Introdução: o transplante renal é o tratamento de escolha para uma significativa porção dos pacientes com perda crônica terminal da função renal. A rejeição aguda é uma importante complicação pós-transplante e entre outras disfunções agudas tem na biópsia do enxerto o padrão ouro para o seu diagnóstico. No entanto as biópsias apresentam uma série de limitações e riscos sendo necessário que se desenvolva biomarcadores não invasivos capazes de identificar disfunções do enxerto. Objetivos: analisar e quantificar a expressão dos microRNAs miR-142-3p, miR-155 e miR-210 em amostras de sangue periférico, urina e tecido renal coletadas de pacientes que submetidos à transplante renal que desenvolveram disfunção do enxerto. Métodos: estudo com delineamento transversal e executado no Laboratório de Biologia Molecular aplicado à Nefrologia (LABMAN), do Centro de Pesquisa Experimental do Hospital de Clínicas de Porto Alegre. As amostras são de pacientes submetidos a transplante renal que necessitaram de biópsia, por critério clínico. A expressão dos miRNAs miR-142-3p, miR-155 e miR-210 nos materiais biológicos (tecido renal, sangue periférico e células do sedimento urinário) foi avaliada através da técnica de reação em cadeia da polimerase quantitativo em tempo real. Resultados: foi encontrada, no sangue periférico uma diminuição estatisticamente significativa na expressão do miR-142-3p no grupo de pacientes com rejeição aguda (n=23) quando comparado ao grupo com outras causas de disfunção do enxerto (n=68) (P = 0,01). Não houve diferença entre os grupos na expressão do miR-155 e do miR-210, tampouco para o miR142-3p nos demais compartimentos. Conclusão: miR-142-3p mostra uma expressão diferenciada de rejeição aguda de enxertos renais, há um envolvimento deste marcador no grupo de biomarcadores moleculares em potencial para a disfunção do enxerto renal. / Background: kidney transplantation is the treatment of choice for a significant portion of patients with end-stage kidney disease. Acute rejection is a major post-transplant complication among other acute disorders and has on graft biopsy the gold standard for diagnosis. Biopsy, however it is an invasive and potentially harmful procedure so it is desirable to develop new noninvasive markers for diagnosing graft dysfunction. Objective: to analyze and quantify the expression of microRNAs miR-142-3p, miR-155 and miR-210 in the peripheral blood, urinary sediment and kidney tissue obtained from patients who developed graft dysfunction after kidney transplantation. Methods: crosssectional study performed at the Laboratory of Molecular Biology applied to Nephrology (Labman), Center of Experimental Research from Hospital de Clinicas de Porto Alegre. The samples are from kidney transplant patients who undertook indication biopsies as a part of investigation of graft dysfunction. Micro-RNAs expression was evaluated by quantitative real-time polymerase chain reaction. Results: it was found that in peripheral blood, a significant decrease in the expression of miR-142-3p occurred in patients with acute rejection (n = 23) as compared to the group of patients with other causes of graft dysfunction (n = 68), (P = 0.01). No other significant differences were found in gene expression of miR-155 and miR-210, neither for miR142-3p in the other urine or kidney tissue. Conclusion: miR-142-3p presents differential expression in the peripheral blood of patients with rejecting kidney grafts. The role of miRNAs as biomarkers for kidney graft dysfunction is worth be further explored.

