This study shows that catheter filling with a solution containing the antimicrobial taurolidine may significantly reduce the incidence of catheter-related sepsis. Taurolidine appears to be effective and safe and does not carry the risk for side effects that have been reported for other antimicrobial lock solutions containing gentamicin or high concentrations of citrate.
We conclude that patients expressing CYP3A5 need more tacrolimus to reach target concentrations and have a lower tacrolimus exposure shortly after transplantation. This delay in reaching target concentrations, however, did not result in an increased incidence of early BPAR and therefore, genotyping for CYP3A5 is unlikely to improve short-term transplantation outcome.
Mycophenolate mofetil (MMF) is an immunosuppressive drug commonly used in the context of kidney transplantation. Exposure to the active metabolite mycophenolic acid (MPA) is associated with risk of allograft rejection. MPA pharmacokinetics varies between individuals, the potential cause being the presence of genetic polymorphisms in key enzymes. We genotyped 338 kidney transplant patients for UGT1A8, UGT1A9, UGT2B7, and MRP2 polymorphisms and recorded MPA exposure and biopsy-proven acute rejections (BPARs) during a 1-year follow-up. Tacrolimus-treated patients who were UGT1A9 -275T>A and/or -2152C>T carriers displayed a 20% lower MPA area under the concentration-time curve from 0 to 12 h (AUC(0-12)) (P = 0.012). UGT1A9*3 carriers displayed a 49% higher MPA AUC(0-12) when treated with tacrolimus and a 54% higher MPA AUC(0-12) when treated with cyclosporine (P < 0.005). Cyclosporine-treated UGT1A8*2/*2 (518GG) patients had an 18% higher MPA AUC(0-12) compared with noncarriers. Carrying the UGT1A9 -275T>A and/or -2152C>T polymorphism significantly predicted acute rejection in fixed-dose (FD) MMF-treated patients receiving tacrolimus (odds ratio 13.3, 95% confidence interval 1.1-162.3; P < 0.05). UGT1A9 -275T>A and/or -2152C>T genotyping may identify patients at risk of MPA underexposure and acute rejection when receiving treatment with MMF and tacrolimus.
Chronic-active antibody-mediated rejection (c-aABMR) is defined as histological evidence of chronic endothelial injury (cg), also known as transplant glomerulopathy, and either microvascular inflammation (MVI) or positivity for C4d. Importantly, the presence of donor-specific antibodies (DSA) is currently still mandatory for the diagnosis of c-aABMR. This retrospective study of 41 c-aABMR patients investigates whether cases suspicious for c-aABMR (DSA negative, n = 24) differ from cases of c-aABMR (DSA positive, n = 17) with respect to renal histology, allograft function and long-term graft survival. All included patients had progressive loss of allograft function and were diagnosed by for cause biopsy and scored according to the Banff '15 criteria. In all DSApos cases, DSA were de novo and the majority was directed against HLA-II being mostly anti-HLA-DQ antibodies. There were no statistically significant differences in clinical characteristics, decline in allograft function and renal allograft survival in cases with or without DSAs. All cases showed chronic histomorphological damage and inflammation, irrespective of the presence of DSA. Renal histology and clinical outcome of patients suspicious for c-aABMR (DSAneg) do not significantly differ from patients with a diagnosis of c-aABMR (DSApos). We believe that our study adds to the ongoing debate regarding the need for DSAs to be present for the diagnosis of c-aABMR.
SummaryPretransplant removal of antiblood group ABO antibodies is the cornerstone of all current ABO-incompatible (ABOi) transplantation programmes. In our protocol, plasmapheresis (PP) is performed with a plasmafilter followed by immunoadsorption (IA) of anti-ABO antibodies. The bleeding complications of this technique are not known. We analysed the data of all 65 consecutive ABOi kidney transplantations between March 2006 and October 2013 and compared these with matched 130 ABO-compatible (ABOc) kidney transplantations. Cases differed from controls in the pre-operative regimen, which included IA-PP and rituximab, tacrolimus, mycophenolate mofetil, prednisone and immunoglobulines. Data on platelet count, blood loss and red blood cell (EC) transfusions during 48 h postoperatively were collected. ABOi patients received EC transfusions more frequently than controls (29% vs. 12%, P = 0.005). Intra-operative blood loss was higher (544 vs. 355 ml, P < 0.005) and they experienced more major bleeding (≥3 EC within 24 h, 15% vs. 2%, P < 0.0005). Platelet count decreased by 28% after the pre-operative IA. In a multivariate model, only the number of pre-operative IAs was associated with the number of ECs given (OR per IA 1.9, P < 0.05). ABOi kidney transplant recipients have a high postoperative bleeding risk, correlating with the number of pre-operative IA sessions performed.
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