Navegando por Palavras-chave "renal transplantation"

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    Association between cytokine gene polymorphisms and outcomes in renal transplantation: a meta-analysis of individual patient data
    (Oxford Univ Press, 2008-09-01) Thakkinstian, Ammarin; Dmitrienko, Svetlana; Gerbase-DeLima, Maria [UNIFESP]; McDaniel, D. Olga; Inigo, Pablo; Chow, Kai Ming; McEvoy, Mark; Ingsathit, Atiporn; Trevillian, Paul; Barber, William Henry; Attia, John; Mahidol Univ; Univ Newcastle; Univ British Columbia; Universidade Federal de São Paulo (UNIFESP); Univ Mississippi; Hosp Clin Barcelona; Chinese Univ Hong Kong; John Hunter Hosp
    Background. Cytokine gene polymorphisms have been associated with poor outcomes after renal transplantation such as chronic allograft nephropathy (CAN), graft rejection (GR) and graft failure (GF), but the effects of these polymorphisms are still controversial. We therefore conducted a systematic review, with individual patient data (IPD) where possible, to determine the association between cytokine polymorphisms (TGF-beta 1, TNF-alpha and IL-10) and outcomes after renal transplantation.Methods. Five investigators were willing to participate and provided IPD. the outcomes of interest were GF, GR and CAN. Subjects with at least one of these were classified as having poor outcomes. Heterogeneity of gene effects was assessed. Multiple logistic regression was applied to assess gene effects, adjusting for clinical variables such as HLA matching and age.Results. One-thousand and eighty-seven subjects were included in the IPD meta-analysis. Pooled results showed no evidence of heterogeneity and indicated that the strongest variables determining poor outcomes are HLA mismatching (OR = 1.6-1.8 for >= 3 HLA-A, -B, -DR mismatches compared with those with < 3 mismatches) and age (OR = 1.2-1.4 for age 45 years or more). Incremental information on risk of a poor outcome is provided by the TGF-beta 1c10 polymorphism (OR = 1.5, P = 0.034, 95% CI: 1.0-2.2 for TC genotype compared to TT genotype). Haplotypes of TGF-beta 1 at c 10 and c25 were inferred and the C-C haplotype was a marker of a poor outcome (OR = 1.3, P = 0.177, 95% CI: 1.0-2.3). Three polymorphisms of the IL-10 gene at -1082, -819, -592 are in strong linkage disequilibrium with each other (correlation coefficients: 0.6-1) and inferred haplotypes between these three loci show some association, with ACC increasing the risk of poor events compared to GCC (OR = 1.3, P = 0.044, 95% CI: 0.9-1.6).Conclusion. Pooled results to date suggest possible association between both the TGF-beta 1 c10 polymorphism and a 3-SNP-haplotype of IL-10 and poor outcomes in renal transplantation, but this needs to be confirmed in larger studies.
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    Caracterização da resposta imune tecidual em pacientes pós-transplante renal com infecção fúngica causada pelo complexo de espécies cryptococcus neoformans / cryptococcus gattii
    (Universidade Federal de São Paulo (UNIFESP), 2014-09-22) Solda, Marcel Vieira [UNIFESP]; Colombo, Arnaldo Lopes Colombo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Yeasts of the Cryptococcus neoformans / C. gattii species complex are an important cause of infection in humans and may cause symptoms of pneumonia and meningoencephalitis. Cryptococcosis is the second major systemic mycosis related to kidney transplantation, which is the most likely group of risk for developing cryptococcosis among solid organ transplant recipients. Aims: The objectives of this work were: a) to identify Cryptococcus spp. isolated from renal transplanted recipients with cryptococcosis, analyzing their intraspecific diversity; b) to characterize the pattern of granulomatous inflammatory response to the fungus in different clinical forms of cryptococcosis; c) to evaluate the in situ profile of T regulatory response in different clinical presentations. Methodology: The casuistic was selected at the Hospital São Paulo (HSP) and the Hospital do Rim e Hipertensão (HR) composed by 13 patients treated in these hospitals, who developed cryptococcal infection between the period of 2005 to 2012. The isolates of C. neoformans / C. gattii complex collected from these patients were identified by biochemical methods and by the Intergenic Spacer 1 (IGS1) ribosomal DNA sequencing, which was also used to assess the haplotype diversity. Paraffin tissue sections from biopsies of these same patients were used for histopathology and immunohistochemistry (IHC). The IHC analysis included the evaluation of cellular markers CD4 and Foxp3, and the cytokines IL-10 and TGF-β. Results: All clinical isolates were identified as C. neoformans var. grubii. The intraspecific analysis of the IGS1 region showed the occurrence of five genotypes, indicating some variability in this population. Histological and immunohistochemical analysis identified three different patterns of granulomas: a) compact, observed in skin biopsies exhibiting high numbers of Treg cells; b) loose, more frequent in lung biopsies and associated with low numbers of Treg cells; c) mixed, observed in lung and skin samples presenting characteristics of the two patterns of granuloma and high count of Treg cells. Conclusions: We conclude that the phenotypic and molecular methods provided accurate identification of the isolates, and intraspecific diversity within the IGS1 region suggests that this genetic target may be used for molecular epidemiology studies. Histopathologic analysis identified three different patterns of granulomatous response which reflect the differences in the efficiency of fungal containment and the extension of the lesion: a) compact epithelioid granulomas; b) loose macrophagic granulomas; c) mixed granulomas. The heterogeneity of tissue responses found in this group of patients may be associated with the immune status of the host, the different stages of infection, as well as the immunosuppressive therapy and antifungal treatment used. The analysis of markers of T regulatory response showed a predominance of this cell population in compact and mixed epithelioid granulomas. This study suggests that Treg cells may have a protective role in cryptococcosis, although more studies are needed to confirm this hypothesis.
