Outcomes of Recipients With Pancreas Transplant Alone Who Develop End-Stage Renal Disease.

Recipients of pancreas transplant alone (PTA) may be at increased risk for developing end-stage renal disease (ESRD). The survival experience of PTA recipients developing ESRD has not been described. Furthermore, the relative survival of these patients as compared to diabetics on chronic dialysis is unknown. We studied all adult PTA recipients from January 1, 1990 to September 1, 2008 using the Scientific Registry of Transplant Recipients. Each PTA recipient developing ESRD was matched to 10 diabetics on chronic dialysis from the United States Renal Data System. Cox proportional hazards models were fitted to determine the relation between ESRD and mortality among PTA recipients, and the relation between PTA and mortality among diabetics on chronic dialysis. There were 1597 PTA recipients in the study, of which 207 developed ESRD. Those with ESRD had a threefold increase in mortality versus those without (adjusted hazard ratio 3.28 [95% confidence interval: 2.27, 4.76]). There was no significant difference in the risk of death among PTA recipients with ESRD versus diabetics on dialysis. PTA recipients developing ESRD are three times more likely to die than PTA recipients without ESRD; however, the risk of death in these patients was similar to diabetics on chronic dialysis without PTA.

First global forum on education on organ donation and transplantation for schools.

The Transplantation Society, in collaboration with the Canadian Society of Transplantation, organized a forum on education on ODT for schools. The forum included participants from around the world, school boards, and representatives from different religions. Participants presented on their countries' experience in the area of education on ODT. Working groups discussed about technologies for education, principles for sharing of resources globally, and relationships between education, and health authorities and non-governmental organizations. The forum concluded with a discussion about how to best help existing programs and those wishing to start educational programs on ODT.

Prolonged lymphopenia following anti-thymocyte globulin induction is associated with decreased long-term graft survival in liver transplant recipients.

BACKGROUND AND AIM: Induction with anti-thymocyte globulin (ATG) during solid organ transplantation is associated with an improved clinical course and leads to prolonged lymphopenia. This study aims to investigate whether prolonged lymphopenia, caused by ATG induction, has an impact on patient and graft survival following liver and kidney transplantation. PATIENTS AND METHODS: This was a single-center, retrospective study. A total of 292 liver and 417 kidney transplants were performed with ATG induction (6 mg/kgr, divided into four doses), and the transplant recipients were followed for at least three months. The average lymphocyte count for the first 30 days after the operation was calculated, and the cut-off value for defining lymphopenia was arbitrarily set to ≤ 500 cells/mm(3). RESULTS: There were 210 liver transplant recipients (71.9%) who achieved prolonged lymphopenia, whereas the remaining 82 recipients (28.1%) did not. The mean survival time of these patient groups was 10.27 and 12.71 years, respectively (p = 0.1217), and the mean graft survival time was 8.98 and 12.25 years, respectively (p = 0.0147). Of the kidney transplant patients, 330 (79.1%) recipients achieved prolonged lymphopenia, whereas the remaining 87 (20.9%) did not. The mean survival time of these patient groups was 13.94 and 14.59 years, respectively, (p = 0.4490), and the mean graft survival time was 11.84 and 11.54 years, respectively (p = 0.7410). CONCLUSION: The efficacy and safety of ATG induction partially depend on decreased total lymphocyte counts. Following ATG induction in liver transplant recipients, a reasonable average lymphocyte count during the first postoperative month would be above 500 cells/mm(3).

The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation.

Voclosporin (VCS, ISA247) is a novel calcineurin inhibitor being developed for organ transplantation. PROMISE was a 6-month, multicenter, randomized, open-label study of three ascending concentration-controlled groups of VCS (low, medium and high) compared to tacrolimus (TAC) in 334 low-risk renal transplant recipients. The primary endpoint was demonstration of noninferiority of biopsy proven acute rejection (BPAR) rates. Secondary objectives included renal function, new onset diabetes after transplantation (NODAT), hypertension, hyperlipidemia and pharmacokinetic-pharmacodynamic evaluation. The incidence of BPAR in the VCS groups (10.7%, 9.1% and 2.3%, respectively) was noninferior to TAC (5.8%). The incidence of NODAT for VCS was 1.6%, 5.7% and 17.7% versus 16.4% in TAC (low-dose VCS, p = 0.03). Nankivell estimated glomerular filtration rate was respectively: 71, 72, 68 and 69 mL/min, statistically lower in the high-dose group, p = 0.049. The incidence of hypertension and adverse events was not different between the VCS groups and TAC. VCS demonstrated an excellent correlation between trough and area under the curve (r(2) = 0.97) and no difference in mycophenolic acid exposure compared to TAC. This 6-month study shows VCS to be as efficacious as TAC in preventing acute rejection with similar renal function in the low- and medium-exposure groups, and potentially associated with a reduced incidence of NODAT.

