Simultaneous pancreas-kidney transplantation in Caucasian versus African American patients: Does recipient race influence outcomes?

The influence of African American (AA) recipient race on outcomes following simultaneous pancreas-kidney transplantation (SPKT) is uncertain. METHODS: From 11/01 to 2/19, we retrospectively studied 158 Caucasian (C) and 57 AA patients (pts) undergoing SPKT. RESULTS: The AA group had fewer patients on peritoneal dialysis (30% C vs. 14% AA), more patients with longer dialysis duration (28% C vs. 51% AA), more sensitized (PRA ≥20%) patients (6% C vs. 21% AA), and more patients with pretransplant C-peptide levels ≥2.0 ng/ml (11% C vs. 35% AA, all P < .05). With a mean 9.2 year follow-up, patient survival (65% C vs. 77% AA, P = .098) slightly favored the AA group, whereas kidney (55% C vs. 60% AA) and pancreas (48% C vs. 54% AA) graft survival rates (GSRs) were comparable. Death-censored kidney (71% C vs. 68% AA) and pancreas (both 62%) GSRs demonstrated that death with a functioning graft (DWFG) was more common in C vs. AA patients (23% C vs. 12% AA, P = .10). The incidence of death-censored dual graft loss (usually rejection) was 7% C versus 21% AA (P = .005). CONCLUSIONS: Following SPKT, AA patients are at a greater risk for dual immunological graft loss whereas C patients are at greater risk for DWFG.

Do pretransplant C-peptide levels predict outcomes following simultaneous pancreas-kidney transplantation? A matched case-control study.

Following simultaneous pancreas-kidney transplantation (SPKT), survival outcomes are reported as equivalent in patients with detectable pretransplant C-peptide levels (Cp+) and a "type 2″ diabetes mellitus (DM) phenotype compared to type 1 (Cp negative [Cp-]) DM. We retrospectively compared 46 Cp+ patients pretransplant (≥2.0 ng/mL, mean 5.4 ng/mL) to 46 Cp- (level < 0.5 ng/mL) case controls matched for recipient age, gender, race, and transplant date. Early outcomes were comparable. Actual 5-year patient survival (91% versus 94%), kidney graft survival (69% versus 86%, p = .15), and pancreas graft survival (60% versus 86%, p = .03) rates were lower in Cp+ versus Cp- patients, respectively. The Cp+ group had more pancreas graft failures due to insulin resistance (13% Cp+ versus 0% Cp-, p = .026) or rejection (17% Cp+ versus 6.5% Cp-, p = .2). Post-transplant weight gain > 5 kg occurred in 72% of Cp+ versus 26% of Cp- patients (p = .0001). In patients with functioning grafts, mean one-year post-transplant HbA1c levels (5.0 Cp+ versus 5.2% Cp-) were comparable, whereas Cp levels were higher in Cp+ patients (5.0 Cp+ versus 2.6 ng/mL Cp-). In this matched case-control study, outcomes were inferior in Cp+ compared to Cp- patients following SPKT, with post-transplant weight gain, insulin resistance, and rejection as potential mitigating factors.

Recipient age and outcomes following simultaneous pancreas-kidney transplantation in the new millennium: Single-center experience and review of the literature.

The influence of recipient age on outcomes following simultaneous pancreas-kidney transplantation (SPKT) in the modern era is uncertain. METHODS: We retrospectively studied 255 patients undergoing SPKT from 11/01 to 8/20. Recipients were stratified according to age group: age <30 years (n = 16); age 30-39 years (n = 91); age 40-49 years (n = 86) and age ≥50 years (n = 62 [24.3%], including 9 patients ≥60 years of age). RESULTS: Three-month and one-year outcomes were comparable. The eight-year patient survival rate was lowest in the oldest age group (47.6% vs 78% in the 3 younger groups combined, p < .001). However, eight-year kidney and pancreas graft survival rates were comparable in the youngest and oldest age groups combined (36.5% and 32.7%, respectively), but inferior to those in the middle 2 groups combined (62% and 50%, respectively, both p < .05). Death-censored kidney and pancreas graft survival rates increased from youngest to oldest recipient age category because of a higher incidence of death with functioning grafts (22.6% in oldest group compared to 8.3% in the 3 younger groups combined, p = .005). CONCLUSIONS: Recipient age did not appear to significantly influence early outcomes following SPKT. Late outcomes are similar in younger and older recipients, but inferior to the middle 2 age groups.

Dual Kidney Transplantation from Donors at the Extremes of Age.