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    Clinical impact of an angiotensin I-converting enzyme insertion/deletion and kinin B2 receptor +9/-9 polymorphisms in the prognosis of renal transplantation
    (Walter de Gruyter & Co, 2013-03-01) Amorim, Carlos E. N. [UNIFESP]; Nogueira, Eliana [UNIFESP]; Almeida, Sandro S. [UNIFESP]; Gomes, Pedro P. G. [UNIFESP]; Bacurau, Reury Frank Pereira; Suzete Ozaki, K. [UNIFESP]; Cenedeze, Marcos A. [UNIFESP]; Pacheco-Silva, Alvaro [UNIFESP]; Câmara, Niels Olsen Saraiva [UNIFESP]; Araujo, Ronaldo C. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Hosp Israelita Albert Einstein
    There is a consensus in the scientific literature that supports the importance of the kallikrein kinin and renin angiotensin systems in renal physiology, but few studies have investigated their importance after renal transplantation. the aim of this study was to investigate the clinical effects of the insertion/deletion polymorphism in the angiotensin I-converting enzyme (ACE) gene and the +9/-9 polymorphism in the kinin B2 receptor (B2R) gene in kidney-transplanted patients (n=215 ACE, n=203 B2R) compared with 443 healthy individuals. Demographic results showed that there is a higher frequency of the D allele (high plasma ACE activity) and +9 allele (lower B2R expression) in transplant patients compared with control individuals. We also observed a higher frequency of these alleles in patients who had an elevated level of plasma creatinine. At day 7 post-transplantation, we found a higher prevalence of individuals with the DD genotype with elevated plasma creatinine level. Furthermore, individuals with the DD genotype had a higher chronic allograft dysfunction and graft loss compared with the II patient genotype, which showed no loss of graft. Taken together, our data suggest that the DD genotype is an indicator of an unfavorable prognosis following renal transplantation and could be related to kinin modulation.
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    Decreased Cytomegalovirus infection after antilymphocyte therapy in sirolimus-treated renal transplant patients
    (Elsevier B.V., 2005-01-01) Ozaki, K. S.; Camara, NOS; Galante, N. Z.; Camargo, LFA; Pacheco-Silva, A.; Universidade Federal de São Paulo (UNIFESP)
    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.
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    Early presence of calcium oxalate deposition in kidney graft biopsies is associated with poor long-term graft survival
    (Blackwell Munksgaard, 2005-02-01) Pinheiro, Helady Sanders; Camara, Niels Olsen Saraiva [UNIFESP]; Osaki, Kikumi Suzete [UNIFESP]; Moura, Luiz Antonio Ribeiro de [UNIFESP]; Pacheco-Silva, Alvaro [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fed Univ Juiz de Fora
    Accumulated oxalate will be excreted after renal transplantation, creating an increased risk of tubular precipitation, especially in the presence of allograft dysfunction. We evaluated calcium oxalate (CaOx) deposition in renal allograft biopsies with early dysfunction, its association with acute tubular necrosis (ATN) and graft survival. We studied 97 renal transplant patients, submitted to a graft biopsy within 3 months post-transplant, and reanalyzed them after 10 years. We analyzed renal tissue under polarized light and quantified CaOx deposits. CaOx deposits were detected in 52.6% of the patients; 26.8% were of mild and 25.8% of moderate intensity. the deposits were more frequent in biopsies performed within 3 weeks post-transplant (82.4 vs. 63.0%, p < 0.05) and in allografts with more severe renal dysfunction (creatinine 5.6 mg/dL vs. 3.4 mg/dL, p < 0.001). ATN incidence was also higher in patients with CaOx deposits (47% vs. 24%, p < 0.001). Twelve-year graft survival was strikingly worse in patients with CaOx deposits compared to those free of deposits (49.7 vs. 74.1%, p = 0.013). Our study shows a high incidence of CaOx deposits in kidney allografts with early dysfunction, implying an additional risk for acute tubular injury, with a negative impact on graft survival.
