Identification of the complement C4d fragment in peritubular capillaries as a specific marker for antibody mediated rejection in renal transplantation revealed the critical role of antibodies in graft survival. In this thesis, I document the design and findings of studies performed to investigate the clinical impact of anti-HLA antibodies present before and/or after transplantation. Over time, the detection techniques for anti-HLA antibodies has evolved from the less sensitive complement-dependent lymphocytotoxicity (CDC) crossmatching (XM) to more sensitive solid phase assays such as Luminex®. Studies have been conducted to compare the predictive value of different antibody detection techniques. The first result chapter presents antibody specificity in positive CDC B-cell crossmatch (BXM), analysed with highly specific Luminex® assays. The study also investigates the predictive value of BXM in the general transplant population. I found that donor-specific anti-HLA antibodies (DSA) are only present in one third of positive BXM and are associated with poor outcomes. The novel finding is that >80% of the DSA detected by BXM are complement-fixing IgG₁ and IgG₃ subclasses. Transplant glomerulopathy (TG) is type of chronic renal graft rejection. The pathogenesis of TG is unclear. In the second result chapter, I report risk factors and involvement of anti-HLA antibodies in the development of TG. This study shows that glomerular rejection, delayed graft function, HLA presensitization and DSA have a univariate effect on TG development. Multivariate analysis revealed that DSA are an independent predictor of TG, after adjustment for other risk factors. I have further investigated the role of BXM in a unique, well-matched, highly sensitized patient group transplanted under the national renal exchange programme. I compared Luminex® antibody analysis with BXM in predicting transplant outcomes. In highly sensitized patients, DSA are found in two thirds of positive BXM. In univariate analyses, BXM is associated with humoral rejection whereas DSA defined by Luminex® are associated with total and all rejection types. The major finding is that, by multivariate analysis, DSA defined by Luminex® are an independent predictor of total and humoral rejection, but BXM are not. These interesting findings are reported in the third result chapter. Studies reported in this thesis define the clinical significance of anti-HLA antibodies in renal transplant outcomes. Method comparison studies provide useful information on antibody specificity and their impact on graft survival. Collectively, a better understanding of alloantibodies associated with graft rejection and limitation of antibody detection methods may facilitate donor selection and choice of immunosuppressants, and consequently improve transplant outcomes. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1379925 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2010

Το tacrolimus παραμένει ο ακρογωνιαίος λίθος στην ανοσοκατασταλτική αγωγή που λαμβάνουν οι ασθενείς με μεταμόσχευση νεφρού. Το στενό θεραπευτικό παράθυρο και η σημαντική ενδοϋποκειμενική και διϋποκειμενική διακύμανση της κινητικής του εκθέτει τον ασθενή στον κίνδυνο υπερδοσολογίας και πιθανής εμφάνισης τοξικότητας ή υποδοσολογίας και κινδύνου απόρριψης του μοσχεύματος. Σκοπός της παρούσας διδακτορικής διατριβής ήταν η φαρμακοκινητική και η φαρμακογενετική προσέγγιση με στόχο την εξατομίκευση της χρήσης του tacrolimus σε ασθενείς με μεταμόσχευση νεφρού. Τον πληθυσμό μελέτης αποτέλεσαν 40 ασθενείς με μεταμόσχευση νεφρού της Νεφρολογικής Κλινικής του Πανεπιστημιακού Γενικού Νοσοκομείου Πατρών. Η γονοτύπιση αφορούσε στην ανεύρεση του CYP3A5*1 και *3 αλληλομόρφου και πραγματοποιήθηκε με τη μεθοδολογία της απόμονωσης DNA από λευκά αιμοσφαίρια περιφερικού αίματος