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Introdução: Diabetes mellitus pós-transplante (DMPT) tem impacto na morbidade e na mortalidade em receptores de transplante renal, uma vez que aumenta o risco de complicações cardiovasculares e de perda do enxerto renal. Os fatores de risco para DMPT podem ser divididos em modificáveis e não modificáveis. Ainda há controversas sobre a influência do sistema de antígenos leucocitários humanos (Human Leukocyte Antigens ou HLA) no risco de DMPT. Objetivo: Verificar prevalência para DMPT e sua relação com fatores genéticos. Métodos: Foram avaliados 450 pacientes submetidos ao transplante renal e realizada a investigação quanto à associação entre antígenos HLA-A, -B e -DR e DMPT. As frequências dos antígenos HLA-A, -B e -DR foram comparadas entre receptores com e sem diagnóstico de DMPT, ao longo de três anos após o transplante. Resultados: Na população de estudo, 60% eram do sexo masculino, 47,2% eram negros e 57,8% receberam rim de doador falecido. DMPT foi diagnosticado em 61 pacientes (13,5%), 315 (70%) permaneceram com níveis glicêmicos normais e 74 (16,5%) desenvolveram glicemia de jejum alterada. Associações positivas de DMPT foram observadas em relação aos antígenos HLA-A23 (18% vs 8,7%, P=0,024) e HLA-A29 (13,1% vs 5,1%, P=0,017) e associação negativa com o antígeno HLA-A68 (4,9% vs 14,1%, P=0,046). Conclusão: Encontramos relação estatística entre DMPT e HLA- A23, HLA-A29 e HLA-A68, porém, estudos com maior número de indivíduos são necessários para comprovar definitivamente a associação entre antígenos HLA e o risco de DMPT.

Background Coronavirus disease 2019 (COVID-19) fatality rate is high among kidney transplant recipients. Among survivors, kidney outcomes, seroconversion, and persistence of viral shedding are unexplored. Methods Single-center prospective cohort study including data from kidney transplant recipients with confirmed COVID-19 between March 20, 2020 and July 31, 2020. Outcomes were adjudicated until August 31, 2020 or the date of death. Results There were 491 patients with COVID-19 among the 11 875 recipients in follow-up. The majority were middle aged with ≥1 comorbidities. Thirty-one percent were treated at home, and 69% required hospitalization. Among the hospitalized, 61% needed intensive care, 75% presented allograft dysfunction, and 46% needed dialysis. The overall 28-day fatality rate was 22% and among hospitalized patients it was 41%. Age (odds ratio, 3.08; 95% confidence interval, 1.86-5.09), diabetes mellitus (odds ratio, 1.69; 95% confidence interval, 1.06-2.72), and cardiac disease (odds ratio, 2.00; 95% confidence interval, 1.09-3.68) were independent factors for death. Among the 351 survivors, 19% sustained renal graft dysfunction, and there were 13 (4%) graft losses. Biopsy (n = 20) findings were diverse but decisive to guide treatment and estimate prognosis. Seroconversion was observed in 79% of the survivors and was associated with disease severity. Persistence of viral shedding was observed in 21% of the patients without detectable clinical implications. Conclusions This prospective cohort analysis confirms the high 28-day fatality rate of COVID-19, associated primarily with age and comorbidities. The high incidence of allograft dysfunction was associated with a wide range of specific histologic lesions and high rates of sequelae and graft loss. Seroconversion was high and the persistence of viral shedding deserves further studies.

Background Pancreas transplant is an effective treatment for insulin-dependent diabetic individuals with end-stage renal disease, yet immunosuppression-associated adverse events may adversely affect patient and graft survival. The aim of the study was to document whether mammalian target of rapamycin inhibitors (mTORi) are safe and effective as a second-line drug after pancreas transplant. Methodology An observational single-center study was performed in a cohort of 490 simultaneous pancreas–kidney transplant and 45 pancreas-after-kidney transplant individuals after conversion to mTORi (n = 13) owing to adverse events of either tacrolimus or mycophenolate. Results mTORi conversion was performed 11.5 ± 10.1 (range, 1-28) months after pancreas transplant, mainly owing to cytomegalovirus infection and gastrointestinal intolerance. We frequently observed clinical complications after mTORi conversion, yet creatinine, eGFR, proteinuria, fasting plasma glucose, HbA1c, and C-peptide remained stable throughout the study (mean follow-up 8.2 ± 5, range 1-17) years, as did the lipid profile (P > .05). However, graft loss occurred in almost 20% of patients owing to chronic alterations. Limitations The small number of patients and a single-center cohort were limitations of the study. Conclusions Late mTORi conversion is a safe and effective approach when tacrolimus or mycophenolate-mediated adverse events occur after pancreas transplant.

Background Jehovah's Witnesses (JWs) refuse blood transfusions due to religious issues. This situation may impact kidney transplantation (KT) outcomes in case of hemorrhagic complications. We evaluated demographic characteristics of this population, hematologic safety, and graft outcomes. Methods This was a retrospective, single-center study comparing KT outcomes in JW patients versus a non-JW control group. Hematologic endpoints included clinical indication for blood transfusion (hemoglobin 2 g/dL or hematocrit >5% in the first week after KT, hemorrhagic complications requiring surgery, and de novo prescription of erythropoiesis-stimulating agents. Secondary endpoints included delayed graft function, treated biopsy-proven acute rejection, renal function, mortality, and graft survival at 12 months. Results From January 1989 to September 2018, we identified 143 JW (10 pediatric) and selected 142 matched control (non-JW) patients. There were no differences in the incidence of clinical indication for transfusion (13.3% versus 11.3%, P = 0.640), but a higher proportion of non-JW patients received transfusions (2.1% versus 9.2%, P = 0.010). There were no differences in the proportion of patients with decreased hemoglobin concentration, in reinterventions due to hemorrhagic complications, in the use of erythropoiesis-stimulating agents at hospital discharge, in the incidence of acute rejection, in renal function, and in mortality or graft survival rate at 12 months. Conclusions In summary, this matched control cohort study suggests that, when clinically indicated, blood transfusions can be safely avoided in the majority of JW kidney transplant, who achieve and maintain comparable hemoglobin concentrations during the first year after transplantation compared with non-JW patients.