Re-vascularization may not increase graft survival after hepatic artery thrombosis in liver transplant recipients.

BACKGROUND AND AIM: Hepatic artery thrombosis (HAT) occurs in 3% to 11% of all liver transplantations. Some authors have reported good outcomes with early thrombectomy. To investgate the impact of re-vascularization on graft survival. METHODS: A total of 566 primary, cadaveric, single organ, adult liver transplants were performed. Hepatic arterial Doppler was performed routinely and patients with abnormal findings during the first two post-operative weeks were reexplored. Abnormal findings after this time-point were verified by non-invasive angiogram. The 47 patients that were diagnosed with arterial thrombosis, either intra-operatively or by angiogram, were divided into three groups. No further action was taken for group A, thrombectomy alone was performed for group B1, thrombectomy and anastomotic revision was employed for group B2. RESULTS: Arterial thrombosis was diagnosed in 47 (8.3%) patients. Mean patient survival was 42, 62 and 98 months for groups A, B1 and B2 respectively (p: 0.0629). Mean graft survival was 24, 29 and 60 months for groups A, B1 and B2 respectively (p: 0.3386). Re-transplant incidence was 8.7%, 40% and 28.6% for groups A, B1, and B2 respectively (p: 0.035). CONCLUSIONS: Early diagnosis of HAT by surveillance Doppler may lead to improved recipient survival secondary to earlier re-transplantation and not because of successful graft re-vascularization.

Recovery of graft function early posttransplant determines long-term graft survival in deceased donor renal transplants.

INTRODUCTION: Because kidneys show remarkable resilience and can recover function, we examined the impact on long-term graft survival in deceased donor renal transplants of both immediate graft function (IGF) and the rate of renal function recovery over the first 3 months after transplantation. METHODS: We included all cadaveric renal transplants from 1990 to 2007 (n = 583). Delayed graft function (DGF) was defined as the need for dialysis in the first 7 days posttransplant. Slow graft function (SGF) and IGF were defined by serum creatinine falls of <20% or >20% in the first 24 hours posttransplant respectively. Recovery of renal function was expressed as either the best creatinine clearance (CrCl) in the first 3 months post-renal transplantation (BCrCl-3mos) as calculated using the Cockcroft-Gault formula or as a percentage of actual versus expected value (as calculated from the donors' CrCl at procurement). RESULTS: There were 140 (23.6%) subjects who received extended criteria donor (ECD) organs. The overall graft survival at 1 and 5 years was 87.8% and 74%, respectively. The 5-year graft survivals for patients with IGF, SGF, and DGF were 85%, 76%, and 54%, respectively (P < .02). ECD kidneys showed twice the DGF rate (49% vs 23%, P < .001). BCrCl-3mos of <30 mL/min displayed a 5-year graft survival of 34%; 30 to 39 mL/min, 72%; 40 to 49 mL/min, 85%; and >50 mL/min, 82% (P < .001). Similarly, a recovery within 90% of expected CrCl in the first 3 months posttransplant correlated with 5-year graft survival of 81%; a recovery of 70% to 90%, with 65%; and a recovery of <70%, with 51% (P < .001). CONCLUSION: Early graft function in the first 3 months showed a significant impact on long-term graft survival after deceased donor renal transplantation.

Delayed graft function has an equally bad impact on deceased donor renal graft survival in both standard criteria donors and expanded criteria donors.