των ασθενών, την αλυσιδωτή αντίδραση πολυμεράσης για τον πολλαπλασιασμό του τμήματος ενδιαφέροντος και την ανάλυση πολυμορφισμού περιοριστικών θραυσμάτων. Για τη στατιστική ανάλυση, χρησιμοποιήθηκαν το Student’s t-test ή τo Mann-Whitney test, ανάλογα με το εάν οι μεταβλητές ακολουθούσαν κανονική ή όχι κατανομή, η μέθοδος της γραμμικής παλινδρόμησης και η μεθόδος των γενικευμένων γραμμικών μοντέλων-ανάλυση επαναλαμβανόμενων μετρήσεων. Η συχνότητα του CYP3A5*3/*3 και CYP3A5*1/*3 γονοτύπου ήταν 87,5% (35/40) και 12,5% (5/40), αντίστοιχα. Δεν ανευρέθησαν ομοζυγώτες για το CYP3A5*1 αλληλόμορφο. Ανεδείχθη συσχέτιση του CYP3A5*1 με χαμηλότερες προβλεπόμενες τιμές της προσαρμοσμένης στη δόση συγκέντρωσης και υψηλότερες προβλεπόμενες τιμές του όγκου κατανομής του υπό μελέτη φαρμάκου. Οι ασθενείς που έφεραν το CYP3A5*1 αλληλόμορφο απαιτούσαν υψηλότερες δόσεις tacrolimus για την επίτευξη της επιθυμητής συγκέντρωσης στο αίμα σε σχέση με τους ομοζυγώτες για το CYP3A5*3 νωρίς αλλά και στην απώτερη φάση μετά τη μεταμόσχευση. Η επίδραση της χρονικής στιγμής, δηλαδή του χρόνου μετά τη μεταμόσχευση, στην κινητική του tacrolimus ήταν σημαντική ενώ δεν ανεδείχθη σημαντική επίδραση του φύλου. Δεν ανευρέθη ανάγκη για πιο τακτικό έλεγχο από το σύνηθες της συγκέντρωσης του tacrolimus σε μεταμοσχευμένους νεφρού που δεν εκφράζουν το CYP3A5 και λαμβάνουν ομεπραζόλη ή στατίνη (ατορβαστατίνη, σιμβαστατίνη, πραβαστατίνη ή φλουβαστατίνη). Η ασφάλεια και η αποτελεσματικότητα των στατινών διατηρήθηκε κατά τη συγχορήγηση με tacrolimus. Η φαρμακοκινητική και η φαρμακογενετική προσέγγιση αναδεικνύουν τις γενετικές και επιγενετικές εκείνες παραμέτρους που επηρεάζουν την κινητική του tacrolimus και συμβάλλουν στην εξατομίκευση της χορήγησής του. / Tacrolimus remains the centerpiece of the maintenance treatment scheme in renal transplant recipients. Both its narrow therapeutic window and its highly pharmacokinetic variance may lead to overtreatment and toxicity or insufficient treatment and transplant rejection, conditions that are usually seen in clinical practice. Our aim was to determine the impact of patient characteristics, drug-to-drug interactions and genotype (presence of CYP3A5*1 and CYP3A5*3) on the kinetics of tacrolimus in renal transplant recipients. Our patient population consisted of 40 renal transplant recipients. CYP3A5 genotyping was performed based on the following procedures: DNA extraction from blood, polymerase chain reaction and accordingly, restriction fragment length polymorphism. Statistical analysis was performed with Student’s t-test or Mann-Whitney test, according to the presence of normality of the studied parameters, linear regression analysis and general linear model-repeated measures. The frequency of CYP3A5*3/*3 genotype was 87.5% (35/40) whereas the frequency of the CYP3A5*1/*3 genotype was 12.5% (5/40). No individual homozygote for CYP3A5*1 was detected. CYP3A5*1 variant was associated with significant lower tacrolimus dose adjusted concentration. Carriers of CYP3A5*1 allele had lower predicted measures for tacrolimus dose adjusted concentration and higher predicted measures for volume of distribution. Timepoint, in contast with gender, had a statistically significant impact on tacrolimus kinetics. No statistically significant difference was observed in tacrolimus kinetics during the coadministration of omeprazole or statin. Statistically significant decrease in serum cholesterol was observed after the initiation of statin whilst renal and hepatic function remained unchanged. No skeletal muscle abnormalities were reported during the coadministration of statin. Pharmacokinetic and pharmacogenetic approach can be used to elucidate genetic and epigenetic factors that influence tacrolimus kinetics and thus, they can contribute to dose individualization.