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    Eficácia, tolerabilidade e segurança do uso do sirolimo após o transplante renal
    (Sociedade Brasileira de Nefrologia, 2009-12-01) Oliveira, Nagilla Ione de [UNIFESP]; Harada, Kelly Miyuki [UNIFESP]; Spinelli, Glaucio Amaral [UNIFESP]; Park, Sung In [UNIFESP]; Sampaio, Edison Luiz Mandia [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]; Tedesco-Silva Junior, Hélio [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    INTRODUCTION: Sirolimus (SRL) is an immunosuppressive drug with confirmed efficacy and safety profile in the prophylaxis of acute rejection after renal transplantation. OBJECTIVES: To assess the efficacy, safety, and tolerability of SRL and prednisone in combination with cyclosporine (CSA) or tacrolimus (TAC) after renal transplantation. METHODS: Retrospective study of 332 renal transplant recipients from 1999 to 2006. Primary outcome included treatment failure, defined as the cumulative incidence of biopsy-proven acute rejection, graft loss, death, or SRL discontinuation. RESULTS: Living donors were the primary source of kidneys (92%). Regarding the recipients, mean age was 37 years, 65% were males, 46% were white, and the prevalence of diabetes was 6%. Sirolimus was combined with CSA and TAC in 70.8% and 29.2% of patients, respectively. Treatment failure rates at the first and fifth year of transplantation were 22.2% and 47.8%, respectively, without difference between the groups receiving CSA and TAC. At five years, the survival rates were as follows: patient's, 92.8%; graft's, 86.1%; deathcensored graft's, 92.7%; and free from biopsy-proven acute rejection, 82.2%. Treatment with SRL was discontinued in 27.1% of the patients, due to adverse effects (22.9%) and inefficacy (3.3%). The main reasons for SRL discontinuation were as follows: dyslipidemia (6%); graft dysfunction (5.2%); proteinuria (4.5%); infection (1.5%); delayed wound healing (1.2%); and anemia (0.9%). CONCLUSION: In this cohort of patients, SRL efficacy and safety were similar when combined with either CSA or TAC. Oral tolerability was adequate, considering the relatively low SRL discontinuation rate.
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    Fatores de riso para infecção e colonização por kpc em transplantados renais
    (Universidade Federal de São Paulo (UNIFESP), 2013-11-27) Taminato, Monica [UNIFESP]; Enfermagem; https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=558774
    Several risk factors are present with infectious complications after renal transplantation. Objective: Verifying if the type of donor is a risk factor for infection in renal transplant patients. Method: Systematic review of the literature with meta-analysis and search on the following databases: Medline, Lilacs, Embase, Cochrane, Web of Science, SciELO and CINAHL. A total of 198 articles were selected and four observational studies with reports of infections among patients distinguishing the donor type were included. Results: It was shown by meta-analysis that in patients who receive a deceased donor transplant, the risk factor for the outcome of infection was 2.65 higher than in those receiving a living donor transplant. Conclusion: The study showed that patients who receive kidneys from a deceased donor are at higher risk for developing infections and the emerging need for establishing and enforcing protocols since the proper management of the ischemia time until the prevention and control of infection in this population.
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    FTY720 and everolimus in de novo renal transplant patients at risk for delayed graft function: results of an exploratory one-yr multicenter study
    (Wiley-Blackwell, 2009-09-01) Tedesco-Silva, H. [UNIFESP]; Lorber, M. I.; Foster, C. E.; Sollinger, H. W.; Mendez, R.; Carvalho, D. B.; Shapiro, R.; Rajagopalan, P. R.; Mayer, H.; Slade, J.; Kahan, B. D.; FTY720A2202 Clinical Study Grp; Universidade Federal de São Paulo (UNIFESP); Yale Univ; UCI Med Ctr; Univ Wisconsin; Natl Inst Transplantat; Hosp Geral Bonsucesso; Univ Pittsburgh; Med Univ S Carolina; Novartis Pharma AG; Novartis Pharmaceut; Univ Texas Med Sch
    This exploratory, multicenter, open-label study evaluated the efficacy and safety of FTY720, as a part of an immunosuppressive regimen, in combination with everolimus and steroids in de novo renal transplant recipients at increased risk of delayed graft function (DGF). Patients received FTY720 (5 mg) and everolimus (4 mg) 2-12 h pre-transplantation, followed by 2.5 mg/d FTY720 and concentration-controlled everolimus (4-8 ng/mL) post-transplant for 12 months. Induction therapy was prohibited. After enrollment of 56 of the planned 200 patients between 2000 and 2002, the recruitment was terminated. the primary endpoint, rate of graft loss, or death at three months was 15.4% and the biopsy-confirmed acute rejection was 42.3%. Death or graft loss at 12 months in the DGF and non-DGF arms was 36.0% and 25.9%, respectively. the mean estimated creatinine clearance at three months was 63 and 55 mL/min in the non-DGF and DGF groups, respectively, while at 12 months it was 56 mL/min in both the groups. Although there was no comparator arm, the results from this exploratory study (compared with data from other phases II and III trials) indicated no apparent benefits of FTY720-based regimens for prevention of acute rejection and preservation of renal function in renal transplant recipients at high risk of DGF.
