Lack of Impact of Acute Pyelonephritis on Kidney Graft Survival.

BACKGROUND: Urinary tract infection is the most common bacterial infection after kidney transplant. Some studies suggested that urinary tract infection could impair graft survival, but this issue remains debated. The objective of this study was to analyze the association between acute pyelonephritis (APN) and the risk of kidney graft failure. METHODS: We performed a retrospective cohort study including patients who received a kidney transplant from 2001 to 2009 at a university hospital in Rio de Janeiro, Brazil. They were followed until December 2015. The primary outcome was graft failure. Follow-up of patients who died with a functioning graft was censored on the date of death. Cox proportional hazards method was used in multivariable analysis to assess risk factors for graft failure. The occurrence of the first episode of APN and acute rejection were modeled as time-dependent variables. RESULTS: A total of 587 patients were included. Of these, 112 recipients (19%) developed 173 episodes of APN. Graft failure occurred in 150 patients (25%) after a median follow-up of 79 months. The factors associated with graft failure in the multivariate analyses were age of the transplant recipient (hazard ratio [HR], 0.97 per year; 95% confidence interval [CI], 0.96-0.99; P < .01), occurrence of delayed graft function (HR, 2.42; 95% CI, 1.72-3.40; P < .01), and acute rejection (HR, 2.71; 95% CI, 1.92-3.82; P < .01). There was no association between APN and graft failure (HR, 1.05; 95% CI, 0.65-1.68; P = .85). CONCLUSIONS: Our results suggest that the occurrence of APN is not associated with a significant reduction in graft survival after kidney transplant.

Prevalence of occult hepatitis B virus infection in kidney transplant recipients.

In this cross-sectional study, 207 hepatitis B surface antigen (HBsAg)-negative kidney transplant recipients were evaluated based on demographic and epidemiological data and on the levels of serological markers of hepatitis B virus (HBV) and hepatitis C virus infection and liver enzymes. Patients with HBV or human immunodeficiency virus infection were excluded. Sera were analysed for the presence of HBV-DNA. HBV-DNA was detected in two patients (1%), indicating occult hepatitis B (OHB) infection (the HBV-DNA loads were 3.1 and 3.5 IU/mL in these patients). The results of the liver function tests were normal and no serological markers indicative of HBV infection were detected. The prevalence of OHB infection was low among kidney transplant recipients, most likely due to the low HBsAg endemicity in the general population of the study area.

Prevalence of occult hepatitis B virus infection in kidney transplant recipients

In this cross-sectional study, 207 hepatitis B surface antigen (HBsAg)-negative kidney transplant recipients were evaluated based on demographic and epidemiological data and on the levels of serological markers of hepatitis B virus (HBV) and hepatitis C virus infection and liver enzymes. Patients with HBV or human immunodeficiency virus infection were excluded. Sera were analysed for the presence of HBV-DNA. HBV-DNA was detected in two patients (1%), indicating occult hepatitis B (OHB) infection (the HBV-DNA loads were 3.1 and 3.5 IU/mL in these patients). The results of the liver function tests were normal and no serological markers indicative of HBV infection were detected. The prevalence of OHB infection was low among kidney transplant recipients, most likely due to the low HBsAg endemicity in the general population of the study area.

A qualitative seminested PCR assay as an alternative to urine cytology for BK polyomavirus screening after renal transplantation.

OBJECTIVE: Polyomavirus-associated nephropathy (PVAN) is a major cause of graft dysfunction after kidney transplantation. Therefore, routine screening for BK polyomavirus (BKV) infection with urine cytology or quantitative PCR-based assays has been recommended. Although less expensive than quantitative tests, qualitative PCR assays are not recommended for screening based on the assumption that their diagnostic accuracy is inferior to urine cytology. However, studies comparing the performance of both methods are scarce. METHODS: We compared the accuracy between a qualitative seminested PCR (snPCR) assay and urine cytology for the screening of BKV viruria in 104 renal transplant recipients. RESULTS: The snPCR assay was more sensitive than cytology (100 and 61%, respectively), yielding better negative predictive value (100 vs. 90%). In 7 (39%) of the 18 PVAN cases, BKV infection was detected exclusively by snPCR. Although the specificity of snPCR (63%) was lower than cytology (74%), their positive predictive values were similar (36 vs. 33%, respectively). In ROC curve analysis, the accuracy of snPCR was significantly higher (p = 0.03). CONCLUSION: This qualitative snPCR assay was more accurate than urine cytology for the detection of BKV viruria in renal transplant patients.