Background Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. Methods We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. Results Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. Conclusions In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

Simultaneous pancreas-kidney transplantation (SPKT) aimed at increasing the life expectancy for diabetic patients with end-stage kidney disease (ESKD). However, the risks of surgery complications and immunosuppression therapy make it unclear if the SPKT positively impacts patient's quality of life (QoL). Using the Kidney Disease Quality of Life-Short-Form Health Survey (KDQOL-SF36) and Problems Areas in Diabetes (PAID) measurement tools, we compared the QoL of 57 patients on the pretransplant waiting list with that of 103 patients who had undergone SPKT. Posttransplantation patients were assessed within different time intervals (1, 1-3, and3 years). Mean KDQOL-SF36 scores were better among posttransplantation patients in the SF36 and KDQOL domains. It was also observed patients' stress reduction in PAID mean score (P = 0.011) after SPKT. We concluded that patients receiving SPKT had a better perception of QoL than did patients on the waiting list, and this positive perception remained almost entirely comparable over the three different intervals of the posttransplantation time. These positive results showed better outcomes when excluding patients that lost pancreas graft function. Further research is needed to compare diabetic patients with kidney transplant alone using specific measurement tools to evaluate patient's QoL.

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Made available in DSpace on 2022-04-28T19:43:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Background: Kidney transplant recipients have higher COVID-19 associated mortality compared to the general population. However, as only symptomatic patients seek medical attention, the current level of exposure, the main sources of acquisition, and the behavior of humoral immunity over time are poorly understood. Methods: This cross-sectional prospective single-center study recruited kidney transplant recipients of any age living in Sao Paulo. A sample size of 401 patients was calculated considering the 17.2% seroprevalence in the municipality population from a published survey, a 95% confidence interval and an absolute error of 2%. Results: Of the 2636 eligible patients, 416 were included. The seroprevalence for IgG anti-SARS-CoV-2 was 8.2%. Seroconversion rate decreased with increasing age, from 15.7% (18–35 years) to 8.3% (36–60 years) and 4.2% (>60 years, p = 0.042). Seropositivity among previously confirmed COVID-19 patients was 68.4%, followed by 9.4% in those with flu-like symptoms and only 4.6% among asymptomatic patients (p

The purpose of this single center retrospective study was to investigate the relationship between HLA and ABO polymorphisms and COVID-19 susceptibility and severity in kidney transplant recipients. It included 720 recipients who had COVID-19 and 1680 controls composed by recipients in follow-up who did not contact the transplantation center for COVID-19 symptoms, up to the moment of their inclusion in the study. HLA-A, -B, and -DRB1 allele groups and ABO frequencies were compared between recipients with COVID-19 (all cases, or separately mild/moderate and severe disease) and controls. The HLA association study was conducted in two case-control series and only associations that showed a p-value

Hypertension (HTN) remains a common complication after kidney transplantation among paediatric patients. Although low birth weight (LBW) has been implicated as an important risk factor for cardiovascular diseases, its effect on transplantation patients has not yet been addressed. It is essential to determine whether children with LBW who undergo transplantation are more likely to develop post-transplantation HTN. For this study, the medical records of 96 kidney recipients were retrospectively examined. A total of 83 patients fulfilled the inclusion criteria. Overall, post-transplantation HTN was observed in 54% of the recipients. Multivariate logistic regression revealed that time from transplantation >14 months (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.31–10.06; P = 0.013), current CKD (OR 2.6; 95% CI 1.01–7.20; P = 0.045), presence of LBW (OR 3.6; 95% CI 1.04–12.32; P = 0.044) and current overweight/obesity (OR 3.7; 95% CI 1.02–13.91; P = 0.047) were associated with post-transplantation HTN. In conclusion, our data provide evidence for the first time that LBW is a significant predictive factor in the development of post-transplantation HTN. This finding has important clinical implications as it serves to alert clinicians about this additional risk factor in paediatric patients undergoing kidney transplant.

Worldwide allocation systems are subjected to regulatory and ethical unique themes prevailing under the local socioeconomic and health care system. We sought to describe kidney allocation system, local transplant regulatory environment, and some general information concerning reimbursement in Brazil. Under a universal health care program, the national transplant system coordinates national transplant activity. Organ procurement occurs through a combination of organ procurement organizations and hospital commissions. Donation after circulatory death is still prohibited. Allocation system is primarily based on HLA compatibility within regional waiting list. In 2017, the number of effective deceased donors was 16.6 per million population (pmp, 23rd in the world) and the number of kidney transplants was 28.8 pmp (33rd in the world). Bundle reimbursements are provided by the federal government for organ procurement and transplantation. Given the wide geographical disparities among the 26 states, performance and outcomes vary considerably. The combination of late referral, inadequate maintenance, and long cold ischemia time results in high incidence of delayed graft function (60–70%), increases costs, and is associated with inferior long-term allograft survival. Cost-effective strategies have been implemented to increase the number of transplants, reduce delayed graft function incidence, reduce geographical disparities, and improve long-term graft survival.

Genotypic diversity and fluconazole susceptibility of 82 Cryptococcus neoformans and Cryptococcus gattii isolates from 60 renal transplant recipients in Brazil were characterized. Clinical characteristics of the patients and prognostic factors were analysed. Seventy-two (87.8%) isolates were C. neoformans and 10 (12.2%) were C. gattii. VNI was the most common molecular type (40 cases; 66.7%), followed by VNII (9 cases; 15%), VGII (6 cases; 10%), VNB (4 cases; 6.7%) and VNI/II (1 case; 1.7%). The isolates showed a high genetic diversity in the haplotype network and six new sequence types were described, most of them for VNB. There was a bias towards skin involvement in the non-VNI population (P = .012). VGII isolates exhibited higher fluconazole minimum inhibitory concentrations compared to C. neoformans isolates (P = 0.008). The 30-day mortality rate was 38.3%, and it was significantly associated with fungemia and absence of headache. Patients infected with VGII had a high mortality rate at 90 days (66.7%). A variety of molecular types produce disease in renal transplant recipients in Brazil and highlighted by VGII and VNB. We report the clinical appearance and impact of the molecular type, fluconazole susceptibility of the isolates, and clinical characteristics on patient outcome in this population.

Introduction Hospital do Rim is a high‐volume kidney transplant (KT) center located in São Paulo, a city with 12.2 million inhabitants. Over the last 18 years, we performed 11 436 KT, 70% of which from deceased donors. To mitigate the effects of reduction in the number of transplants on the waiting list, sequential measures were implemented when COVID‐19 was declared pandemic. Methods The first step was to provide SARS‐COV‐2 RT‐PCR testing for all symptomatic employees and patients and the compulsory use of personal protective equipment in the hospital facilities. Living donor KT were postponed, and all deceased donors and recipients were tested before the transplantation. The immunosuppressive protocols were maintained, and telehealth strategies were developed. Results Among the 1013 employees, there were 214 cases of COVID‐19, nine required ward hospitalization, and no deaths occurred. In 26%, the probable source of contamination was occupational. From the first patient diagnosed with COVID‐19 in 03/20/2020 till 10/21/2020, 523 deceased KT were performed, a 21% increase compared with 2019, with no confirmed donor‐derived SARS‐CoV‐2 infection. Four patients were transplanted with a positive pretransplant SARS‐CoV‐2 test, but none of them developed the disease. Overall, of 11 875 KT followed in our center, 674 developed COVID‐19. Among the hospitalized, 53% required mechanical ventilation, and 45% required hemodialysis. Their overall mortality rate was 27.5%. Conclusion This experience shows the challenges that transplant centers faced as the pandemic unfolded and illustrates the effectiveness of the sequential measures implemented to provide a safe environment for transplantation.

