Outcomes and Allograft Survival of Patients Who Underwent a Second Kidney Transplant and Were Followed Up for 10 Years.

BACKGROUND: Kidney transplantation is the treatment of choice for end-stage kidney disease, and a second transplantation becomes an opportunity for a better chance for long-term survival and quality of life. This study aimed to evaluate the outcomes and graft survival of patients transplanted a second time in comparison with single kidney transplant patients. METHODS: This retrospective observational study was conducted using a cohort of kidney transplant patients from 2008 to 2018. Fifty patients who underwent first transplant were randomly selected as group 1 (G1), and 31 patients who received a second kidney transplant as group 2 (G2). Outcomes, graft, and patient survival were assessed. RESULTS: G2 patients had higher proportions of rejection episodes and graft loss than G1. Fifteen (48.39%) patients from G2 maintained functioning grafts during follow-up, while 16 (51.61%) lost their grafts. The 10-year graft survival rate for patients with first transplant was 76.66%; it was 46.09% for retransplanted patients (P = 0.005). There was no statistically significant difference in patient survival between G1 and G2. CONCLUSIONS: Allograft survival rates of the first and second transplant with living donors had no statistically significant difference, but for deceased donors, poor graft survival was observed for the second allograft.

Clinical Outcome of Kidney Transplant Patients on the Allograft Function, Loss, Effects of HLA-DQB1-DSA+, and Graft Survival.

INTRODUCTION: Matching for HLA-DQB1 molecules and anti-DQ donor-specific antibodies (DSAs) has been less studied to allocate transplants from deceased donors in developed countries. The aim of this study was to evaluate the clinical outcome of 519 kidney transplant recipients on the allograft function, loss, and survival and with emphasis on effects of HLA-DQB1-DSA+ at minimum of 10 years' follow-up. METHODS: Five hundred nineteen kidney transplant patients were allocated into 3 groups (G) by immunologic profiles, namely, G1 (SPI-SAB HLA-DQ negative [DQ-]), G2 (SPI-SAB HLA-DQ positive DSA negative [DQ+/DSA-]), and G3 (SPI-SAB HLA-DQ DSA positive [DQ+ DSA+]), and the outcomes were reported until 10 years after transplantation. RESULTS: The proportion of rejection episodes was higher in G3 (25.0% and 26.32%, respectively) than in G1 (8.63% and 6.82%, respectively) and G2 (10.0% and 0%, respectively; P = .047 and P = .014, respectively). In G3, 3 patients lost their grafts by antibody-mediated rejection. Patients who received kidneys from deceased donors (G3) showed worse graft survival rates than those from G1 donors (P = .001). Patients from G3 had a 2.18-fold higher risk of graft loss than patients from G1 (P = .028). CONCLUSION: Allograft function was worse in G3 than in G2 or G1, and graft losses were more frequent by T-cell-mediated rejection in G1, and graft losses by antibody-mediated rejection were similar in G1 and G3 due to HLA class I (A1, 11 and B 8, 52) and HLA class II by DR7 and DQ 2, 5, 9 DSA, respectively. Allograft survival decreased in patients with HLA-DQB1 DSA. The risk of graft loss was 1.75-fold that in patients who received transplants from living donors.

An open-label randomized clinical trial to evaluate the efficacy of everolimus versus tacrolimus in triple maintenance immunosuppressive therapy for kidney transplant patients.