BACKGROUND: The study purpose was to analyze outcomes in recipients of pediatric dual en bloc (PEB) kidneys from small pediatric donors (SPDs, age ≤ 3 years) and dual kidney transplants (KTs) from adult marginal deceased donors (DDs) in the context of the Kidney Donor Profile Index (KDPI). STUDY DESIGN: This was a single center retrospective review. Recipient selection included primary transplant, low BMI, low immunologic risk, and informed consent. All patients received antibody induction with FK/MPA/± prednisone. RESULTS: From 2002 to 2015, we performed 34 PEB and 73 adult dual KTs. Mean donor ages were 17 months for the PEB and 59 years for the dual KTs; mean KDPIs were 73% for PEB and 83% for dual KT, and mean cold ischemia times were 21.0 hours for PEB and 26.5 hours for dual KT. Adult dual KT recipients were older (mean age 38 years for PEB and 60 years for dual KT) and had shorter waiting times (mean 25 months for PEB and 12 months for dual KT). With a mean follow-up of 7.6 years, actual patient survival (88% for PEB and 62% for dual KT) and graft survival (71% for PEB and 44% for dual KT) rates were higher in PEB compared with dual KT. Death-censored kidney graft survival rates were 77% for PEB and 58% for dual KT. Delayed graft function (DGF) rates were 15% for PEB and 23% for dual KT; incidences of DGF in single kidney transplantations from SPDs and adult nonmarginal DDs were 20% and 32%, respectively. Based on actual 5-year graft survival rates, the adjusted KDPIs for dual PEB and dual KTs were 3% and 60%, respectively. CONCLUSIONS: Acceptable mid-term outcomes are associated with PEB and adult dual KTs, which may expand the donor pool and prevent kidney discard. The KDPI is inaccurate for predicting outcomes from either PEB from SPDs or dual KT from adult marginal DDs, which may prevent acceptance of these organs.

Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single-center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) <20 hours, 27 patients; (ii) 20-30 hours, 52 patients; (iii) 30-40 hours, 30 patients; (iv) ≥40 hours, nine patients. The overall incidence of delayed graft function DGF was 41.5%. According to increasing CIT category, DGF rates were 30%, 42%, 40%, and 78%, respectively (P = .03). With a mean follow-up of 48 months, overall patient and graft survival rates were 91% and 81%. Death-censored graft survival (DCGS) rates were 84% and 88% for patients with and without DGF (P = NS). DCGS rates were 92% in patients with CIT <20 hours compared to 85% with CIT >20 hours (P = NS). In the nine patients with CIT >40 hours, the 4-year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged.

Analysis of local versus imported expanded criteria donor kidneys: A single-center experience with 497 ECD kidney transplants.

BACKGROUND: The value of importing expanded criteria donor (ECD) kidneys is uncertain. METHODS: We retrospectively reviewed our single-center experience with ECD kidney transplants (KT). RESULTS: Over 12.8 years, we performed 497 ECD KTs including 247 local and 250 imported from other donor service areas. The import ECD group had more donors (16% vs 9%) ≥ age 70, more zero human leukocyte antigen mismatches (14% vs 2%), more KTs with a cold ischemia time >30 hours (46% vs 19%), and fewer kidneys managed with pump preservation (78% vs 92%, all P≤.05) compared to the local ECD group. Mean Kidney Donor Profile Index were 80% import vs 84% local. With a mean follow-up of 55 months, actual patient and graft survival rates were 71% and 58% in import vs 76% and 58% in local ECD KTs, respectively. Death-censored graft survival rates were 70% in import vs 69% in local ECD KTs. Delayed graft function occurred in 28% import vs 23% local ECD KTs (P=NS) whereas the incidence of primary nonfunction was slightly higher with import ECD kidneys (4.8% vs 2.4%, P=.23). CONCLUSIONS: Midterm outcomes are remarkably similar for import vs local ECD KTs, suggesting that broader sharing of ECD kidneys may improve utilization without compromising outcomes.

Single vs dual (en bloc) kidney transplants from donors ≤ 5 years of age: A single center experience.