Bakgrund: Efter en njurtransplantation väntar en livslång behandling som kan bidra till många biverkningar och komplikationer som påverkar livskvaliteten på ett negativt sätt. Syftet: Att undersöka patienters upplevelser av livskvaliteten efter en genomförd njurtransplantation.  Metod: En litteraturstudie där resultatet baserades på 10 artiklar från databaserna CINAHL, PubMed och Scopus. Artiklarna kvalitetsgranskades och analyserades. Orems egenvårdsteori användes som teoretiskt ramverk till studien.  Resultat: Studien identifierade sex olika teman: positiva upplevelser av livet, sociala relationer, fysiska biverkningar, psykiska påfrestningar, rädsla för avstötning och anpassningsstrategier. Studien visar på att patienterna upplevde positiva effekter då transplantationen gav dem en känsla av frihet och autonomi. Patienterna beskrev även vikten av att ha ett socialt stöd och ekonomisk stabilitet. Transplantationen bidrog till psykiska påfrestningar som var en reaktion på de många fysiska biverkningar patienterna upplevde. Det som patienterna upplevde som svårast att hantera var oron för en avstötning av njuren. Studien visar även hur för höga förväntningar på patientens egna tillfrisknande bidrog till en sämre livskvalitet. Patienterna utvecklade därmed olika anpassningsstrategier för att hantera olika psykiska påfrestningar. Slutsats: Alla patienter hade varierande upplevelser av sin livskvalitet efter en njurtransplantation. Anledningarna till sänkt livskvalitet grundade sig ofta i fysiska biverkningar och förväntningar kring dessa. Sjuksköterskan har därmed en stor uppgift i ge olika individanpassade hjälpmedel och anpassningsstrategier till patienterna. / Background: After a renal transplantation a lifelong treatment awaits, this contributes to many side effects and complications that effects patients quality of life. Aim: To investigate patients experience of quality of life after a renal transplantation. Method: A literature review based on 10 articles from databases CINAHL, PubMed and Scopus. The articles quality were examined and analyzed. The self-care deficit nursing theory by Orem was used as a theoretical framework for this study. Result: The study identified six different themes: positive experiences of life, social relations, physical side effects, fear of rejection and coping strategies. The study showed that the patients experienced positive effects due to the transplant giving them a feeling of freedom and autonomy. The patients also described the importance of having social support and economic stability. The transplantation contributed to psychological difficulties, this was a reaction to the many physical side effects the patients experienced. The fear of rejection of the kidney was the one thing patients hade most difficulty to cope with. The study also shows how too high expectations on the recovery contributed to low quality of life. Therefore the patients developed different kinds of coping strategies to handle the psychological hardships. Conclusion: All patients had various experiences of quality of life after the renal transplantation. The reasons for this was usually based on the physical side effects and high expectations. The nurse therefore has a big part in giving individual adjusted tools and coping strategies for the patients to use

Introdução. Hepatite B oculta é caracterizada pela presença do HBV-DNA em pacientes que não expressam o antígeno B de superfície (HBsAg) e é relatada com maior freqüência em pacientes infectados pelo vírus da hepatite C (HCV). Nesse estudo avaliamos a prevalência de hepatite B oculta em transplantados renais infectados ou não pelo HCV e avaliamos a função hepática nos diferentes grupos. Material e métodos. Amostras de soro de 101 pacientes transplantados renais foram avaliadas para testes de função hepática, marcadores sorológicos e reação de polimerização em cadeia (PCR) para o HBV-DNA. Todos os pacientes eram HBsAg negativos e havia 51 pacientes anti- HCV reagentes e 50 pacientes não reagentes. A pesquisa do HBV-DNA foi feita por técnica de PCR aninhado para os genes S e “core”. Resultados. A pesquisa do gene S do HBV-DNA resultou positiva em 2 pacientes, sendo um do grupo anti-HCV reagente e o outro do grupo não reagente. A pesquisa do gene da região do “core” foi positiva em um paciente do grupo anti-HCV não reagente. A análise demonstrou que os pacientes do grupo anti-HCV reagente apresentam maior tempo de tratamento dialítico (50,8 + 34,6 e 32,02 + 20,87; p<0,001). Da mesma forma o grupo anti-HCV reagente apresentou valores mais elevados de aminotransferases: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); gama glutamiltranspeptidase : 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) e fosfatase alcalina : 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Os níveis de ciclosporina sérica também mais elevados também foram encontrados no grupo anti-HCV reagente 170.9 ± 69.8 and 135.0 ± 48.1 respectivamente (P < 0.02). No modelo de análise multivariada evidenciou-se que apenas a presença de infecção pelo HCV é determinante das alterações nas provas de função hepática. Conclusão. Hepatite B oculta foi um achado infreqüente na nossa população de pacientes transplantados renais, não tendo sido encontrada diferença na sua prevalência em pacientes infectados ou não pelo HCV. Pacientes anti-HCV reagentes apresentam alterações significativas das provas de função hepática e dos níveis sangüíneos de ciclosporina. / Background: Occult hepatitis B (HB) is characterized by the presence of HBV-DNA in patients who do not present HB surface antigen (HBsAg) detectable in sera. This condition is frequently described in patients with hepatitis C virus (HCV) infection and its clinical implications are uncertain. Since transplant patients were at risk for hepatitis B and/or C infection by blood transfusions, dialysis treatment and the transplant procedure itself we aimed to evaluate the prevalence of occult HB either with or without HCV infection. Patients and Methods: One hundred and one HBsAg negative renal transplant patients were evaluated. Fifty-one were anti-HCV reagents (Elisa III). Sera was analyzed for the presence of the S and core genes of the HBV-DNA by a nested PCR technique. Serological markers of HBV infection, liver function testes and ciclosporine through levels were also analysed. Results: The core gene of the HBV-DNA was identified in one HCV infected patient and in one anti-HCV negative who also presented the S gene (prevalence: 2% and 1% for each gene respectivelly). HCV infected patients presented longer pre-transplant dialysis time (50.8 ± 34.6 versus 32.0 ± 20.9; p<0,001). Results of liver function tests were also increased in the HCV infected group: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); GGT: 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) and alkaline phosphatase: 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Ciclosporine through levels were also significantly higher in HCV infected patients 170.9 ± 69.8 and 135.0 ± 48.1 respectivelly (P < 0.02). Multivariate analysis revealed that only HCV infection was determinant of the increased results of the LFTs. Conclusion: We found that occult hepatitis B is infrequent condition in our population of renal transplant patients and that HCV infection seems not to be a risk factor. In accordance with our previous work HCV we showed that infected renal transplant patients present evidence of liver damage and altered metabolism evidenced by the elevated liver function testes a higher ciclosporine through levels.

