Thesis (Ph.D. )--University of Tennessee Health Science Center, 2008. / Title from title page screen (viewed on April 24, 2008 ). Research advisor: Shelly White-Means, Ph.D. Document formatted into pages (xi, 101 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 94-100).

Crianças pequenas representam um grupo desafiador no transplante renal. O estudo analisa os resultados, do ponto de vista cirúrgico, do transplante renal em crianças com peso inferior a 15 kg utilizando o acesso cirúrgico extraperitoneal. Métodos: Foram revisados retrospectivamente os prontuários de 62 crianças com peso inferior a 15 kg submetidas a transplante renal entre 1998 e 2010, utilizando o acesso extraperitoneal e anastomose dos vasos renais dos doadores com a aorta ou artéria ilíaca comum e com a veia cava inferior ou ilíaca comum dos receptores. O ureter foi anastomosado à bexiga pela técnica extravesical de Lich- Grégoir. Resultados: Dos 62 transplantes, 32 enxertos (51,6%) eram provenientes de doadores vivos e 30 (48,4%) de doadores falecidos, sendo 28 deles pediátricos. A média de idade no transplante foi de 3,7 ± 2,2 anos (1 a 12), e o peso médio, de 12,3 ± 2,1 kg (5,6 a 14,9), sendo que 10 tinham peso inferior a 10 kg. Em 10 crianças (16,1%) o transplante foi preemptivo e em 5 (8,1%) havia trombose do sistema venoso prévio ao transplante. Em 1 e 5 anos, a sobrevida do paciente foi de 93,2% e 84,2% e a sobrevida do enxerto de 85,2% e 72,7%, respectivamente, sem diferença entre doadores vivos e falecidos. A função do enxerto com doador vivo foi melhor em 1 e 3 meses, mas a partir do 6o mês foi similar. Houve 6 complicações vasculares, sendo 4 tromboses vasculares, 1 laceração e 1 estenose de artéria renal e 2 coleções líquidas. Houve 17 perdas de enxerto, 6 por morte, sendo 5 com enxerto funcionante, 5 por complicações cirúrgicas, 3 por rejeição crônica e 3 por recorrência da doença de base. Conclusão: O acesso extraperitoneal é uma técnica válida no transplante renal de crianças com peso inferior a 15 kg, assegurando boa sobrevida do paciente e do enxerto e aceitável taxa de complicações, independentemente do tipo de doador, se vivo ou falecido, ou do tamanho do enxerto, se de adulto ou de criança. / Small children are a challenging group for kidney transplantation. This study analyzes the results of kidney transplantation in children weighing less than 15 kg using the extraperitoneal surgical access. Methods: A retrospective review of the records of 62 children weighting less than 15 kg was done. The kidney transplantation were performed between 1998 and 2010 using the extraperitoneal access and anastomosis of the renal vessels of donors to the aorta or common iliac artery and to the inferior vena cava or common iliac vein of the recipients. The ureter was anastomosed to the bladder using the Lich-Grégoir extravesical technique. Results: Thirty-two (51.6%) grafts of the 62 transplants were from living donors and 30 (48.4%) from deceased donors, 28 of them pediatric. The mean age at transplantion was 3.7 ± 2.2 years (1 to 12), and the mean weight, 12.3 ± 2.1 kg (5.6 to 14.9), and 10 of them weighed less than 10 kg. In 10 children (16.1%) the transplant was preemptive. Five 5 (8.1%) children presented previous thrombosis of the venous system. At 1 and 5 years, patient survival was 93.2% and 84.2% and graft survival was 85.2% and 72.7%, respectively, and there was no difference between living and deceased donors. The graft function of the living donor was better at 1 and 3 months, but was similar from the 6th month onward. There were 6 vascular complications (4 of them vascular thromboses, 1 laceration and 1 renal artery stenosis) and 2 perirenal collections. Seventeen grafts were lost, 6 due to death, 5 with a functioning graft, 5 due to surgical complications, 3 due to chronic rejection and 3 due to recurrence of the original disease. Conclusion: The extraperitoneal access is a valid kidney transplantantion technique in children weighing less than 15 kg, ensuring good patient and graft survival, and an acceptable rate of complications, independent of source of donor, living or deceased, or size of graft, whether from an adult or from a child.