Optimizing antithymocyte globulin (rATG) dosage is critical for high immunological risk patients undergoing a repeat kidney transplant. This natural retrospective cohort study compared clinical outcomes of two successive cohorts of consecutive recipients of retransplants receiving 5 x 1 mg/kg (rATG-5, n = 100) or a single 3 mg/kg (rATG-3, n = 110) dose of rATG induction therapy. All patients had negative complement-dependent cytotoxicity crossmatch and no anti-HLA A, B, DR donor-specific antibodies (DSA). The primary endpoint was efficacy failure (first biopsy-proven acute rejection, graft loss, or death) at 12 months. There was no difference in the cumulative incidence of efficacy failure (18.0% vs. 21.8%, HR = 1.22, 95% CI 0.66–2.25), respectively. There were no differences in 3-years freedom from biopsy proven acute rejection, and patient, graft, and death-censored graft survivals. There were no differences in the incidence of surgical complications (25.0% vs. 18.2%; p 0.151), early hospital readmission (27.8% vs. 29.5%; p = 0.877) and CMV infections (49% vs. 40%; p = 0.190). There were also no differences in the incidence (59.6% vs. 58.7%, p = 0.897) and duration of delayed graft function but a stable difference in estimate glomerular filtration rate was observed from month 1 (54.7±28.8 vs. 44.1±25.3 ml/min/1.73 m2, p = 0.005) to month 36 (51.1±27.7 vs. 42.5±24.5, p = 0.019). Mean urinary protein concentration (month 36: 0.38±0.81 vs. 0.70±2.40 g/ml, p = 0.008) and mean chronic glomerular Banff score in for cause biopsies (months 4–36: 0.0±0.0 vs. 0.04±0.26, p = 0.044) were higher in the rATG-3 group. This cohort analysis did not detect differences in the incidence of efficacy failure and in safety outcomes at 12 months among recipients of kidney retransplants without A, B, and DR DSA, receiving induction therapy with a single 3 mg/kg rATG dose or the traditional 5 mg/kg rATG.

Background: The emergence of multidrug-resistant NDM-1-producing enterobacteriaceae strains has become a threat to inpatients, especially to immunosuppressed ones, such as kidney transplant recipients. NDM-1 is a carbapenemase that makes gram-negative bacteria resistant to many types of antibiotics. The incidence of carbapenemase-producing enterobacteria infection in solid organ transplant recipients is around 3 to 10%, with a mortality rate of up to 30%. Methods: We present a case series of 4 patients with NDM-1-producing enterobacteria isolated in urine cultures or rectal swabs. We also conducted a cross-sectional study 30 days after patient identification, collecting surveillance cultures (rectal swab) from all inpatients to assess the extent of spread of this resistance mechanism; a total of 101 patients were included. Results: Two patients were adequately treated with negative control cultures. The other two patients were not treated because they were asymptomatic and had subsequent negative urine cultures. No new colonization was identified in the cross-sectional screening, and no new cases of urinary NDM-1 infection were recorded after a 4-year follow-up. Conclusion: Surveillance for infections caused by multidrug-resistant strains in hospitals treating immunosuppressed patients should be continued and prompt action should be taken in cases of outbreaks of multidrug-resistant infections. Resumo Histórico: O surgimento de cepas multirresistentes de enterobacteriaceae produtoras de NDM-1 tornou-se uma ameaça para pacientes hospitalizados, especialmente para os imunossuprimidos, como os receptores de transplante renal. NDM-1 é uma carbapenemase que torna as bactérias gram-negativas resistentes a muitos tipos de antibióticos. A incidência de infecção por enterobactérias produtoras de carbapenemas em receptores de transplante de órgãos sólidos é de cerca de 3 a 10%, com uma taxa de mortalidade de até 30%. Métodos: Apresentamos uma série de casos de 4 pacientes com enterobactérias produtoras de NDM-1 isoladas em culturas de urina ou esfregaços retais. Também realizamos um estudo transversal 30 dias após a identificação do paciente, coletando culturas de vigilância (esfregaço retal) de todos os pacientes internados para avaliar a extensão de disseminação deste mecanismo de resistência; foram incluídos um total de 101 pacientes. Resultados: Dois pacientes foram tratados adequadamente com culturas de controle negativo. Os outros dois pacientes não foram tratados porque eram assintomáticos e tiveram culturas de urina negativas subsequentes. Não foi identificada nenhuma nova colonização na triagem transversal, e não foram registrados novos casos de infecção urinária por NDM-1 após um acompanhamento de 4 anos. Conclusão: A vigilância de infecções causadas por cepas multirresistentes em hospitais que tratam pacientes imunossuprimidos deve ser continuada e devem ser tomadas medidas imediatas em casos de surtos desses tipos de infecções.

Aim: To analyze the expression of urinary exosome-derived miRNAs (exo-miRs) in kidney recipients on tacrolimus-based therapy. Patients & methods: Clinical and drug monitoring data were recorded from 23 kidney recipients. Expression of 93 exo-miRs was measured by quantitative PCR array and mRNA targets were explored. Results: 16 exo-miRs were differentially expressed, including marked upregulation of miR-155-5p, and downregulation of miR-223-3p and miR-1228-3p. Expression of miR-155-5p and miR-223-3p correlated with tacrolimus dose (p

Cryptococcosis is the second most common invasive fungal infection reported in renal transplant recipients. Tissue granulomatous inflammation is necessary to contain Cryptococcus infection. This study aims to analyze the granuloma patterns and in situ expression of regulatory T (Treg) immune response in tissue samples from 12 renal transplant recipients with cryptococcosis. Fungal isolates were molecularly identified as Cryptococcus neoformans species complex. A detailed characterization of granulomas in tissue samples from 12 kidney transplant recipients with cryptococcosis was described by checking six lung and six skin biopsies by conventional histology and for immunohistochemical detection of CD4 and Treg markers: forkhead box P3 (FoxP3), interleukin (IL)-10 and transforming-growth factor (TGF)-β. Granulomas were classified as compact, loose or mixed. Patients with mixed (n = 4) and compact (n = 3) granulomatous inflammation patterns were associated with a better prognosis and presented a higher number of CD4+FoxP3+T cells compared to the group of patients with loose granulomas. In counterpart, three out of five patients with loose granulomas died with cryptococcosis. We suggest that Treg may have a protective role in the tissue response to Cryptococcus infection given its association with compact and mixed granulomas in patients with better clinical outcomes.