In renal transplantation, immunosuppressants are prescribed to patients to prevent graft loss. Although the extent of adherence required for such treatment to prevent graft loss has not been determined, it is thought to be high. Despite this, research suggests adherence rates for renal transplant recipients to be only between 50% and 95%. Considering the impact of graft loss on the renal patient, the national healthcare budget and on the limited resource of donor organs, it is important to identify and understand factors that contribute to nonadherence, and thereafter to address those that are most influential. This thesis seeks to understand adherence of renal transplant recipients, and to identify the cognitive and behavioural factors influencing this behaviour. To achieve this, three main activities were performed, a literature review, an interview study and a questionnaire study, the methods and findings of which are presented following an overview of two social cognition models, used in two of the activities, and renal disease. The first activity, a comprehensive literature review, identified 55 research articles that explored factors influencing adherence of renal transplant recipients to immunosuppressant drug therapy. It included original research studies published between 1980 and 2009, and was updated in 2011. The findings were categorised into the five dimensional framework suggested by the World Health Organisation: patient- related factors; socio-economic factors; condition-related factors; therapy-related factors; and healthcare team and system-related factors. Secondly, a semi-structured interview study with 27 renal transplant recipients was conducted. The study explored their attitude towards and behaviours related to taking immunosuppressants. The interview schedule was informed by the health belief model, and framework analysis of the data identified five key themes. These were: satisfaction with renal replacement therapy; the importance of taking immunosuppressants; perception of side effects and risks; responding to side effects and risks; and 'compliance is routine'. Finally, a questionnaire was developed using the theory of planned behaviour and the findings of the previous two activities. Its purpose was to determine the predictors of renal transplant recipients' self-reported adherence and to explain their adherence. A logistic regression model of 528 survey responses suggested respondents were more likely to be highly adherent if they, in descending order of influence: had well- established habits; were unemployed; had a better prospective memory; were a shorter time post-transplantation; had higher levels of anticipated affect; and lower levels of perceived behavioural control. The thesis concludes with discussing the findings of the studies, their strengths and limitations, and their implications for practice and future research. The findings of this thesis suggest unintentional nonadherence to prevail and encourage the development of interventions which promote habit formation and maintenance.