Crianças pequenas representam um grupo desafiador no transplante renal. O estudo analisa os resultados, do ponto de vista cirúrgico, do transplante renal em crianças com peso inferior a 15 kg utilizando o acesso cirúrgico extraperitoneal. Métodos: Foram revisados retrospectivamente os prontuários de 62 crianças com peso inferior a 15 kg submetidas a transplante renal entre 1998 e 2010, utilizando o acesso extraperitoneal e anastomose dos vasos renais dos doadores com a aorta ou artéria ilíaca comum e com a veia cava inferior ou ilíaca comum dos receptores. O ureter foi anastomosado à bexiga pela técnica extravesical de Lich- Grégoir. Resultados: Dos 62 transplantes, 32 enxertos (51,6%) eram provenientes de doadores vivos e 30 (48,4%) de doadores falecidos, sendo 28 deles pediátricos. A média de idade no transplante foi de 3,7 ± 2,2 anos (1 a 12), e o peso médio, de 12,3 ± 2,1 kg (5,6 a 14,9), sendo que 10 tinham peso inferior a 10 kg. Em 10 crianças (16,1%) o transplante foi preemptivo e em 5 (8,1%) havia trombose do sistema venoso prévio ao transplante. Em 1 e 5 anos, a sobrevida do paciente foi de 93,2% e 84,2% e a sobrevida do enxerto de 85,2% e 72,7%, respectivamente, sem diferença entre doadores vivos e falecidos. A função do enxerto com doador vivo foi melhor em 1 e 3 meses, mas a partir do 6o mês foi similar. Houve 6 complicações vasculares, sendo 4 tromboses vasculares, 1 laceração e 1 estenose de artéria renal e 2 coleções líquidas. Houve 17 perdas de enxerto, 6 por morte, sendo 5 com enxerto funcionante, 5 por complicações cirúrgicas, 3 por rejeição crônica e 3 por recorrência da doença de base. Conclusão: O acesso extraperitoneal é uma técnica válida no transplante renal de crianças com peso inferior a 15 kg, assegurando boa sobrevida do paciente e do enxerto e aceitável taxa de complicações, independentemente do tipo de doador, se vivo ou falecido, ou do tamanho do enxerto, se de adulto ou de criança. / Small children are a challenging group for kidney transplantation. This study analyzes the results of kidney transplantation in children weighing less than 15 kg using the extraperitoneal surgical access. Methods: A retrospective review of the records of 62 children weighting less than 15 kg was done. The kidney transplantation were performed between 1998 and 2010 using the extraperitoneal access and anastomosis of the renal vessels of donors to the aorta or common iliac artery and to the inferior vena cava or common iliac vein of the recipients. The ureter was anastomosed to the bladder using the Lich-Grégoir extravesical technique. Results: Thirty-two (51.6%) grafts of the 62 transplants were from living donors and 30 (48.4%) from deceased donors, 28 of them pediatric. The mean age at transplantion was 3.7 ± 2.2 years (1 to 12), and the mean weight, 12.3 ± 2.1 kg (5.6 to 14.9), and 10 of them weighed less than 10 kg. In 10 children (16.1%) the transplant was preemptive. Five 5 (8.1%) children presented previous thrombosis of the venous system. At 1 and 5 years, patient survival was 93.2% and 84.2% and graft survival was 85.2% and 72.7%, respectively, and there was no difference between living and deceased donors. The graft function of the living donor was better at 1 and 3 months, but was similar from the 6th month onward. There were 6 vascular complications (4 of them vascular thromboses, 1 laceration and 1 renal artery stenosis) and 2 perirenal collections. Seventeen grafts were lost, 6 due to death, 5 with a functioning graft, 5 due to surgical complications, 3 due to chronic rejection and 3 due to recurrence of the original disease. Conclusion: The extraperitoneal access is a valid kidney transplantantion technique in children weighing less than 15 kg, ensuring good patient and graft survival, and an acceptable rate of complications, independent of source of donor, living or deceased, or size of graft, whether from an adult or from a child.

