Strong expression of CD55 and CD59 completely protected porcine kidneys from hyperacute rejection and allowed a detailed analysis of xenograft rejection in the absence of immunosuppression. Coagulopathy appears to be a common feature of pig-to-baboon renal transplantation and represents yet another major barrier to its clinical application.

ABO-incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited

Although it is established that the immunosuppressant cyclosporin-A (CsA) and calcium antagonists [Nifedipine (Nif) and Diltiazem (Dz)] can independently induce gingival enlargement, little has been documented on the significance of the salivary CsA levels and the combined effect of CsA and a calcium antagonist upon gingival tissues. In the present cross-sectional investigation, clinical periodontal parameters and the pharmacologic profiles of CsA, Nif, and Dz were determined for 66 renal transplant recipients. Subjects were divided into the following groups: Group (Gp) 1: CsA [n = 18]; Gp 2: CsA + Nif [n = 15]; Gp 3: CsA + Dz [n = 12] and a negative Control Gp 4: azathioprine [n = 21]. A gingival enlargement score was assessed for each patient from study models using a hyperplastic index (HI). Pharmacologic profiles included CsA whole blood and whole saliva levels as measured by fluorescence polarization immunoassay. The HI scores between Gp 1, 2 and 3 were not significantly different. However, when compared with controls (Gp 4), there was a significant difference in HI and all individual groups (Gp 1, 2, 3) (p < 0.05). Gingival hyperplasia was only weakly related to plaque and calculus but was unrelated to CsA dose (mg/kg/day), duration of CsA therapy (months), CsA blood or saliva levels (ng/ml), or the concurrent administration of a Nif or Dz. Gingival enlargement was found to occur in 49% of subjects who were either on CsA or CsA and a calcium antagonist. It is concluded that CsA alone or in combination with a calcium antagonist caused a significant increase in gingival enlargement compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed rejection of pig kidney xenografts by primates is associated with vascular injury that may be accompanied by a form of consumptive coagulopathy in recipients. Using a life-supporting pig-to-baboon renal xenotransplantation model, we have tested the hypothesis that treatment with recombinant human antithrombin III would prevent or at least delay the onset of rejection and coagulopathy. Non-immunosuppressed baboons were transplanted with transgenic pig kidneys expressing the human complement regulators CD55 and CD59. Recipients were treated with an intravenous infusion of antithrombin III eight hourly (250 units per kg body weight), with or without low molecular weight heparin. Antithrombin-treated recipients had preservation of normal renal function for 4-5 days, which was twice as long as untreated animals, and developed neither thrombocytopenia nor significant coagulopathy during this period. Thus, recombinant antithrombin III may be a useful therapeutic agent to ameliorate both early graft damage and the development of systemic coagulation disorders in pig-to-human xenotransplantation.

Background:A new three-layered cast polyurethane vascular access graft (Thoratec@ VAG) is the most recent addition to the list of materials used in the search for the perfect prosthetic graft material for haemodialysis vascular access. Despite its use in 23 countries, a clinical assessment has not been published. Methods: An independent retrospective evaluation by questionnaire was obtained for 145 implantation procedures performed by 30 surgeons. Results: Ninety-two per cent of procedures were performed for an acute need for vascular access and 73% had prior failed vascular access surgery. Patients were hospitalized for a median of 4 days and the graft was initially used at a median of 3 days. Median follow-up was 306 days. Thoratec@ VAG had a problem-free (primary) patency of 44.9% and a functional (secondary) patency 64.5% at 1 year. Major causes of graft loss were thrombosis (17%) and infection (1 1%).Intra-operative thrombosis was the only significant risk factor for subsequent thrombosis (P = 0.013). Infection was less in patients with antibiotic prophylaxis that included vancomycin (P = 0.02). Conclusion:The ability to use the graft soon after surgery is a major advance for patients who urgently need reliable medium to long-term haemodialysis access.