Kidney transplantation is the treatment of choice for patients with chronic kidney disease, bringing survival and quality of life over dialysis. Mortality associated with renal transplantation increase in the proportion of deaths related to cardiovascular diseases, which are the main manifestations of atherosclerotic disease. The aim of this study is to evaluate the prevalence of carotid atherosclerosis in patients on the waiting list for renal transplantation and transplant already in attendance at the University Hospital of Santa Maria through ultrasound of carotid arteries and correlate their presence with the Framingham score. We conducted a cross sectional study of 59 prospective kidney transplant patients transplanted and not waiting on the waiting list for kidney transplantation who attended the outpatient Renal Transplantation, University Hospital of Santa Maria from January 2012 to March 2013. Held ultrasound of carotid arteries for diagnosis and quantification of carotid atherosclerosis, as well as calculation of the Framingham score using the variables collected. The prevalence of carotid plaques was 59,38% in patients undergoing renal transplantation, and 70,37% of those on the waiting list. No significant association was found between the groups regarding the presence of carotid plaques (p = 0,379) or severity (p = 0,704). The group undergoing kidney transplantation compared to patients on the waiting list was longer on dialysis (55,25 + 44,16 months vs. 28,15 + 36,50 months, p = 0,00079), had lower mean age (45,09 + 13,04 vs. 52,48 + 14,18 years, p = 0,042), fewer diabetic patients (9% vs. 52%, p = 0,00033) and lower Framingham risk score (8,72% + 7,5 vs. 16,51% + 11,97, p = 0,002). There was no significant difference between the presence of carotid plaque and the time of renal transplantation (p = 0,399) or type of immunosuppressive regimen (p = 0,939). Intermediate correlation was found (Spearman coeff = 0,47, p = 0,0065) between the degree of Framingham and severity of carotid plaque in patients undergoing renal transplantation and lack of correlation (Spearman coeff = 0,28, p = 0,152) in the group on the waiting list. In logistic regression analysis for factors associated with the presence / absence of carotid plaque, an association was found between the Framingham score and chance of carotid plaque (OR = 1,104 [1,008 to 1,210, CI OR 95%], p = 0,033). The carotid atherosclerotic disease has a high prevalence in both patients on the waiting list, as in patients already undergoing renal transplant. The traditional cardiovascular risk factors used in the Framingham score plays an important role in the development of carotid plaques. / O transplante renal é o tratamento de escolha para pacientes com doença renal crônica terminal, trazendo sobrevida e qualidade de vida superiores a terapia dialítica. Nos últimos anos, vem ocorrendo um aumento na proporção de óbitos relacionados às doenças cardiovasculares em pacientes transplantados renais, que são a principal manifestação da doença aterosclerótica. O objetivo deste estudo é avaliar a prevalência de aterosclerose carotídea em pacientes em lista de espera para o transplante renal e já transplantados em acompanhamento ambulatorial no Hospital Universitário de Santa Maria por meio de ecografia de artérias carótidas e correlacionar sua presença com o escore de Framingham. Realizou-se estudo transversal, prospectivo de 59 pacientes transplantados renais e não transplantados que aguardavam em lista de espera para transplante renal que frequentaram o ambulatório de Transplante Renal do Hospital Universitário de Santa Maria entre janeiro de 2012 a março de 2013. Realizou-se ecografia de artérias carótidas para diagnóstico e quantificação de aterosclerose carotídea, bem como cálculo do escore de Framingham por meio das variáveis coletadas. A prevalência de placas carotídeas foi de 59,38% nos pacientes submetidos ao transplante renal e de 70,37% naqueles em lista de espera. Não houve associação significativa entre os grupos quanto a presença de placas carotídeas (p=0,379) ou de sua gravidade (p=0,704). O grupo submetido ao transplante renal quando comparado ao grupo em lista de espera, esteve maior tempo em terapia dialítica (55,25 + 44,16 meses vs. 28,15 + 36,50 meses, p=0,00079), tinha menor média de idade (45,09 + 13,04 vs. 52,48 + 14,18 anos, p=0,042), menor número de pacientes diabéticos (9% vs. 52%, p=0,00033) e menor escore de Framingham (8,72% + 7,5 vs. 16,51% + 11,97, p=0,002). Não houve diferença significativa entre a presença de placa carotídea e o tempo de transplante renal (p=0,399) ou o tipo de esquema imunossupressor (p=0,939). Encontrou-se correlação intermediária (coef. Spearman =0,47, p=0,0065) entre o grau de Framingham e a gravidade da placa carotídea nos pacientes submetidos ao transplante renal e ausência de correlação (coef. Spearman=0,28, p=0,152) no grupo em lista de espera. Na análise de regressão logística para fatores associados a presença/ausência de placa carotídea, encontrou-se associação entre o Escore de Framingham e chance de placa carotídea (OR=1,104 [1,008-1,210, IC OR 95%], p=0,033). A doença aterosclerótica carotídea apresenta prevalência elevada tanto nos pacientes em lista de espera, quanto nos pacientes já submetidos ao transplante renal. Os fatores de risco cardiovasculares tradicionais, utilizados no escore de Framingham têm um papel importante no desenvolvimento das placas carotídeas.