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    FTY720 versus mycophenolate mofetil in de novo renal transplantation: Six-month results of a double-blind study
    (Lippincott Williams & Wilkins, 2007-10-15) Tedesco-Silva, Helio; Szakaly, Peter; Shoker, Ahmed; Sommerer, Claudia; Yoshimura, Norio; Schena, Francesco Paolo; Cremer, Malika; Hmissi, Abdel; Mayer, Hartmut; Lang, Philippe; FTY720 2218 Clinical Study Grp; Universidade Federal de São Paulo (UNIFESP); Med Univ Pecs; Royal Univ Hosp; Univ Heidelberg; Kyoto Prefectural Univ Med; Univ Bari; Novartis Pharma AG; Univ Paris 07
    Background. FTY720 is a novel immunomodulator that was developed to produce optimal graft protection with improved safety and tolerability. Phase II studies have demonstrated the efficacy of FTY720 up to the doses of 2.5 mg with full-dose cyclosporine (FDC).Methods. This multicenter, double-blind, Phase IIb, randomized study evaluated the safety and efficacy of 5 mg FTY720 (n=87; Group 1) vs. 2.5 mg FTY720 (n=90; Group 2) vs. mycophenolate mofetil (MMF; n=94; Group 3) in de novo renal transplant patients receiving FDC and prednisone.Results. the primary efficacy endpoint was the occurrence of treated biopsy-proven acute rejection, graft loss, death, or premature study discontinuation (composite endpoint) within 6 months. the primary endpoint was superior in Group 1 (24%) and statistically noninferior in Group 2 compared to Group 3 (24.1% vs. 29.2% vs. 39.4%; P=0.025 and 0.0039, respectively). FTY720 plus FDC was generally well tolerated, with a similar incidence of adverse events across all groups. FTY720 was associated with higher incidence of bradycardia (Group 1: 26.4%, P=0.0002 and Group 2: 15.6%, P=0.046, vs. Group 3: 6.4%), respiratory disorders (Group 1: 40.2%, not significant [P=NS] and Group 2: 34.4%, P= NS vs. Group 3: 28.7%). One macular edema occurred in Group 2. Lower creatinine clearances were observed with FTY720 versus MMF (Group 1: 52.4 ml/min, P=NS and Group 2:51.7 ml/min, P=0.039 vs. Group 3:62.5 ml/min).Conclusions. Although FTY720 with FDC provided adequate protection from acute rejection the safety profile was less favorable for adverse events than current standard immunosuppression in de novo renal transplant patients.