Introdução: A globulina anti-timocitária (ATG) é um anticorpo policlonal depletor de linfócitos amplamente utilizado no transplante de órgãos. O monitoramento deste agente em receptores de transplante renal pode ser realizado por contagem de linfócitos totais e células T CD3+ no sangue periférico. Objetivo: Avaliar a correlação entre estas duas formas de monitorização. Métodos: Estudo retrospectivo, centro único, avaliou 226 pacientes que receberam enxerto renal entre 2008 e 2013 e que foram tratados com ATG para terapia de indução ou para tratamento de rejeição celular aguda grave. A primeira dose foi administrada no intra-operatório e as subsequentes de acordo com os níveis de células T CD3+ ou número de linfócitos totais no sangue periférico. Os coeficientes de correlação e concordância foram avaliados em amostras pareadas. Resultados: No total 664 amostras pareadas foram analisadas para o número de linfócitos totais e células T CD3+. O coeficiente de correlação de Spearman enre os resultados foi 0.416 (P <0.001) para a amostra geral, 0.435 (P < 0.001) para os pacientes em indução e 0.285 (P<0.005) para os pacientes em tratamento de rejeição. O coeficiente de concordância Kappa entre as amostras gerais foi 0.267 (P < 0.001), 0.280 (P < 0.001) para indução e 0.155 (P<0.081) para pacientes em tratamento. Os parâmetros diagnósticos para a contagem de linfócitos totais foram calculados usando o número de células T CD3+ como padrão-ouro com o ponto de corte de > 20 células/mm³. Na curva ROC o melhor ponto (256 linfócitos/mm3) apresenta área sobre a curva de 0.71 (95% CI: 0.67-0.75) com sensibilidade de 66.8%, especificidade 66.5%, valor preditivo positivo 46.6% e valor preditivo negativo 82.1%. Conclusão: Baseados nestes resultados consideramos que a monitorização da administração e do intervalo das doses de ATG deva ser realizada através da contagem de células T CD3+, por citometria de fluxo, em detrimento dos linfócitos totais no sangue periférico. / Background: Anti-thymocyte globulin (ATG) is a preparation of depleting antibodies largely utilized in organ transplantation. The monitoring of this agent in renal transplant recipients can be accomplished by counting total lymphocytes and CD3+T cells in the peripheral blood. Objective: Evaluated the correlation between these two measurements. Methods: Retrospective study, single center study that evaluated 226 patients who received a kidney graft between 2008 and 2013 and where treated with ATG either for induction therapy or for treatment a severe acute cellular rejection. The first dose was given intra-operatively and subsequent doses were administered according to the levels of CD3+ T cells or number of total lymphocytes in the peripheral blood. Correlation and concordance coefficients were evaluated in paired samples. Results: A total of 664 paired samples were analyzed for the number of lymphocytes and CD3+ T. The Spearman’s correlation coefficient between the results was 0.416 (P < 0.001) to all samples, 0.435 (P < 0.001) for induction therapy samples and 0.285 (P<0.005) for therapeutic samples. The Kappa’s concordance coefficient between samples was 0.267 (P < 0.001) to all samples, 0.280 (P < 0.001) for induction therapy samples and 0.155 (P<0.081) for therapeutic samples. The diagnostic parameters for the total lymphocyte counting were calculated using number of CD3+ T cells as the gold standard at the cut off at > 20 cells/mm³. At the ROC curve using the best cut off (256 lymphocytes/mm3) an AUC of 0.71 (95% CI: 0.67-0.75) was found along with a sensitivity 68.8%, specificity 66.5%, positive predictive value 46.6% and negative predictive value 82.1%. Conclusion: Based upon these results it is not possible to reliably replace the flow cytometric assay for CD3+ T cells by the counting of total lymphocytes in the peripheral blood in the monitoring of ATG administration in kidney transplant recipients.