Introdução. Hepatite B oculta é caracterizada pela presença do HBV-DNA em pacientes que não expressam o antígeno B de superfície (HBsAg) e é relatada com maior freqüência em pacientes infectados pelo vírus da hepatite C (HCV). Nesse estudo avaliamos a prevalência de hepatite B oculta em transplantados renais infectados ou não pelo HCV e avaliamos a função hepática nos diferentes grupos. Material e métodos. Amostras de soro de 101 pacientes transplantados renais foram avaliadas para testes de função hepática, marcadores sorológicos e reação de polimerização em cadeia (PCR) para o HBV-DNA. Todos os pacientes eram HBsAg negativos e havia 51 pacientes anti- HCV reagentes e 50 pacientes não reagentes. A pesquisa do HBV-DNA foi feita por técnica de PCR aninhado para os genes S e “core”. Resultados. A pesquisa do gene S do HBV-DNA resultou positiva em 2 pacientes, sendo um do grupo anti-HCV reagente e o outro do grupo não reagente. A pesquisa do gene da região do “core” foi positiva em um paciente do grupo anti-HCV não reagente. A análise demonstrou que os pacientes do grupo anti-HCV reagente apresentam maior tempo de tratamento dialítico (50,8 + 34,6 e 32,02 + 20,87; p<0,001). Da mesma forma o grupo anti-HCV reagente apresentou valores mais elevados de aminotransferases: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); gama glutamiltranspeptidase : 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) e fosfatase alcalina : 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Os níveis de ciclosporina sérica também mais elevados também foram encontrados no grupo anti-HCV reagente 170.9 ± 69.8 and 135.0 ± 48.1 respectivamente (P < 0.02). No modelo de análise multivariada evidenciou-se que apenas a presença de infecção pelo HCV é determinante das alterações nas provas de função hepática. Conclusão. Hepatite B oculta foi um achado infreqüente na nossa população de pacientes transplantados renais, não tendo sido encontrada diferença na sua prevalência em pacientes infectados ou não pelo HCV. Pacientes anti-HCV reagentes apresentam alterações significativas das provas de função hepática e dos níveis sangüíneos de ciclosporina. / Background: Occult hepatitis B (HB) is characterized by the presence of HBV-DNA in patients who do not present HB surface antigen (HBsAg) detectable in sera. This condition is frequently described in patients with hepatitis C virus (HCV) infection and its clinical implications are uncertain. Since transplant patients were at risk for hepatitis B and/or C infection by blood transfusions, dialysis treatment and the transplant procedure itself we aimed to evaluate the prevalence of occult HB either with or without HCV infection. Patients and Methods: One hundred and one HBsAg negative renal transplant patients were evaluated. Fifty-one were anti-HCV reagents (Elisa III). Sera was analyzed for the presence of the S and core genes of the HBV-DNA by a nested PCR technique. Serological markers of HBV infection, liver function testes and ciclosporine through levels were also analysed. Results: The core gene of the HBV-DNA was identified in one HCV infected patient and in one anti-HCV negative who also presented the S gene (prevalence: 2% and 1% for each gene respectivelly). HCV infected patients presented longer pre-transplant dialysis time (50.8 ± 34.6 versus 32.0 ± 20.9; p<0,001). Results of liver function tests were also increased in the HCV infected group: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); GGT: 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) and alkaline phosphatase: 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Ciclosporine through levels were also significantly higher in HCV infected patients 170.9 ± 69.8 and 135.0 ± 48.1 respectivelly (P < 0.02). Multivariate analysis revealed that only HCV infection was determinant of the increased results of the LFTs. Conclusion: We found that occult hepatitis B is infrequent condition in our population of renal transplant patients and that HCV infection seems not to be a risk factor. In accordance with our previous work HCV we showed that infected renal transplant patients present evidence of liver damage and altered metabolism evidenced by the elevated liver function testes a higher ciclosporine through levels.