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    Glomeruloesclerose segmentar e focal após-transplante renal: evolução clínica e fatores de progressão
    (Universidade Federal de São Paulo (UNIFESP), 2016-12-31) Mata, Gustavo Ferreira da [UNIFESP]; Kirsztajn, Gianna Mastroianni Kirsztajn [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Background: In spite of advances in dialysis therapies, renal transplantation is the best therapy for the treatment of end stage renal disease (ESRD). However, graft survival depends on varied factors: graft age, cold ischemia time, occurrence of rejections, adherence to treatment, immunosuppressive drugs, compatibility, donor type, recipient disease, others. Among glomerular diseases that progress to ESRD, focal segmental glomerulosclerosis (FSGS) occupies a prominent position due to its prevalence and its high recurrence after renal transplantation. After transplantation, the disease can recur in 15-52% of cases and, if left untreated, leads to early graft loss in more than 50% of cases. Objective: To perform a descriptive analysis of a cohort of patients with post-transplant FSGS in terms of recipient and donor demographic characteristics, clinical course, response to treatment and progression of glomerular disease to "graft loss". Material and Methods: This is a retrospective cohort study, including adolescent and adult patients, submitted to renal transplantation with live and deceased donors between January 1999 and September 2014 in the Transplant Section (Division of Nephrology) of the Federal University of São Paulo/Hospital do Rim, São Paulo (SP), Brazil. Results: 88 patients with post-transplant FSGS were identified along the period of this study. The mean age of the patients in this sample was 29.1 ± 13.3 years at the time of transplantation, with predominance of male and white patients. Transplants with deceased donors predominated (60.9%). Of these, 25.6% were performed with an expanded criterion donor. Delay graft function occurred in 47.6% of recipients. The mean time to onset of proteinuria greater than 0.5 g / g was 20.51 ± 20.88 days. The indication of biopsy of the renal graft due to the suspicion of FSGS occurred with a median of 79 days, and histological characteristics of the FSGS were verified, in most cases, only in the subsequent biopsies, with a mean time of appearance of the histological changes of 164.56 ± 375.89 days. Only 21.5% of the patients had histological characteristics of FSGS in the first graft biopsy. The vast majority of patients (90.80%) underwent pulse therapy with methylprednisolone associated with plasmapheresis (70.10%). Taking a period of 60 months after kidney transplantation, 44.16% of the patients had partial remission, 25.97% complete remission and 29.87% had no remission. However, 50.60% of the patients evolved with graft loss (77.27% secondary to FSGS). After 12 months of transplantation, mean serum creatinine was 1.94 ± 1.02 mg/dL. The main complication of the treatment was infection/sepsis (67.5%). Eight patients (9.4%) died in the 60-month period, five (62.5%) deaths were attributed to infection. Conclusion: FSGS after renal transplantation presented a high rate of recurrence, usually early in the course of the disease. The histological changes in light microscopy were not simultaneous to the appearance of proteinuria. The infection rate during follow-up was high and related to mortality. The graft loss rate attributed to the post-transplant FSGS was elevated throughout the follow-up and corresponded to half of the individuals affected. Plasmapheresis therapy was an effective measure for the treatment of post-transplant FSGS and was able to contribute to partial or total response in more than 70% of the patients.
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    High expression of TIM-3 mRNA in urinary cells from kidney transplant recipients with acute rejection
    (Blackwell Publishing, 2007-06-01) Renesto, P. G.; Ponciano, V. C.; Cenedeze, Marcos Antonio [UNIFESP]; Camara, N. O. Saraiva; Pacheco-Silva, Alvaro [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    TIM-3 is a recently described molecule specifically expressed on Th1 differentiated T cells. We explored the usefulness of urinary mRNA profiles in the diagnosis of renal acute rejection (AR). Sixty urinary samples from renal transplant recipients simultaneously collected to allograft biopsy, (AR = 30 and No-AR =30), and 12 urinary samples from stable renal transplants were analyzed. Urinary mRNA encoding for TIM-3 and IFN-gamma were quantified using real time RT-PCR. TIM-3 mRNA was highly expressed in AR (559.19 +/- 644.41) compared to No-AR (3.78 +/- 7.20), and stable transplants (0.54 +/- 0.76), p < 0.001. To a lesser degree, IFN-gamma mRNA transcripts were also increased in AR (50.40 +/- 38.71), compared with No-AR (4.69 +/- 12.62), and stable transplants (0.38 +/- 0.44) p < 0.001. the highest expression of TIM-3 in AR makes it a promising noninvasive test for its diagnosis.
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    Human papillomavirus detected in viral warts of renal transplant recipients
    (Wiley-Blackwell, 2016) Martelli-Marzagao, F. [UNIFESP]; Santos Junior, G. F.; Ogawa, M. M. [UNIFESP]; Enokihara, M. M. S. S. [UNIFESP]; Porro, A. M. [UNIFESP]; Tomimori, J. [UNIFESP]
    ObjectivesFew studies have been conducted in South America regarding the detection and genotyping of human papillomavirus (HPV) in viral warts of renal transplant recipients (RTRs). The characterization of the population most susceptible to the development of warts and the knowledge of the main HPV types in this environment prompted this study, which focuses on the detection and typing of HPV in RTRs in Brazil. MethodsFifty-eight patients with viral warts from the Hospital SAo Paulo/Federal University of SAo Paulo were included in this study. HPV was detected by polymerase chain reaction (PCR) using combinations of the following primers: PGMY 09/11, RK 91, CP 65/70, and CP 66/69. Restriction fragment length polymorphism and automated sequencing techniques were used for HPV typing. ResultsHPV was detected by PCR in 89.7% of viral wart samples. The most frequently detected HPV types included 57, 27, 1a, 2a, and 20. Other types of HPV-epidermodysplasia verruciformis were also detected, including 14, 15, 19, 20, 21, 23, 36, and 38. Rare HPV types were also detected in our environment, including RTR X1, RTR X7, and 100. The time after transplant was correlated with an increased number of lesions and beta papillomavirus genus infection. ConclusionsThe HPV types detected in the RTR population were similar to those described in immunocompetent populations. However, the diversity of the HPV types identified and the number of lesions were increased in the RTR population.