AIM: To compare outcomes between single and dual en bloc (EB) kidney transplants (KT) from small pediatric donors. METHODS: Monocentric nonprospective review of KTs from pediatric donors ≤ 5 years of age. Dual EB KT was defined as keeping both donor kidneys attached to the inferior vena cava and aorta, which were then used as venous and arterial conduits for the subsequent transplant into a single recipient. Donor age was less useful than either donor weight or kidney size in decision-making for kidney utilization as kidneys from donors < 8 kg or kidneys < 6 cm in length were not transplanted. Post-transplant management strategies were standardized in all patients. RESULTS: From 2002-2015, 59 KTs were performed including 34 dual EB and 25 single KTs. Mean age of donors (17 mo vs 38 mo, P < 0.001), mean weight (11.0 kg vs 17.4 kg, P = 0.046) and male donors (50% vs 84%, P = 0.01) were lower in the dual EB compared to the single KT group, respectively. Mean cold ischemia time (21 h), kidney donor profile index (KDPI; 73% vs 62%) and levels of serum creatinine (SCr, 0.37 mg/dL vs 0.49 mg/dL, all P = NS) were comparable in the dual EB and single KT groups, respectively. Actuarial graft and patient survival rates at 5-years follow-up were comparable. There was one case of thrombosis resulting in graft loss in each group. Delayed graft function incidence (12% dual EB vs 20% single KT, P = NS) was slightly lower in dual EB KT recipients. Initial duration of hospital stay (mean 5.4 d vs 5.6 d) and the one-year incidences of acute rejection (6% vs 16%), operative complications (3% vs 4%), and major infection were comparable in the dual EB and single KT groups, respectively (all P = NS). Mean 12 mo SCr and abbreviated MDRD levels were 1.17 mg/dL vs 1.35 mg/dL and 72.5 mL/min per 1.73 m(2) vs 60.5 mL/min per 1.73 m(2) (both P = NS) in the dual EB and single KT groups, respectively. CONCLUSION: By transplanting kidneys from young pediatric donors into adult recipients, one can effectively expand the limited donor pool and achieve excellent medium-term outcomes.

Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

BACKGROUND: The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. STUDY DESIGN: We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. RESULTS: Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for patients receiving single KTs. CONCLUSIONS: Dual kidney transplantation using kidneys from adult marginal DDs that otherwise might be discarded offer a viable option to counteract the growing shortage of acceptable single kidneys. Excellent medium-term outcomes can be achieved and waiting times can be reduced in a predominantly older recipient population.

Donor-derived myeloid sarcoma in two kidney transplant recipients from a single donor.

We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH) and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.

A Single Center 11 Year Experience with 202 Pancreas Transplants in the New Millennium: Evolving Trends.

Our single center experience with pancreas transplantation (PTx) over an 11+ year period is reviewed. METHODS: We retrospectively studied outcomes in 202 consecutive PTxs in 192 patients at our center. All patients received either rabbit anti-thymocyte globulin (rATG) or alemtuzumab (Alem) induction with tacrolimus/mycophenolate mofetil and tapered steroids or early withdrawal. 179 PTxs (89%) were performed with portal-enteric and 23 with systemic-enteric drainage. RESULTS: From 11/01 to 3/13, we performed 162 simultaneous kidney-PTxs (SKPT), 35 sequential PTxs after kidney, and 5 PTx alone (40 solitary PTxs, SPT). 186 PTxs (92%) were primary and 16 were pancreas retransplants. With a mean follow-up of 5.5 years, overall patient (86% SKPT versus 87% SPT), kidney (74% SKPT versus 80% SPT), and pancreas graft survival (both 65%) rates were comparable. Causes of PTx loss were also similar between SKPT and SPT; the rates of early thrombosis were 8.6% and 5%, respectively. Acute rejection rates were similar between groups (SKPT 29% versus SPT 28%, p= not significant). A randomized trial of Alem versus rATG induction in SKPT demonstrated lower rates of acute rejection and infection in the Alem group. Consequently, Alem induction has been used exclusively in all PTxs since 2009. Early steroid elimination has been feasible in most patients. Surveillance PTx biopsy-directed immunosuppression has contributed to equivalent long-term outcomes in SKPT and SPT. Good results have been achieved in African-American patients and in patients with a type 2 diabetes phenotype. CONCLUSIONS: Excellent 5-year outcomes following PTx can be achieved as >86% of patients are alive, >87% of surviving patients are dialysis-free, 80% of surviving patients remain insulin-free, and 88% of surviving patients have detectable C-peptide levels.

Pancreas transplantation: The Wake Forest experience in the new millennium.

AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American (AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/mL. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit anti-thymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient (86% SKPT vs 87% SPT) and kidney (74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates (both 65%) were similar (P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively (P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients (P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a "type 2 diabetes" phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels. CONCLUSION: In the new millennium, acceptable medium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.

Influence of recipient age on deceased donor kidney transplant outcomes in the expanded criteria donor era.