Crianças pequenas representam um grupo desafiador no transplante renal. O estudo analisa os resultados, do ponto de vista cirúrgico, do transplante renal em crianças com peso inferior a 15 kg utilizando o acesso cirúrgico extraperitoneal. Métodos: Foram revisados retrospectivamente os prontuários de 62 crianças com peso inferior a 15 kg submetidas a transplante renal entre 1998 e 2010, utilizando o acesso extraperitoneal e anastomose dos vasos renais dos doadores com a aorta ou artéria ilíaca comum e com a veia cava inferior ou ilíaca comum dos receptores. O ureter foi anastomosado à bexiga pela técnica extravesical de Lich- Grégoir. Resultados: Dos 62 transplantes, 32 enxertos (51,6%) eram provenientes de doadores vivos e 30 (48,4%) de doadores falecidos, sendo 28 deles pediátricos. A média de idade no transplante foi de 3,7 ± 2,2 anos (1 a 12), e o peso médio, de 12,3 ± 2,1 kg (5,6 a 14,9), sendo que 10 tinham peso inferior a 10 kg. Em 10 crianças (16,1%) o transplante foi preemptivo e em 5 (8,1%) havia trombose do sistema venoso prévio ao transplante. Em 1 e 5 anos, a sobrevida do paciente foi de 93,2% e 84,2% e a sobrevida do enxerto de 85,2% e 72,7%, respectivamente, sem diferença entre doadores vivos e falecidos. A função do enxerto com doador vivo foi melhor em 1 e 3 meses, mas a partir do 6o mês foi similar. Houve 6 complicações vasculares, sendo 4 tromboses vasculares, 1 laceração e 1 estenose de artéria renal e 2 coleções líquidas. Houve 17 perdas de enxerto, 6 por morte, sendo 5 com enxerto funcionante, 5 por complicações cirúrgicas, 3 por rejeição crônica e 3 por recorrência da doença de base. Conclusão: O acesso extraperitoneal é uma técnica válida no transplante renal de crianças com peso inferior a 15 kg, assegurando boa sobrevida do paciente e do enxerto e aceitável taxa de complicações, independentemente do tipo de doador, se vivo ou falecido, ou do tamanho do enxerto, se de adulto ou de criança. / Small children are a challenging group for kidney transplantation. This study analyzes the results of kidney transplantation in children weighing less than 15 kg using the extraperitoneal surgical access. Methods: A retrospective review of the records of 62 children weighting less than 15 kg was done. The kidney transplantation were performed between 1998 and 2010 using the extraperitoneal access and anastomosis of the renal vessels of donors to the aorta or common iliac artery and to the inferior vena cava or common iliac vein of the recipients. The ureter was anastomosed to the bladder using the Lich-Grégoir extravesical technique. Results: Thirty-two (51.6%) grafts of the 62 transplants were from living donors and 30 (48.4%) from deceased donors, 28 of them pediatric. The mean age at transplantion was 3.7 ± 2.2 years (1 to 12), and the mean weight, 12.3 ± 2.1 kg (5.6 to 14.9), and 10 of them weighed less than 10 kg. In 10 children (16.1%) the transplant was preemptive. Five 5 (8.1%) children presented previous thrombosis of the venous system. At 1 and 5 years, patient survival was 93.2% and 84.2% and graft survival was 85.2% and 72.7%, respectively, and there was no difference between living and deceased donors. The graft function of the living donor was better at 1 and 3 months, but was similar from the 6th month onward. There were 6 vascular complications (4 of them vascular thromboses, 1 laceration and 1 renal artery stenosis) and 2 perirenal collections. Seventeen grafts were lost, 6 due to death, 5 with a functioning graft, 5 due to surgical complications, 3 due to chronic rejection and 3 due to recurrence of the original disease. Conclusion: The extraperitoneal access is a valid kidney transplantantion technique in children weighing less than 15 kg, ensuring good patient and graft survival, and an acceptable rate of complications, independent of source of donor, living or deceased, or size of graft, whether from an adult or from a child.