The influence of carbapenem resistance on mortality in solid organ transplant recipients with Acinetobacter baumannii infection.

BACKGROUND: Infection with carbapenem-resistant Acinetobacter baumannii has been associated with high morbidity and mortality in solid organ transplant recipients. The main objective of this study was to assess the influence of carbapenem resistance and other potential risk factors on the outcome of A. baumannii infection after kidney and liver transplantation. METHODS: Retrospective study of a case series of A. baumannii infection among liver and renal transplant recipients. The primary outcome was death associated with A. baumannii infection. Multivariate logistic regression was used to assess the influence of carbapenem resistance and other covariates on the outcome. RESULTS: Forty-nine cases of A. baumannii infection affecting 24 kidney and 25 liver transplant recipients were studied. Eighteen cases (37%) were caused by carbapenem-resistant isolates. There were 17 (35%) deaths associated with A. baumannii infection. In unadjusted analysis, liver transplantation (p = 0.003), acquisition in intensive care unit (p = 0.001), extra-urinary site of infection (p < 0.001), mechanical ventilation (p = 0.001), use of central venous catheter (p = 0.008) and presentation with septic shock (p = 0.02) were significantly related to a higher risk of mortality associated with A. baumannii infection. The number of deaths associated with A. baumannii infection was higher among patients infected with carbapenem-resistant isolates, but the difference was not significant (p = 0.28). In multivariate analysis, the risk of A. baumannii-associated mortality was higher in patients with infection acquired in the intensive care unit (odds ratio [OR] = 34.8, p = 0.01) and on mechanical ventilation (OR = 15.2, p = 0.04). Appropriate empiric antimicrobial therapy was associated with significantly lower mortality (OR = 0.04, p = 0.03), but carbapenem resistance had no impact on it (OR = 0.73, p = 0.70). CONCLUSION: These findings suggest that A. baumannii-associated mortality among liver and kidney transplant recipients is influenced by baseline clinical severity and by the early start of appropriate therapy, but not by carbapenem resistance.

Immunosuppressants: implications in Orthodontics

INTRODUCTION: There are medications capable of affecting bone metabolism and the rate of tooth movement. Among these medications are the immunosuppressants, which act by repressing the action of T lymphocytes, however they can cause bone loss and consequently lead to osteoporosis. Osteoporosis is a common complication following kidney, heart, liver or lung transplantation. The immunosuppressant treatment for preventing organ rejection after transplantation, in general, includes glucocorticoids, cyclosporine, tacrolimus, and sirolimus. All these drugs can have jeopardizing effects on bone mineral homeostasis and consequently influence tooth movement. In recent years, however, the increasing use of immunosuppressants has raised questions about their effects on bone metabolism in patients undergoing orthodontic treatment. OBJECTIVE: The objective of this review study was to inform orthodontists about the influence of immunosuppressants on bone metabolism and tooth movement.

Simultaneous cytomegalovirus and Mycobacterium tuberculosis infection presenting as hemorrhagic colitis 3 years after a kidney transplant.

Cytomegalovirus is an important cause of colonic disease in solid organ transplant recipients. Although several reports have shown that simultaneous infection with other pathogens may aggravate the course of cytomegalovirus colitis, to our knowledge, no case of colitis caused by simultaneous cytomegalovirus and Mycobacterium tuberculosis has been previously reported. We describe a case of hemorrhagic colitis associated with simultaneous cytomegalovirus/ Mycobacterium tuberculosis infection in a 26-year-old woman, 38 months after a kidney transplant. Initial results of histopathologic analyses of gastrointestinal biopsies showed that tuberculosis was the only cause of colitis, as no morphologic alteration suggestive of cytomegalovirus infection was observed on hematoxylin-eosin staining. However, further analysis with immunoperoxidase staining confirmed the clinical suspicion of cytomegalovirus infection. This report shows that cytomegalovirus/tuberculosis coinfection may be a cause of late-onset colitis among solid organ transplant recipients. It also illustrates that coinfection with other pathogens may pose an additional challenge for diagnosing gastrointestinal cytomegalovirus disease.

