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1.
Kidney Int ; 96(5): 1100-1104, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31526513

RESUMO

In an attempt to clarify the mechanisms of post-transplant bone disease we investigated the bone content and gene expression of several bone-related proteins. After a successful kidney transplant, the content of sclerostin in bone biopsies was found to be increased as measured by immunohistochemistry, multiplex assay, and gene expression despite a concomitant decrease of sclerostin in the serum. The phosphorylation of beta-catenin was increased, confirming Wnt pathway inhibition, an effect accompanied by an increase of the receptor activator of nuclear factor kappa-Β ligand (RANKL) and a decrease of osteoprotegerin protein levels in both serum and bone. Thus, changes in circulating biomarkers after kidney transplantation cannot be easily extrapolated to concomitant changes occurring in the bone. Hence, overall treatment decisions post kidney transplant should not be based on serum biochemistry alone.

2.
Clin Transplant ; 33(8): e13658, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31271675

RESUMO

BACKGROUND: Cardiovascular mortality is increased in chronic kidney disease, a condition with a high prevalence of periodontal disease. Whether periodontitis treatment improves prognosis is unknown. METHODS: The effect of periodontal treatment on the incidence of cardiovascular events and death in 206 waitlist hemodialysis subjects was compared with that in 203 historical controls who did not undergo treatment. Patients were followed up for 24 months or until death or transplantation. RESULTS: The prevalence of moderate/severe periodontitis was 74%. Coronary artery disease correlated with the severity of periodontal disease (P = .02). Survival free of cardiovascular events (94% vs 83%, log-rank 0.009), coronary events (97% vs 89%, log-rank = 0.009), and cardiovascular death (96% vs 87%, log-rank = 0.037) was higher in the evaluated group. Death by any cause did not differ between groups. Multivariate analysis showed that treatment was associated with reduction in cardiovascular events (HR 0.43; 95% CI 0.22-0.87), coronary events (HR 0.31; 95% CI 0.12-0.83), and cardiovascular deaths (HR 0.43; 95% CI 0.19-0.98). CONCLUSION: Periodontal treatment reduced the 24-month incidence of cardiovascular events and cardiovascular death, suggesting that periodontal treatment may improve cardiovascular outcomes. We suggest that periodontal screening and eventual treatment may be considered in patients with advanced renal disease.

3.
Transpl Infect Dis ; 21(4): e13133, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31233669

RESUMO

Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus denominated Tricodisplasia Polyomavirus (TSPyV). We report a case of TS 6 months after kidney transplantation in a 65 years-old woman under immunosuppression therapy with prednisone, mycophenolate and tacrolimus. The patient developed follicular papules on the face with a thickening of the skin and alopecia of the eyebrows, leading to distortion of the face and a leonine appearance characteristic of the disease. The skin biopsy confirmed the clinical diagnosis and the presence of TSPyV DNA in the skin was detected. Staining for SV40 was positive. Immunosuppression was changed: mycophenolate was withdrawn, tacrolimus reduced and everolimus added. Intravenous cidofovir and later on leflunomide were added. Although the literature has reported clinical success with topical cidofovir, we were unable to use it because this drug is not available. There was an improvement of skin lesions and on cosmetic appearance. The patient had three rejections (one clinically diagnosed and two other biopsy proven), progressed with renal failure and graft loss. Retrospective analysis of stored urine and blood samples detected TSPyV DNA in some of those samples two months before the TS clinical development. This case highlights the TSPyV detection in blood and urine samples before the development of skin lesions.

