obstetrical monitoring.

Pancreas preservation fluid microbial contamination is associated with poor islet isolation outcomes - a multi-centre cohort study.

The microbiological safety of islet preparations is paramount. Preservation medium contamination is frequent, and its impact on islet yield and function remains unclear. Microbiological samples collected during islet isolations from 2006 to 2016 were analyzed and correlated to isolation and allo- and autotransplantation outcomes. Microbial contamination of preservation medium was found in 64.4% of processed donor pancreases (291/452). We identified 464 microorganisms including Staphylococcus (253/464, 54.5%), Streptococcus (31/464, 6.7%), and Candida species (25/464, 5.4%). Microbial contamination was associated with longer warm and cold ischemia times and lower numbers of postpurification islet equivalents, purity, transplant rate, and stimulation index (all P < 0.05). Six percent of the preparations accepted for transplantation showed microbial contamination after isolation (12/200); 9 of 12 were Candida species. Six patients were transplanted with a sample with late microbial growth discovered after the infusion. Insulin independence rate was not affected. This risk of transplanting a contaminated islets preparation was reduced by half following the implementation of an additional sampling after 24 h of islet culture. Pancreas preservation fluid microbial contamination is associated with lower transplant rate and poorer in vitro function, but not with changes in graft survival. Culture medium testing 1 day after isolation reduces the risk of incidental transplantation with contaminated islets.

Low risk of anti-human leukocyte antigen antibody sensitization after combined kidney and islet transplantation.

Anti-human leukocyte antigen (HLA) antibody could lead to humoral rejection and a decrease in graft survival after kidney transplantation. A recent report has suggested that islet transplantation alone is associated with a high rate of sensitization. The withdrawal of the immunosuppressive therapy because of the progressive nonfunction of the islets could explain the high rate of sensitization. Because the specific risk of immunization of multiple islet infusions remains unknown, we studied the immunization rate in our cohort of multiple islet infusions transplant recipients. De novo anti-HLA antibodies were analyzed in 37 patients after islets alone (n=8), islet-after-kidney (n=13), and simultaneous islet-kidney (n=16) transplantation by solid phase assays over time. The rate of immunization was 10.8% that is comparable with the risk of immunization after kidney transplantation alone. Multiple islet infusions do not represent a specific risk for the development of anti-HLA antibodies after combined kidney-islets transplantation.

Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection.

Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models. Live imaging revealed that DSAs were sequestrated in the circulation of the recipients and failed to reach the endocrine cells of grafted islets. We used murine heart transplantation models to confirm that endothelial cells were the only accessible targets for DSAs, which induced the development of typical microvascular lesions in allogeneic transplants. In contrast, the vasculature of DSA-exposed allogeneic islet grafts was devoid of lesions because sprouting of recipient capillaries reestablished blood flow in grafted islets. Thus, we conclude that endothelial chimerism combined with vascular sequestration of DSAs protects islet grafts from humoral rejection. The reduced immunoglobulin concentrations in the interstitial tissue, confirmed in patients, may have important implications for biotherapies such as vaccines and monoclonal antibodies.

Multicenter Assessment of Animal-free Collagenase AF-1 for Human Islet Isolation.