Induction therapy with rabbit anti-thymocyte globulin (rATG) in low-risk kidney transplant recipients (KTR) remains controversial, given the associated increased risk of cytomegalovirus (CMV) infection. This natural experiment compared 12-month clinical outcomes in low-risk KTR without CMV prophylaxis (January/3/13–September/16/15) receiving no induction or a single 3 mg/kg dose of rATG. We used logistic regression to characterize delayed graft function (DGF), negative binomial to characterize length of hospital stay (LOS), and Cox regression to characterize acute rejection (AR), CMV infection, graft loss, death, and hospital readmissions. Recipients receiving 3 mg/kg rATG had an 81% lower risk of AR (aHR (0.14)0.19(0.25), P < 0.001) but no increased rate of hospital readmissions because of infections ((0.68)0.91(1.21), P = 0.5). There was no association between 3 mg/kg rATG and CMV infection/disease (aHR (0.86)1.10(1.40), P = 0.5), even when the analysis was stratified according to recipient CMV serostatus positive (aHR (0.94)1.25(1.65), P = 0.1) and negative (aHR (0.28)0.57(1.16), P = 0.1). There was no association between 3 mg/kg rATG and mortality (aHR (0.51)1.25(3.08), P = 0.6), and graft loss (aHR (0.34)0.73(1.55), P = 0.4). Among low-risk KTR receiving no CMV pharmacological prophylaxis, 3 mg/kg rATG induction was associated with a significant reduction in the incidence of AR without an increased risk of CMV infection, regardless of recipient pretransplant CMV serostatus.

We describe cases of donor-derived transmission of Cryptococcus deuterogattii in 2 kidney transplant recipients in Brazil and published information on other cases. Prompt reduction of immunosuppression and initiation of antifungal therapy was required to successfully control the fungal infections and preserve engraftment.

BACKGROUND: Genetic and epigenetics factors have been implicated in drug response, graft function and rejection in solid organ transplantation. Differential expression of genes involved in calcineurin and mTOR signaling pathway and regulatory miRNAs was analyzed in the peripheral blood of kidney recipient cohort (n=36) under tacrolimus-based therapy. METHODS: PPP3CA, PPP3CB, MTOR, FKBP1A, FKBP1B and FKBP5 mRNA expression and polymorphisms in PPP3CA and MTOR were analyzed by qPCR. Expression of miRNAs targeting PPP3CA (miR-30a, miR-145), PPP3CB (miR-10b), MTOR (miR-99a, miR-100), and FKBP1A (miR-103a) was measured by qPCR array. RESULTS: PPP3CA and MTOR mRNA levels were reduced in the first three months of treatment compared to pre-transplant (PA (GG genotype) and MTOR c.2997C>T (TT genotype) were associated with reduced expression of PPP3CA mRNA and MTOR, respectively. FKBP1B mRNA levels were higher in patients with acute rejection (P=0.026). CONCLUSIONS: The expression of PPP3CA, MTOR and miR-99a in the peripheral blood of renal recipients is influenced by tacrolimus-based therapy and by PPP3CA and MTOR variants. These molecules can be potential biomarkers for pharmacotherapy monitoring.

Modifiable and nonmodifiable risk factors for developing posttransplant diabetes mellitus (PTDM) have already been established in kidney transplant setting and impact adversely both patient and allograft survival. We analysed 450 recipients of living and deceased donor kidney transplants using current immunosuppressive regimen in the modern era and verified PTDM prevalence and risk factors over three-year posttransplant. Tacrolimus (85%), prednisone (100%), and mycophenolate (53%) were the main immunosuppressive regimen. Sixty-one recipients (13.5%) developed PTDM and remained in this condition throughout the study, whereas 74 (16.5%) recipients developed altered fasting glucose over time. Univariate analyses demonstrated that recipient age (46.2±1.3vs.40.7±0.6years old, OR 1.04;P=0.001) and pretransplant hyperglycaemia andBMI≥25 kg/m2(32.8%vs. 21.6%, OR 0.54;P=0.032and 57.4%vs. 27.7%, OR 3.5;P<0.0001, respectively) were the pretransplant variables associated with PTDM. Posttransplant transient hyperglycaemia (86.8%. 18.5%, OR 0.03;P=0.0001), acute rejection (P=0.021), calcium channel blockers (P=0.014), TG/HDL (triglyceride/high-density lipoprotein cholesterol)ratio≥3.5at 1 year (P=0.01) and at 3 years (P=0.0001), and tacrolimus trough levels at months 1, 3, and 6 were equally predictors of PTDM. In multivariate analyses, pretransplant hyperglycaemia (P=0.035),pretransplant BMI≥25 kg/m2(P=0.0001), posttransplant transient hyperglycaemia (P=0.0001), andTG/HDL ratio≥3.5at 3-year posttransplant (P=0.003) were associated with PTDM diagnosis and maintenance over time. Early identification of risk factors associated with increased insulin resistance and decreased insulin secretion, such as pretransplant hyperglycaemia and overweight, posttransplant transient hyperglycaemia, tacrolimus trough levels, and TG/HDL ratio may be useful for risk stratification of patients to determine appropriate strategies to reduce PTDM.

Aim: The influence of variants in pharmacokinetics-related genes on long-term exposure to tacrolimus (TAC)-based therapy and clinical outcomes was investigated. Patients & methods: Brazilian kidney recipients were treated with TAC combined with everolimus (n = 178) or mycophenolate sodium (n = 97). The variants in CYP2C8, CYP2J2, CYP3A4, CYP3A5, POR, ABCB1, ABCC2, ABCG2, SLCO1B1 and SLCO2B1 were analyzed. Main results: CYP3A5*3/*3 genotype influenced increase in TAC concentration from week 1 to month 6 post-transplantation (p

Background Kidney transplant recipients (KTR) receive fixed daily doses of mycophenolate sodium as part of the immunosuppressive regimen. Dose reductions occur primarily due to adverse events and may be associated with an increased risk of acute rejection and graft loss. Objectives To evaluate the tolerability of mycophenolate in kidney transplant recipients receiving tacrolimus and prednisone. Setting The study was performed at Hospital do Rim, Federal University of São Paulo in Brazil. Method This was a retrospective cohort study including 506 patients. Tolerability of mycophenolate sodium was classified into the following groups: Temporary reduction (TR), definitive reduction (DR), temporary interruption (TI), permanent discontinuation (PD) and without modification (WM). Main outcome measure The cause of mycophenolate dose change and its influence on rejection-free survival during the first 3 years after transplantation. Results The cumulative incidence of dose change was 51.2% (11%TR, 44%DR, 24%TI, and 21%PD). Gastrointestinal (45.3%), infection (31.9%) and hematological (14.9%) systems accounted for most of the dose changes. The adverse events with higher incidence were diarrhea, cytomegalovirus (CMV) infection and leukopenia. Changes in dose of mycophenole were associated with reduced acute rejection-free survival compared with patients WM group (71.4%TR, 58.9%DR, 56.7%TI, 53.7%PD vs. 74.2%WM, p = 0.020). Only patients with PD showed inferior patient (59.3% vs. 94.4%, p = 0.001) and death-censored graft (83.3% vs. 92.5%, p = 0.074) survivals compared to patients WM. Conclusion In this cohort, changes in the dose of mycophenolate were associated with increased risk of acute rejection and permanent discontinuation was associated with inferior patient and graft survival.