Molecular characterization of BK polyomavirus subtypes in renal transplant recipients in Brazil.

BK polyomavirus (BKV) is highly prevalent in the world population. Different reports indicate that BKV subtypes and subgroups present an uneven geographical distribution which might be correlated with human migration. However, there is a lack of data on the BKV subtype distribution in the South American population. The occurrence of BKV subtypes and subgroups detected in 51 kidney transplant recipients in Rio de Janeiro, Brazil is described. According to genetic studies, the population in this region descends mainly from European or African immigrants, with a relatively low genetic background from the Amerindians. By sequencing the VP1 region of BKV, subgroups Ib1 and Ia of subtype I were found in 34 (67%) and 15 (29%), respectively, of samples, while subtype II was present in 2 (4%) of the samples. Subtypes III and IV were not detected. Phylogenetic analysis indicated similarities between Brazilian BKV subgroup Ia and East African lineages; and subgroup Ib-1 with Asian and North American lineages, while subtype II samples were similar to sequences from Japan and the UK. This is the first report that describes distribution of BKV subtypes in South America. The high prevalence of BKV subgroup Ia probably reflects the high proportion of African descendants in this population. On the other hand, the predominance of subgroup Ib-1 and the absence of Ib-2 in an area with a high proportion of European ancestry was unexpected. Further studies in South American populations are needed to provide a better understanding of the epidemiology of BKV in this region.

Evaluation of atherosclerosis in renal transplanted patients by non-invasive methods.

BACKGROUND: Endothelial dysfunction can be considered an early atherogenic event. OBJECTIVE: To assess atherosclerosis in renal transplanted patients through the coronary calcium score, carotid duplex scan and brachial reactivity through ultrasonography. METHODS: We assessed 30 renal transplanted male patients with stable renal function, with a mean age of 41.3 years. RESULTS: The detection of the atherosclerotic load in this population was very significant when the brachial reactivity technique was used (86.7%); it was less frequent when based on the presence of carotid plaque (33.3%) or the coronary calcium score (20%). The carotid plaque was considered when the thickness was > 12 mm. The coronary calcium score was abnormal when > 80 according to the Agatston scale, being observed in a low percentage of patients (21.7%), possibly due to the fact that the tomography is not the ideal method to detect atherosclerosis in renal patients, as it does not differentiates intimal calcifications of the medial layer. The adequate clinical control, the low age range and the factors related to the time of pre-transplant dialysis or the anti-inflammatory effect of the post-transplant drugs can delay the onset of the calcifications. CONCLUSION: The evaluation of the atherosclerotic load through the carotid duplex scan (33,3%) and the coronary calcium score (20%) was not frequent; there was no correlation with the high rate of endothelial dysfunction detection observed with the brachial reactivity assessment (86.7%).

Avaliação de aterosclerose em transplantados renais através de métodos não invasivos / Evaluation of atherosclerosis in renal transplanted patients by non-invasive methods / Evaluación de aterosclerosis en trasplantados renales mediante métodos no invasivos

Fundamento: A disfunção endotelial pode ser considerada um evento precoce da aterogênese. Objetivo: Avaliar a aterosclerose em transplantados renais através do escore de cálcio coronariano, do duplex scan das carótidas e da reatividade braquial através do ultra-som. Métodos: Avaliamos trinta transplantados renais do sexo masculino com função renal estável, idade média de 41,3 anos.Resultados: A detecção da carga aterosclerótica nesta população foi significativa quando utilizada a técnica da reatividade braquial (86,7%), menos freqüente baseando-se na presença de placa carotídea (33,3%) ou no escore de cálcio coronariano (20%). Placa carotídea foi considerada quando a espessura era superior a 12 mm. O escore de cálcio coronariano foi anormal quando acima de oitenta pela escala de Agatston, sendo observado em um percentual baixo (21,7%) dos pacientes, possivelmente porque a tomografia pode não ser o método ideal para detectar aterosclerose em doentes renais, por não distinguir calcificações intimais da camada média. O controle clínico adequado, a baixa faixa etária e fatores relacionados ao tempo de diálise pré-transplante ou ao efeito antiinflamatório das drogas pós- transplante podem retardar o aparecimento das calcificações. Conclusão: A avaliação da carga aterosclerótica através do duplex scan das carótidas (33,3%) e do escore de cálcio coronariano (20%) não foi freqüente, não havendo correlação com o elevado índice de detecção de disfunção endotelial observado com o exame da reatividade braquial (86,7%).