Tacrolimus (TAC), a calcineurin inhibitor, and everolimus (EVL), an mTOR inhibitor, have been used as immunosuppressive (ISS) drugs in post-kidney transplantation therapy. The objective of this study was to compare the efficacy of EVL vs TAC in the ISS maintenance triple therapy. Ninety-seven kidney transplant patients, who received triple maintenance therapy with TAC, mycophenolate mofetil (MMF), and methyl prednisone (PRED), were evaluated. After four months of post-kidney transplant therapy, 30 patients enrolled in a randomized controlled clinical trial, in which 16 patients received TAC+MMF+PRED (cohort 1), and 14 patients switched to EVL+MMF+PRED (cohort 2). The patients were followed-up for 36 months. Two patients from cohort 1 lost their grafts after one year due to non-adherence. Two patients from cohort 2 had intolerance to mTOR inhibitors and were switched back to TAC from EVL. One case (6.25%) in cohort 1 and three cases (21.43%) in cohort 2 of acute T-cell-mediated rejection was observed. Antibody-mediated acute rejection (ABMAR) was observed in four patients (25.0%) in cohort 1, and antibody-mediated chronic rejection (ABMCR) was observed in two patients (12.50%). One patient from cohort 2 lost the graft after 15 months due to polyomavirus infection. The graft survival rate was 87.50% in cohort 1 and 92.86% in cohort 2. This clinical trial showed that the EVL+MMF+PRED triple maintenance therapy was efficacious compared with TAC during 32 months of follow-up. However, further studies are needed to confirm the efficacy of this regimen for long-term graft survival.

An open-label randomized clinical trial to evaluate the efficacy of everolimus versus tacrolimus in triple maintenance immunosuppressive therapy for kidney transplant patients

Tacrolimus (TAC), a calcineurin inhibitor, and everolimus (EVL), an mTOR inhibitor, have been used as immunosuppressive (ISS) drugs in post-kidney transplantation therapy. The objective of this study was to compare the efficacy of EVL vs TAC in the ISS maintenance triple therapy. Ninety-seven kidney transplant patients, who received triple maintenance therapy with TAC, mycophenolate mofetil (MMF), and methyl prednisone (PRED), were evaluated. After four months of post-kidney transplant therapy, 30 patients enrolled in a randomized controlled clinical trial, in which 16 patients received TAC+MMF+PRED (cohort 1), and 14 patients switched to EVL+MMF+PRED (cohort 2). The patients were followed-up for 36 months. Two patients from cohort 1 lost their grafts after one year due to non-adherence. Two patients from cohort 2 had intolerance to mTOR inhibitors and were switched back to TAC from EVL. One case (6.25%) in cohort 1 and three cases (21.43%) in cohort 2 of acute T-cell-mediated rejection was observed. Antibody-mediated acute rejection (ABMAR) was observed in four patients (25.0%) in cohort 1, and antibody-mediated chronic rejection (ABMCR) was observed in two patients (12.50%). One patient from cohort 2 lost the graft after 15 months due to polyomavirus infection. The graft survival rate was 87.50% in cohort 1 and 92.86% in cohort 2. This clinical trial showed that the EVL+MMF+PRED triple maintenance therapy was efficacious compared with TAC during 32 months of follow-up. However, further studies are needed to confirm the efficacy of this regimen for long-term graft survival.

Six novel HLA-B, -DRB1, and -DQB1 alleles identified in Brazilian individuals.

The novel HLA alleles B*40:331, B*40:343, B*42:24, DRB1*01:74, DQB1*03:243, and DQB1*03:02:20 were identified in Brazilian individuals.

Delayed Graft Function, Predictive Factors, and 7-Year Outcome of Deceased Donor Kidney Transplant Recipients With Different Immunologic Profiles.

BACKGROUND: Delayed graft function (DGF) is the major post-transplant cause of deleterious effects to the allograft and is associated with poor allograft survival. The aim of this study was to report the outcomes of 236 kidney transplant recipients with different immunologic profiles. METHODS: All patients underwent transplantation (2008-2016) with a deceased donor at the University Hospital of the Faculty of Medical Science, Belo Horizonte, Minas Gerais, Brazil. Patients were classified into 3 groups according to immunologic profiles: nonsensitized (NS), sensitized without donor-specific antibody (SDSA-), or sensitized with donor-specific antibody (SDSA+). RESULTS: DGF was observed in 128 (54.24%), including 63 (49.22%) NS, 51 (39.84%) SDSA-, and 14 (10.94%) SDSA+ patients. The development of DGF was associated with dialysis for ≥49.25 months (odds ratio [OR] 2.30), donor age ≥42.25 years (OR 1.77), donor end creatinine level >1.22 mg/dL (OR 1.94), and cold ischemia time >12 hours (OR 2.45). Of the 55 patients with rejections, 37 (15.68%) had T-cell-mediated rejection (TCMR) and 18 (7.63%) had antibody-mediated rejection (AMR). Nine patients (16.36%) exhibited graft loss, 2 (0.85%) via TCMR in the SDSA- DGF+ group and 7 (2.97%) via AMR, including 2 NS DGF-, 2 SDSA- DGF-, 1 SDSA- DGF+, and 2 SDSA+ DGF+ patients. Graft survival significantly differed between the NSDGF- and SDSA- DGF+ groups (P = .014) and between the NS DGF- and SDSA+ DGF- groups (P = .036). CONCLUSION: In the 7-year period following transplantation, TCMR was more prevalent than AMR among patients with DGF. Graft loss was less prevalent among patients with TCMR than among those with AMR.