Accurate pre-transplant prediction of late graft function remains an unmet need in kidney transplantation. The aim of this study was to evaluate HLA genes expression levels in pre-implantation biopsies (PIB) of deceased donor kidneys as markers for long-term graft outcome.HLA genes expression analysis was initially performed using microarray data of 53 PIB, previously generated by our laboratory. The validation analysis was performed by real-time PCR in 116 PIB from an independent cohort.The microarray data showed association between high expression levels of HLA class II genes, especially HLA-DQB1 and -DQB2, in kidneys from young (18 to 49-year-old) donors and poor (eGFR 45 mL/min/1.73 mHeightened expression of HLA-DQB1 and -DQB2 in PIB are promising tools for pre-transplant risk assessment of poor late graft function in transplants with kidneys from 18 to 49-year-old donors.

BACKGROUND Initially described as a relatively benign condition, recent studies report graft loss in up to 50% of the patients with post-transplant IgA nephropathy. There is no evidence for the best therapeutic approach, and prognostic factors remain to be elucidated. MATERIAL AND METHODS Single center retrospective analysis of patients >12 years old, with clinically relevant post-transplant IgA nephropathy (proteinuria ≥1.0 g/g and/or graft dysfunction) and ≥6 months follow-up after diagnosis (n=47). RESULTS Living donor transplants represented 85% of cases. Dysmorphic hematuria (100%), blood pressure elevation (95.7%), renal dysfunction (70.2%) and subnephrotic proteinuria (60.6%) predominated at presentation. Using the Oxford Classification, mesangial proliferation was the main histological lesion (91%). Treatment consisted mostly of blockade of the renin angiotensin system (89.4%) and modification of immunosuppression (85.1%), mainly by increasing oral steroids dose (83%), with venous pulse therapy in 63.8% of cases. Partial and complete remission occurred in 48.9% and 17% of cases, respectively. One patient died (sepsis) and 15 patients (31.9%) lost their grafts due to nephropathy. The percentage of decrease in glomerular filtration rate at diagnosis was independently associated with partial remission (HR 0.97, 95% CI 0.94-0.99, p=0.01) and graft loss (HR 1.13, 95% CI 1.06-1.20, p

AIMS The objective of this study was to evaluate the expression of bladder receptors in patients with defunctionalized bladder (DB) and to assess voiding behavior after refunctionalization. METHODS A total of 68 pretransplant patients were divided in two groups: DB (diuresis

Background: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). Methods: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on protocol biopsies at 12 months, and the incidence of acute rejection, estimated glomerular filtration rate (eGFR) and proteinuria at 36 months. Results: At 12 months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At 36 months, there were no differences in the incidence of treatment failure (19.0 vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8 vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 ± 1.05 vs. 0.62 ± 0.75 vs. 0.71 ± 1.24). eGFR was lower in the BAS/EVR compared to that in the BAS/MPS group (53.4 ± 20.9 vs. 50.8 ± 19.5 vs. 60.7 ± 21.2 mL/min/1.73 m2, p = 0.017) but comparable using a sensitive analysis (49.5 ± 23 vs. 47.5 ± 22.6 vs. 53.6 ± 27.8 mL/min/1.73 m2, p = 0.207). Conclusion: In this cohort, the use of EVR and reduced TAC concentrations were associated with comparable efficacy, renal function, and histological parameters compared to the standard-of-care immunosuppressive regimen.

Background After renal transplantation (RTx) hepatitis C virus (HCV) is associated with higher morbidity and mortality resulting in lower patient and graft survival. Few studies have investigated the evolution of renal transplant patients with cirrhosis owing to HCV. The objectives were to evaluate the post-transplant evolution of cirrhotic patients and to compare them with noncirrhotic patients considering the outcomes, including hepatic decompensation, graft loss, and death. Methods The retrospective-cohort study analyzed the data of patients undergoing RTx between 1993 and 2014, positive anti-HCV, HCV-RNA before RTx, and availability of data for assessment of cirrhosis. Demographic, clinical, and laboratory variables were compared between the groups according to the outcomes. The same were made between cirrhotic patients with and without portal hypertension (PH). Survival curves were constructed by the Kaplan-Meier test and compared by the log-rank test. Variables associated with the outcomes were analyzed using Cox regression. Results This study included noncirrhotic (n = 201) and cirrhotic patients (n = 23). In cirrhotic patients, they were significantly older (49 vs 41.6 years) and mostly male (87% vs 65%), with a greater number of previous RTx (48% vs 18%), less frequent use of azathioprine (26% vs 54%), cyclosporine (13% vs 46.5%), more frequent use of tacrolimus (87% vs 55%), lower count of platelets × 1000 cells/mm3(110 vs 187), and higher pre-RTx international normalized ratio (1.20 vs 1.1).The Kaplan-Meier survival differed in cirrhotic vs noncirrhotic patients only in hepatic decompensation. Cox regression analysis identified pretransplant cirrhosis (hazard ratio 6.64, 95% confidence interval, 2.59-17.06) and tacrolimus (hazard ratio 3.17,95% confidence interval, 1.05-9.58) as variables independently associated with decompensation. Conclusions Patients with HCV and cirrhosis exhibit higher morbidity when submitted to RTx than noncirrhotic patients, with a higher risk of hepatic decompensation. However, no difference was observed in liver-related mortality, suggesting that RTx is a feasible option in cirrhotic patients without decompensation, even if they have PH.