4.
Am J Transplant ; 19(12): 3356-3366, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31152474

RESUMO

We determined peripheral blood (PB) and biopsy (Bx) RNA expression signatures in a Brazilian and US cohort of kidney transplant patients. Phenotypes assigned by precise histology were: acute rejection (AR), interstitial fibrosis/tubular atrophy/chronic rejection (CR), excellent functioning transplants (TX), and glomerulonephritis recurrence (GN). Samples were analyzed on microarrays and profiles from each cohort were cross-validated on the other cohort with similar phenotypes. We discovered signatures for each tissue: (1) AR vs TX, (2) CR vs TX, and (3) GN vs TX using the Random Forests algorithm. We validated biopsies signatures of AR vs TX (area under the curve [AUC] 0.97) and CR vs TX (AUC 0.87). We also validated both PB and Bx signatures of AR vs TX and CR vs TX with varying degrees of accuracy. Several biological pathways were shared between AR and CR, suggesting similar rejection mechanisms in these 2 clinical phenotypes. Thus, we identified gene expression signatures for AR and CR in transplant patients and validated them in independent cohorts of significantly different racial/ethnic backgrounds. These results reveal that there are strong unifying immune mechanisms driving transplant diseases and identified in the signatures discovered in each cohort, suggesting that molecular diagnostics across populations are feasible despite ethnic and environmental differences.

5.
Clin Infect Dis ; 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31077273

RESUMO

A kidney transplanted patient, unvaccinated against yellow fever, developed high fever and progressed rapidly to hepatic insufficiency, coma and died eight days later. RT-PCR for YF virus collected on the 7th day of symptoms was positive. Autopsy showed disseminated infection and midzonal hepatitis with apoptotic hepatocytes, and minimal inflammatory reaction.

7.
Transpl Infect Dis ; 21(2): e13056, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30712328

RESUMO

BACKGROUND: Polyoma viremia is associated with damage to renal tubular and urothelial cells. This may imply that a certain level of viremia, even cleared thereafter, could be associated with long-term renal dysfunction. METHODS: We, retrospectively, analyzed 390 first renal transplants adult recipients (≥18 years) who were monitored for BK viremia in the first 12 months and evaluated estimated GFR (MDRD-4 equation) at 1 month and at the last follow-up (959 ± 392 days). RESULTS: One hundred and ninety-nine patients (51%) developed at least one positive viremia: 105 (53%) low viremia (<104  copies/mL), 36 (18%) high viremia (4 × 104  > viremia ≥ 104  copies/mL) and 58 (15%) viremia (≥4 × 104  copies/mL) consistent with polyoma virus associated nephropathy (PyVAN). Out of these 58 patients, 24 (6%) developed bx-proven (SV40+) PyVAN and 34(8.7%) presumptive PyVAN (SV40-). Baseline characteristics, immunosuppression, KDRI, rejection episodes, etc., did not differ among groups but there were more deceased donors and ATG induction therapy in the high viremia group. At last follow-up, all patients in the low, high viremia and presumptive PyVAN (except 2) had cleared BK viremia. Bx-proven PyVAN led to 14 graft losses, 10 due to PyVAN. In the presumptive PyVAN there was only one graft loss registered as due to PyVAN. eGFR, at 1 month after KTx, did not differ among groups (51 ± 22 vs 48 ± 24 vs 45 ± 27 vs 43 ± 18 vs 46 ± 22 mL/min/1.73 m2 ), for no, low and high viremia as well for presumptive PyVAN and bx-proven PyVAN groups, respectively. At the last follow-up, eGFR did not differ between the no, low, and high viremia compared to baseline and to each other but was statistically lower in the presumptive and bx-proven PyVAN (38 ± 15 and 17 ± 7 mL/min/1.73 m2 ) either compared to baseline or to the other groups. CONCLUSIONS: This study shows that low and high levels of BK viremia do not lead to GFR changes although very high viremia levels, compatible with presumptive or bx-proven PyVAN, even if cleared thereafter, lead to allograft damage and decreased GFR.


Assuntos
Transplante de Rim , Rim/fisiologia , Infecções por Polyomavirus/patologia , Infecções Tumorais por Vírus/patologia , Viremia , Adulto , Aloenxertos , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/virologia , Masculino , Pessoa de Meia-Idade , Polyomavirus , Complicações Pós-Operatórias , Estudos Retrospectivos , Transplante Homólogo , Carga Viral
8.
Eur J Clin Microbiol Infect Dis ; 38(4): 755-765, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30680569