INTRODUÇÃO: O objetivo deste estudo foi avaliar prospectivamente os anticorpos anti-HLA após o transplante renal e associar estes achados com episódios de rejeição aguda, marcação por C4d e sobrevida do enxerto. MÉTODOS: Foram avaliados 926 soros de 111 pacientes no primeiro ano pós-transplante ou até a perda do enxerto. Os anticorpos foram analisados por PRA-ELISA (Panel Reactive Antibodies by Enzyme Linked Immuno Sorbent Assay). Anticorpos anti-HLA doador-específicos foram detectados por provas-cruzadas e caracterizados pelo método de microesferas marcadas com antígenos HLA. Episódios de rejeição aguda foram classificados conforme os Critérios de Banff 97, atualizados em 2003. RESULTADOS: Conforme o PRA-ELISA pós-transplante os pacientes foram classificados em 5 Grupos: Grupo A (n=80): sem evidência de anticorpos pré e pós-transplante; Grupo B (n=8): pacientes com anticorpos de novo; Grupo C (n=5): pacientes sensibilizados que permaneceram com mesmo nível de PRA-ELISA; Grupo D (n=4): pacientes sensibilizados que elevaram o nível de PRA-ELISA e Grupo E (n=14): pacientes sensibilizados que diminuíram o nível de PRA-ELISA durante o primeiro ano pós-transplante. A incidência de rejeição aguda foi de 23,4%. Pacientes dos Grupos B, C e D apresentaram mais episódios de rejeição aguda (respectivamente, 57%; 60% e 100%) que os dos Grupos A (18%) e E (7%), (p<0,001). Rejeições ocorridas no Grupo A foram histologicamente menos severas do que as dos outros Grupos (p=0,03) e com menor incidência de C4d+ (p<0,001). Entre os pacientes com rejeição aguda, 44% deles apresentaram anticorpos no momento da rejeição, sendo que em 90% dos casos esses anticorpos foram doadorespecíficos. Rejeição mediada por células, ou seja, sem anticorpos e com C4d-, ocorreu em 56% dos casos. A incidência global de rejeição mediada por anticorpos (RMA) foi de 11%. A sobrevida do enxerto censurada para óbito foi menor em pacientes com rejeição aguda (p<0,001), especialmente naqueles com anticorpos anti-HLA doador-específicos (p<0,001), com C4d+ (p=0,003) e nos casos de RMA (p<0,003). CONCLUSÃO: Nossos dados sugerem que a monitorização dos anticorpos anti-HLA após o transplante renal pode ser útil no diagnóstico das respostas mediadas por anticorpos e tem implicações em termos de sobrevida do enxerto. / INTRODUCTION: The aim was to follow prospectively anti-HLA antibodies (Abs) after kidney transplantation and to evaluate their association with acute rejection episodes, C4d staining and graft survival. METHODS: We analyzed 926 sera from 111 transplanted patients until graft lost or during 1 year posttransplant. The antibodies were analyzed using Panel Reactive Antibodies by Enzyme Linked Immuno Sorbent Assay (PRA-ELISA). Donor-specific antibodies (DSA) were detected by crossmatch tests and characterized by single antigen beads. Acute rejections (AR) were classified by Banff 97 criteria, updated in 2003. RESULTS: According to post-transplant PRAELISA the patients were classified in 5 groups: Group A (n=80): no evidence of Abs pre and post-transplant; Group B (n=8): patients with Abs de novo; Group C (n=5): sensitized patients who sustained the same PRA-ELISA levels; Group D (n=4): sensitized patients who increased PRA-ELISA levels and Group E (n=14): sensitized patients who decreased PRA-ELISA levels during the first year. The overall incidence of acute rejection was 23,4%. Patients from Groups B, C and D had more AR (respectively, 57%; 60% and 100%) than patients from Groups A (18%) and E (7%), (p<0.001). Patients from Group A had lower Banff scores than other groups (p=0.03) and lower rates of C4d positivity on AR biopsies (p<0.001). Among patients with AR, 44% of them had antibodies which appeared/increased during the AR episodes, and 90% were DSA. AR were pure cell-mediated (C4d-/Abs-) in 56% of the cases. The overall incidence of antibody-mediated rejection (AMR) was 11%. One-year censored graft survival was lower in patients with AR (p<0.001), specially in those with DSA (p<0.001), C4d+ (p=0.003), and AMR (p<0.003). CONCLUSION: Our data suggest that monitoring of anti- HLA antibodies post-transplantation is an useful tool for the diagnosis of antibody-mediated responses, and has prognostic implications in terms of graft survival.