METHODS: We performed a retrospective single-center review of 884 deceased donor (DD) kidney transplants (KTs) in patients (pts) aged ≥40 yr. RESULTS: One hundred and four (11.8%) pts were ≥70 (mean 74), 286 (32.3%) were 60-69 (mean 64), and 494 (55.9%) were 40-59 (mean 51) yr of age; the proportion receiving expanded criteria donor (ECD) kidneys were 66%, 49%, and 30%, respectively (p < 0.001). Mean waiting time (15 months) was shorter for pts ≥70 yr compared to the other two groups combined (23 months, p = 0.002). With mean follow-up ranging from 54 to 70 months, actual pt (81% vs. 72%, p = 0.002) and graft (66% vs. 58.5%, p = 0.03) survival rates were higher in the younger compared to the two older groups, whereas death-censored graft survival was similar (76% vs. 73%, p = NS). The incidence of death with a functioning graft correlated with older recipient age group, increasing from 13% to 18% to 23% (p = 0.01). The incidence of delayed graft function was similar (31.8% overall), and renal function, morbidity, and resource utilization were similar among groups. CONCLUSIONS: By directing ECD kidneys to selected older pts, waiting times are reduced and censored survival outcomes are similar to middle-aged patients, suggesting that matching strategies for graft and patient lifespan are warranted.

Depleting antibody induction in simultaneous pancreas-kidney transplantation: a prospective single-center comparison of alemtuzumab versus rabbit anti-thymocyte globulin.

BACKGROUND: The study purpose was to analyze midterm outcomes in a prospective trial of alemtuzumab (Alem) versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous pancreas-kidney transplantation (SPKT). METHODS: From February 2005 to October 2008, 46 SPKTs (45 portal-enteric drainage) were prospectively randomized as part of a larger kidney transplant study to receive either single-dose Alem (30 mg intraoperatively) or multiple-dose rATG antibody induction (starting intraoperatively, minimum three doses administered) with tacrolimus/mycophenolate ± steroids. RESULTS: Of 222 kidney transplant patients enrolled in the study, 46 received SPKTs; 28 (61%) received Alem and 18 (39%) rATG induction. Follow-up ranged from 67 to 111 months (mean 80 months). There were no significant differences between the two groups in 5 years actual patient (86% Alem vs 89% rATG), kidney (82% Alem vs 61% rATG, p = 0.17) or pancreas (68% Alem vs 56% rATG) graft survival rates. Five years death-censored kidney (92% Alem vs 69% rATG, p = 0.09) and pancreas (76% Alem vs 56% rATG, p = 0.198) graft survival rates were slightly higher in patients receiving Alem. Acute rejection (21% Alem vs 44% rATG, p = 0.12) and major infection (39% Alem vs 67% rATG, p = 0.13) rates were slightly lower in the Alem group; cytomegalovirus infections were significantly lower (0 Alem vs 17% rATG, p = 0.05). The incidence of late acute rejection was low in both groups. There were no differences in early pancreas thrombosis (3.6% Alem vs 11% rATG), postoperative bleeding (11% Alem vs 0 rATG), other surgical complications, readmissions or freedom from steroids between groups. In patients with functioning grafts, 5 years mean serum creatinine (1.4 Alem vs 1.6 mg/dl rATG), calculated abbreviated modification of diet in renal disease glomerular filtration rate (55 Alem vs 52 ml/min/1.73 m(2) rATG), hemoglobin A1c (both 5.4%) and C-peptide (2.6 Alem vs 2.3 ng/ml rATG) levels were similar. CONCLUSIONS: Single-dose Alem and multiple-dose rATG induction provide similar midterm patient survival and graft functional outcomes with no major differences in morbidity or resource utilization.

Pancreas transplantation: lessons learned from a decade of experience at Wake Forest Baptist Medical Center.

This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature.

Cost-effective immunosuppressive options for solid organ transplantation: a guide to lower cost for the renal transplant recipient in the USA.

Of the numerous risks associated with immunotherapy for the prevention of rejection, cost is perhaps the most universal. In the USA and some other countries, the costs of immunosuppression make transplantation unavailable for some medically viable transplant candidates, and for others who receive a transplant, the long-term costs are economically crippling. Minimization and tapering of immunosuppression, use of generics, manipulation of metabolism, infection surveillance instead of prophylaxis, and advantageous routes of administration are some strategies that can be employed to reduce immunotherapy expense. Using these strategies, we describe an immunosuppression regimen for kidney transplantation that might be only a third of the cost of current 'standard' regimens in the USA. Such a regimen might allow some patients who might not otherwise qualify economically to safely receive a kidney transplant. The purpose of creating an alternative, lower-cost immunotherapy regimen is to give patients a choice. Responsible stewardship of scarce donor organs is the primary, and clearly appropriate, limiting factor.