RESUMO

Kidney transplant recipients are at risk for infections due to carbapenem-resistant Enterobacteriaceae (CRE). Polymyxin-resistant CRE (PR-CRE) infections are especially difficult to treat. The aim of this study was to characterize PR-CRE infections among kidney transplant recipients and identify risk factors for treatment failure. This retrospective cohort study involved all kidney transplant recipients with PR-CRE infection between 2013 and 2017 at our center. Minimal inhibitory concentrations for polymyxin B were determined by broth microdilution. Carbapenem-resistant genes (blaKPC, blaNDM, and blaOXA-48), aminoglycoside-resistance genes, and polymyxin-resistant gene mcr-1 were identified by polymerase chain reaction. All but one of the 47PR-CRE infections identified were due to Klebsiella pneumoniae. The most common type of infection (in 54.3%) was urinary tract infection (UTI). Monotherapy was used in 10 cases. Combined treatment regimens included double-carbapenem therapy in 19 cases, oral fosfomycin in 19, and amikacin in 13. Treatment failure occurred in 21 cases (45.7%). Clinical success was achieved 78.9% of patients who used aminoglycosides versus 37.0% of those who not used this drug (p = 0.007). Multivariate analysis showed diabetes mellitus to be a risk factor for treatment failure; amikacin use and UTI were found to be protective. Nine strains were RmtB producers. Although aminoglycosides constitute an important therapeutic option for PR-CRE infection, the emergence of aminoglycoside resistance could have a major impact on the management of CRE infection.


Assuntos
Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Polimixinas/farmacologia , Adulto , Idoso , Amicacina/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Quimioterapia Combinada , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/mortalidade , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Feminino , Fosfomicina/uso terapêutico , Humanos , Transplante de Rim , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Transplantados , Falha de Tratamento , Resultado do Tratamento
9.
J Appl Oral Sci ; 27: e20180435, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30673031

RESUMO

OBJECTIVES: This study aimed to verify the presence of polyomavirus BK (BKPyV) in the saliva of kidney transplant recipients and to correlate it with blood viremia. MATERIAL AND METHODS: We have conducted a cross-sectional study with a sample involving 126 renal transplant recipients. 126 samples of saliva and 52 samples of blood were collected from these patients. Detection and quantification of BKPyV were performed using a real-time PCR. To compare the presence of BKPyV in blood and saliva, the binomial proportion test was used. To verify associations between salivary shedding BKPyV and post-transplant periods (in months), the Mann-Whitney test was used. Spearman's correlation was used to correlate the viral load in the saliva with blood of kidney transplant recipients. RESULTS: The mean age of the study group was 51.11±12.45 years old, and 69 participants (54.8%) were female, with a mean post-transplantation time of 4.80±6.04 months. BKPyV was quantified in several samples of saliva and blood, with medians of 1,108 cp/mL and 1,255 cp/mL, respectively. Only 16/52 (30.8%) participants presented BKPyV in blood, and 59/126 (46.8%) excreted the virus in saliva (p=0.004). BKPyV shedding was found in patients at a shorter post-transplantation period (3.86±5.25, p=0.100). A weak correlation was observed between viral quantification in saliva and blood (Spearman's correlation coefficient=0.193). CONCLUSION: The results of this study suggested that, although saliva excretes more BKPyV than blood, there is no reliable correlation between salivary shedding and blood viremia, showing two independent compartments of viral replication.


Assuntos
Vírus BK/isolamento & purificação , Transplante de Rim/efeitos adversos , Saliva/virologia , Transplantados , Viremia/virologia , Eliminação de Partículas Virais , Adulto , Estudos Transversais , Feminino , Humanos , Imunocompetência , Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas , Infecções Tumorais por Vírus/virologia , Carga Viral
10.
J Am Soc Nephrol ; 30(2): 355-365, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30606784