Animal-free (AF) SERVA Collagenase AF-1 and Neutral Protease (NP) AF GMP Grade have recently become available for human islet isolation. This report describes the initial experiences of 3 different islet transplant centers. Thirty-four human pancreases were digested using 1 vial of the 6 different lots of Collagenase AF-1 (2,000-2,583 PZ-U/vial) supplemented with 4 different lots of NP AF in a range of 50 to 160 DMC-U per pancreas. Isolation, culture, and quality assessment were performed using standard techniques as previously described. All data are presented as mean ± standard error of the mean (SEM). Variability of pancreas weight was associated with a wide range of collagenase and NP activities, ranging from 12.7 to 46.6 PZ-U/g (26.0 ± 1.5 PZ-U/g) and 0.4 to 3.0 DMC-U/g (1.5 ± 0.1 DMC-U/g), respectively. Postpurification islet yield was 296,494 ± 33,620 islet equivalents (IEQ) equivalent to 3,274 ± 450 IEQ/g with a purity of 55.9% ± 3.2%. Quality assessment performed after 2 to 4 d of culture demonstrated a viability of 88.1% ± 1.5% and a stimulation index of 3.7 ± 0.7. Eighteen of the 34 preparations were transplanted into type 1 diabetic patients equivalent to a transplantation rate of 52.9%. Six preparations, which were infused into patients as first transplant, could be analyzed and increased the fasting C-peptide level from 0.11 ± 0.08 pretransplant to 1.23 ± 0.24 and 2.27 ± 0.31 ng/mL 3 and 6 mo posttransplant ( P < 0.05), respectively. Insulin requirements were simultaneously reduced at the same time from 39.2 ± 3.8 IU/d before transplantation to 10.8 ± 4.1 and 4.0 ± 2.3 IU/d, after 3 and 6 mo posttransplant ( P < 0.05), respectively. This study demonstrates the efficiency of AF SERVA Collagenase AF-1 and NP AF for clinical islet isolation and transplantation. The new plant-based production process makes these products a safe new option for the islet field.

Immunogenicity of Anti-HLA Antibodies in Pancreas and Islet Transplantation.

The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor-specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity, and anti-HLA antibody characteristics were collected. Between January 2008 and July 2014, 18 patients received islet transplants, and 26 patients received a pancreas transplant. Eleven out of 18 patients (61.1%) in the islet group and 12 out of 26 patients (46.2%) in the pancreas group had anti-HLA antibodies. Six patients (33.3%) developed DSAs against HLA of the islets, and 10 patients (38.4%) developed DSAs against HLA of the pancreas. Most of the DSAs were at a low level. Several parameters such as gender, number of times cells were transplanted, HLA mismatch, eplet mismatch and PIRCHE-II numbers, rejection, and infection were analyzed. Only the number of PIRCHE-II was associated with the development of anti-HLA class II de novo DSAs. Overall, the development of de novo DSAs did not influence graft survival as estimated by insulin independence. Our results indicated that pretransplant DSAs at low levels do not restrict islet or pancreas transplantation [especially islet transplantation (27.8% vs. 15.4.%)]. De novo DSAs do occur at a similar rate in both pancreas and islet transplant recipients (mainly of class II), and the immunogenicity of donor HLA is a parameter that should be taken into consideration. When combined with an immunosuppressive regimen and close follow-up, development of low levels of DSAs was not found to result in reduced graft survival or graft function in the current study.

Alloimmune Monitoring After Islet Transplantation: A Prospective Multicenter Assessment of 25 Recipients.

Islet transplantation is an effective treatment for selected patients with type 1 diabetes. However, an accurate test still lacks for the early detection of graft rejection. Blood samples were prospectively collected in four university centers (Geneva, Grenoble, Montpellier, and Strasbourg). Peripheral blood mononuclear cells were stimulated with donor splenocytes in the presence of interleukin-2. After 24 h of incubation, interferon- (IFN-) ELISpot analysis was performed. After a total of 5 days of incubation, cell proliferation was assessed by fluorescence-activated cell sorting (FACS) analysis for Ki-67. Immunological events were correlated with adverse metabolic events determined by loss of 1 point of -score and/or an increased insulin intake 10%. Twenty-five patients were analyzed; 14 were recipients of islets alone, and 11 combined with kidney. Overall, 76% (19/25) reached insulin independence at one point during a mean follow-up of 30.7 months. IFN- ELISpot showed no detectable correlation with adverse metabolic events [area under the curve (AUC)=0.57]. Similarly, cell proliferation analysis showed no detectable correlation with adverse metabolic events (CD3+/CD4+ AUC=0.54; CD3+/CD8+ AUC=0.55; CD3/CD56+ AUC=0.50). CD3/CD56+ cell proliferation was significantly higher in patients with combined kidney transplantation versus islet alone (6 months, p=0.010; 12 months, p=0.016; and 24 months, p=0.018). Donor antigen-stimulated IFN- production and cell proliferation do not predict adverse metabolic events after islet transplantation. This suggests that the volume of transplanted islets is too small to produce a detectable systemic immune response and/or that alloimmune rejection is not the sole reason for the loss of islet graft function.