Samples from 93 of 115 consecutive cadaveric renal transplants were selected to define polymorphisms in both IFN-γ and IL-10. A 12 CA repeat IFN-γ polymorphic allele was found in 73 patients (70 in patients analysed further). This polymorphism was associated with high IFN-γ production in vitro. According to the presence or not of the 12 CA repeat allele patients were separated in high and low producer genotype groups. The incidence of acute rejection was 54.3% in this high IFN-γ genotype group, contrasting with 44.4% in the low IFN-γ. Requirement for ATG therapy was greater in the high IFN-γ group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-γ high producer genotype was more strongly associated with rejection (OR=1.6). In the cyclosporine monotherapy subgroup, 11 out of 14 patients with IFN-γ high genotype (78%) had acute rejection (OR=2.88, p=0.09). Graft survival was similar between the two IFN-γ groups. When the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-γ genotype patients had serum creatinine levels above 200 micromoles/L contrasting with only 14.3% of the low IFN-γ genotype recipients at 5 years after transplantation (p=0.05). In a regression model of creatinine at 1 year the significant variables were the presence of DGF, donor age greater than 50, greater than two rejection episodes, DR mismatch, donor female to male recipient sex, IL-10 high genotype, and IFN-γ high genotype. Conclusion: The 12 CA repeat IFN-γ polymorphic allele is associated with high IFN-γ production. We have shown that this high producer genotype for IFN-γ influences acute rejection in kidney transplantation, particularly in high-risk groups; it is also associated with worse long-term graft function.

8 ABSTRACT Author: Bc. Lucie Moravcová Supervisor: MUDr. Vít Řeháček Charles University, Faculty of Pharmacy in Hradec Králové Title of master's thesis: Kidney transplantation: donor-recipient pairing in University Hospital Hradec Králové Background: The aim of this study was to determine HLA, blood group, age and sex match in donor-recipient pairing in kidney transplantation. HLA alleles of deceased donors were typed in Transfusion Department of the University Hospital Hradec Králové. Methods: Donor's HLA-A*, HLA-B* and HLA-DRB1* alleles were typed by PCR - SSP method. Complex data evaluating and processing was then performed. Results: 97 deceased donors were tested between 2013 and 2018. A total of 98 kidneys received from them were subsequently transplanted to 98 recipients in University Hospital Hradec Králové. 60,2 % of the donors were men, 63,3 % of the recipients were men. Most of the donors, as well as the recipients, were 51-70 years old (50,0 % and 59,2 %, respectively). The most common diagnoses in the group of deceased donors were associated with brain damage (66,3 %), the most common cause of renal failure in the group of recipients was chronic inflammatory kidney disease (41,8 %). All 98 transplantations (100,0 %) were AB0 compatible. 74 transplantations (75,5 %) were RhD compatible. 5...