RESUMO

BACKGROUND: Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD). METHODS: In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. We used dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone biopsies to evaluate changes in bone in the 32 evaluable participants between the time of KTx and 12 months post-transplant. RESULTS: Both groups of patients experienced decreased bone turnover after KTx, but zoledronate itself did not affect this outcome. Unlike previous studies, DXA showed no post-transplant bone loss in either group; we instead observed an increase of bone mineral density in both lumbar spine and total hip sites, with a significant positive effect of zoledronate. However, bone biopsies showed post-transplant impairment of trabecular connectivity (and no benefit from zoledronate); HR-pQCT detected trabecular bone loss at the peripheral skeleton, which zoledronate partially attenuated. CONCLUSIONS: Current immunosuppressive regimens do not contribute to post-transplant central skeleton trabecular bone loss, and zoledronate does not induce ABD. Because fractures in transplant recipients are most commonly peripheral fractures, clinicians should consider bisphosphonate use in patients at high fracture risk who have evidence of significantly low bone mass at these sites at the time of KTx.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/prevenção & controle , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Ácido Zoledrônico/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos
11.
J Med Virol ; 91(6): 1136-1141, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30680753

RESUMO

BK virus is the causative agent of polyomavirus-associated nephropathy, a major cause of kidney transplant failure affecting 1%-10% of recipients. Previous studies that investigated the viral source on the kidney recipient pointed that the donor is implicated in the origin of human polyomavirus BK (BKPyV) infection in recipients, but giving the low genetic variability of BKPyV this subject is still controversial. The aim of this study was to determine if BKPyV replicating in kidney recipients after transplantation is always originated from the donor. Urine and blood samples from 68 pairs of living donors and kidney recipients who underwent renal transplantation from August 2010-September 2011 were screened for BKPyV by real time polymerase chain reaction. Only three recipients presented viremia. When both donors and recipients were BKPyV positive, a larger fragment of VP1 region was obtained and sequenced to determine the level of similarity between them. A phylogenetic tree was built for the 12 pairs of sequences obtained from urine and high level of similarity among all sequences was observed, indicating that homology inferences for donor and recipient viruses must be cautiously interpreted. However, a close inspection on the donor-recipient pairs sequences revealed that 3 of 12 pairs presented considerably different viruses and 4 of 12 presented mixed infection, indicating that the source of BKPyV infection is not exclusively derived from the donor. We report that about 60% of the renal recipients shed BKPyV genetically distinct from the donor, confronting the accepted concept that the donor is the main source of recipients' infection.

12.
J. appl. oral sci ; 27: e20180435, 2019. tab
Artigo em Inglês | LILACS-Express | ID: biblio-975897

RESUMO

Abstract Objectives: This study aimed to verify the presence of polyomavirus BK (BKPyV) in the saliva of kidney transplant recipients and to correlate it with blood viremia. Material and Methods: We have conducted a cross-sectional study with a sample involving 126 renal transplant recipients. 126 samples of saliva and 52 samples of blood were collected from these patients. Detection and quantification of BKPyV were performed using a real-time PCR. To compare the presence of BKPyV in blood and saliva, the binomial proportion test was used. To verify associations between salivary shedding BKPyV and post-transplant periods (in months), the Mann-Whitney test was used. Spearman's correlation was used to correlate the viral load in the saliva with blood of kidney transplant recipients. Results: The mean age of the study group was 51.11±12.45 years old, and 69 participants (54.8%) were female, with a mean post-transplantation time of 4.80±6.04 months. BKPyV was quantified in several samples of saliva and blood, with medians of 1,108 cp/mL and 1,255 cp/mL, respectively. Only 16/52 (30.8%) participants presented BKPyV in blood, and 59/126 (46.8%) excreted the virus in saliva (p=0.004). BKPyV shedding was found in patients at a shorter post-transplantation period (3.86±5.25, p=0.100). A weak correlation was observed between viral quantification in saliva and blood (Spearman's correlation coefficient=0.193). Conclusion: The results of this study suggested that, although saliva excretes more BKPyV than blood, there is no reliable correlation between salivary shedding and blood viremia, showing two independent compartments of viral replication.

