An open randomized study comparing immunosuppression therapy initiated before or after kidney transplantation in haploidentical living recipients

Background: Acute rejection is the most important risk factor for graft survival. Although many centers start immunosuppressive therapy days before the surgery in living donors, there is no systematic study concerning the possible advantages of this procedure. in this open randomized study, we compared the efficacy and safety of administration of cyclosporine (CSA; Neoral((R))) and azathioprine before renal transplantation with the administration of the same schema after transplantation, in HLA haploidentical grafts.Methods: Sixty renal transplant recipients of an HLA haploidentical allograft from living donors were randomized in two groups: (A) patients that started immunosuppression 3 d before transplantation (n = 30) and (B) those who started the drug schema on the first day after surgery (n = 30). We analyzed the incidence and severity of acute rejection, graft function and infection during the first 3 months after transplantation.Results: the group of patients who started immunosuppression before had a mean trough level of CSA (299.70 +/- 154.03 ng/mL) in the expected range for an efficacious prevention of acute rejection at the surgery day. Thirteen patients (43.3%) in each group had acute rejection during the follow up (p = 1.00). Two grafts losses (3.3%) occurred, one in each group. Both groups had similar 3-month rejection-free graft survival (56.7 and 56.3%). the incidence of infection was also statistical comparable between groups A and B (56.7 vs. 46.7, p = 0.430). Graft function was similar in patients from both groups.Conclusions: Pre-transplant administration of immunosuppression did not reduce the incidence or severity of acute rejection episodes during the first 3 months of transplantation. Immunosuppressive drugs administered before engraftment did not increase the incidence of graft dysfunction or infection.Universidade Federal de São Paulo, Escola Paulista Med, Div Nephrol, BR-04023900 São Paulo, BrazilHosp Rim & Hipertensao, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Div Nephrol, BR-04023900 São Paulo, BrazilWeb of Scienc

Decreased Cytomegalovirus infection after antilymphocyte therapy in sirolimus-treated renal transplant patients

Cytomegalovirus (CMV) infection is highly prevalent in transplant patients, especially in those submitted to a more intense immunosuppression. We monitored CMV infection in 34 patients during 60 days after antilymphocyte therapy without CMV prophylaxis. Six patients received sirolimus and 28 received no sirolimus as immunosuppression. During 60 days, of follow-up time, 24/28 (86%) patients who did not use sirolimus developed CMV infection at a mean time of 32.43 +/- 13.61 days after antilymphocyte treatment. in contrast, no patient on sirolimus had CMV infection during the same follow-up (p<0.001). During a further 4-month follow-up, six patients on sirolimus-free therapy had recurrence of CMV 46.5 +/- 18.5 days after them first episode. During this same period, one patient receiving sirolimus had one positive cell for CMV antigenemia, 169 days, after antilymphocyte therapy. in conclusion, the use of sirolimus significantly reduced the incidence of CMV infection in patients treated with antilymphocyte antibodies. (C) 2004 Elsevier B.V. All rights reserved.Universidade Federal de São Paulo, Div Nephrol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, Escola Paulista Med, Hosp Rim & Hipertensao, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, Escola Paulista Med, Hosp Rim & Hipertensao, São Paulo, BrazilWeb of Scienc

Urinary retinol binding protein is a good marker of progressive cyclosporine nephrotoxicity after heart transplant

Universidade Federal de São Paulo, Div Nephrol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, BR-04023900 São Paulo, BrazilWeb of Scienc

Modulation of peripheral blood T-lymphocytes in kidney transplant recipients treated with low dose OKT3 therapy