Introdução: O transplante renal é a terapia substitutiva de escolha para a insuficiência renal crônica. O número absoluto de transplantes renais vem aumentando mundialmente e consequentemente as complicações deste procedimento têm sido evidenciadas com maior recorrência, dentre elas a estenose na artéria renal transplantada. A técnica endovascular vem mostrando bons resultados iniciais, com boa taxa de perviedade e baixa taxa de complicações pósoperatórias quando comparadas a técnica aberta para tratamento da estenose. O objetivo deste estudo foi avaliar os resultados primários da angioplastia da artéria renal do rim transplantado secundário a processo de re-estenose. Métodos: Realizado estudo retrospectivo no período de setembro de 2009 a outubro de 2015, baseado em protocolos de seguimento pós-transplante com perfil dos pacientes submetidos a tratamento por estenose em artéria de rim transplantado e o seguimento em curto prazo com critérios clínicos, laboratoriais e ultrassonográficos. Resultados: Dentre um total de 391 transplantes, 19 pacientes foram diagnosticados com Estenose na Artéria renal transplantada. Evidenciado um tempo médio entre o transplante e o diagnóstico de 172,6 dias. As estenoses ou acotovelamentos com alterações hemodinâmicas foram evidenciadas na anastomose (47%), no terço proximal (35%) e terço médio (18%) da artéria transplantada. Todos os pacientes foram submetidos a angioplastia com balão e posicionamento de stent metálico com sucesso técnico de 94,7 %. A creatinina média evoluiu de 3,63 mg/dl para 2,69 mg/dl em 24h e para 1,81 mg/dl em 30 dias (p<0.05). A taxa de filtração glomerular melhorou de 32,66 ml/min para 41,61 ml/min após 24 horas e 51,05 ml/min após 30 dias (p<0.05). Os critérios ultrassonográficos avaliados de velocidade da artéria renal e índice reno-iliaco (368,9 cm/seg e 3,71 pré angioplastia) normalizaram e se estabilizaram durante o período estudado (211,45 cm/seg e 1,69 90 dias pós angioplastia; p<0.05). Conclusão: A abordagem endovascular utilizando de angioplastia primária e colocação de stent metálico foi segura com boa uma taxa de sucesso técnico. O procedimento foi efetivo na melhora da função renal do enxerto transplantado e na correção das alterações ultrassonográficas evidenciadas no pré-operatório. / Introduction: Renal transplantation is the substitutive therapy of choice for chronic renal failure. The absolute number of renal transplants has increased worldwide and consequently the complications of this procedure have been evidenced with greater recurrence, among them stenosis in the transplanted renal artery. The endovascular technique has shown good initial results, with good patency rate and low rate of postoperative complications when compared to the open technique for stenosis treatment. The aim of this study was to evaluate the primary results of ATP from the renal artery of the transplanted kidney secondary to the restenosis process. Methods: A retrospective study was carried out from September 2009 to October 2015, based on post-transplant follow-up protocols with a profile of patients submitted to stenosis in a transplanted kidney artery and a short-term follow-up with clinical, laboratory and ultrasonographics criteria. Results: Out of a total of 391 transplants, 19 patients were diagnosed with transplanted renal artery stenosis. An average time between transplantation and the diagnosis of 172.6 days was evidenced. Stenting or flexing with hemodynamic changes were evident in the anastomosis (47%), in the proximal third (35%) and the middle third (18%) of the transplanted artery. All patients underwent balloon angioplasty and metallic stent placement with technical success of 94.7%. Mean creatinine increased from 3.63 mg / dL to 2.69 mg / dL in 24 hours and to 1.81 mg / dL in 30 days (p <0.05). The glomerular filtration rate improved from 32.66 ml / min to 41.61 ml / min after 24 hours and 51.05 ml / min after 30 days (p <0.05). The ultrasound criteria evaluated for renal artery velocity and reno-iliac index (368.9 cm / sec and 3.71 pre angioplasty) normalized and stabilized during the study period (211.45 cm / sec and 1.69 Angioplasty, p <0.05). Conclusion: The endovascular approach using primary angioplasty and stent placement was safe with good technical success rate. The procedure was effective in improving the renal function of the transplanted graft and in correcting the ultrasound changes evidenced in the preoperative period.