OBJECTIVES To describe the incidence of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving an mTOR-inhibitor-containing immunosuppressive regimen without prophylactic CMV treatment. METHODS This single-center retrospective cohort analysis included all de novo kidney transplant recipients (09/15/2015-07/31/2017) receiving 3 mg/kg single dose of rabbit antithymocyte globulin induction, tacrolimus, everolimus, and prednisone. Preemptive therapy was initiated only in patients deemed at higher risk for CMV infection: (a) D+/R- CMV patients; (b) after treatment for acute rejection (ARt); and (c) after everolimus discontinuation (EVRd). RESULTS Of 230 patients, there were no episodes of CMV disease among 217 (94%) without criteria to initiate preemptive therapy. Of 77 (33.5%) patients initiating preemptive therapy, 13 were D+/R-, 30 were ARt, and 34 were EVRd. The overall incidence of first CMV infection/disease was 6% (46.1% in D+/R-, 13.3% ARt [all patients had also discontinued everolimus], and 11.8% after early [

Background The prevalence and clinical epidemiological profile of hepatitis C virus (HCV) infection have changed over time. Aim This study aimed to evaluate these changes in renal transplant recipients (RTx) comparing two different decades. Materials and methods RTx with HCV referred to RTx from 1993 to 2003 (A) and from 2004 to 2014 (B) were studied retrospectively. The demographic and clinical characteristics and different outcomes were compared between groups A and B. Variables that were statistically different were tested for inclusion in a multivariate Cox proportional hazard model predicting patient survival within the group. Results Among 11 715 RTx, the prevalence of HCV was 7% in A and 4.9% in B. In the more recent period (B), the mean age was older (46.2 vs. 39.5 years), with more males (72 vs. 60.7%), larger number of deceased donors (74 vs. 55%), higher percentage of previous RTx (27 vs. 13.7%), less frequent history of blood transfusion (81 vs. 89.4%), lower prevalence of hepatitis B virus coinfection (4.7 vs. 21.4%), and higher percentage of cirrhotic patients (13 vs. 5%). Patients of group B more frequently underwent treatment of HCV (29 vs. 9%), less frequently used azathioprine (38.6 vs. 60.7%) and cyclosporine (11.8 vs. 74.7%), and more frequently used tacrolimus (91 vs. 27.3%). In the outcomes, graft loss showed no difference between periods; however, decompensation was more frequent (P = 0.007) and patients' survival was lower in the more recent period (P = 0.032) compared with the earlier one. Conclusion The profile of RTx with HCV has changed over the last 20 years. Despite a decrease in the prevalence of HCV, new clinical challenges have emerged, such as more advanced age and a higher prevalence of cirrhosis.

RESUMO Objetivo: avaliar o impacto financeiro das complicações pós-operatórias no transplante simultâneo pâncreas-rim durante a internação hospitalar. Métodos: estudo retrospectivo dos dados da internação hospitalar dos pacientes submetidos consecutivamente ao transplante simultâneo pâncreas-rim no período de janeiro de 2008 a dezembro de 2014 no Hospital do Rim/Fundação Oswaldo Ramos. As principais variáveis estudadas foram a reoperação, pancreatectomia do enxerto, óbito, complicações pós-operatórias (cirúrgicas, infecciosas, clínicas e imunológicas) e os dados financeiros da internação para o transplante. Resultados: a amostra foi composta de 179 pacientes transplantados. As características dos doadores e receptores foram semelhantes nos pacientes com e sem complicações. Na análise dos dados, 58,7% dos pacientes apresentaram alguma complicação pós-operatória, 21,8% necessitaram de reoperação, 12,3%, de pancreatectomia do enxerto e 8,4% evoluíram para o óbito. A necessidade de reoperação ou pancreatectomia do enxerto aumentou o custo da internação em 53,3% e 78,57%, respectivamente. A presença de complicação pós-operatória aumentou significativamente o custo. Entretanto, a presença de óbito, hérnia interna, infarto agudo do miocárdio, acidente vascular cerebral e disfunção do enxerto pancreático não apresentaram significância estatística no custo, cuja média foi de US$ 18,516.02. Conclusão: complicações pós-operatórias, reoperação e pancreatectomia do enxerto aumentaram significativamente o custo médio da internação hospitalar do SPK, assim como as complicações cirúrgicas, infecciosas, clínicas e imunológicas. No entanto, o óbito durante a internação, a hérnia interna, o infarto agudo do miocárdio, o acidente vascular cerebral e a disfunção do enxerto pancreático não interferiram estatisticamente neste custo. ABSTRACT Objective: considering simultaneous pancreas-kidney transplantation cases, to evaluate the financial impact of postoperative complications on hospitalization cost. Methods: a retrospective study of hospitalization data from patients consecutively submitted to simultaneous pancreas-kidney transplantation (SPKT), from January 2008 to December 2014, at Kidney Hospital/Oswaldo Ramos Foundation (Sao Paulo, Brazil). The main studied variables were reoperation, graft pancreatectomy, death, postoperative complications (surgical, infectious, clinical, and immunological ones), and hospitalization financial data for transplantation. Results: the sample was composed of 179 transplanted patients. The characteristics of donors and recipients were similar in patients with and without complications. In data analysis, 58.7% of the patients presented some postoperative complication, 21.8% required reoperation, 12.3% demanded graft pancreatectomy, and 8.4% died. The need for reoperation or graft pancreatectomy increased hospitalization cost by 53.3% and 78.57%, respectively. The presence of postoperative complications significantly increased hospitalization cost. However, the presence of death, internal hernia, acute myocardial infarction, stroke, and pancreatic graft dysfunction did not present statistical significance in hospitalization cost (in average US$ 18,516.02). Conclusion: considering patients who underwent SPKT, postoperative complications, reoperation, and graft pancreatectomy, as well as surgical, infectious, clinical, and immunological complications, significantly increased the mean cost of hospitalization. However, death, internal hernia, acute myocardial infarction, stroke, and pancreatic graft dysfunction did not statistically interfere in hospitalization cost.

The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single-center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r-ATG/EVR, n = 88), or mycophenolate (r-ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy-proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06-0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r-ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r-ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).

Monitoring of immunosuppressive drugs, such as calcineurin and mTOR inhibitors, is essential to avoid undesirable kidney transplant outcomes. Polymorphisms in pharmacokinetics-related genes have been associated with variability in blood levels of immunosuppressive drugs and adverse effects, but influence of pharmacodynamics-related genes remains to be elucidated. The influence of polymorphisms in genes of the mTOR and calcineurin signaling pathways on long-term clinical outcomes was investigated in Brazilian kidney transplant recipients within the 1-year post-transplant. Two-hundred and sixty-nine kidney transplant recipients were enrolled at a kidney transplant center in São Paulo city, Brazil, and treated with tacrolimus plus everolimus or mycophenolate sodium (clinical trial NCT01354301). Clinical and laboratory data, including renal function parameters and drug blood levels were recorded. Genomic DNA was extracted from blood samples. Polymorphisms in MTOR rs1057079 (c.4731G>A), rs1135172 (c.1437T>C), and rs1064261 (c.2997C>T); PPP3CA rs3730251 (c.249G>A); FKBP1A rs6033557 (n.259+24936T>C); FKBP2 rs2159370 (c.-2110G>T); and FOXP3 rs3761548 (c.-23+2882A>C) and rs2232365 (c.-22-902A>G) were analyzed by real-time PCR. Frequencies of gene polymorphisms did not differ among the treatment groups. Analysis of primary outcomes showed that patients carrying MTOR c.1437CC and FOXP3 c.-23+2882CC genotypes had higher serum creatinine than non-carriers (p < 0.05) at 1-year post-transplant. MTOR c.4731G allele (AG+GG genotype) was associated with increased risk for acute rejection (OR = 3.53, 95% CI = 1.09–11.48, p = 0.037). Moreover, 1-year cumulative incidence of rejection was higher in MTOR c.4731G allele carriers compared to AA genotype carriers (p = 0.027). Individually, analysis of secondary outcomes revealed that FKBP2 c.-2110GG genotype carriers had higher risk of leukopenia, FKBP1A n.259+24936C allele carriers had increased risk of constipation, and FOXP3 c.-22-902A or c.-23+2882A allele had higher risk of gastrointestinal disorders (p < 0.05). However, these results were not maintained in the multivariable analysis after p-value adjustment. In conclusion, variants in genes of mTOR and calcineurin pathways are associated with long-term impaired renal function, increased risk of acute rejection, and, individually, with adverse events in Brazilian kidney transplant recipients.