Genetic Mechanisms Involved in the Generation of HLA Alleles in Brazilians: Description and Comparison of HLA Alleles.

BACKGROUND: The HLA genes show high levels of diversity as indicated by the number of HLA alleles. There are almost 11,000 classical HLA-A, -B, -DRB1 alleles in populations around the world, making the search for compatible donors difficult. HLA diversity is generated by different genetic mechanisms, such as point mutations, which result in single nucleotide polymorphisms, insertion and deletion, and recombination. The aim of this study was to describe genetic mechanisms involved in the generation of HLA alleles in Brazilians. METHODS: Twenty-six alleles indentified in the Brazilian bone marrow donors were include in the study. Data regarding new HLA alleles by sequence-based typing were also used to elucidate what genetics mechanism was involved in the HLA variability. The new alleles were officially named by the World Health Organization Nomenclature Committee. RESULTS: The new alleles described were HLA-DRB1*11:04:14, HLA-A*33:117, and HLA-B*41:48. The DRB1*11:04:14 allele was generated by synonymous point mutation at codon 48. The A*33:117 allele was generated by nonsynonymous nucleotide mutation leading to amino acid substitution at codon 74. The B*41:48 allele was generated by an intralocus gene conversion between the HLA alleles from groups HLA-B*13, B*35, B*53, or B*58 and an allele from the HLA-B*41 group. CONCLUSIONS: Different genetic mechanisms introduce new mutant HLA alleles into the human population requiring attentive and rigorous specialists and the use of different methodologies to identify these mutations in HLA typing routine.

Identification of the novel allele, HLA-B*14:56, in a Brazilian individual.

Novel allele, HLA-B*14:56, generated by a gene conversion event was identified in a Brazilian individual.

Two novel alleles, HLA-A*02:643N and HLA-B*53:44, identified in Brazilian individuals.

Two novel alleles, HLA-A*02:643N and HLA-B*53:44, generated by different mechanisms, were identified in Brazilian individuals.

Kidney transplantation: evaluation and clinical outcome of 237 recipients at low, medium, high, or strong immunological risk of rejection.

BACKGROUND: Donor-specific antibodies (DSAs) play a fundamental role in kidney transplantation. The identification of DSAs is an essential rejection parameter. PATIENTS AND METHODS: We evaluated a protocol in 237 patients receiving kidneys from living (LDs) and deceased donors (DDs). Recipients were classified as being at low (LR), medium (MR), high (HR), or strong (SR) risk of rejection based on Luminex panel reactive antibody (PRA)-single antigen beads (SABs). Grafts that survived for 1 year were evaluated. RESULTS: Of the 237 transplanted patients, 129 (54.43%) received a kidney from an LD and 108 (45.57%) from a DD. Of 95 LR recipients receiving kidneys from LDs, 2 patients lost the graft due to non-immunological causes. Of 34 MR recipients, 13 had rejection episodes, and 2 lost the graft by AMR and one by cellular rejection (CR). Of 108 recipients receiving a kidney from a DD, 59 (54.63%) were LR, 31 (28.70%) MR, 11 (10.19%) HR, and 7 (6.48%) SR. Twenty of all transplanted recipients lost their grafts; 4 were due to clinical causes, 4 by cellular rejection, and 12 by antibody-mediated rejection (AMR) with PRA-SAB mean fluorescent intensity of 530 to 12,591. One-year graft survival for LD transplanted LR and MR patients was 97.6% and 94.1%, respectively (P = .004). In DD recipients, the LR vs MR SD was P = .011, and for LR vs HR + SR it was P = .001. For MR vs HR+SR no SD was found (P = .323). CONCLUSION: Rejections were detected in 51 patients (21.52%). Graft failure occurred in 16 patients (6.75%). A total of 218 (91.98%) recipients maintained good kidney function after 1 year. This protocol based on fluxogram risk assessment of AMR provided fast and precise immunological evaluation of recipients and donors and stratification by immunological risk of AMR.