O transplante de órgãos é hoje uma opção de tratamento de várias doenças terminais. Apesar de todos os progressos no campo do transplante, o principal problema enfrentado ainda é a rejeição. As principais moléculas responsáveis pela resposta alogeneica e subsequente rejeição ao enxerto, são os antígenos leucocitários humanos (HLA, do inglês Human Leucocyte Antigens). Porém, existem evidências que anticorpos dirigidos a antígenos não-HLA estão associados com rejeição de transplantes. Neste estudo, foi investigada a presença de anticorpos anti-célula endotelial (AACE) em 11 pacientes que perderam seus rins transplantados devido à rejeição humoral irreversível e em 2 com perda por trombose de veia renal. A ausência de anticorpos anti-HLA contra o doador foi verificada antes do transplante, da rejeição e antes e depois da transplantectomia, através da realização de provas cruzadas usando as técnicas mais sensíveis. Anticorpos não-HLA presentes em nove eluatos reagiram com EAHy.926. Eluatos positivos e negativos contra linhagem EAHy.926 foram testados contra cortes histológicos de 6 rins sadios para detecção de quais estruturas renais são reconhecidas por esses anticorpos. A reação foi avaliada pelo método de imunofluorescência indireta. Dos 13 eluatos testados, 4 (isotipo IgG) e 5 (isotipo IgM) reagiram com forte fluorescência nos glomérulos e endotélio arterial, mas não foi verificada reação na cápsula de Bowman e no epitélio tubular. Não foi observado polimorfismo na reatividade dos eluatos. Em onclusão, verificamos que os anticorpos não-HLA têm um importante papel na rejeição humoral. Estes estão reconhecendo antígenos de um sistema provavelmente não-polimórfico nas células de endoteliais presentes, principalmente, nos capilares glomerulares. / The transplant of organs is today an option of treatment to several terminal diseases. In spite of all the progress in the field of the transplants, the rejection remains a problem to be solved. The main target molecules for the allogenic response and subsequent allograft rejection are the human leukocyte antigens (HLA). However, there are growing evidences that non-HLA antibodies are associated with transplant rejection. In this study it was investigated the presence of anti-endothelial cell antibodies (AECA) in 11 patients who had early lost their transplanted kidney by irreversible humoral rejection and in 2 ones from renal venal thrombosis. The absence of anti-HLA antibodies against the donor was verified by the negativity of crossmatches performed using the most sensitive assays, at the transplant, at the rejection, and before and after the transplantectomy Antibodies from 9 eluates bound to EAHy.926. Positive and negatives eluates were tested against frozen sections from 6 normal kidneys in order to define the structures to which they were reactive. The reactivity was identified by indirect immunofluorescence method. From 13 eluates evaluated, 4 (isotipe IgG) and 5 (isotipe IgM) reacted to the glomerulus and renal arterial endothelium with intense fluorescence but they did not react to the Bowmans capsule and tubular epithelium. No polymorphism was observed in eluates reactivity. In conclusion, we have shown that non-HLA antibodies may represent a cause of the humoral rejection. These antibodies are probably recognizing antigens of a nonpolymorphic system in endothelial cells present, mainly, in the glomerular capillaries.