BACKGROUND Polymorphisms in genes encoding transport proteins and metabolizing enzymes involved in tacrolimus (TAC) disposition may be important sources of individual variability during treatment. OBJECTIVE The 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 METHODS Brazilian 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. RESULTS Frequencies 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

Background Highly active antiretroviral therapy has turned human immunodeficiency virus (HIV)-infected patients with end-stage renal disease into suitable candidates for renal transplantation. We present the Brazilian experience with kidney transplantation in HIV-infected recipients observed in a multicenter study. Methods HIV-infected kidney transplant recipients and matched controls were evaluated for the incidence of delayed graft function (DGF), acute rejection (AR), infections, graft function, and survival of patients and renal grafts. Results Fifty-three HIV-infected recipients and 106 controls were enrolled. Baseline characteristics were similar, but a higher frequency of pre-transplant positivity for hepatitis C virus and cytomegalovirus infections were found in the HIV group. Immunosuppressive regimens did not differ, but a trend was observed towards lower use of anti-thymocyte globulin in the group of HIV-infected recipients (P = 0.079). The HIV-positive recipients group presented a higher incidence of treated AR (P = 0.036) and DGF (P = 0.044). Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate was similar at 6 months (P = 0.374) and at 12 months (P = 0.957). The median number of infections per patient was higher in the HIV-infected group of patients (P = 0.018). The 1-year patient survival (P < 0.001) and graft survival (P = 0.004) were lower, but acceptable, in the group of HIV-infected patients. Conclusions In the Brazilian experience, despite somewhat inferior outcomes, kidney transplantation is an adequate therapy for selected HIV-infected recipients. This article is protected by copyright. All rights reserved.

BACKGROUND Conversion from cyclosporine (CsA) to everolimus (EVR) in kidney transplant recipients receiving mycophenolate sodium (MPS) and corticosteroids has been used to reduce CsA associated toxicities. Nevertheless, exposures produced by the initial EVR dose, the steady state pharmacokinetic and long-term safety and tolerability have not been explored in detail. METHODS Twenty-four stable kidney transplant recipients receiving CSA, MPS, and corticosteroids were converted from CSA to EVR. The initial EVR dose was 3 mg BID. Weekly monitoring of EVR blood concentrations was followed by a full 12 hour pharmacokinetic profile 28 days after conversion. Therapeutic drug monitoring, safety, and tolerability were analyzed during 5 years of follow-up. RESULTS The study population was relatively young (mean of 42 years) with a predominance of males (62%) and White (67%) recipients of kidneys from living (54%) or deceased (46%) donors. Mean time of the conversion was 61 months after transplantation. In the first 7 patients, the initial EVR dose of 3 mg BID resulted in mean EVR trough blood concentration of 14.7 ± 3.7 ng/mL at day 7. The initial EVR dose was then reduced to 2 mg BID for the following 17 patients. Four weeks after conversion, mean EVR dose was 1.7 ± 0.5 mg BID (7 patients were receiving 1 mg BID and 17 were receiving 2 mg BID) resulting in mean EVR trough blood concentration of 4.0 ± 1.4 ng/mL. Whereas mean maximum concentration (13.4 ± 2.8 versus 22.9 ± 7.4 ng/mL, P = 0.003) and mean apparent clearance (232 ± 79 versus 366 ± 173 mL/min, P = 0.016) were higher, mean area under the curve (78.2 ± 22.1 versus 102.5 ± 38.5 ng.h/mL, P = 0.067) and mean C0 (3.7 ± 1.3 versus 4.1 ± 1.5 ng/mL, P = 0.852) were no different comparing patients receiving 1 mg and 2 mg EVR BID. Mean inter-subject variability of area under the curve, trough concentration, and maximum concentration was 38%, 36%, and 38%. EVR treatment was discontinued in 29% of patients due to proteinuria (N = 2), pneumonia (N = 2), dyslipidemia (N = 2), and anemia (N = 1) and MPS dose was reduced in 58% of patients. CONCLUSIONS The initial 3 mg BID dose produced high EVR trough blood concentrations. The 2 mg BID dose appears to be the appropriate initial dose to provide therapeutic concentrations but still requires initial intensive therapeutic monitoring to achieve and maintain blood concentrations within the therapeutic target concentration. The combination of EVR and full dose MPS has limited long-term tolerability and safety.

BACKGROUND There is no evidence on the incidence of subclinical inflammation and scaring lesions in patients receiving tacrolimus (TAC) minimization and elimination immunosuppressive regimens. METHODS This study analyzed preimplantation, 3 and 24 months protocol biopsies and anti-HLA donor-specific antibodies (DSA) in 140 low immunological risk kidney transplant recipients receiving reduced TAC exposure, prednisone, and mycophenolate, randomized at 3 months to be converted or not to sirolimus (SRL). RESULTS Mean TAC concentrations were 6.0 ± 2.4 ng/mL and 5.8 ± 2.2 ng/mL at 3 and 24 months. The incidence of subclinical inflammation lesions at 3 months was 9.3%. The incidence of (interstitial fibrosis) IF/(tubular atrophy) TA at month 24 was 57.6%, higher in SRL compared to TAC group (68.8 vs 44.4%; P = 0.022). Patients converted to SRL showed higher incidence of acute rejection (7.3% vs 0%), proteinuria (59.6% vs 25%; P = 0.001), and DSA (17.8% vs 7.3%; P = 0.201), respectively. Biopsy-proven acute rejection (odds ratio [OR] 2.32, 95% confidence interval [95% CI], 0.979-5.518, P = 0.056), subclinical inflammation lesions at 3 months (OR, 11.75; 95% CI, 1.286-107.474; P = 0.029) and conversion to SRL (OR, 2.72; 95% CI, 1.155-6.383; P = 0.022) were associated with IF/TA at month 24. Black ethnicity (OR, 0.22; 95% CI, 0.058-0.873; P = 0.031), donor age (OR, 2.74; 95% CI, 1.329-5.649; P = 0.006), and conversion to SRL (OR, 2.34; 95% CI, 1.043-5.267; P = 0.039) were associated with inferior renal function at 24 months. CONCLUSIONS In kidney transplant recipients receiving reduced TAC exposure, subclinical inflammation lesions at 3 months were associated with IF/TA at 24 months. Conversion from TAC to SRL was associated with inferior renal function, higher incidence of IF/TA, and trends to higher incidence of DSA at 24 months.