13.
BMC Nephrol ; 19(1): 229, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30208881

RESUMO

BACKGROUND: Long-term outcomes in kidney transplantation (KT) have not significantly improved during the past twenty years. Despite being a leading cause of graft failure, glomerular disease (GD) recurrence remains poorly understood, due to heterogeneity in disease pathogenesis and clinical presentation, reliance on histopathology to confirm disease recurrence, and the low incidence of individual GD subtypes. Large, international cohorts of patients with GD are urgently needed to better understand the disease pathophysiology, predictors of recurrence, and response to therapy. METHODS: The Post-TrANsplant GlOmerular Disease (TANGO) study is an observational, multicenter cohort study initiated in January 2017 that aims to: 1) characterize the natural history of GD after KT, 2) create a biorepository of saliva, blood, urine, stools and kidney tissue samples, and 3) establish a network of patients and centers to support novel therapeutic trials. The study includes 15 centers in America and Europe. Enrollment is open to patients with biopsy-proven GD prior to transplantation, including IgA nephropathy, membranous nephropathy, focal and segmental glomerulosclerosis, atypical hemolytic uremic syndrome, dense-deposit disease, C3 glomerulopathy, complement- and IgG-positive membranoproliferative glomerulonephritis or membranoproliferative glomerulonephritis type I-III (old classification). During phase 1, patient data will be collected in an online database. The biorepository (phase 2) will involve collection of samples from patients for identification of predictors of recurrence, biomarkers of disease activity or response to therapy, and novel pathogenic mechanisms. Finally, through phase 3, we will use our multicenter network of patients and centers to launch interventional studies. DISCUSSION: Most prior studies of post-transplant GD recurrence are single-center and retrospective, or rely upon registry data that frequently misclassify the cause of kidney disease. Systematically determining GD recurrence rates and predictors of clinical outcomes is essential to improving post-transplant outcomes. Furthermore, accurate molecular phenotyping and biomarker development will allow better understanding of individual GD pathogenesis, and potentially identify novel drug targets for GD in both native and transplanted kidneys. The TANGO study has the potential to tackle GD recurrence through a multicenter design and a comprehensive biorepository.

14.
Artigo em Inglês | MEDLINE | ID: mdl-30229398

RESUMO

BACKGROUND AND OBJECTIVES: Elderly patients are increasingly likely to be recipients of transplants. However, the pharmacokinetics of mycophenolic acid (MPA) in this population are yet to be studied in detail. The objective of this study was to assess whether there were differences in MPA pharmacokinetic parameter values between elderly recipients and younger-adult recipients during the 6 months immediately following renal transplantation. METHODS: In this analysis, the longitudinal 12-h pharmacokinetics of MPA, administered as enteric-coated mycophenolate sodium (EC-MPS), were evaluated in 44 elderly renal transplant recipients and compared with the corresponding pharmacokinetics of MPA in 31 younger adult recipients. Measurements were performed at 7, 30, 60, 90, and 180 days post-transplantation. All patients received tacrolimus and prednisone. RESULTS: The elderly patients were 30 years older than the younger controls, with a predominance of males and Caucasians. Elderly patients had lower serum albumin than the younger controls during the first 6 months after transplantation. The mean estimated total body MPA clearance of the elderly recipients was not significantly different from that of the controls at any analyzed time point (the mean clearance across all time points was 0.31 ± 0.17 vs 0.30 ± 0.25 L/h/kg). MPA exposure, as evaluated from the area under the 12-h time versus measured MPA concentration (adjusted for dose/body weight) curve, did not differ between the groups at any time point (mean exposure across all time points was 4.68 ± 3.61 vs 5.95 ± 4.29 µg·h/mL per mg/kg for the elderly recipients and the controls). CONCLUSIONS: These data show that the pharmacokinetics of MPA in elderly renal transplant recipients were no different to those of younger-adult recipients in this study population. CLINICALTRIALS.GOV: NCT 01631058.