Introdução. Hepatite B oculta é caracterizada pela presença do HBV-DNA em pacientes que não expressam o antígeno B de superfície (HBsAg) e é relatada com maior freqüência em pacientes infectados pelo vírus da hepatite C (HCV). Nesse estudo avaliamos a prevalência de hepatite B oculta em transplantados renais infectados ou não pelo HCV e avaliamos a função hepática nos diferentes grupos. Material e métodos. Amostras de soro de 101 pacientes transplantados renais foram avaliadas para testes de função hepática, marcadores sorológicos e reação de polimerização em cadeia (PCR) para o HBV-DNA. Todos os pacientes eram HBsAg negativos e havia 51 pacientes anti- HCV reagentes e 50 pacientes não reagentes. A pesquisa do HBV-DNA foi feita por técnica de PCR aninhado para os genes S e “core”. Resultados. A pesquisa do gene S do HBV-DNA resultou positiva em 2 pacientes, sendo um do grupo anti-HCV reagente e o outro do grupo não reagente. A pesquisa do gene da região do “core” foi positiva em um paciente do grupo anti-HCV não reagente. A análise demonstrou que os pacientes do grupo anti-HCV reagente apresentam maior tempo de tratamento dialítico (50,8 + 34,6 e 32,02 + 20,87; p<0,001). Da mesma forma o grupo anti-HCV reagente apresentou valores mais elevados de aminotransferases: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); gama glutamiltranspeptidase : 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) e fosfatase alcalina : 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Os níveis de ciclosporina sérica também mais elevados também foram encontrados no grupo anti-HCV reagente 170.9 ± 69.8 and 135.0 ± 48.1 respectivamente (P < 0.02). No modelo de análise multivariada evidenciou-se que apenas a presença de infecção pelo HCV é determinante das alterações nas provas de função hepática. Conclusão. Hepatite B oculta foi um achado infreqüente na nossa população de pacientes transplantados renais, não tendo sido encontrada diferença na sua prevalência em pacientes infectados ou não pelo HCV. Pacientes anti-HCV reagentes apresentam alterações significativas das provas de função hepática e dos níveis sangüíneos de ciclosporina. / Background: Occult hepatitis B (HB) is characterized by the presence of HBV-DNA in patients who do not present HB surface antigen (HBsAg) detectable in sera. This condition is frequently described in patients with hepatitis C virus (HCV) infection and its clinical implications are uncertain. Since transplant patients were at risk for hepatitis B and/or C infection by blood transfusions, dialysis treatment and the transplant procedure itself we aimed to evaluate the prevalence of occult HB either with or without HCV infection. Patients and Methods: One hundred and one HBsAg negative renal transplant patients were evaluated. Fifty-one were anti-HCV reagents (Elisa III). Sera was analyzed for the presence of the S and core genes of the HBV-DNA by a nested PCR technique. Serological markers of HBV infection, liver function testes and ciclosporine through levels were also analysed. Results: The core gene of the HBV-DNA was identified in one HCV infected patient and in one anti-HCV negative who also presented the S gene (prevalence: 2% and 1% for each gene respectivelly). HCV infected patients presented longer pre-transplant dialysis time (50.8 ± 34.6 versus 32.0 ± 20.9; p<0,001). Results of liver function tests were also increased in the HCV infected group: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); GGT: 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) and alkaline phosphatase: 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Ciclosporine through levels were also significantly higher in HCV infected patients 170.9 ± 69.8 and 135.0 ± 48.1 respectivelly (P < 0.02). Multivariate analysis revealed that only HCV infection was determinant of the increased results of the LFTs. Conclusion: We found that occult hepatitis B is infrequent condition in our population of renal transplant patients and that HCV infection seems not to be a risk factor. In accordance with our previous work HCV we showed that infected renal transplant patients present evidence of liver damage and altered metabolism evidenced by the elevated liver function testes a higher ciclosporine through levels.

Introdução: O transplante renal é amplamente reconhecido como a melhor forma de tratamento para os pacientes que necessitam de terapia de substituição renal, e isso o torna vítima de seu próprio sucesso. Apesar de ser considerado um triunfo clínico-cirúrgico, é igualmente uma fonte de frustração, pela carência de doadores de órgãos e pelo crescimento das listas de espera. Há necessidade do desenvolvimento de estratégias que tornem maior o número de rins disponíveis para transplante. A idade do doador, o tempo de isquemia fria (TIF) e o HLA (antígeno leucocitário humano de histocompatibilidade) são fatores que estão relacionados à sobrevida do enxerto e, desta forma, envolvidos na diminuição da demanda e no aumento da oferta de órgãos. Objetivos: Avaliar o impacto das variáveis, idade do doador, compatibilidade HLA e tempo de isquemia fria, na sobrevida do enxerto de pacientes submetidos à alotransplantes renais com doador cadáver. Materiais e Métodos: Foram analisados retrospectivamente 454 pacientes submetidos a transplantes renais com doadores cadáveres realizados de abril de 1987 a dezembro de 2003, no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP). Resultados: Das variáveis analisadas, a idade do doador foi a de maior impacto estatístico na sobrevida dos transplantes renais estudados. A sobrevida dos enxertos oriundos de doadores com idade de 16 a 40 anos (143,30 meses em média), foi