<p>Bakgrund: Antalet patienter i behov av njurtransplantation per år är cirka 400-500, varav endast cirka 350 kommer att bli transplanterade. Bristen på organ är tydligt framträdande. I väntan på transplantation behöver patienten dialysbehandling, vilket ofta upplevs vara tidskrävande och utmattande. Sjuksköterskor bör ha kunskap om patienters upplevelser i samband med väntan på transplantation för att kunna utvecklas i sin roll som sjuksköterska och få en djupare förståelse för deras situation.</p><p>Syfte: Syftet var att beskriva kroniskt njursjuka patienters upplevelser av att leva med dialysbehandling och väntan på transplantation.</p><p>Metod: Studien är en litteratursammanställning av tio kvalitativa och kvantitativa vetenskapliga artiklar inom området, vilka har granskats, analyserats och sammanställts.</p><p>Resultat: I resultatet framkom flera olika upplevelser, så som längtan efter frihet, utmattning, höga förväntningar, frustration och rädsla inför framtiden i samband med dialysbehandlingen och väntan på transplantationen.</p><p>Slutsats: Kroniskt njursjuka patienters upplever sin situation som psykiskt, fysiskt och socialt påfrestande. En av sjuksköterskans viktigaste uppgifter i samband med bemötandet av patienter under dialysbehandling är att vara tillgänglig. Med en tillgänglig och öppen inställning till patienterna blir sjuksköterskan mer mottaglig för patienternas individuella behov.</p> / <p>Background: The number in need of kidney transplants per year is approximately 400-500, of which only about 350 will be transplanted. The shortage of organs is clearly prominent. In anticipation of the transplant patient needs dialysis, which is perceived to be time consuming and exhausting. Nurses should have knowledge of patients' experiences in connection with awaiting transplantation to be able to evolve in her role as a nurse and get a deeper understanding of the patients’ situation.</p><p>Aim: The aim of this study was to describe patients’ experiences of living with chronic kidney failure with dialysis and awaiting transplantation.</p><p>Method: The study is a literature compilation of ten qualitative and quantitative scientific articles in the field. The articles have been reviewed, analyzed and compiled. Results: The results revealed several different experiences, such as yearning for freedom, fatigue, high expectations, frustration and fear for the future in connection with the dialysis treatment and awaiting transplantation.</p><p>Conclusion: Chronic kidney disease patients perceive their situation as mentally, physically and socially stressful. One of the nurse's most important tasks in connection with the treatment of patients in dialysis is to be available. With an accessible and open approach to the patient in general, a nurse becomes more responsive to patient's individual needs.</p>

Bakgrund: Antalet patienter i behov av njurtransplantation per år är cirka 400-500, varav endast cirka 350 kommer att bli transplanterade. Bristen på organ är tydligt framträdande. I väntan på transplantation behöver patienten dialysbehandling, vilket ofta upplevs vara tidskrävande och utmattande. Sjuksköterskor bör ha kunskap om patienters upplevelser i samband med väntan på transplantation för att kunna utvecklas i sin roll som sjuksköterska och få en djupare förståelse för deras situation. Syfte: Syftet var att beskriva kroniskt njursjuka patienters upplevelser av att leva med dialysbehandling och väntan på transplantation. Metod: Studien är en litteratursammanställning av tio kvalitativa och kvantitativa vetenskapliga artiklar inom området, vilka har granskats, analyserats och sammanställts. Resultat: I resultatet framkom flera olika upplevelser, så som längtan efter frihet, utmattning, höga förväntningar, frustration och rädsla inför framtiden i samband med dialysbehandlingen och väntan på transplantationen. Slutsats: Kroniskt njursjuka patienters upplever sin situation som psykiskt, fysiskt och socialt påfrestande. En av sjuksköterskans viktigaste uppgifter i samband med bemötandet av patienter under dialysbehandling är att vara tillgänglig. Med en tillgänglig och öppen inställning till patienterna blir sjuksköterskan mer mottaglig för patienternas individuella behov. / Background: The number in need of kidney transplants per year is approximately 400-500, of which only about 350 will be transplanted. The shortage of organs is clearly prominent. In anticipation of the transplant patient needs dialysis, which is perceived to be time consuming and exhausting. Nurses should have knowledge of patients' experiences in connection with awaiting transplantation to be able to evolve in her role as a nurse and get a deeper understanding of the patients’ situation. Aim: The aim of this study was to describe patients’ experiences of living with chronic kidney failure with dialysis and awaiting transplantation. Method: The study is a literature compilation of ten qualitative and quantitative scientific articles in the field. The articles have been reviewed, analyzed and compiled. Results: The results revealed several different experiences, such as yearning for freedom, fatigue, high expectations, frustration and fear for the future in connection with the dialysis treatment and awaiting transplantation. Conclusion: Chronic kidney disease patients perceive their situation as mentally, physically and socially stressful. One of the nurse's most important tasks in connection with the treatment of patients in dialysis is to be available. With an accessible and open approach to the patient in general, a nurse becomes more responsive to patient's individual needs.

