S. J. Cohney

Successful ABO-incompatible kidney transplantation with antibody removal and standard immunosuppression.

ABO‐incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited by the requirement for additional immunosuppression. Here, we describe the outcomes of 37 patients undergoing ABOi kidney transplantation utilizing perioperative antibody depletion and receiving an identical tacrolimus‐based immunosuppressive regimen to contemporaneous ABO‐compatible (ABOc) recipients, with the exception that mycophenolate was commenced earlier (7–14 days pretransplant). Antibody depletion was scheduled according to baseline anti‐ABO antibody titer (tube IAT method: median 1:128, range 1:8 to 1:4096). Patient and graft survival for the 37 ABOi recipients was 100% after a median 26 months (interquartile range [IQR] 18–32). Eight rejection episodes (two antibody‐mediated and six cellular) in ABOi recipients were successfully treated with biopsy‐proven resolution. Latest median eGFR is 50 mL/min × 1.73 m2 (IQR 40–64) for ABOi patients and 54 mL/min × 1.73 m2 (IQR 44–66) in the ABOc patients (p = 0.25). We conclude that ABOi transplantation can be performed successfully with perioperative antibody removal and conventional immunosuppression. This suggests that access to ABOi transplantation can include a broader range of end‐stage kidney disease patients.

Down-regulation of Gal alpha(1,3)Gal expression by alpha1,2-fucosyltransferase: further characterization of alpha1,2-fucosyltransferase transgenic mice.

BACKGROUND In pig-to-primate transplantation, antibody-mediated hyperacute rejection is the consequence of binding of natural antibodies to Gal alpha(1,3)Gal on pig endothelium. The elimination of the Gal alpha(1,3)Gal antigen from pig cells should prevent hyperacute rejection. Using in vitro techniques, we have previously reported that using the alpha1,2-fucosyltransferase gene induces the preferential expression of H substance with a concomitant reduction in the expression of Gal alpha(1,3)Gal. The aim of the present study was to examine the effect of expressing the alpha1,2-fucosyltransferase gene in vivo on Gal alpha(1,3)Gal. METHODS Three alpha1,2-fucosyltransferase transgenic lines of mice were produced and characterized serologically and histologically. RESULTS Immunohistological studies showed heavy staining for H substance in liver, spleen, kidney, and heart, with a reduction in staining for Gal alpha(1,3)Gal. In addition, there was a reduction in the binding of human anti-Gal alpha(1,3)Gal antibody to lymphocytes from alpha1,2-fucosyltransferase transgenic mice and a substantial decrease in complement-mediated cytolysis of alpha1,2-fucosyltransferase transgenic lymphocytes when compared with that obtained with normal mice. CONCLUSIONS The findings have important implications, in that alpha1,2-fucosyltransferase transgenic pigs could be produced as a source for humans. Such pigs should have a reduced expression of Gal alpha(1,3)Gal.

Impact of statin treatment on 1-year functional and histologic renal allograft outcome

Background. Statins are antilipidemic agents that exhibit a variety of cellular effects independent of their lipid-lowering action. A retrospective study was undertaken to establish the impact of statins on graft outcome in the first year posttransplantation. Methods. Data from patients with uniform immunosuppression (cyclosporine, mycophenolate mofetil, and prednisolone) who underwent transplantation at the authors’ unit from 1997 to 2002 were reviewed. Patients prescribed statins were compared with those not on a statin. Mean change in creatinine clearance (CrCl) from 3 to12 months posttransplantation was calculated. Histomorphometric analysis was used to quantify fractional interstitial area and collagen III deposition in matched preperfusion and 12-month protocol biopsy specimens. Results. Seventy-seven patients met study criteria: statin, n=44 patients; nonstatin, n=33 patients. Median time to commencing a statin was 5 weeks. At 3 months, CrCl (±SEM) was similar: 51.6±2.9 mL/min (statin) versus 51.3±1 mL/min (nonstatin). At 12 months, the mean change in CrCl was 4.1±1 mL/min (statin) compared with –2.0±1.8 mL/min (nonstatin), resulting in a difference of 6.13 mL/min at 12 months (P<0.005). Mean preperfusion fractional interstitial areas were similar (23.9±1.6%; P=not significant [NS]). On 12-month biopsy specimens, the frac-tional interstitial area had increased to 34±3.2% in the nonstatin group (P<0.005), with no change in the statin group. Interstitial collagen III deposition was similar in preperfusion biopsy specimens (10.4±1%; P=NS), but at 12 months it was significantly greater in the nonstatin group (17.6±1%; P<0.05) Conclusions. Early introduction of statins may be associated with improved 1-year graft outcome.

KHA‐CARI guideline: KHA‐CARI adaptation of the KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients

The latest Caring for Australians with Renal Impairment (CARI) guideline detailing renal transplant care, developed as a local modification of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines.

New onset diabetes after kidney transplantation in autosomal dominant polycystic kidney disease: A retrospective cohort study

Background:  New onset diabetes after transplantation (NODAT) is a common adverse outcome of organ transplantation that increases the risk of cardiovascular disease, infection and graft rejection. In kidney transplantation, apart from traditional risk factors, autosomal dominant polycystic kidney disease (ADPKD) has also been reported by several authors as a predisposing factor to the development of NODAT, but any rationale for an association between ADPKD and NODAT is unclear. We examined the cumulative incidence of NODAT in or own transplant population comparing ADPKD patients with non‐ADPKD controls.

ABOi With Conventional Immunosuppression Alone–Antiblood Group Antibody Isn't the Only Contributor to Antibody‐Mediated Rejection and/or Thrombotic Microangiopathy

We thank Dr. Focosi et al and Dr. Krishan et al for their comments regarding the recent article describing ABOincompatible renal transplantation (ABOi) without antibody removal using conventional immunosuppression alone (1,2). In the manuscript, we highlighted the role of antiblood group antibody (ABGAb) titer as themajor predictor of antibody-mediated rejection (AbMR) in ABOi. The occurrence of AbMR in only 1 of 20 low-titer patients in conjunction with the series of 10 low-titer patients from Cambridge without AbMR (3), and multiple reports of AbMR occurring primarily in patients with moderate to high baseline ABGAb strongly suggest that titer is the prime (though not sole) predictor of AbMR.

TN08 THE EARLY EXPERIENCE OF ABO‐INCOMPATIBLE RENAL TRANSPLANTATION IN AUSTRALIA

Purpose  In the presence of static cadaveric donation rates, renal transplantation relies increasingly on living donors. ABO blood group incompatibility has traditionally prevented many potential living donors from donating because risk of hyperacute rejection/antibody‐mediated rejection (AbMR) with graft loss, with or without need for concurrent splenectomy and intense immunosuppression. Pre‐ and post‐transplant antibody removal and monitoring anti‐blood group antibody levels have allowed this to become a clinical possibility. We report results on the first ten ABO incompatible kidney transplants performed in Australia at The Royal Melbourne and Melbourne Private Hospitals, without splenectomy.