BACKGROUND Urinary tract infections are frequent complications early after kidney transplantation, and the use of antimicrobial coated catheters in settings other than transplantation has shown promising results for infection prevention. The purpose of this study was to compare the efficacy of Nitrofurazone-coated silicone urinary catheters with non-impregnated silicone urinary catheters in reducing bacteriuria and urinary tract infections in kidney transplant recipients. METHODS This single-center study, randomized controlled trial at the Hospital do Rim, a tertiary referral center in kidney transplantation, located in Sao Paulo, Brazil. Subjects involved living donor kidney transplant recipients, and were randomized 1:1 ratio with a computer-generated system to a Nitrofurazone-coated silicone urinary catheter and non-impregnated silicone urinary catheter from March 2013 to December 2014. Patients with asymptomatic bacteriuria or urinary tract infection at baseline, deceased kidney transplant donors, patients with known hypersensitivity to nitrofurantoin, pregnancy, and those refusing to sign the informed consent form were excluded from the study. RESULTS Two hundred fourteen subjects were randomized and one hundred seventy-six completed the study. There were no differences in the rates of asymptomatic bacteriuria (12.5% in the Nitrofurazone group and 11.4% in the control group, P = 0.99) and urinary tract infection (8% and 6.8%, P = 0.99) and the incidence of side effects was more frequent in the Nitrofurazone-impregnated silicone urinary catheter group (46.6% and 26.1%, P = 0.007). CONCLUSION The study suggests that there is no beneficial effect of the employment of Nitrofurazone-coated urinary catheter. TRIAL REGISTRATION NUMBER ISRCTN57888785.

Introduction: The risk of death after kidney transplant is associated with the age of the recipient, presence of comorbidities, socioeconomic status, local environmental characteristics and access to health care. Objective: To investigate the causes and risk factors associated with death during the first 5 years after kidney transplantation. Methods: This was a single-center, retrospective, matched case-control study. Results: Using a consecutive cohort of 1,873 kidney transplant recipients from January 1st 2007 to December 31st 2009, there were 162 deaths (case group), corresponding to 5-year patient survival of 91.4%. Of these deaths, 25% occurred during the first 3 months after transplant. The most prevalent cause of death was infectious (53%) followed by cardiovascular (24%). Risk factors associated with death were history of diabetes, dialysis type and time, unemployment, delayed graft function, number of visits to center, number of hospitalizations, and duration of hospital stay. After multivariate analysis, only time on dialysis, number of visits to center, and days in hospital were still associated with death. Patients who died had a non-significant higher number of treated acute rejection episodes (38% vs. 29%, p = 0.078), higher mean number of adverse events per patient (5.1 ± 3.8 vs. 3.8 ± 2.9, p = 0.194), and lower mean eGFR at 3 months (50.8 ± 25.1 vs. 56.7 ± 20.7, p = 0.137) and 48 months (45.9 ± 23.8 vs. 58.5 ± 20.2, p = 0.368). Conclusion: This analysis confirmed that in this population, infection is the leading cause of mortality over the first 5 years after kidney transplantation. Several demographic and socioeconomic risk factors were associated with death, most of which are not readily modifiable. RESUMO Introdução: O risco de óbito após transplante renal está associado à idade do receptor, presença de comorbidades, condição socioeconômica, às características ambientais locais e ao acesso a serviços de atenção à saúde. Objetivo: Investigar as causas e fatores de risco associados ao óbito nos primeiros cinco anos após o transplante renal. Métodos: Este é um estudo unicêntrico retrospectivo com pareamento dos grupos caso e controle. Resultados: Em uma coorte consecutiva de 1.873 receptores de transplante renal atendidos de 1/1/2007 a 31/12/2009 foram registrados 162 óbitos (grupo caso), correspondendo a uma taxa de sobrevida após cinco anos de 91,4%. Dos óbitos registrados, 25% ocorreram nos primeiros três meses após o transplante. A causa de óbito mais prevalente foi infecção (53%), seguida de doença cardiovascular (24%). Os fatores de risco associados a mortalidade foram histórico de diabetes, tipo e tempo em diálise, desemprego, função tardia do enxerto, número de consultas, número de hospitalizações e tempo de internação hospitalar. Após análise multivariada, apenas o tempo em diálise, o número de consultas e dias de internação permaneceram associados a mortalidade. Os pacientes que foram a óbito tiveram um número não significativamente maior de tratamentos de episódios de rejeição aguda (38% vs. 29%; p = 0,078), maior número médio de eventos adversos por paciente (5,1 ± 3,8 vs. 3,8 ± 2,9; p = 0,194) e TFGe média mais baixa aos três meses (50,8 ± 25,1 vs. 56,7 ± 20,7; p = 0,137) e 48 meses (45,9 ± 23,8 vs. 58,5 ± 20,2; p = 0,368). Conclusão: A presente análise confirmou que nessa população, a infecção foi a principal causa de mortalidade nos primeiros cinco anos após transplante renal. Vários fatores de risco demográficos e socioeconômicos foram associados a mortalidade, a maioria não prontamente modificável.

A 56-year-old man was submitted to a simultaneous pancreas-kidney transplant 6 years ago. He received induction therapy with thymoglobulin, and maintenance immunosuppressive regimen consisted of tacrolimus (trough levels 6–8 ng/mL), prednisone and mycophenolate. Pulmonary tuberculosis was treated in the first year post-transplant. He reported cough, nasal congestion, and anosmia for at least 6 months. No fever was documented. Chest CT was normal. Sinus CT showed opacification in the right maxillary and ethmoidal sinuses without bone involvement. A biopsy was taken during endoscopic ethmoidectomy and antrostomy sinus surgery. Review the high-quality, interactive digital Aperio slides at http://virtualacp.com/JCPCases/jclinpath-2018-205258.R1\_1/,http://virtualacp.com/JCPCases/jclinpath-2018-205258.R1\_2/, http://virtualacp.com/JCPCases/jclinpath-2018-205258.R1_3/ and consider your diagnosis. 1. Post-transplant lymphoproliferative disorder 2. Hyalohyphomycosis (Aspergillosis or Fusariosis) 3. Adenovirus 4. Histoplasmosis 5. Mucormycosis The correct answer is after the discussion. The differential diagnosis of dry cough, nasal congestion and anosmia …