Logistics and transplant coordination activity in the GRAGIL Swiss-French multicenter network of islet transplantation.

BACKGROUND: Since the Edmonton trial in 2000, increasing numbers of transplant centers have been implementing islet transplantation programs. Some institutions have elected to associate in multicenter networks, such as the Swiss-French GRAGIL (Groupe Rhin-Rhône-Alpes-Genève pour la Transplantation d'Ilots de Langerhans) consortium. METHODS: All pancreata offers to the University of Geneva Cell Isolation and Transplantation Center from within the network in 2002 and 2003 were reviewed. Islet preparations were attributed to the most suitable recipient on a centrally managed waiting list. All shipments were performed by ambulance in less than 5 hr. RESULTS: Over the period of study, 260 pancreata were offered, from a total of 1,304 cadaveric donors in the four allocation regions (20%). Fifty-two patients were on the waiting list at any time during this 2-year period. The percentage of organs offered varied in the range of 0.5% to 42%, depending on region of origin, with a correlation with number of patients on the waiting list in each region. Of these, 104 (40%) were accepted for processing. Ninety-two pancreata were actually processed, resulting in 42 islet preparations being transplanted. The number of international equivalents of transplanted preparations was 378,500+/-16,000 versus 165,400+/-15,400 (P<0.0001) for nontransplanted preparations. Total cold ischemia time was 6+/-0.3 hr for transplanted preparations versus 6.7+/-0.4 hr for nontransplanted preparations (not significant). CONCLUSIONS.: A high rate of pancreas offers, successful isolation, and islet transplantation can be achieved in multicenter networks such as GRAGIL. Such an approach can expand both the donor pool and the recipient population.

Calcineurin inhibitor-free immunosuppressive regimen in type 1 diabetes patients receiving islet transplantation: single-group phase 1/2 trial.

BACKGROUND: Our final objective is to develop an adoptive therapy with tolerogenic donor-specific type 1 T regulatory cells for patients with type 1 diabetes undergoing islet transplantation. The achievement of this objective depends on the availability of an immunosuppressive treatment compatible with the survival, function, and expansion of type 1 T regulatory cells. METHODS: For this purpose, we designed a single-group, phase 1 to 2 trial with an immunosuppression protocol including: (i) rapamycin treatment before the first islet infusion (starting ≥ 30 days before transplantation); (ii) induction therapy with anti-thymocyte globulin (ATG) instead of anti-interleukin-2Ra monoclonal antibody (after the first islet infusion only); (iii) short-term treatment with steroids and interleukin-1Ra (right before and for 2 weeks after each infusion); rapamycin+mycophenolate mofetil treatment as maintenance therapy. The target enrollment was 10 patients. RESULTS: Ten of 15 patients who started the pretransplant rapamycin treatment completed it. Nine of 10 patients did not complete the induction therapy with ATG, and three of 10 required adaptation of maintenance immunosuppression caused by side effects. Four of 10 patients acquired insulin independence which can be maintained up to year 3 after last infusion. All six other patients have lost their graft, and the early graft loss was associated with lower dose of ATG during induction. CONCLUSION: This protocol resulted feasible, safe but less efficient in maintaining graft survival during the time than other T-cell depletion-based protocols. An adequate induction at the first infusion should be considered to improve the overall clinical outcome.

Pancreas retransplantation: a second chance for diabetic patients?

BACKGROUND: If pancreas transplantation is a validated alternative for type 1 diabetic patients with end-stage renal disease, the management of patients who have lost their primary graft is poorly defined. This study aims at evaluating pancreas retransplantation outcome. METHODS: Between 1976 and 2008, 569 pancreas transplantations were performed in Lyon and Geneva, including 37 second transplantations. Second graft survival was compared with primary graft survival of the same patients and the whole population. Predictive factors of second graft survival were sought. Patient survival and impact on kidney graft function and survival were evaluated. RESULTS: Second pancreas survival of the 17 patients transplanted from 1995 was close to primary graft survival of the whole population (71% vs. 79% at 1 year and 59% vs. 69% at 5 years; P=0.5075) and significantly better than their first pancreas survival (71% vs. 29% at 1 year and 59% vs. 7% at 5 years; P=0.0008) regardless of the cause of first pancreas loss. The same results were observed with all 37 retransplantations. Survival of second simultaneous pancreas and kidney transplantations was better than survival of second pancreas after kidney. Patient survival was excellent (89% at 5 years). Pancreas retransplantation had no impact on kidney graft function and survival (100% at 5 years). CONCLUSION: Pancreas retransplantation is a safe procedure with acceptable graft survival that should be proposed to diabetic patients who have lost their primary graft.

