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Background: In the treatment of refractory antibody-mediated rejection (AMR), splenectomy has been associated with surprisingly rapid recovery of renal function. The mechanism is still unclear., Methods: We review 11 recipients, who underwent rescue splenectomy (RS) as a treatment of AMR within 3 months after kidney transplantation. At transplantation, all patients had undergone desensitization for initially positive crossmatch to their prospective donors. The cellular populations of the spleen were analyzed by immunohistochemistry. For comparison, we obtained spleen specimens from eight controls who were non-transplantation patients., Results: Rejection occurred in all the patients early after transplantation (mean [SD], 7.1 [5.7] days). One graft was lost 4 weeks after kidney transplantation. A significantly higher number of plasma cells (PCs) (P=0.049) and lower number of T and B lymphocytes (P=0.02 and P=0.005, respectively) were detected in the RS group compared with the control group. By analyzing the PC variations in the RS group, significantly lower numbers of PCs were detected in the spleens of patients who received rituximab before splenectomy (P=0.0004). In contrast, a higher number of PCs were found in patients (n=3) who did not respond to splenectomy and subsequently underwent bortezomib treatment and recovered their renal function (P=0.02)., Conclusions: Splenectomy may reverse AMR by debulking PCs. Our analysis suggests that patients with a very high load of PCs may not be rescued by splenectomy alone and may need additional treatments.

To date, there have been no reports of successful ABO blood group incompatible renal transplantation in HIV patients. We describe a case of a 47-year-old African American man with end-stage renal disease secondary to HIV-induced nephropathy who underwent a live unrelated (spouse) donor ABO blood group incompatible transplant using an intravenous immunoglobulin/plasmapheresis preconditioning regimen with interleukin-2 receptor antagonist induction along with tacrolimus and mycophenolate mofetil maintenance. The postoperative course was complicated by two acute cellular rejection (Banff Ia) episodes that were successfully managed with corticosteroid boluses and the addition of corticosteroids to maintenance immunosuppression. Antibody-mediated rejection was not observed on biopsy. The patient reached a serum creatinine nadir of 2.0 mg/dL on postoperative day 20, which has now been maintained for 170 days. His current CD4 count was 410 cells/microL.

Immunosuppressive protocols for ABO-incompatible (ABOI) and positive cross-match (PCM) solid organ transplant (SOT) recipients have included the use of rituximab (RTX). Infectious complications (IC) have been reported after the use of RTX for other indications, but have not been well studied in the SOT population. We performed a retrospective review of IC occurring within six months of ABOI and PCM renal transplantation (RT) in recipients receiving RTX. Medical records were reviewed for bloodstream, lung, gastrointestinal tract, allograft, or soft tissue infection. Between July 2001 and December 2004, 34 ABOI or PCM RT were performed at University of Illinois at Chicago, 25 of which received RTX with plasmapheresis and antithymocyte globulin (ATG) (eight ABOI and 17 PCM). Among the RTX recipients, the rate of IC was 48% compared with 11% among historical controls who did not receive RTX (p = 0.107). There were 21 episodes of IC in 13 patients including skin and soft tissue infection (8), bloodstream infection (5), esophagitis (3), peritonitis (3), pneumonia (1), and colitis (1). There was no difference in the rate of rejection, graft survival or patient survival between the two groups. These data suggest that there is a trend toward an increased rate of IC with RTX therapy in ABOI and PCM RT recipients.

In the past, ABO incompatibility has been considered an absolute contraindication for living donor kidney transplantation. Over the past 25 years, advances in immunosuppressive therapy and progressively more refined desensitization protocols have allowed increasingly successful transplantations across the ABO barrier. Current results of kidney transplants from ABO-incompatible living donors are quite favorable and comparable in the long term with the outcome of ABO-compatible organs both in Japan and in the United States. The present article reviews the history, outcomes, and current issues in kidney transplantation with ABO-incompatible living donors in adult and pediatric recipients.

Antibody-mediated rejection (AMR) commonly occurs after transplantation of ABO-incompatible and sensitized renal transplant. Treatment regimens commonly include a combination of plasmapheresis (PL) and intravenous immunoglobulin (IVIG). However, some cases of AMR remain refractory to treatment. We report a case series of four patients with AMR refractory to standard therapy (ST) who resolved after splenectomy. Four living donor kidney transplant recipients were diagnosed with AMR. Two patients were ABO incompatible, one was cross-match positive and one had no obvious predisposing factors. After failure of therapy with corticosteroids, PL, IVIG, Thymoglobulin, and Rituximab (three patients) or Campath (one patient), AMR was treated with laparoscopic splenectomy. After an average of 11 days of ST, laparoscopic splenectomy was performed for rescue. The urinary output improved immediately in all patients, serum creatinine levels decreased within 48 hr, and ABO titers fell in the ABO-incompatible patient and the cross-match became negative in the two sensitized patients. Splenectomy may play a role in the treatment of AMR refractory to ST.

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.

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.

The Division of Transplantation at the University of Illinois at Chicago (UIC) was established in 1968 by Dr. Olga M. Jonasson, who performed the first living related kidney transplant in Illinois. The UIC Hospital is a typical inner city hospital serving primarily minorities and under-privileged populations with significant challenge for issues such as compliance, insurance coverage, low income, and degree of education. We analyzed the outcomes of 67 pediatric and 801 adult consecutive renal allotransplantations performed at the University of Illinois at Chicago (UIC) from January 1988-December 2002 and more recent information in relation to newly developed programs (robotic living donation, transplantation in sensitized patients, early steroid discontinuation, ethnicity tailored immunosuppression) until November 2004 (21 pediatric and 172 adults). The one-year graft survival has improved comparing the cases performed between 1988-1998 versus cases after 1998 from 82-88%, with similar patient survival. However, the overall 5-year patient and graft survival has not changed significantly in the 2 different eras and is currently 85% and 65%, respectively. With the use of minimally invasive, robotic-assisted living donor nephrectomy, the use of living donors has increased and these now represent 75% of the kidney donors at UIC. Transplantation in highly sensitized recipients has become more successful with the use of plasmapheresis resulting in 100% patient and graft survival and a 10% acute rejection rate in the first series of 20 patients. Early steroid discontinuation (steroid discontinued at day 6 after transplantation) has allowed for significant improvement of results in pediatric recipients. We have 100% one-year patient and graft survival and no acute rejections in a series of 13 children, compared with a 25% rejection rate in 13 children with steroid-containing immunosuppession. Tailored immunosuppression with early steroid discontinuation now achieves equal early results in African American as in any other ethnic group with 98-99% patient and graft survival and acute rejection rates below 10%. Of interest will be the future evolution of long-term patient and graft survival under the new immunosuppressive protocols with early steroid discontinuation achieving very low acute rejection rates and impressive one-year survival rates. There is reason for optimism that the improved early results will translate into better long-term outcomes.