Background: Endothelial dysfunction can be considered an early atherogenic event. Objective: To assess atherosclerosis in renal transplanted patients through the coronary calcium score, carotid duplex scan and brachial reactivity through ultrasonography.Methods: We assessed 30 renal transplanted male patients with stable renal function, with a mean age of 41.3 years. Results: The detection of the atherosclerotic load in this population was very significant when the brachial reactivity technique was used (86.7%); it was less frequent when based on the presence of carotid plaque (33.3%) or the coronary calcium score (20%). The carotid plaque was considered when the thickness was > 12 mm. The coronary calcium score was abnormal when > 80 according to the Agatston scale, being observed in a low percentage of patients (21.7%), possibly due to the fact that the tomography is not the ideal method to detect atherosclerosis in renal patients, as it does not differentiates intimal calcifications of the medial layer. The adequate clinical control, the low age range and the factors related to the time of pre-transplant dialysis or the anti-inflammatory effect of the post-transplant drugs can delay the onset of the calcifications. Conclusion: The evaluation of the atherosclerotic load through the carotid duplex scan (33,3%) and the coronary calcium score (20%) was not frequent; there was no correlation with the high rate of endothelial dysfunction detection observed with the brachial reactivity assessment (86.7%).

Fundamento: Se puede considerar la disfunción endotelial como un evento precoz de la aterogénesis. Objetivo: Evaluar la aterosclerosis en trasplantados renales con el empleo del score de calcio coronario y del duplex scan de las carótidas y la reactividad braquial mediante el ultrasonido. Métodos: Evaluamos a 30 trasplantados renales del sexo masculino con función renal estable, edad promedio de 41,3 años. Resultados: La detección de la carga aterosclerótica en esta población fue significativa cuando utilizada la técnica de la reactividad braquial (86,7%), menos frecuente, basándose en la presencia de placa carotídea (33,3%) o en el score de calcio coronario (20%). Se tomó en cuenta la placa carotídea cuando el espesor era superior a 12 mm. El score de calcio coronario fue anormal cuando >80 por la escala de Agatston, y se lo observó en un porcentaje bajo (21,7%) de los pacientes, posiblemente porque la tomografía puede no ser el método ideal para detectar aterosclerosis en enfermos renales, por no distinguir calcificaciones intimales de la capa media. El control clínico adecuado, la baja franja de edad y factores relacionados al tiempo de diálisis pre-transplante o al efecto antiinflamatorio de los fármacos post-trasplante pueden retardar el aparecimiento de las calcificaciones. Conclusión: La evaluación de la carga aterosclerótica con el empleo del duplex scan de las carótidas (33,3%) y del score de calcio coronario (20%) no fue frecuente, no habiendo correlación con el elevado índice de detección de disfunción endotelial observado con el examen de la reactividad braquial (86,7%).

Histomorphometric study of alveolar bone after therapy with immunosuppressant FK506

Aim: Several medications affect bone metabolism and the rate of tooth movement. The objective of the present study was to test the hypothesis that treatment with immunosuppressant tacrolimus (FK506) can interfere with bone turnover, decreasing the rate of tooth movement. Methods: Sixty male Wistar rats were divided into four groups of 15 animals each: Group 1: rats subjected to orthodontic movement plus treatment with saline solution vehicle; Group 2: rats subjected to orthodontic movement plus treatment with FK506; Group 3: rats treated with FK506 only; and Group 4: rats treated with saline solution vehicle only. The FK506 dose was 2 mg/kg/day. The treatment was initiated 14 days before the appliance installation and then kept for up to 14 days. In addition to the administration of the immunosuppressive drug, 10 mg/kg of oxytetracycline were injected at intervals of three days in order to show osteoblastic activity and bone growth at a histological level. Results: Histomorphometrical measurements showed greater tooth movement in Group 1 than in Group 2 at all periods (days 3, 7 and 14), though significant difference (p < 0.05) was observed only on days 7 and 14. Conclusions: FK506 significantly influenced the rate of tooth movement in rats subjected to the application of this medication.