15.
Transpl Infect Dis ; 20(5): e12969, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30074295

RESUMO

BACKGROUND: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is a consequence of BKPyV replication in the urinary tract in kidney transplant recipients (KTR). OBJECTIVES: The objectives were to determine the prevalence of BKPyV replication and BKPyVAN, risk factors associated to sustained viremia and BKPyVAN, and viremia cut-off that best predict the occurrence of sustained viremia and nephropathy in KTR of a single University Hospital Kidney Transplant Center. PATIENTS AND METHODS: All KTR undergoing transplantation from August 2010 to December 2011 were enrolled and monitored up to 2 years posttransplantation for BKPyV viruria by decoy cells shedding or polymerase chain reaction (PCR) and viremia by PCR. Kidney biopsy was indicated if sustained viremia (two or more viremia above 10 000 copies/mL) to confirm BKPyVAN diagnosis. RESULTS: In this study, 326 transplants were performed and 246 patients were included. Prevalence of viruria was 36.9%, viremia 22.3% and nephropathy 3.2%. Male gender was the only risk factor associated to sustained viremia or nephropathy. Cut-off value of viremia that best discriminates the progression to sustained viremia and to BKPyVAN was 37 488 and 44 956 copies/mL, respectively. CONCLUSIONS: Prevalence of viruria, viremia, and nephropathy were similar to those reported in literature but the cut-off value of viremia that best discriminates the risk of progression to nephropathy was greater than the value usually reported, which is 10 000 copies/mL.

16.
J Transplant ; 2018: 8316860, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850195

RESUMO

The impact of the kinetics of the anti-HLA antibodies after KTx on the occurrence of acute rejection as well as the better time-point to monitor anti-HLA Abs after transplantation is not completely defined. This prospective study followed 150 patients over 12 months after transplantation. Serum IgG anti-HLA Abs were detected by single antigen beads after typing donors and recipients for loci A, B, C, DR, and DQ. Before KTx, 89 patients did not present anti-HLA Abs and 2% developed "de novo" Abs during the 1st year, 39 patients were sensitized without DSAs, and 13% developed DSA after surgery; all of them presented ABMR. Sensitized patients presented higher acute rejection rates (36.4% versus 13.5%, p < 0.001), although 60% of the patients did not present ABMR. Patients, in whom DSA-MFI decreased during the first two weeks after surgery, did not develop ABMR. Those who sustained their levels presented a rate of 22% of ABMR. 85% of patients developed ABMR when MFIs increased early after transplantation (which occurred in 30% of the DSA positive patients). In the ABMR group, we observed an iDSA-MFI sharp drop on the fourth day and then an increase between the 7th and 14th POD, which suggests DSA should be monitored at this moment in sensitized patients for better ABMR prediction.

17.
Transpl Infect Dis ; 20(4): e12923, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29797681

RESUMO

The incidence of urinary tract infection (UTI) after kidney transplantation (KT) caused by multidrug-resistant (MDR) bacteria is growing. The aim of this study was to analyze the impact of UTI caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) in the survival of graft and recipients following KT. This was a retrospective cohort study involving patients who underwent KT between 2013 and 2016. Patients were followed since the day of the KT until loss of graft, death or end of the follow-up period (31th December 2016). The outcomes measured were UTI by MDR following KT and graft and patient survival. Analyses were performed using Cox regression; for the graft and patient survival analysis, we used a propensity score for UTI by CR-GNB to matching a control group. UTI was diagnosed in 178 (23.9%) of 781 patients, who developed 352 UTI episodes. 44.6% of the UTI cases were caused by MDR bacteria. Identified risk factors for UTI by MDR bacteria were DM, urologic disease as the cause of end-stage renal failure, insertion of ureteral stent, carbapenem use, and delayed graft function (DGF). Risk factors for death during the follow-up period were female gender, patients over 60 years old at the time of KT, DM, body mass index over 31.8, UTI caused by CR-GNB. In conclusion, UTIs caused by CR-GNB have great impact on patients' survival after KT.


Assuntos
Carbapenêmicos/farmacologia , Rejeição de Enxerto/epidemiologia , Bactérias Gram-Negativas/fisiologia , Transplante de Rim/efeitos adversos , Infecções Urinárias/epidemiologia , Resistência beta-Lactâmica , Fatores Etários , Função Retardada do Enxerto/epidemiologia , Feminino , Seguimentos , Rejeição de Enxerto/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Incidência , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
18.
Ther Drug Monit ; 40(4): 411-416, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29746396