Tsang Kam Sze, Kent. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 155-174). / Abstract --- p.i / Acknowledgements --- p.v / List of Abbreviations --- p.viii / Table of Contents --- p.x / List of Figures --- p.xvi / List of Tables --- p.ixx / Chapter Chapter 1. --- Introduction --- p.1 / Chapter 1.1. --- Idiotype Network --- p.2 / Chapter 1.2. --- Anti-idiotype Classification --- p.8 / Chapter 1.3. --- Blood Transfusion Effect --- p.11 / Chapter 1.4. --- Transfusion Protocol --- p.12 / Chapter 1.5. --- Mechanism of Beneficial Transfusion Effect --- p.15 / Chapter 1.5.1. --- Donor Selection --- p.15 / Chapter 1.5.2. --- Clonal Deletion --- p.16 / Chapter 1.5.3. --- Suppressor Cells Induction --- p.18 / Chapter 1.5.4. --- Prostaglandins Mediation --- p.19 / Chapter 1.5.5. --- Mixed Chimerism Motivation --- p.20 / Chapter 1.5.6. --- Fc-receptor Blocking Antibodies Stimulation --- p.22 / Chapter 1.5.7. --- Anti-idiotypic Antibodies Instigation --- p.23 / Chapter 1.6. --- Study Aims --- p.25 / Chapter 1.7. --- Technical Strategy --- p.26 / Chapter Chapter 2. --- Materials and Methods --- p.30 / Chapter 2.1. --- Materials --- p.31 / Chapter 2.1.1. --- Patient Population --- p.31 / Chapter 2.1.2. --- Normal Control Group --- p.31 / Chapter 2.1.3. --- Serum Samples --- p.32 / Chapter 2.1.4. --- Additional Specimens --- p.32 / Chapter 2.1.5. --- Chemicals --- p.32 / Chapter 2.1.6. --- Antisera --- p.34 / Chapter 2.1.7. --- Buffers --- p.35 / Chapter 2.1.8. --- Consumables --- p.38 / Chapter 2.1.9. --- Apparatus and Equipment --- p.39 / Chapter 2.2. --- Methods --- p.40 / Chapter 2.2.1. --- Purification of Human Polyclonal Anti-HLA Antisera --- p.40 / Chapter 2.2.1.1. --- Affinity Chromatography --- p.41 / Chapter 2.2.1.2. --- Dialysis --- p.41 / Chapter 2.2.1.3. --- Concentration --- p.42 / Chapter 2.2.1.4. --- Quantitation --- p.42 / Chapter 2.2.2. --- Generation of F(ab')2 fragments from the Purified Human Anti-HLA Antibodies --- p.42 / Chapter 2.2.2.1. --- Buffer Exchange --- p.43 / Chapter 2.2.2.2. --- Pepsin Digestion --- p.43 / Chapter 2.2.2.3. --- Purification of (ab')2、 --- p.43 / Chapter 2.2.3. --- Enzyme-Linked Immunosorbent Assay for anti-Idiotypes against anti-HLA antibodies --- p.44 / Chapter 2.2.3.1. --- Optimization --- p.44 / Chapter 2.2.3.2. --- Quality Control --- p.45 / Chapter 2.2.3.2.1. --- F(ab')2 Specificity --- p.45 / Chapter 2.2.3.2.2. --- Fc Contamination --- p.46 / Chapter 2.2.3.2.3. --- Precision Test --- p.47 / Chapter 2.2.4. --- Anti-Casein Interference --- p.47 / Chapter 2.2.5. --- Test Protocol --- p.48 / Chapter 2.3. --- Statistical Analysis --- p.48 / Chapter Chapter 3. --- Purification of Anti-HLA IgG and F(ab')2 --- p.50 / Chapter 3.1. --- Immunoglobulin Concentration --- p.51 / Chapter 3.2. --- F(ab')2 Specificity --- p.51 / Chapter 3.3. --- Fc-fragments Contamination --- p.53 / Chapter 3.4. --- Discussion --- p.56 / Chapter Chapter 4. --- ELISA Optimization --- p.57 / Chapter 4.1. --- Coating F(ab')2 Quantitation --- p.58 / Chapter 4.2. --- Blocking and Diluting Agent Concentration --- p.61 / Chapter 4.3. --- Serum Analyte Dilution --- p.61 / Chapter 4.4. --- Conjugated Detector Antibody Titration --- p.64 / Chapter 4.5. --- Discussion --- p.66 / Chapter Chapter 5. --- Quality Control --- p.70 / Chapter 5.1. --- Avoidance of Prozone Phenomenon --- p.71 / Chapter 5.2. --- Inter-assay and Intra-assay Precision --- p.71 / Chapter 5.3. --- Discussion --- p.74 / Chapter Chapter 6. --- Adjustment of Anti-casein Interference --- p.77 / Chapter 6.1. --- Casein Allergy --- p.78 / Chapter 6.2. --- Prevalence of Anti-casein --- p.80 / Chapter 6.3. --- Discussion --- p.81 / Chapter Chapter 7. --- Prevalence of Anti-idiotypic Antibodies --- p.86 / Chapter 7.1. --- Formation Kinetics --- p.87 / Chapter 7.2. --- Occurrence in Transplant