Endocrine secretory reserve and proinsulin processing in recipients of islet of langerhans versus whole pancreas transplants.

OBJECTIVE: ß-Cells have demonstrated altered proinsulin processing after islet transplantation. We compare ß-cell metabolic responses and proinsulin processing in pancreas and islet transplant recipients with respect to healthy control subjects. RESEARCH DESIGN AND METHODS: We studied 15 islet and 32 pancreas transplant recipients. Islet subjects were subdivided into insulin-requiring (IR-ISL, n = 6) and insulin-independent (II-ISL, n = 9) groups. Ten healthy subjects served as control subjects. Subjects were administered an intravenous arginine stimulation test, and insulin, C-peptide, total proinsulin, intact proinsulin, and proinsulin fragment levels were determined from serum samples. Acute insulin response (AIR) and proinsulin processing rates were calculated. RESULTS: We found that basal insulin and C-peptide levels were higher in the pancreas group than in all other groups. II-ISL patients had basal insulin and C-peptide levels similar to healthy control subjects. The IR-ISL group had significantly lower AIRs than all other groups. Basal processing rates were higher in the pancreas and II-ISL groups than in healthy control subjects and the IR-ISL group. After arginine stimulation, all groups had elevated processing rates, with the exception of the IR-ISL group. CONCLUSIONS: Our data suggest that II-ISL transplant recipients can maintain basal metabolic parameters similar to healthy control subjects at the cost of a higher rate of proinsulin processing. IR-ISL transplant recipients, on the other hand, demonstrate both lower insulin response and lower basal rates of proinsulin processing even after arginine stimulation.

Posttransplant cellular immune reactivity against donor antigen correlates with clinical islet transplantation outcome: towards a better posttransplant monitoring.

The aim of the present study was to assess the efficiency of cell-based immune assays in the detection of alloreactivity after islet transplantation and to correlate these results with clinical outcome. Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients (n = 14), donors, or third party. The immune reactivity was assessed by the release of IFN-γ (ELISpot), cell proliferation (FACS analysis for Ki67), and cytokine quantification (Bioplex). Islet function correlated with the number of IFN-γ-secreting cells following incubation with donor cells (p = 0.007, r = -0.50), but not with third party cells (p = 0.61). Similarly, a high number of donor-specific proliferating cells was associated with a low islet function (p = 0.006, r = -0.51). Proliferating cells were mainly CD3(+)CD4(+) lymphocytes and CD3(-)CD56(+) natural killer cells (with low levels of CD3(+)CD8(+) lymphocytes). Patients with low islet function had increased levels of CD4(+)Ki67(+)cells (p ≤ 0.0001), while no difference was observed in CD8(+)Ki67(+) and CD56(+)Ki67(+) cells. IFN-γ, IL-5, and IL-17 levels were increased in patients with low islet function, but IL-10 levels tended to be lower. IFN-γ-ELISpot, proliferation, and cytokines were similarly accurate in predicting clinical outcome (AUC = 0.77 ± 0.088, 0.85 ± 0.084, and 0.88 ± 0.074, respectively). Cellular immune reactivity against donor cells correlates with posttransplant islet function. The tested assays have the potential to be of substantial help in the management of islet graft recipients and deserve prospective validation.

Comparative impact on islet isolation and transplant outcome of the preservation solutions Institut Georges Lopez-1, University of Wisconsin, and Celsior.