Influência dos imunossupressores no metabolismo ósseo e movimento dentário: revisão de literatura / Influence of immunosuppressants on bone metabolism and tooth movement: a literature review

O objetivo desta revisão de literatura é discutir a influência dos imunossupressores no metabolismo ósseo e movimento dentário em Ortodontia. O movimento dentário ocorre em função do processo de remodelação do tecido ósseo e do ligamento periodontal. Existem medicamentos capazes de afetar o metabolismo ósseo e a taxa de movimento dentário, tais como os imunossupressores. Os imunossupressores agem reprimindo a ação dos linfócitos T, podem causar perda óssea e levar a um quadro de osteoporose, a qual é uma complicação comum após os transplantes de rim, coração, fígado e pulmão. Os esquemas imunossupressores para evitar a rejeição do órgão enxertado após o transplante frequentemente incluem glicocorticóides, ciclosporina A, tacrolimus e sirolimus, os quais podem causar efeitos danosos sobre a homeostase mineral óssea. O movimento dentário é dependente da força ortodôntica, dose e duração da terapia imunossupressora, além da resposta individual de cada indivíduo. Assim, todos os pacientes transplantados e usuários de imunossupressores deveriam ser submetidos a monitoramento e prevenção de perda óssea antes e durante o tratamento ortodôntico.

The objective of this literature review is to discuss the influence of immunosuppressants on bone metabolism and tooth movement in Orthodontics. Tooth movement occurs as a result of bone and periodontal ligament remodeling. Some medications such as immunosupressants can affect bone metabolism and the rate of tooth movement. Immunosupressants act by repressing the action of T lymphocytes, may cause bone loss, and lead to osteoporosis, which is a common complication following kidney, heart, liver, or lung transplantation. The use of immunosuppressants to prevent rejection after organ transplantation includes glucocorticoids, cyclosporine A, tacrolimus, and sirolimus, which may cause damaging effects on the bone mineral homeostasis. Tooth movement depends on orthodontic force, dosage, and duration of immunosuppressive therapy, and individual response of each patient. Therefore, all patients who have received transplants should be closely monitored to prevent bone loss before and during orthodontic treatment.

Avaliação do esquema de imunossupressão composto por sirolimo, ciclosporina e prednisona em um grupo de receptores de enxerto renal / Evaluation of the immunossupressive regimen composed of sirolimus, cyclosporin and prednisone in a group of renal graft recipients

Os inibidores da calcineurina causam hipertensão arterial, dislipidemia, hiperglicemia, nefrotoxicidade e reduzem o ritmo de filtração glomerular,contribuindo para a nefropatia crônica do enxerto. Sendo assim, o principal objetivo deste estudo foi avaliar se a suspensão da ciclosporina do esquematríplice sirolimo, ciclosporina e prednisona conduziria a uma melhora da função renal, sem o comprometimento da eficácia e da segurança do esquema de imunossupressão. Avaliamos treze pacientes, os quais foram separados randomicamente em dois grupos: um grupo com 7 pacientes (GI), em que aciclosporina foi mantida em baixas doses após o terceiro mês, e outro grupo com 6 pacientes (GII), em que a ciclosporina foi suspensa após o 3º mês. O esquema de imunossupressão foi semelhante até o 3º mês. Os resultados mostraram que a função renal foi significativamente maior no GII no 12º mês de pós-transplante, quantificada pelo clearance da creatinina estimado pela equação de Cockcroft-Gault no 12º mês (GI vs GII, 40,40±18,07 vs72,8±18,73ml/min, respectivamente, P<0,05). Não observamos episódio de rejeição aguda e houve melhor controle da pressão arterial no grupo GII apóso terceiro mês. Além disso, o nível de LDL-colesterol foi maior no grupo GI quando comparado ao GII ao final do 12º mês (194,2±49,2 and 133,0±12,8,respectivamente, P<0,05). Em conclusão, no grupo em que houve a suspensão da ciclosporina após o terceiro mês pós-transplante renal, encontramos um melhor controle da pressão arterial, menor colesterol LDL, e uma melhor função renal ao final do 12º mês de terapia. Estes fatores podem contribuir para um aumento da sobrevida de pacientes e enxertos a médio e longo prazo.