Patients --- p.87 / Chapter 7.3. --- Transfusion Effect --- p.101 / Chapter 7.3.1. --- Comparison between Transfused Transplant Patients and Normal Controls --- p.103 / Chapter 7.3.2. --- Comparison between Transfused Transplant Patients and Non-transfused Transplant Patients --- p.116 / Chapter 7.3.3. --- Association with Graft Survival --- p.117 / Chapter 7.4. --- Discussion --- p.128 / Chapter Chapter 8. --- Correlation of Transfusion with the Outcome of Transplant --- p.137 / Chapter 8.1. --- Rejection Episode --- p.138 / Chapter 8.2. --- Graft Survival --- p.139 / Chapter 8.3. --- Discussion --- p.142 / Chapter Chapter 9. --- General Conclusions --- p.149 / References --- p.153

by Wing-cheung Pang. / Thesis (M.Sc.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 45-56.

Mycophenolate mofetil (MMF) is widely used to minimise acute rejection following solid organ transplantation as it inhibits inosine monophosphate dehydrogenase (IMPDH) and thereby reduces lymphocyte activation. The effects of MMF and azathioprine on renal allograft outcome were examined by analysis of the national transplant database held at National Health Service (NHS) Blood and Transplant, Stoke Gifford, Bristol, UK. In a paired kidney analysis, MMF treated patients had a 3 year death censored graft survival of 91% (n=217) contrasts to 97% (n=231) in azathioprine treated patients (p=0.07) with an increased acute rejection rate in the first year after transplantation (44 v 31%, n=105 v 74, p<0.01). In a further study, 13% (n=71) of patients were found to be taking less than 1 g of MMF which was associated with a 3-fold increased risk of graft failure and inferior graft function up to 36 months. One strategy to improve graft outcome would entail targeting MMF dose according to pre-transplant IMPDH activity, which is known to display wide variability between patients, in order to maximize efficacy and minimize toxicity. Therefore, it was decided to measure pre-transplant IMPDH activity and to investigate associations with renal allograft outcome and MMF dose tolerated after transplantation. IMPDH activity was measured by detection of generated XMP by a validated HPLC method in the peripheral mononuclear cells of 55 patients waiting for renal transplantation and was found to exhibit a 4-fold variation of IMPDH activity. Black males had significantly increased IMPDH activity contrasts to Black females (p=0.01). Within the first year of transplantation, 71% (n=12) patients required a reduction in MMF dose. There was no association between pre-transplant IMPDH activity and MMF dose achieved at 1 year or MMF associated side effects or eGFR up to 36 months. It was proposed that the inter-individual variability of IMPDH activity may be associated with genetic polymorphisms and therefore sequencing of the exons of IMPDH I and II was undertaken. Two novel single nucleotide polymorphisms (SNPs), Leu244Leu and Ala285Thr, were identified in the IMPDH I gene. Patients with these variants did not exhibit differential IMPDH activity. Genotyping for established intronic SNPs was undertaken in our patient cohort as well as a random sample of 1040 recipients from the Collaborative Transplant Study DNA bank based at the University of Heidelberg, Germany. The presence of these SNPs did not increase the risk of rejection or affect graft function or MMF dose tolerated at 1 year after transplantation and there was no association between pre-transplant IMPDH activity, 5 year graft and patient survival and genotype. In our study, MMF treatment did not result in improved renal allograft outcomes in comparison to azathioprine therapy. Furthermore, we suggest that measurement of pre-transplant IMPDH activity or genotyping of the IMPDH enzymes is unlikely to assist in optimizing MMF dose and renal allograft outcome.