Enamel demineralization and bracket bond strength when etching with acid and /or Er:YAG laser.

BACKGROUND: Enamel etching for brackets is usually done with phosphoric acid. Er:YAG lasers have been recently used for this purpose with conflicting results. The effects of lasers on tooth demineralization and the effects of different combinations of laser treatments and bonding agents were evaluated in this study. METHODS: The enamel contents of fluorine, calcium oxide and phosphorus pentoxide (P(2) O(5)) were analysed using acid etching, laser treatment or both. The tensile bond strength of metallic and ceramic brackets using Transbond XT and Fuji Ortho LC were also tested, using acid etching, laser treatment or a combination of both. RESULTS: All treatments reduced the contents of fluorine, P(2)O(5) and calcium oxide, and acid reduced P(2) O(5) levels more than laser. The bond strength with laser was weaker than with acid, and stronger when combining both. When using laser, the best adhesive was the Fuji Ortho LC. The combination of laser and acid produced the best results when using Transbond XT. CONCLUSIONS: The demineralization promoted by laser was lower than the one produced with acid. Laser treatment produced lower tensile stress strength than acid, but still enough to produce clinically efficient retention. The combination of laser and acid produced the best retention results.

Detection of cheese whey in raw milk preserved with bronopol® through high performance liquid chromatography / Detecção de soro lácteo por cromatografia líquida de alta eficiência em amostras de leite cru conservadas por bronopol®

High performance liquid chromatography was used in order to detect cheese whey in samples of raw milk preserved with Bronopol®. Six samples were collected and divided in 45 aliquots of 40mL. From these, 15 were used as control and stored frozen, 15 were added with Bronopol® and stored at 7ºC, and the other 15 were added with Bronopol® and stored at 30ºC. In all groups, five levels of cheese whey addition (0, 2, 5, 10, and 20 percent) were tested. The samples were submitted to high performance liquid chromatography on the 2nd, 4th, and 8th days of storage. A completely random design was used, following the factorial scheme (5x3x3) and the results were compared through the non-parametric Kruskal-Wallis test. There was no difference among the treatments (P>0.05), which allows the conclusion that raw milk preserved with Bronopol® may be used for the determination of cheese whey addition in milk through high performance liquid chromatography.

O objetivo deste trabalho foi avaliar a viabilidade do uso de amostras de leite cru conservadas com Bronopol® na pesquisa de soro de queijo por cromatografia líquida de alta eficiência (CLAE). Seis amostras foram coletadas e subdivididas em 45 alíquotas de 40mL. Destas, 15 compuseram o grupo controle e foram armazenadas sob congelamento, 15 amostras foram adicionadas de Bronopol® e armazenadas a 7ºC e outras 15 foram adicionadas de bronopol e estocadas a 30º C. Em todos os grupos, cinco porcentagens de soro de queijo foram adicionados, 0, 2, 5, 10 e 20 por cento. As amostras foram submetidas à cromatografia líquida de alta eficiência no segundo, quarto e oitavo dias de armazenamento. Foi utilizado o delineamento inteiramente ao acaso, com os tratamentos em esquema fatorial 5x3x3 e os resultados comparados por meio do teste não paramétrico de Kruskal Wallis. Não houve diferença (P>0,05) entre os tratamentos, concluindo-se que é possível utilizar amostras de leite cru conservadas com Bronopol® para pesquisa de soro de queijo em leite por CLAE.

Mucosa-associated lymphoid tissue gastric lymphoma regression in a renal transplant patient after conversion of the immunosuppression to sirolimus: a case report.