BACKGROUND: Institut Georges Lopez-1 (IGL-1) is a preservation solution similar to University of Wisconsin (UW) with reversed Na/K contents. In this study, we assessed the impact of IGL-1, UW, and Celsior (CS) solutions on islet isolation and transplant outcome. METHODS: We retrospectively analyzed 376 islet isolations from pancreases flushed and transported with IGL-1 (n=95), UW (n=204), or CS (n=77). We determined isolation outcome and ß-cell function in vitro. Transplanted patients were divided into three groups depending on preservation solution of pancreas, and islet graft function was assessed by decrease in daily insulin needs, C-peptide/glucose ratios, ß-scores, and transplant estimated function at 1- and 6-month follow-up. RESULTS: IGL-1, UW, and CS groups were similar according to donor age, body mass index, and pancreas weight. There was no difference in islet yields between the three groups. Success rates, transplant rates, ß-cell secretory function, and viability were similar for all three groups. We observed no difference in decreased insulin needs, C-peptide glucose ratios, ß-scores, and transplant estimated function at 1- and 6-month follow-up between IGL-1, UW, and CS groups. CONCLUSIONS: Our study shows that IGL-1 is equivalent to UW or CS solutions for pancreas perfusion and cold storage before islet isolation and transplantation.

Islet autotransplantation after extended pancreatectomy for focal benign disease of the pancreas.

BACKGROUND: Extended pancreatectomy is associated with the risk of surgical diabetes. Islet autotransplantation is successful in the prevention of diabetes after pancreas resection for chronic pancreatitis (CP), with insulin independence rates of 50% at 1 year. The aim of the present study is to demonstrate the safety and efficiency of islet autotransplantation after extended left pancreatectomy for benign disease. METHODS: Between 1992 and 2009, 25 patients underwent extended pancreatectomy and islet autotransplantation for benign disease. Of these, 15 patients were operated for focal lesions located at the neck of the pancreas (14 benign tumors and 1 traumatic pancreatic section), the remainder being CP cases. After unequivocal diagnosis of benignity, the rest of the pancreas was processed and infused into the portal vein. Metabolic results were analyzed and isolation results were compared with those obtained from patients with CP or donors with brain death (DBD). RESULTS: There was no mortality and a low morbidity (Streptococcus mitis bacteremia in 1 patient), no portal thrombosis or pancreatic fistula occurred. Median follow-up was 90 months. Actuarial patient survival was 100% at 10 years. Actuarial insulin independence was 94% at 10 years. All patients had positive basal and stimulated C-peptide levels and normal HbA1c. Mean islet yields were 5455 IEQ/gram vs. 1457 in CP (P=0.001) and 3738 in DBD (P=0.003). CONCLUSIONS: Islet autotransplantation after extensive pancreatic resection for benign disease is a safe and successful procedure. Islet yields after isolation, which are equivalent to the live donor situation, are significantly better than those from DBD donors.

Influence of donor age on islet isolation and transplantation outcome.

BACKGROUND: It has been suggested that the age of human organ donors might influence islet isolation and transplantation outcome in a negative way due to a decrease of in vivo function in islets isolated from older donors. METHODS: We retrospectively analyzed 332 islet isolations according to donor age. We determined isolation outcome by islet yields, transplantation rates, and [beta]-cell function in vitro. Transplanted patients were divided into two groups depending on donor age (n=25 and n=31 patients for <=45- and >45-year-old donors, respectively). We assessed islet graft function by C-peptide/glucose ratio, [beta] score, secretory units of islets in transplantation index, and insulin independence rate at 1, 6, and 12 months after transplantation. RESULTS: There was no difference in islet yields between the two groups (251,900+/-14,100 and 244,600+/-8400 islet equivalent for <=45- and >45-year-old donors, respectively). Transplantation rates and stimulation indices were similar in both groups as well. All islet graft function parameters were significantly higher at 1-month follow-up in patients who had received islets from younger donors. At 6-month follow-up after second or third injection and at 12-month follow-up, secretory units of islets in transplantation indices and C-peptide/glucose ratios were significantly higher in patients with donors aged 45 years or younger. CONCLUSIONS: These data suggest that, despite similar outcomes of the isolation procedure, islet graft function is significantly influenced by donor age. These results may have important consequences in the definition of pancreas allocation criteria.