INTRODUCTION: The use of expanded criteria donors (ECDs) is still limited because of inferior graft survival compared to standard criteria donors (SCDs). We assessed the impact of immediate graft function (IGF) on renal graft survival among recipients of SCD and ECD grafts to determine whether these kidneys performed equally well under "ideal" conditions favoring IGF. METHODS: We included all cadaveric renal transplants performed from 1990 to 2002 (n = 335). Delayed graft function (DGF) was defined as the need for dialysis in the first 7 days posttransplant. Slow graft function (SGF) and IGF were defined as a serum creatinine fall by <20% versus >20% in the first 24 hours posttransplant, respectively. Non-death censored actual graft survivals are reported herein. RESULTS: Seventy-two of the 335 subjects (21.5%) received organs from ECDs and displayed IGF in 54.7%, SGF 16.2%, and DGF 29.1%. Among SCDs, the SGF and DGF rates were 15.3% and 23.4%, respectively. In ECD, the SGF and DGF rates were 19.4% and 50% (P < .02). Actual graft survivals at 1 and 5 years was 86.3% and 70.4%, respectively. Patients with IGF had higher actual graft survival at 5 years compared to SGF and DGF (83.5% vs 74.1% vs 45.4%). DGF had an equally bad impact on actual 5-year graft survival in SCDs and ECDs (42.6% vs 50%). CONCLUSION: DGF has a strong detrimental impact on 5-year graft survival. There is a higher rate of DGF in ECD versus SCD kidneys. The detrimental impact on 5-year actual graft survival is equal in SCD and ECD kidneys. Minimizing DGF should be our goal.

The clinical impact of an early decline in kidney function in patients following heart transplantation.

Renal dysfunction is a well-known complication following heart transplantation. We examined an early decline in kidney function as a predictor of progression to end-stage renal disease and mortality in heart transplant recipients. We performed a retrospective cohort study of 233 patients who received a heart transplant between July 1985 and July 2004, and who survived >1 month. The decline in estimated creatinine clearance (CrCl) was used to predict the outcomes of need for chronic dialysis or mortality >1-year posttransplant. The earliest time to chronic dialysis was 484 days. A 30% decline in CrCl between 1 month and 12 months predicted the need for chronic dialysis (p = 0.01), all-cause mortality (p < 0.0001) and time to first CrCl 1-year posttransplant (p = 0.02). A 30% decline in CrCl between 1 month and 3 months also independently predicted the need for chronic dialysis (p = 0.04) and time to first CrCl 1-year posttransplant (p = 0.01). In conclusion, an early drop in CrCl within the first year is a strong predictor of chronic dialysis and death >1-year postheart transplantation. Future studies should focus on kidney function preservation in those identified at high risk for progression to end-stage kidney disease and mortality.

The outcome of heart transplant recipients following the development of end-stage renal disease: analysis of the Canadian Organ Replacement Register (CORR).

End-stage renal disease is a significant complication of heart transplantation (HTx), but our understanding of dialysis outcomes in HTx recipients remains limited. We performed a retrospective analysis looking at dialysis mortality in HTx recipients as compared to a matched dialysis cohort. We also examined outcomes with respect to kidney transplantation (KTx) in these cohorts. 2709 incident HTx recipients were captured from the Canadian Organ Replacement Register between 1981 and 2002. The incidence of dialysis after HTx was 3.9% (n = 105) and carried a greater crude mortality compared to HTx recipients not requiring dialysis (56.2% vs. 35.9%, p < 0.001). Compared to the matched dialysis cohort, survival of HTx patients on dialysis was also significantly worse (19% vs. 40%, p = 0.003). In those receiving a KTx, survival did not differ between the two cohorts; however, in those that did not receive a KTx the survival was significantly lower in the dialysis post-HTx group compared to the matched dialysis cohort (15.7% vs. 35.2%, p < 0.025). Our analysis suggests mortality on dialysis following HTx is greater than would be expected from a similar dialysis population, and KTx may abrogate some of this increased risk. Attention should be placed on preventing chronic kidney disease progression following HTx.

The impact of thymoglobulin on renal function and calcineurin inhibitor initiation in recipients of orthotopic liver transplant: a retrospective analysis of 298 consecutive patients.