The treatment of B-cell non-Hodgkin lymphoma, the most common posttransplant lymphoproliferative disorder, is not well defined. Herein we have reported a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with rapid, persistent, and complete remission after conversion of the immunosuppression from cyclosporine (CsA) to sirolimus (SRL). A 42-year-old woman underwent renal transplantation in 1992 with no major abnormalities until 2006 when a gastroscopy performed to investigate dyspeptic symptoms showed a mixed MALT gastric lymphoma (with low- and high-grade components) associated with the presence of Helicobacter pylori infection. Two therapeutic interventions in a 1-week interval were performed: treatment of the H. pylori infection (omeprazole, amoxicillin, and clarithromycin for 14 days) and modification of the immunosuppression by substitution of CsA and azathioprine (AZA) with SRL. Control endoscopy performed 1 month later showed persistence of H. pylori infection and absence of the gastric tumor. New endoscopies performed at 2 and 7 months after therapy confirmed the absence of neoplasia and H. pylori eradication. Currently, the patient has no complaints, displaying a creatinine value of 1.8 mg/dL and a hemoglobin of 9.4 mg/dL using SRL and ibersatan. SRL has been studied extensively as an anticancer drug, acting as a mammalian target for rapamycin (mTOR) inhibitor. Accumulating data support the role of mTOR in lymphomagenesis. In conclusion, our case of gastric MALT lymphoma in a renal transplant patient displayed a complete remission after alteration of the immunosuppressive scheme with the introduction of SRL.

Progression of the renal graft: treatment of acute rejection based on a biopsy against a presumptive diagnosis.

The aim of this study was to compare the progression of renal grafts following treatment of an acute rejection event based on the histological diagnosis of a graft biopsy compared to a presumptive (clinical and laboratory) diagnosis. A historical cohort was used to study 44 patients undergoing a living haploidentical related donor renal transplant, using a similar immunosuppressive treatment: cyclosporine, azathioprine, and prednisone. Acute rejection events were treated with methylprednisolone (250 mg for 3 to 5 days) based on a histological diagnosis (biopsy group = 14) or on a clinical and laboratory diagnosis (presumptive group = 30), which consisted of an elevation over 20% in plasma creatinine in 24 hours and renal ultrasound or scintigraphy findings. The study demonstrated no significant difference in renal function (plasma creatinine) and other outcomes 2 years following transplantation in both groups. The results show that treatment of acute rejection based on a presumptive diagnosis is not a risk factor for unfavorable outcomes following 2 years of renal transplantation monitoring.

Absence of retinoblastoma gene product in human primary oral cavity carcinomas.

Oral cavity cancer is a major health concern worldwide. Despite advances in surgery, radiotherapy and chemotherapy over the past 35 years, there has been no significant enhancement in the survival of oral cavity cancer patients. Improved survival will require identification of reliable prognostic markers that provide a rational basis for assessment of risk for progression. The altered retinoblastoma (RB) gene has been linked to the hereditary retinoblastoma. This gene is defective in several types of human malignancies. The intent of this study was to evaluate the role of the RB gene in oral cavity tumorigenesis and to explore whether or not there is a relationship between the loss of RB protein and each of several clinicopathological parameters in oral cavity carcinomas. We have analysed the expression of the RB gene in four cell lines (J82, ML1, SaOS2 and WERI-RB-1), 182 oral cavity carcinomas (75 T1 and 107 T3 and T4 lesions) and 55 normal tissues adjacent to cancer by means of an immunohistochemical method and Western immunoblotting. The expression of RB protein was then correlated with clinical outcome in the patients with primary tumours. The significantly higher rate of altered RB expression was found in advanced oral cavity tumours (40 of 107; 37%) in comparison with low grade tumours (9 of 75; 7%). In T3 and T4 tumours, RB gene expression did not correlate with presence or absence of lymph node metastasis, degree of differentiation and patient survival. However, in the T1 cohort, poorer survival rate was seen for those patients who had a tumour with loss of RB protein. This study suggests that tumours in which the RB protein was altered were more aggressive than tumours in which the RB protein was present and that loss of RB protein in oral cavity cancer may be a prognostic variable of tumour progression.