significativamente maior em comparação com a sobrevida nos grupos com doadores acima de 40 anos (66,46 meses) (p= 0,005) e nos doadores de 0 a 10 anos de idade (63,29 meses) (p= 0,01). A compatibilidade HLA e o TIF não interferiram de modo significativo na sobrevida dos transplantes estudados (p= 0,98 e p= 0,16 respectivamente). Conclusões: O tempo de isquemia fria (TIF) e a compatibilidade HLA não apresentaram impacto na sobrevida dos transplantes renais analisados. Os doadores cadáveres com idade de 16 a 40 anos podem ser considerados ideais, uma vez que demonstraram, de modo estatisticamente significativo, impacto favorável na sobrevida dos rins por eles doados. / Introduction: Renal transplantation is world wide recognized as the best therapy for patients that need kidney substitution treatment. It can be considered a clinical and surgical triumph and at the same time, its a form of frustration by the few organs donations available and by the growth of the waiting lists. New strategies are needed to be developed to increase the numbers of kidneys for transplantation. Donors aged, cold ischemia time (CIT) and human leukocyte antigen (HLA) compatibility are correlated with graft survival and consequently, with a diminished organs demand. Objectives: To study the impacts of donors age, cold ischemia time and HLA compatibility, on graft survival patients submitted to cadaver kidney allograft transplantation. Materials and Methods: Records from 454 patients, submitted to cadaver kidneys allograft transplantations between April/1987 and December/2003 by Division of Urology of the Clinical Hospital of Ribeirao Pretos School of Medicine at Sao Paulo University, were analyzed. Results: The age of kidneys donors was the most statistically significant data in the survival graft rate. Donors between 16 and 40 years old had a median survival rate about 143.30 months, that was significantly higher when compared with aged donors above 40 years (66.46 months) (p= 0.005) and below 10 years old (63,29 months) (p= 0.01). In our study, HLA compatibility and cold ischemia time didnt have statistically significant impact on renal allograft survival rate (p= 0.98 and p= 0.16, respectively). Conclusions: HLA compatibility and cold ischemia time didnt have significantly impact on renal allograft survival rate. Donors between 16 and 40 years old can be considered the ideal donors age, since they demonstrated statistically a favorable impact on grafts survival rate.

Introdução - As doenças renais terminais têm elevada prevalência. O transplante renal é sabidamente a melhor opção de tratamento, porém há considerável carência de rins de cadáver. A doação intervivos é uma alternativa que propicia redução do tempo em fila de espera, aliada a outras vantagens, contudo, com riscos para o doador. Prefere-se o rim esquerdo por ter veia renal mais longa que o rim contralateral. O rim direito pode ser utilizado em determinados casos, apesar dos riscos impostos pela menor extensão da sua veia. Objetivou-se avaliar as perdas de extensão de veia renal com os métodos de clampeamento mais freqüentemente utilizados, assim como a comparação entre os comprimentos obtidos das veias renais direita e esquerda, antes do seu clampeamento e secção e após. Métodos - Por meio de dissecção de cadáveres, avaliou-se o comprimento da veia renal direita, antes de ser clampeada e seccionada e após, utilizando-se três métodos de clampeamento: com pinça vascular Satinsky, com sutura mecânica (Stapler) e clipe vascular Hem-o-lok®. Empregaram-se os testes Qui-quadrado, T-pareado e ONEWAY-ANOVA para a análise estatística dos dados obtidos. Resultados - Verificou-se que a veia renal direita é significativamente menor que a veia renal esquerda, considerandose o seu comprimento útil em todas as condições. Dentre os três métodos utilizados, evidenciou-se maior comprimento da veia renal direita com o emprego da pinça vascular Satinsky. Não houve diferença estatisticamente significativa entre Stapler e Hem-o-lok®, apesar de o primeiro ter mostrado valores maiores em relação ao segundo. Conclusões - Concluiu-se que a veia renal direita é significativamente menor que a veia renal esquerda, considerando-se o seu comprimento útil. A veia renal direita é 13,7% menor que a veia renal esquerda e não há diferença estatisticamente significativa quando comparadas as medidas entre os três métodos de clampeamento vascular. / Introduction - End-stage renal diseases have high incidence. Renal transplantation is the best approach to such conditions. Live donor transplants offer shorter waiting times, and less surgical stress, but pose risks to the donor. The left kidney is preferred because the left renal vein is longer. The right kidney may be used in selected cases, in spite of the risks due to its shorter vein. The preferred clamping method to minimize right renal vein length waste has not been defined. Methods - The length of the right renal vein was assessed in cadavers, before and after clamping and section, with comparison of three clamping methods: Satinsky vascular clamp; Stapler; and Hem-o-lock® vascular clip. The chi-squared, paired t, and ONEWAY ANOVA tests were used for statistical analysis. Results - The right renal vein was found to be significantly shorter than the left one. The Satinsky method produced the greatest length of the right renal vein. The Stapler and Hem-o-lock® methods did not significantly differ, although the former produced values constantly higher than the latter. Conclusions - The right renal vein is significantly shorter (13.7%) than the left one, and the measures obtained with the three vascular clamping methods did not statistically differ