The calcineurin inhibitors cause arterial hypertension, dyslipidemia, hyperglycemia, nephrotoxicity, and decrease in glomerular filtration rate, thus contributing to chronic allograft nephropathy. Therefore, the main objective of this study was to investigate whether the withdrawal of cyclosporin from thetriple therapy, which includes sirolimus, cyclosporin and prednisone, would lead to an improvement of renal function without affecting the efficacy and safetyof the immunossupression. We then evaluated thirteen patients, which were randomized into two groups: one group (GI), with 7 patients, cyclosporin waskept in low doses after the 3rd month, and the other group (GII), comprised of 6 patients, in which cyclosporin was withdrawn after the 3rd month. Bothgroups had similar immunossupression regimen until the 3rd month. The results showed that the renal function was significantly higher in GII at the end ofthe 12th month, as estimated by the Cockcroft-Gault equation (GI vs GII, 40.40±18.07 vs 72.8±18.73ml/min, respectively, P<0.05). After the 3rd month there was no acute rejection episode, and the hypertension was better controlled in the group GII after the 3rd month. In addition, the level of LDL-cholesterol washigher in GI, compared to GII at the end of the 12th month (194.2±49.2 and 133.0±12.8, respectively, P<0.05). In conclusion, the group in which cyclosporine was withdrawn after the third month post renal transplantation, we found better control of arterial pressure, lower LDL-colesterol, and increased renal functionat the end of the 12th month of therapy. These factors may contribute to an increase in medium and long-term graft and patients survival.

Pseudo-aneurisma arterial pós-transplante renal / Posttransplant renal artery pseudoaneurysm

Vascular complications after kidney transplantation have been described and pseudoaneurysms represent a well-recognized vascular complication. Although the incidence of pseudoaneurysm is low, it may potentially cause graft loss or may even be fatal for the patients if it is not diagnosed and treated quickly. The authors report a case of renal artery pseudoaneurysm diagnosed two months posttransplantation with cadaveric graft, the treatment and literature data.

Perinephric abscess caused by Streptococcus agalactiae after renal transplantation.

We describe the case of a 37 year-old diabetic woman who presented with a multiloculated perinephric abscess caused by Streptococcus agalactiae 12 months after receiving a living-related kidney graft. Infection was successfully treated with surgical drainage and a four-week course of antibiotic therapy. To our knowledge, this is the first report of a perinephric abscess caused by this agent in a renal transplant recipient.

Avaliação de transplantes renais utilizando-se 99mTc-leucócitos mononucleares / Evaluation of renal allografts using 99mTc-mononuclear leukocytes

A rejeição aguda do enxerto renal deve ser diagnosticada precocemente, uma vez que a reversibilidade da rejeição está relacionada com a rapidez na qual o tratamento é iniciado. Os objetivos deste estudo foram: 1) estabelecer um método quantitativo para avaliação da rejeição e necrose tubular aguda (NTA) do rim transplantado; 2) determinar o papel em potencial da cintilografia com leucócitos mononucleares marcados com tecnécio-99m no diagnóstico precoce da rejeição do rim transplantado e no diagnóstico diferencial da NTA. Cento e sessenta estudos cintilográficos foram realizados no primeiro e no quinto dia pós-operatório em 80 pacientes transplantados. Células autólogas foram utilizadas para marcação. Imagens foram obtidas 30 minutos, 3 horas e 24 horas após injeção de 444 MBq (12 mCi) das células marcadas. Houve captação anormal das células marcadas em 27 de 31 casos de rejeição e em seis de oito casos de NTA. Os resultados foram comparados com a clínica de cada paciente. Ultra-sonografias com Doppler detectaram 18 de 31 casos de rejeição. A sensibilidade e a especificidade para rejeição foram, respectivamente, de 87,1 por cento e 100 por cento para a cintilografia e 58,1 por cento e 100 por cento para a ultra-sonografia. Foram realizadas biópsias em oito pacientes, que mostraram sete rejeições e uma NTA. Os resultados sugerem que a cintilografia com leucócitos mononucleares marcados com tecnécio-99m pode ser útil no diagnóstico de rejeição e diagnóstico diferencial de NTA.