Impact of the number of infusions on 2-year results of islet-after-kidney transplantation in the GRAGIL network.

BACKGROUND: Insulin independence after islet transplantation is generally achieved after multiple infusions. However, single infusion would increase the number of recipients. Our aim was to evaluate the results of islet-after-kidney transplantation according to the number of infusions. METHODS: Islets were isolated at the Geneva University, shipped, and transplanted into French patients from the Swiss-French GRAGIL network, on the "Edmonton" immunosuppression protocol between 2004 and 2010. RESULTS: Nineteen patients were transplanted with 33 preparations. Fifteen patients reached 24 months follow-up; eight subjects were single-graft recipients and seven were double-graft recipients. Finally, single-graft recipients received a median of 5312 islet equivalents/kg (5186-6388) vs. 10,564 (10,054-11,375) for double-graft recipients (P=0.0003) with similar islet mass at first infusion. Insulin independence was achieved in five of eight single-graft subjects (62.5%) versus five of seven in double-graft subjects (71.4%), not significant. Median insulin independence duration was 4.7 (3.1-15.2) months after one infusion vs. 19 (9.6-20.8) months after two infusions (not significant). At 24 months posttransplant, comparing single- with double-graft patients, insulin doses were 0.23 (0.11-0.34) U/kg vs. 0.02 (0.0-0.23) U/kg, P=0.11; HbA1c was 6.5% (5.9%-6.8%) vs. 6.2% (5.9%-6.3%), P=0.16; and basal C-peptide was 302 (143-480) pmol/L vs. 599 (393-806) pmol/L, P=0.05. Only 37.5% of single-graft patients had a ß-score ≥4 compared with 100% of double-graft patients (P=0.03). Two recipients experienced postinfusion bleeding, and two patients (13%) showed renal dysfunction in the absence of biopsy-proven rejection. CONCLUSIONS: One infusion achieves good glycemic control and sometimes insulin independence. However, double-graft patients remain insulin-free longer, tend to have lower HbA1c, and show better graft function 24 months after transplant.

Impact of HLA matching on the outcome of simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation has become the therapy of choice for type 1 diabetic patients with end-stage renal disease. The current analysis examined the impact of human leukocyte antigen (HLA) matching on graft outcome following SPK transplantation. The study population was obtained from patients enrolled in the Euro-SPK 001 study. METHODS: The effect of HLA matching on graft function and survival was assessed in 180 SPK recipients in whom complete donor-recipient HLA data were available. A group of 45 patients with 0-3 HLA mismatches (MM) was compared with a group of 135 patients with 4-6 MM. RESULTS: There were no differences in 3-year kidney, pancreas or patient survival between the 0-3 and 4-6 MM groups. Biological parameters of kidney and pancreas graft function were similar in both groups. Significantly more patients with 0-3 MM (66%) were rejection-free at 3 years than was the case among those with 4-6 MM (41%; P = 0.003). The relative risk of acute rejection was 2.6 times higher among patients with 4-6 MM than among those with 0-3 MM. CONCLUSIONS: There was no evidence that HLA matching was associated with improved kidney or pancreas survival. However, a higher rate of acute rejection was observed with poor HLA match, which may impact long-term survival.

Impairment of renal function after islet transplant alone or islet-after-kidney transplantation using a sirolimus/tacrolimus-based immunosuppressive regimen.

The immunosuppressive (IS) regimen based on sirolimus/low-dose tacrolimus is considered a major determinant of success of the Edmonton protocol. This regimen is generally considered safe or even protective for the kidney. Herein, we analyzed the impact of the sirolimus/low-dose tacrolimus combination on kidney function. The medical charts of islet transplant recipients with at least 6 months follow up were reviewed. There were five islet-after-kidney and five islet transplantation alone patients. Serum creatinin, albuminuria, metabolic control markers and graft function were analyzed. Impairment of kidney function was observed in six of 10 patients. Neither metabolic markers nor IS drugs levels were significantly associated with the decrease of kidney function. Although a specific etiology was not identified, some subsets of patients presented a higher risk for decline of kidney function. Low creatinin clearance, albuminuria and long-established kidney graft were associated with poorer outcome.