RESUMO

BACKGROUND: Enteric-coated mycophenolate sodium is frequently used in renal transplantation. The pharmacokinetic profile of mycophenolic acid (MPA) shows a broad range of time-to-maximum concentration (Tmax) that limits the use of a single MPA concentration to calculate the area under the time-concentration curve (AUC). For both research and clinical MPA monitoring, measuring a complete AUC is troublesome to the center and patients. METHODS: We obtained 171 complete MPA-AUC12h (0, 20, 40, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes) from 59 adult (54 ± 16 years) patients (29 men and 43 whites) who have been receiving stable doses of tacrolimus/enteric-coated mycophenolate sodium and steroids. We used the 59 curves drawn at 31 ± 4 days after transplantation to develop the abbreviated equations, and the remaining 112 curves drawn at 109 ± 59 days were used to validate them. We used 5 other proposed equations to estimate MPA-AUC (eAUC) (4 with enzyme-multiplied immunoassay technique assay and one with high-performance liquid chromatography [HPLC]) and then used these results to compare with our measured AUC, the bias, and the 10% and 30% accuracy. MPA was measured by ultraperformance liquid chromatography coupled to a tandem mass spectrometry, and AUC was calculated by the trapezoidal rule. RESULTS: For both MPA-measuring methods, enzyme-multiplied immunoassay technique and ultraperformance liquid chromatography coupled to a tandem mass spectrometry, the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) equations, and others that measure MPA up to 6 hours after the dose had an acceptable low bias with more results in the 10%-30% range than those using data collected until 4 hours. A highly adequate eAUC is obtained using blood collected at 8 hours. CONCLUSIONS: This analysis offers blood-sampling alternatives for MPA monitoring depending on the precision needed.

19.
Transpl Infect Dis ; 20(5): e12929, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29809309

RESUMO

BACKGROUND: Anti-thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. METHODS: We studied a retrospective cohort of 423 RTx (2010-2014) CMV-seropositive adults given ATG induction therapy. RESULTS: 54 (13%) patients developed CMV disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no-CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤40 ml/min/1.73 m2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤45 and lymphocyte count ≤800 cells/mm3 at the end of prophylaxis remained predictive of late CMV disease occurrence. CONCLUSIONS: These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease.

20.
PLoS One ; 13(5): e0197994, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29799857

RESUMO

PURPOSE: Osteoblasts and adipocytes are derived from mesenchymal stem cells. An imbalance in the differentiation of these lineages could affect the preservation of bone integrity. Several studies have suggested the importance of this imbalance in the pathogenesis of osteoporosis after kidney transplant (KT), but the role of bone marrow adiposity in this process is not well known, and if the treatment with the anti-absorptive (zoledronic acid-ZA) drugs could attenuate bone loss. Thus, our objective was compare bone marrow adiposity, osteoblasts and osteocytes before and after KT, verify an association between bone remodeling process (Turnover, Volume, and Mineralization-TMV classification), the osteocyte sclerostin expression to evaluate if there is a role of Wnt pathway, as well as the effect of ZA on these cells. METHODS: We studied 29 new living-donor KT patients. One group received ZA at the time of KT plus cholecalciferol for twelve months, and the other group received only cholecalciferol. Bone biopsies were performed at baseline and after 12 months of treatment. Histomorphometric evaluation was performed in bone and bone marrow adipocytes. Sclerostin (Scl) expression in osteocytes was evaluated by immunohistochemistry. RESULTS: Some bone marrow adiposity parameters were increased before KT. After KT, some of them remained increased and they worsened with the use of ZA. In the baseline, lower bone Volume and Turnover, were associated with increased bone marrow adiposity parameters (some of them). After KT, both groups showed the same associations. Osteocyte Scl expression after KT decreased with the use of ZA. We observed also an inverse association between bone adiposity parameters and lower osteocyte sclerostin expression 12 months after KT. CONCLUSION: In conclusion, the present study suggests that KT fails to normalize bone marrow adiposity, and it even gets worse with the use of ZA. Moreover, bone marrow adiposity is inversely associated with bone Volume and Turnover, which seems to be accentuated by the antiresorptive therapy.


Assuntos
Adiposidade/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Difosfonatos/farmacologia , Imidazóis/farmacologia , Transplante de Rim , Vitamina D/farmacologia , Adulto , Medula Óssea/fisiologia , Remodelação Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Proteína 1 de Leucemia Linfocítica Aguda de Células T/metabolismo , Adulto Jovem , Ácido Zoledrônico
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