BACKGROUND: Renal dysfunction remains the Achilles' heel of calcineurin inhibitor (CI)use. The purpose of this study was to assess our institutional, renal-sparing strategy using thymoglobulin (TMG) in recipients of orthotopic liver transplants. METHODS: We performed a retrospective analysis of data from 298 adult recipients who were transplanted between 1991 and 2002. The patients were divided into two groups: those induced with TMG (group 1) and those that were not treated with this agent (group 2). A subgroup analysis was performed of patients with baseline serum creatinine values above 1.5 mg/dL (group 1A received TMG; group 2A did not). All patients received tacrolimus or cyclosporine (CyA) maintenance immunosuppression. RESULTS: Indications and demographics were similar between the two groups. Although there was no difference in patient and graft survivals, there was a statistically significant benefit in the rejection-free graft survival at 1 year for group 1 (51% vs 39%; P =.02). Furthermore, serum creatinine at 6 months was lower for group 1, despite a similar baseline creatinine. Subgroup analysis for patients with baseline abnormal serum creatinines showed that group 1A displayed an improved rejection-free graft survival at 1 month but not at 1 year. CONCLUSIONS: Thymoglobulin induction therapy may allow a delay in the initiation of CI therapy without compromising patient and graft survival, while preventing early rejection, even among patients with baseline renal dysfunction.

History of C2 monitoring in heart and liver transplant patients treated with cyclosporine microemulsion.

Therapeutic drug monitoring of CsA has evolved since the introduction of CsA microemulsion. The purpose of the present review is to summarize the history of CsA concentration 2 hours postdose (C2) monitoring in heart and liver transplantation. C2 has been shown to be the best single time point that correlates with the area-under-the-curve, with a correlation coefficient (r2) ranging between .83 and.93. C2 monitoring (300 to 600 ng/mL) has resulted in a significant clinical benefit in long-term heart and liver transplant patients compared to trough level (C0) monitoring. Moreover, a C2 range of 300 to 600 ng/mL resulted in a similar calcineurin inhibition compared to a C2 range of 700 to 1000 ng/mL or a C0 range of 100 to 200 ng/mL while being less injurious to renal function. In de novo liver transplant patients not receiving induction therapy, the achievement of a target C2 of 850 to 1400 ng/mL by postoperative day 3 has resulted in a low acute rejection rate. Furthermore, C2 monitoring has been associated with a lower rejection rate in hepatitis C virus (HCV)-negative patients and with an overall lesser severity of acute rejection compared to C0 monitoring. In de novo heart transplant patients who receive antithymocyte globulin induction, a lower C2 range may be sufficient to prevent rejection and renal dysfunction. Future studies should help to fine-tune the optimal C2 range in heart or liver transplant patients receiving induction therapy and different maintenance immunosuppressive combinations.

Do biliary endoprostheses decrease biliary complications after liver transplantation?

AIM: Most technical complications after orthotopic liver transplantation (OLT) are related to the biliary tree. This report reviews the role of routine intraoperative placement of stents to reduce biliary complications. METHODS: We retrospectively analyzed 396 consecutive OLTs. We reviewed rates of biliary complications after hepaticojejunostomy (HJA) as well as following choledochocholedochostomy (CCA) groups: "experimental" group (routine intraoperative biliary stenting, last 10 months), "recent" control group (nonstented, previous 10 months), "historical" control group (prior to that period of time). RESULTS: All groups were matched for donor/recipient characteristics and for graft cold/warm ischemia time. The overall prevalence of biliary complications was 30.7% after CCA versus 35% after HJA. In the experimental group 21 patients had a 4.8% biliary complication rate compared to the recent control and historical groups, where biliary complication rates were 30% and 32.6%, respectively (P <.05). CONCLUSIONS: The intraoperative use of biliary stents is feasible and appears to decrease the rate of biliary complications. These results support the need for a prospective randomized trial.

Pseudoaneurysm of the superior mesenteric artery after pancreas transplantation treated by endovascular stenting.

Pseudoaneurysm after pancreas transplantation can have serious consequences, including rupture, hemorrhage, and graft loss. We describe a 38-year-old patient who presented with a pseudoaneurysm of the donor superior mesenteric artery 1 month after pancreas transplantation. Selective arteriography was performed and the lesion was repaired with endovascular placement of a 28-mm covered stent. Laparotomy was avoided. The pancreatic graft was continuing to function well 9 months later. As far as we know, this minimally invasive approach was not previously reported. According to published series, pseudoaneurysms often occur secondary to infection and require operative intervention necessitating graft pancreatectomy. Patients can present with serious symptoms including hypotension and shock. Therefore, it is important to detect pseudoaneurysm in a timely manner. Computed tomography and Doppler ultrasound are important diagnostic tools in this regard. We demonstrated the utility of endovascular stenting in the treatment of pseudoaneurysm after pancreas transplantation. When used in a timely manner in well selected patients, endovascular stenting can abrogate the need for operative intervention and its attendant morbidity.