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Primary nonfunction is a severe complication after kidney transplantation. Residual renal function could be a risk factor for this complication in the current era of kidney transplantation from extended criteria donors (ECD). This is a single-center case-control study. Between 2000 and 2012, 1112 patients received a kidney transplant from a deceased donor. We identified 56 cases of early graft loss (kidney that never recover renal function and/or graft thrombosis

Experimental studies have shown that rabbit antithymocyte polyclonal globulin (ATG) can expand human CD4+CD25++Foxp3+ cells (Tregs). We investigated the major biological effects of a self-manufactured rabbit polyclonal anti-rat thymoglobulin (rATG) in vitro, as well as its effects on different peripheral T-cell subsets. Moreover, we evaluated the allogeneic suppressive capacity of rATG-induced Tregs in an experimental rat renal transplant model. Our results show that rATG has the capacity to induce apoptosis in T lymphocyte lymphocytes as a primary mechanism of T-cell depletion. Our in vivo studies demonstrated a rapid but transient cellular depletion of the main T cell subsets, directly proportional to the rATG dose used, but not of the effector memory T cells, which required significantly higher rATG doses. After rATG administration, we observed a significant proliferation of Tregs in the peripheral blood of transplanted rats, leading to an increase in the Treg/T effector ratio. Importantly, rATG-induced Tregs displayed a strong donor-specific suppressive capacity when assessed in an antigen-specific allogeneic co-culture. All of these results were associated with better renal graft function in rats that received rATG. Our study shows that rATG has the biological capacity immunomodulatory to promote a regulatory alloimmune milieu during post-transplant homeostatic proliferation.

The advent of novel immunosuppressive strategies in renal transplantation, with immunomodulatory properties, might facilitate long-term allograft survival. T-cell depletion, costimulation-blockade and mTor inhibition have been shown to favour anti-donor hyporesponsiveness. Recently, the combination of rATG, belatacept (Bela) and sirolimus (SRL) has been used in kidney transplantation, showing very low incidence of acute rejection and excellent 12-month graft and patient survival. Herein, we have analysed the 1-year evolution of memory/effector and regulatory T cells and assessed the donor-specific T-cell alloimmune response in a group of these patients and compared with others treated with a calcineurin-inhibitor(CNI)-based (rATG/tacrolimus/MMF), and two other Bela-based regimens (rATG/Bela/MMF and basiliximab/Bela/MMF/steroids). During the first year after transplantation, patients receiving rATG/Bela/SRL had significantly higher percentage of Tregs upon the memory T-cell compartment and showed a potent anti-donor suppressive activity. In an in vitro naive and memory/effector T-cell co-culture, the combination of costimulation-blockade and SRL could abrogate both antigen-specific T-cell responses as efficiently as using a CNI drug. The combination of T-cell depletion, costimulation-blockade and mTor inhibition seems to be able to allow Treg survival and inhibit donor-specific alloreactive effector immune responses after kidney transplantation in humans.

We describe the development of a lymphoma in a liver allograft shortly after orthotopic liver transplantation. Aspiration and core biopsies of the nodule were persistently negative so that a diagnosis could not be made until the patient underwent retransplantation, when examination of the liver resection specimen revealed a B-cell lymphoma. Using a rapid technique based on the polymerase chain reaction, we were able to demonstrate that the tumor was of donor origin.

Platelet activating factor is involved in warm ischemic damage. We studied the effect of the PAF receptor antagonist BN 52021 in an experimental model of 60 min of renal warm ischemia in which the left kidney was flushed with Euro-Collins solution and a right nephrectomy was performed. Eighty Wistar rats were divided into a sham-operated group, two control groups, and four study groups, according to the dosage and route of BN 52021 administration. BN 52021 was used in the flush solution at concentrations of 0.1 and 0.5 mg/ml, or intravenously prior to ischemia at 5 and 10 mg/kg body weight. Creatinine clearance per 100 g body weight, fractional sodium excretion, and conventional histology were studied. Rats that received BN 52021 intravenously showed a significantly higher creatinine clearance than controls. Intravenous BN 52021 produced a higher acceleration of renal function recovery at 10 mg/kg than at 5 mg/kg body weight. Conventional histology was better in animals that received BN 52021 at 10 mg/kg body weight than in controls. Addition of BN 52021 to Euro-Collins flushing solution showed no protective effect. We conclude that intravenous BN 52021 shows a renal protective effect against warm ischemia.