Tyrimo tikslas buvo įvertinti sensitizaciją ŽLA antigenais, inksto transplantatų recipientams, kurie greta standartinės imunosupresijos vartojo monokloninius antikūnus prieš IL-2 receptorių ir monokloninių antikūnų nevartojusiems recipientams. Tyrime dalyvauja VULSK pacientai, kuriems 2000-2005 metais imtinai buvo atliktos inkstų transplantacijos (Tx), bei kurie prieš ir po Tx buvo tirti dėl teigiamai su limfocitų panele reaguojančių antikūnų skaičiaus, išreikšto procentais (PRA). Iš viso tyrime dalyvauja 189 recipientai. Dalis jų (n=83) greta standartinės imunosupresijos vartojo monokloninius antikūnus prieš IL-2 receptorių (basiliksimabą ar daklizumabą), kiti (n=106) gavo tik standartinę imunosupresiją. Pagrindiniai sensitizaciją ŽLA antigenais lemiantys veiksniai abiejose grupėse pasiskirstė nevienodai. Didesnė monokloninius antikūnus vartojusių dalis gavo kraujo perpylimus (72% vs. 57,3%), šioje grupėje taip pat daugiau buvo pakartotinų Tx (9,6% vs. 7,5%), tik gimdžiusių moterų skaičius didesnis buvo monokloninių antikūnų nevartojusioje grupėje (47,7% vs. 30,8%). Tirtos ligonių grupės palygintos taikant &#967;² kriterijų, skirtumas laikytas statistiškai reikšmingas, kai p<0,05. Išanalizavus recipientų sensitizaciją prieš Tx paaiškėjo, kad dauguma (58%; 110/189) buvo nesensitizuoti (PRA 0-10%), likę 42% (79/189) - sensitizuoti, iš kurių 14% (11/189) – labai sensitizuoti (PRA 50-100%). Po Tx monokloninius antikūnus vartojusių recipientų grupėje (n=83) 2% padaugėjo... [toliau žr. visą tekstą] / The aim of this study was to evaluate the sensitization with HLA antigens in kidney transplant recipients, who received induction therapy with monoclonal antibodies against IL-2R and in the group of patients, who were only under the triple drug therapy. This study comprises recipients, who received kidney transplant in the year 2000-2005, and who were tested for panel reactive antibody test before and after transplantation (Tx). The total number of 189 kidney transplant recipients takes part in this study. 83 received monoclonal antibodies against IL-2R (basiliximab or daclizumab), others (n=106) – did not. These groups were unequal in comparison to the main factors causing sensitization with HLA antigens. The group of patients, who received induction therapy with monoclonal antibodies had more blood transfuzions (72% vs. 57,3%), and previous transplantations (9,6% vs. 7,5%), in comparison with the other group. Only the number of pregnancies was higher in the group of patients who were only under the triple drug therapy (47,7% vs. 30,8%). Statistical analyses were caried out using chi-square test, differences were considered significant at p<0,05. 58% (110/189) of kidney transplant recipients were unsensitized (PRA 0-10%) before Tx, the rest 42% (79/189) were sensitized, from which 14% (11/189) were highly sensitized (PRA 50-100%). After Tx the number of medium sensitized (PRA 11-50%) kidney transplant recipients, who received induction therapy by monoclonal antibodies... [to full text]

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.