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    Human papillomavirus detected in viral warts of renal transplant recipients
    (Wiley-Blackwell, 2016) Martelli-Marzagao, F. [UNIFESP]; Santos Junior, G. F.; Ogawa, M. M. [UNIFESP]; Enokihara, M. M. S. S. [UNIFESP]; Porro, A. M. [UNIFESP]; Tomimori, J. [UNIFESP]
    ObjectivesFew studies have been conducted in South America regarding the detection and genotyping of human papillomavirus (HPV) in viral warts of renal transplant recipients (RTRs). The characterization of the population most susceptible to the development of warts and the knowledge of the main HPV types in this environment prompted this study, which focuses on the detection and typing of HPV in RTRs in Brazil. MethodsFifty-eight patients with viral warts from the Hospital SAo Paulo/Federal University of SAo Paulo were included in this study. HPV was detected by polymerase chain reaction (PCR) using combinations of the following primers: PGMY 09/11, RK 91, CP 65/70, and CP 66/69. Restriction fragment length polymorphism and automated sequencing techniques were used for HPV typing. ResultsHPV was detected by PCR in 89.7% of viral wart samples. The most frequently detected HPV types included 57, 27, 1a, 2a, and 20. Other types of HPV-epidermodysplasia verruciformis were also detected, including 14, 15, 19, 20, 21, 23, 36, and 38. Rare HPV types were also detected in our environment, including RTR X1, RTR X7, and 100. The time after transplant was correlated with an increased number of lesions and beta papillomavirus genus infection. ConclusionsThe HPV types detected in the RTR population were similar to those described in immunocompetent populations. However, the diversity of the HPV types identified and the number of lesions were increased in the RTR population.
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    Improved renal function after kidney transplantation is associated with heme oxygenase-1 polymorphism
    (Wiley-Blackwell, 2008-09-01) Ozaki, K. S.; Marques, G. M.; Nogueira, E.; Feitoza, R. Q.; Cenedeze, M. A.; Franco, M. F. [UNIFESP]; Mazzali, M.; Soares, M. P.; Pacheco-Silva, A.; Camara, N. O. S. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP); Gulbenkian Inst Sci; Universidade de São Paulo (USP)
    Heme oxygenase-1 (HO-1) has a microsatellite polymorphism based on the number of guanosine-thymidine nucleotide repeats (GT) repeats that regulates expression levels and could have an impact on organ survival post-injury. We correlated HO-1 polymorphism with renal graft function. the HO-1 gene was sequenced (N = 181), and the allelic repeats were divided into subclasses: short repeats (S) (< 27 repeats) and long repeats (L) (>= 27 repeats). A total of 47.5% of the donors carried the S allele. the allograft function was statistically improved six months, two and three yr after transplantation in patients receiving kidneys from donors with an S allele. for the recipients carrying the S allele (50.3%), the allograft function was also better throughout the follow-up, but reached statistical significance only three yr after transplantation (p = 0.04). Considering only those patients who had chronic allograft nephropathy (CAN; 74 of 181), allograft function was also better in donors and in recipients carrying the S allele, two and three yr after transplantation (p = 0.03). Recipients of kidney transplantation from donors carrying the S allele presented better function even in the presence of CAN.
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    Influence of the CYP3A4/5 genetic score and ABCB1 polymorphisms on tacrolimus exposure and renal function in Brazilian kidney transplant patients
    (Lippincott Williams & Wilkins, 2016) Genvigir, Fabiana D. V.; Salgado, Patricia C.; Felipe, Claudia Rosso [UNIFESP]; Luo, Elena Y. F.; Alves, Camila; Cerda, Alvaro; Tedesco-Silva Junior, Hélio [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; Oliveira, Nagilla Ione de [UNIFESP]; Rodrigues, Alice C.; Doi, Sonia Q.; Hirata, Mario H.; Hirata, Rosario D. C.