Sir: We read with interest the article by J. P. Lerut et al. about liver transplantation (OLT) and portal vein anomalies [2]. This paper analyzes a very large (53 patients), but quite heterogeneous, group of patients. Preoperative portal vein thrombosis (PVT), phlebitis, and previous surgery for portal hypertension are difficult situations in OLT, and it is our opinion that the surgical management is not the same for all of them. With regard to PVT, it can be concluded from Lerut et al.’s study that blind or, more recently, eversion portal venous thrombectomy is the preferred surgical technique in 26 out of 32 cases (81 %). Mortality after this procedure was high (4/26; 15 %), and severe intraand postoperative bleeding were frequent complications (7/26; 27 %). Portal vein rethrombosis is another complication that has been frequently reported after this procedure [3,5]. Their experience with splenomesenteric confluence dissection is even worse, with 80 % mortality (4/5).

Sir: Among the vascular anomalies encountered during orthotopic liver transplantation (OLT), those involving the recipient's hepatic artery stand out because they are so difficult to solve. We describe the case of a 38-year-old male patient who underwent OLT due to posthepatitis liver cirrhosis. The patient was in Child's "B" stage with ascites and significant hemostasis impairment. The surgical technique used was the usual one, described by Starzl and Putnam [2]; arterial reconstruction was performed by anastomosis of the donor's celiac trunk to the recipient's common hepatic artery. The postoperative course was good and the patient was discharged 16 days later. The patient was readmitted 30 days after the OLT due to a cholangitis with dilatation and segmental stenosis of the intrahepatic bile ducts in the transhepatic cholangiography. Laboratory tests revealed cholestasis with increased bilirubin and alkaline phosphatase. An arteriography was performed that showed thrombosis of the common hepatic artery with the liver graft revascularizing from the superior mesenteric artery through the gastroduodenal artery. The patient's condition became progressively worse, with increased jaundice, weight loss, and denutrition. He underwent a second transplant operation 130 days after the first OLT with a diagnosis of sclerosing cholangitis secondary to hepatic ischemia, due to thrombosis of the hepatic artery. The cava preservation technique [4] was used in the operation. The vascular reconstructions were performed by end-to-end anastomosis from the donor's vena cava to the cuff of the recipient's suprahepatic veins, anastomosis of the portal vein following the usual technique, and an end-to-end anastomosis from the donor's common hepatic artery to the recipient's splenic artery, which had been previously cut and ligated at its distal end. The postoperative course was good except for positive viremia for CMV and leakage from the biliary anasto

Kidney grafts from suboptimal donors are more likely to suffer the nephrotoxic side-effects of cyclosporine than kidneys from standard donors. In an attempt to avoid the use of cyclosporine, we carried out a prospective study in low-immunological risk recipients of suboptimal kidneys, using an immunosuppressive protocol combining Thymoglobuline in induction with a bi-therapy of mycophenolate mofetil (MMF) and steroids. Patients with panel reactive antibodies (PRA)50% receiving a first renal transplant from a suboptimal donor (ageor=50, non heart beating, arterial hypertension, or acute renal failure) or a kidney at risk of delayed graft function (DGF) because of a prolonged cold ischaemia time (CIT) of 24 h or more, were eligible for this trial. Between September 1996 and December 1999, 30 patients were enrolled for the trial and treated with MMF 2 g orally, pre-operatively, and 3 g daily, post-operatively; Thymoglobuline 2 mg/kg IV pre-operatively, 1.5 mg/kg IV the next day, and for doses of 1 mg/kg IV given on alternate days; and prednisolone 0.25 mg/kg per day, reduced progressively from the end of the first month to 0.1 mg/kg per day by 3 months post-transplant. Cyclosporine was added only if rejection grade II or higher, or a reduction in MMF below 1 g daily, occurred. Ten patients (30%) suffered from DGF, and one kidney suffered primary non function. Seven patients (24%) suffered acute rejection (six were biopsy proven, 3 grade I and 3 grade II). MMF dosage was reduced in 28 patients because of adverse events, and calcineurin inhibitors were introduced in 16 patients. There were 14 episodes of opportunistic infection (cytomegalovirus (CMV 10), Herpes zoster 2, Listeria monocytogenes 1, Pseudomonas aeuruginosa 1), and 7 malignancies (skin 2, thyroid 1, lung 1, Kaposi's sarcoma 2, post-transplantation lymphoproliferative disorder 1). Mean serum creatinine was 178, 199, 213, and 218 micromol/l at 1, 2, 3 and 5 years after transplantation, respectively. Actuarial patient and graft (after censoring for death) survival was 94% and 83% after 1 year and 79% and 65% after 5 years, respectively. These results show that with the combination of MMF, Thymoglobuline and steroids the use of cyclosporine can be delayed, and in a few cases completely avoided, with good efficacy in terms of prevention of rejection and recovery of renal function. Regardless of acceptable patient and graft survival, side-effects of MMF at the doses used in this protocol were common and led to overimmunosuppression in the long-term. Starting MMF at low dose, MPA monitoring and probably CMV prophylaxis may improve the results of this regimen.