The immunosuppressive effect of OKT3 depends upon both T cell depletion and antigenic modulation of CD3 complex. To establish the effect of low doses of OKT3 on peripheral T lymphocytes, we analyzed 47 kidney transplant recipients receiving OKT3 for the first time. OKT3 was used as rescue therapy in 39 patients and as part of induction protocols in 8. the mean age of patients was 39 1 10 years, 30 were females and 9 were re-transplants. Half of them (51.1%) received kidney from cadaver donors. Among those receiving OKT3 as rescue therapy, 82% recovered graft function, including patients with severe BANFF-graded rejections. After the first dose of OKT3, it a pronounced T cell depletion was observed followed by an increase in CD4 and CD8 expression in CD3 negative T cells, supporting the idea that T cell modulation was present. in conclusion, low dose OKT3 was effective in treating severe allograft rejection by inducing a sustained TCR/CD3 down modulation without long-lasting T cell depletion. (C) 2003 Elsevier B.V. All rights reserved.Universidade Federal de São Paulo, Dept Med, Lab Imunol Clin & Expt, Disciplina Nefrol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Lab Imunol, Disciplina Doencas Infecciosas & Parasitarias, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Lab Imunol Clin & Expt, Disciplina Nefrol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Lab Imunol, Disciplina Doencas Infecciosas & Parasitarias, São Paulo, BrazilWeb of Scienc

Cyclooxygenase 1 and/or 2 blockade ameliorates the renal tissue damage triggered by ischemia and reperfusion injury

Ischemia-reperfusion injury (IRI) is a common event in organ transplantation. being implicated as a potential contributor for the development of chronic allograft nephropathy. There are new evidences showing a tissue inflammatory response following renal IRI Cyclooxygenases (COX) 1 and 2 can be detected in tissue submitted to IRI and may have impact on organ function outcome. We evaluated the role of COX inhibition on the renal tissue damage that follows M. Mice were submitted to 45 min of renal pedicle ligature and allowed to reperfuse for 24, 48, 72 and 120 h. Blood and kidney samples were collected at reperfusion times. mRNA was extracted from the kidney samples to amplify, COX-1: COX-2 and beta-actin genes. Animals were pretreated with indomethacin or rofecoxib before the surgery. Indomethacin treatment induced a better renal function (serum urea) when compared to control animals at 24, 48 and 72 h (219 +/- 54.5 vs. 338 +/- 51 mg/dl: 106 +/- 51 vs. 326 +/- 86 mg/dl; 94 +/- 14 vs. 138 +/- 38 mg/dl, respectively). Surprisingly, rofecoxib use was associated with even better renal improvement following IR. Animals treated with the later drug showed lower urea values at 24 h post reperfusion compared to indomethacin-treated animals (128 +/- 33 vs. 219 +/- 54.5 mg/dl, P < 0.05). Blockade of COX-1 and -2 resulted in a decrease of tubular necrosis. mRNA COX-2 was up-regulated post IRI and considerable inhibited after indomethacin or rofecoxib treatment. Our data show COX-1/-2 participates in the inflammatory tissue response to IR injury and its inhibition is associated with an improvement in renal function. (C) 2004 Elsevier B.V. All rights reserved.Universidade Federal de São Paulo, Clin & Expt Immunol Lab, Dept Med, Disciplina Nefrol,Hosp Rim & Hipertensao, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Clin & Expt Immunol Lab, Dept Med, Disciplina Nefrol,Hosp Rim & Hipertensao, BR-04023900 São Paulo, BrazilWeb of Scienc

The role of B cells in COVID-19 infection and vaccination

B cells secrete antibodies and mediate the humoral immune response, making them extremely important in protective immunity against SARS-CoV-2, which caused the coronavirus disease 2019 (COVID-19) pandemic. In this review, we summarize the positive function and pathological response of B cells in SARS-CoV-2 infection and re-infection. Then, we structure the immunity responses that B cells mediated in peripheral tissues. Furthermore, we discuss the role of B cells during vaccination including the effectiveness of antibodies and memory B cells, viral evolution mechanisms, and future vaccine development. This review might help medical workers and researchers to have a better understanding of the interaction between B cells and SARS-CoV-2 and broaden their vision for future investigations