    BackgroundPolymorphisms in genes encoding transport proteins and metabolizing enzymes involved in tacrolimus (TAC) disposition may be important sources of individual variability during treatment.ObjectiveThe aim of this study was to investigate the effect of combined CYP3A4 and CYP3A5 variants, using a CYP3A4/5 genetic score, and ABCB1 polymorphisms on therapeutic TAC monitoring and their relationship with clinical outcomes.Material and methodsBrazilian kidney transplant recipients (n=151), who received TAC over 3 months after transplantation, were genotyped for CYP3A4 rs2242480 (g.20230G>A), CYP3A5 rs15524 (g.31611C>T) and rs776746 (g.6986A>G), ABCB1 rs1128503 (c.1236C>T), rs1045642 (c.3435C>T), and rs2032582 (c.2677G>T/A) polymorphisms.ResultsFrequencies of CYP3A4 g.20230A, CYP3A5 g.31611C, and g.6986A were 0.37, 0.26, and 0.28, respectively. These alleles were associated with TAC rapid metabolization and were used for CYP3A4/5 genetic score construction. A higher CYP3A4/5 genetic score was associated with higher TAC dose and lower concentrations for dose administered (Co/D, P<0.05). Ninety days after transplantation, the presence of two or more rapid metabolization alleles contributed toward 27.7% of Co/D variability and was associated with a lower estimated glomerular filtration rate values (P<0.05). For ABCB1, the frequencies of c.1236T, c.3435T, and c.2677T/A alleles were 0.42, 0.42, and 0.33/0.04. At 30 days after transplantation, patients carrying ABCB1 c.1236TT+c.3435TT+(c.2677TT+TA) genotypes had higher TAC Co/D than those with common or heterozygous genotypes (P<0.05).ConclusionThe results show the impact of the CYP3A4/5 genetic score on TAC exposure and renal function in Brazilian patients. Furthermore, ABCB1 polymorphisms, in a combined analysis, influenced TAC Co/D at 30 days after transplantation.
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    Minor H antigen matches and mismatches are equally distributed among recipients with or without complications after HLA identical sibling renal transplantation
    (Wiley-Blackwell, 2013-11-01) Dierselhuis, M. P.; Spierings, E.; Drabbels, J.; Hendriks, M.; Alaez, C.; Alberu, J.; Alvarez, M. B.; Burlingham, W.; Campos, E. [UNIFESP]; Christiaans, M.; Claas, F.; Fasano, M. E.; Gerbase-DeLima, M.; Gervais, T.; Gorodezky, C.; Larriba, J.; Lardy, N. M.; Latinne, D.; Morales-Buenrostro, L-E; Moreno, M. J.; Oguz, F.; Opelz, G.; Sergeant, R.; Tambutti, M.; Teper, S.; Tilanus, M.; Turkmen, A.; Warrens, A. N.; Weimar, W.; Goulmy, E.; Leiden Univ; Univ Med Ctr Utrecht; Inst Diagnost & Referencia Epidemiol; Inst Nacl Ciencias Med & Nutr Salvador Zubiran; Ctr Inmunol Genet & Mol; Univ Wisconsin; Universidade Federal de São Paulo (UNIFESP); Associacao Fundo Incent Pesquisa; Maastricht Univ; Immunol Trapianti Genet; Catholic Univ Louvain; Hosp Italiano Buenos Aires; Sanquin Diagnost Serv; CEMIC Ctr Educ Med & Invest Clin Norberto Quirno; Istanbul Univ; Heidelberg Univ; Imperial Coll Healthcare NHS Trust; Erasmus MC
    Studies of the effect of minor H antigen mismatching on the outcome of renal transplantation are scarce and concern mainly single center studies. the International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. in collaboration with 16 laboratories of the IHIW, the role of 15 autosomal, 10 Y-chromosome encoded minor H antigens and 3 CD31 polymorphisms, was investigated in relation to the incidence of renal graft rejection and graft loss in 444 human leukocyte antigens (HLA)-identical sibling renal transplantations. Recipient and donor DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, C19Orf48, LB-ECGF-1, CTSH, LRH-1, LB-ADIR and HY. the correlation between minor H antigen mismatch and the primary outcome graft rejection or graft loss was statistically analyzed. the incidence of rejection was very low and no correlation was observed between one or more minor H antigen mismatch(es) and a rejection episode (n=36), of which only eight resulted in graft loss. in summary, in our study cohort of 444 renal transplants, mismatching for neither autosomal nor HY minor H antigens correlate with rejection episodes or with graft loss.
