Lessons learned in pediatric small bowel and liver transplantation from living-related donors.

BACKGROUND: Children are the primary candidates for intestinal transplant with more than 70% requiring a combined liver-bowel transplant. We report our single-center experience with living donor intestinal transplantation (LDITx) and combined living donor intestinal and liver transplant (CLDILTx) in pediatric patients. PATIENTS AND METHODS: Between October 2002 and June 2006, 13 living donor intestinal grafts were transplanted in 10 recipients. In five cases CLDILTx was performed. The intestinal grafts consisted of a 150-cm segment of ileum, whereas the liver transplant was completed using standard left lateral grafts. RESULTS: No complications occurred in any donors. In CLDILTx recipients, the patient survival at 1 and 2 years was 100%, the liver graft survival 100%, and the bowel graft survival 80%; the patient who lost the initial intestinal graft was successfully retransplanted. In LDITx recipients, the patient and graft survival at 1 and 3 years were 60% and 50%, respectively. Two isolated LDITx recipients, both 6 months of age and low body weight (mean, 6 vs. 9 kg) died within 4 months posttransplant. One LDITx recipient developed chronic rejection 3.5 years after the original transplant and died after retransplant. All patients who are alive with functioning grafts are currently on full enteral feeding without need for any intravenous supplementation, except for a recipient of CLDILTx, currently on total parenteral nutrition for late fistula. CONCLUSIONS: The early outcomes of intestinal transplantation from living donors are promising, particularly for candidates in need of CLDLITx. In this subgroup, the elimination of the high mortality on the cadaver waiting list (approximately 30%) represents a substantial advantage.

Living donor kidney transplantation across positive crossmatch: the University of Illinois at Chicago experience.

BACKGROUND: To increase living donation for kidney transplantation, we investigated desensitization of recipients with positive crossmatch against a potential living donor. METHODS: Between June 2001 and March 2007, 57 consecutive sensitized candidates for kidney transplantation, with crossmatch positive potential living donors, were treated with various desensitization protocols. All patients received plasmapheresis every other day with intravenous immune globulin 100 mg/kg starting 1 week before the scheduled transplant. Postoperatively, the recipients continued to receive every other day plasmapheresis with intravenous immune globulin for the initial week. Immunosuppression therapy consisted of induction with thymoglobulin and a combination of tacrolimus, mycophenolate, and corticosteroids. RESULTS: Six patients failed to convert with pretransplant immunomodulation and were not transplanted; 51 underwent live donor kidney transplant. Mean follow-up was 23 months and 36 patients have more than 1-year follow-up. One-year patient and graft survivals were 95% and 93%, respectively. There were 25 episodes of biopsy-proven or clinically presumed rejection in 22 patients in the first year. Of the 17 biopsy-proven episodes, 12 were antibody-mediated rejection and five were acute cellular rejection. Of the patients with antibody-mediated rejection (biopsy proven or empiric), two patients (12%) lost their graft by 1 year. The median modification of diet in renal disease at 6 and 12 months was 55 mL/min (range 9-104 mL/min) and 48 mL/min (range 8-99), respectively. CONCLUSIONS: Despite increased rejection rates, graft and patient survivals indicate that desensitization of positive crossmatch patients is a reasonable alternative for a sensitized patient who could potentially wait 10 or more years for a suitable cadaveric kidney.

Living donor liver graft salvage after rupture of hepatic artery pseudoaneurysm.

Hepatic artery pseudoaneurysm (HAP) is an uncommon but life-threatening complication of liver transplantation (LTx). It is often associated with a local infection. Prompt diagnosis and intervention are necessary. We report the first occurrence of such complication in the setting of adult living donor liver transplant. A 48-year-old female with primary sclerosing cholangitis underwent living donor right lobe LTx. Her postoperative course was uneventful. A month later, she developed massive gastrointestinal bleeding, with negative endoscopy and angiography. She rebled 2 weeks later, and an HAP was shown on angiography. On exploration, she was found to have an HAP caused by bile leakage from an accessory bile duct and a dissection of the native artery, likely a result of the angiography. The liver was revascularized using a cadaveric iliac artery conduit between the donor hepatic artery and the aorta, and the hepaticojejunostomy was reconstructed. Biliary complications are the most frequent complications in living donor LTx. A clinically silent bile leak can cause an HAP, resulting in massive gastrointestinal bleeding. Surgical repair and biliary reconstruction can yield an excellent clinical result.

Early discontinuation of steroids is safe and effective in pediatric kidney transplant recipients.

In pediatric kidney transplantation, steroid induced growth retardation and cushingoid features are of particular concern. In children, gradual steroid withdrawal late after kidney transplantation increases the risk of rejection. In this pilot study, we investigated the outcome of pediatric renal transplantation with an early steroid withdrawal protocol. This is a retrospective case-control study of pediatric renal transplants with age-matched historical control. Groups were comparable in terms of HLA matching, donor type and graft ischemia time. In the steroid withdrawal group (SWG, n = 13), induction therapy included mycophenolate mofetil (MMF) and a 5-day course of steroids with Thymoglobulin in 11 and basiliximab in two other patients. In the steroid group (SG, n = 13), in addition to steroids, four patients were given basiliximab, eight were given Thymoglobulin, and one OKT3. Maintenance therapy included tacrolimus (SWG n = 11, SG n = 3) or cyclosporine (SWG n = 2, SG n = 10). Azathioprine was given to all the patients in the SG, except the last two patients of this series who were prescribed MMF. MMF was given to all in the SWG. Patient and graft survival rates were 100% in both groups. In the SWG, no acute rejection episode was detected. In the steroid group, three patients (25%) presented with an acute rejection episode. All but one patient in either group showed immediate graft function. Patients in the steroid-withdrawal group exhibited a significantly higher creatinine clearance at 6 and 12 months post-transplant (95.8 +/- 23.3 vs. 71.3 +/- 21.9, p = 0.03; and 91.3 +/- 21.6 vs. 69.6 +/- 28.6, p = 0.04). In the SWG delta BMI was significantly lower and delta height Z score was significantly higher, and we observed significantly less hyperlipidemia, body disfigurement, and need for anti-hypertensive medication. Early steroid withdrawal in pediatric renal transplant recipients is efficacious and safe and does not increase risk of rejection, preserving optimal growth and renal function, and reducing cardiovascular risk factors.

Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury.

BACKGROUND: Interventions that minimize hepatic ischemia/reperfusion injury (IRI) can expand the donor organ pool. Thymoglobulin (TG) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients. This controlled randomized trial was designated to assess the ability of TG to protect against IRI in liver transplant recipients. PATIENTS AND METHODS: Twenty-two cadaveric liver transplant recipients were randomized to receive either TG (1.5 mg/kg/dose) during the anhepatic period and QOD x2 doses or no TG. No differences in recipients' demographics were present and donor characteristics were similar in terms of age, cause of death, and cold ischemia time. Maintenance immunosupression consisted of Tacrolimus (or Cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage and 1 h after re-vascularization. Post-operative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary non-function and rate of rejection were assessed. RESULTS: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft non-function and no need for re-transplantation. The incidence of acute rejection was similar between the two groups. Patients in the TG group had significant decreases in alanine aminotransferase test at day 1 compared to the control group (p = 0.02). There were also near significant decreases of total bilirubin at day 5 and shorter length of hospitalization. Liver biopsy (at procurement, when cold, and post-reperfusion) of TG group demonstrated a trend for increased central ballooning. CONCLUSION: The TG allowed for more compromised liver grafts to be transplanted with less clinical evidence of IRI and improved function. Further studies on the degree of apoptosis in the liver biopsy post-reperfusion are underway.

Increased risk of post-transplant diabetes mellitus despite early steroid discontinuation in Hispanic kidney transplant recipients.

Early steroid discontinuation (ESD) has been associated with a lower incidence of post-transplant diabetes mellitus (PTDM). We retrospectively reviewed the incidence of PTDM in relation to racial groups in kidney transplant recipients treated with ESD. Between January 2002 and September 2003, 125 consecutive primary adult kidney transplants were performed. Group A (n = 91) had steroids discontinued on postoperative day 6 and maintenance immunosuppression of Tacrolimus and mycophenolate mofetil. Group B (n = 34), received the same immunosuppression but was maintained on steroids indefinitely. Induction consisted of thymoglobulin in African-Americans; all others received Simulect. At 1 yr, patient/graft survival, serum creatinine and rate of acute rejection were similar in both groups. The incidence of PTDM was significantly lower in group A (7%) compared with group B (26%, p = 0.0209). The incidence of PTDM in group A was limited to Hispanic patients with a family history of diabetes mellitus. African-Americans and Caucasians in group A did not experience PTDM (p = 0.005 compared with African-American in group B). Our steroid free protocol nearly eliminated the incidence of PTDM in African-Americans and Caucasians, but was still associated with significant rate of PTDM in Hispanic recipients. Alternative immunosuppression may benefit this population.

Role of CD4+ and CD8+ T cells in the rejection of concordant pancreas xenografts.

BACKGROUND: We studied the ability of CD4 and CD8 T cells to induce rejection of pancreas xenografts in a concordant combination using rat pancreas xenografts as donors and chemically induced diabetic mice as recipients. METHODS: Lewis rat (2 to 3 weeks old) pancreas xenografts were transplanted into streptozotocin (STZ)-induced diabetic mice. Lymphocyte proliferation and cytokine production were analyzed in vitro. All pancreas xenografts were assessed by functional (blood glucose) and histopathologic examinations. RESULTS: Lewis rat pancreas grafts were rejected within 10 to 13 days, with mononuclear cell infiltrate and tissue necrosis in STZ-induced diabetic mice. A predominant T cell receptor alphabeta -CD4 cell (on day 4) and T cell receptor alphabeta -CD8 cell (on day 8) infiltrate and IgM deposition were found in the pancreas xenografts after transplantation. Anti-CD4 (GK1.5), but not anti-CD8 (YTS169.4), monoclonal antibodies resulted in a prolonged survival of Lewis rat pancreas xenografts. Lewis pancreas xenografts were permanently accepted by CD4 knockout mice but not by CD8 knockout mice. The pancreas xenografts were acutely rejected with a mean survival time of 15.3 days in B cell-deficient mice (microMT/microMT). Transfer of CD4 but not CD8 spleen cells from naïve C57BL/6 mice into Rag2 mice led to acute rejection of transplanted pancreas xenografts. However, activated CD8 spleen cells elicited rejection of Lewis rat pancreas xenografts in SZT-induced diabetic mice. CONCLUSION: The current results show that CD4 T cells are necessary and sufficient for mediating the rejection of Lewis rat pancreas xenografts in STZ-induced diabetic mice. However, CD8 cells, when activated, can also induce acute rejection of concordant pancreas xenografts.