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    Mutação G20210A no gene da protrombina, fator V de Leiden e anticorpos anticardiolipina não influenciam a sobrevida do enxerto renal após o transplante
    (Sociedade Brasileira de Nefrologia, 2009-12-01) Rocha, Luis Klaus A. da [UNIFESP]; Galante, Nelson Zocoler [UNIFESP]; Alvarez, Vivian Angélica Castilho; Areco, Kelsy C. N. [UNIFESP]; Noguti, Maria Aparecida Eiko [UNIFESP]; Amaral, Rogério Q. [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Peres, Clovis de Araujo [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; Lourenco, Dayse Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidad de Antofagasta Departamento de Tecnologia Medica
    INTRODUCTION: Thromboembolic complications are important risk factors for graft failure and worse renal transplantation outcome. Patients with thrombophilic disorders have a higher risk of thromboembolic complications. The prevalence of thrombophilic disorders and the associated risk for graft failure and for intravascular thrombosis were analyzed in renal transplant recipients. METHODS: This is a cohort study of 388 adult recipients investigated regarding the presence of thrombophilia, through the search for anticardiolipin antibodies (aCL) via ELISA and FV G1691A and PT G20210A gene mutations by multiplex PCR. RESULTS: Thrombophilic disorders were identified in 25.8% of the patients. The 2-year graft survival was similar among patients with and without thrombophilic disorder (94% versus 94%, p = 0.53), and so was the survival free of intravascular thrombosis (97% versus 97%, p = 0.83). The prevalence of intravascular thrombosis was similar in both groups (3% versus 3.5%, p = 0.82). Patients with previous kidney transplantation had a higher risk of graft failure (OR 20.8, p < 0.001) and of intravascular thrombosis (OR 6.8, p = 0.008). CONCLUSIONS: The prevalences of FV G1691A and PT G20210A gene mutations in this cohort of patients were similar to those of the general non-transplanted population. The prevalence of aCL antibodies was higher in this cohort than that observed in healthy individuals. The thrombophilic markers studied did not predict the medium-term survival of renal transplant.
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    Myocardial revascularization in renal transplant patients
    (Sociedade Brasileira de Cardiologia - SBC, 2002-11-01) Delgado, Daniel de Souza [UNIFESP]; Gerola, Luís Roberto [UNIFESP]; Hossne Junior, Nelson Americo [UNIFESP]; Branco, João Nelson Rodrigues [UNIFESP]; Buffolo, Enio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVE: To assess the results of surgical myocardial revascularization in renal transplant patients. METHODS: From 1991 to 2000, 11 renal transplant patients, whose ages ranged from 36 to 59 (47.5±8) years, 8 males and 3 females, underwent myocardial revascularization. The time interval between renal transplantation and myocardial revascularization ranged from 25 to 120 (mean of 63.8±32.7) months. RESULTS: The in-hospital mortality rate was 9%. One patient died on the 4th postoperative day from septicemia and respiratory failure. The mean graft/patient ratio was 2.7±0.8. Only 1 patient required slow hemodialysis during 24 hours in the postoperative period, and no patient had a definitive renal lesion or lost the transplanted kidney. The actuarial survival curves after 1, 2, and 3 years were, respectively, 90.9%, 56.8%, and 56.8%. CONCLUSION: Renal transplant patients may undergo myocardial revascularization with no lesion in or loss of the transplanted kidney.
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    An open randomized study comparing immunosuppression therapy initiated before or after kidney transplantation in haploidentical living recipients
    (Blackwell Munksgaard, 2004-08-01) Camara, NOS; Dias, MFL; Pacheco-Silva, A.; Universidade Federal de São Paulo (UNIFESP); Hosp Rim & Hipertensao
    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.
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    Post-transplant lymphoproliferative disorders (PTLD) after renal transplantation: Management and evolution of seven cases among 1002 renal transplants in São Paulo, Brazil
    (Harwood Acad Publ Gmbh, 2000-09-01) Colleoni, GWB; Oliveira, JSR; Borducchi, DMM; Fernandes, MACF; Da Silva, H. T.; Alves, A. C.; De Franco, M. F.; Kerbauy, J.; Pestana, JOM; Universidade Federal de São Paulo (UNIFESP)
    We reported seven cases (0.7%) of PTLD among 1002 renal transplants performed at Renal Transplant Service from Hospital São Paulo - Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, Brazil, between 1976 and 1997. There were three male and four female patients with median age of 37 year-old. According to Ann Arbor staging system there were four localized extra-nodal intermediate-grade NHL, one disseminated low-grade NHL and two polyclonal lymphoid hyperplasia. Four patients received cadaveric, two received related and one received unrelated renal transplant. PTLD occurred after a median latency period of 36 months (ranging from 5 to 84 months). in situ hybridization for EBER1 was performed in five patients and molecular evidence of EBV was found in 3 cases (two DLCL and one lymphoplasmocytoid lymphoma). All patients were treated with immunosuppression withdrawal, four patients received anthracyclin-based chemotherapy for control of localized or systemic clonal disease and three were treated with resection of primary PTLD. Four of seven patients (57%) are in complete remission 11, 20, 25 and 79 months after PTLD onset. One patient lost follow-up and two patients died due to lymphoma relapse, respectively 4 and 10 months after completion of treatment. in conclusion, our experience with this small group of patients showed that: I) immunosuppression withdrawal is not necessarily associated with loss of renal transplant and can he used as the only treatment for polyclonal PTLD; 2) chemotherapy can simultaneously lead to clonal PTLD remission and periodic immunosuppression, avoiding graft rejection after immunosuppression withdrawal.