Transplant Biology at a Crossroads: Surgeons can now give patients a new hand or even a new face, but they still can't provide any guarantees that the benefits are worth the risks.

Despite major advances in transplantation biology, allowing transplants not just of critical organs like heart and kidney but also of limbs and faces, researchers are still struggling to minimize the risks from achieving the level of immunosuppression needed to make the body accept foreign tissues

Epithelial-Mesenchymal Transitions of Bile Duct Epithelial Cells in Primary Hepatolithiasis

The purpose of this study was to explore the role of epithelial-mesenchymal transition in the pathogenesis of hepatolithiasis. Thirty-one patients with primary hepatolithiasis were enrolled in this study. Expressions of E-cadherin, α-catenin, α-SMA, vimentin, S100A4, TGF-β1 and P-smad2/3 in hepatolithiasis bile duct epithelial cells were examined by immunohistochemistry staining. The results showed that the expressions of the epithelial markers E-cadherin and α-catenin were frequently lost in hepatolithiasis (32.3% and 25.9% of cases, respectively), while the mesenchymal markers vimentin, α-SMA and S100A4 were found to be present in hepatolithiasis (35.5%, 29.0%, and 32.3% of cases, respectively). The increased mesenchymal marker expression was correlated with decreased epithelial marker expression. The expressions of TGF-β1 and P-smad2/3 in hepatolithiasis were correlated with the expression of S100A4. These data indicate that TGF-β1-mediated epithelial-mesenchymal transition might be involved in the formation of hepatolithiasis

Kidney Transplantation Outcomes across Autosomal Dominant Polycystic Kidney Disease at Siriraj Hospital

Background: Thailand has a population of 65 million. The estimated incidence of chronic kidney disease (CKD) patients is approximately 17%. Siriraj Hospital has performed kidney transplantations since 1973. With 43 years of experience, a total of 1,150 kidney transplantations (65.5% were deceased donors and 34.5% were living donors) were performed at Siriraj Hospital. Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent, potentially lethal, monogenetic disorder with the prevalence of 1:500-1:1000 worldwide. It is the fourth leading cause of end-stage renal disease (ESRD). The characteristic of ADPKD is the enlargement of kidney from numerous cysts present on the renal tubules which gradually grow resulting in the decline of glomerular filtration rate (GFR) and eventually turning into ESRD. Objective: We aimed to study the outcome of kidney transplantation in ADPKD recipients at Siriraj Hospital. Methods: Thirty-one ESRD-ADPKD patients (male 22, female 9) received kidney transplantation at Siriraj Hospital. Twenty-eight patients (90.3%) were deceased donors and 3 patients (9.7%) were living donors. All living donors were performed genetic tests, including linkage study and mutation test, to exclude ADPKD relatives who carried abnormal PKD genes. Results: The kidney allograft survival at 1-, 5- and 10-years were 81%, 81% and 54%, respectively. The results of patient survival at 1-, 5- and 10-years were 94%, 90% and 75%, respectively. Conclusion: Kidney transplantation provides excellent patient and graft survival rates and is the preferred treatment option for patients with ADPKD and ESRD

Mycophenolic acid AUC in Thai kidney transplant recipients receiving low dose mycophenolate and its association with UGT2B7 polymorphisms

Manop Pithukpakorn,1 Tiwat Tiwawanwong,2 Yupaporn Lalerd,3 Anunchai Assawamakin,3,4 Nalinee Premasathian,2 Adis Tasanarong,5 Wanna Thongnoppakhun,3 Attapong Vongwiwatana2 1Division of Medical Genetics, 2Division of Nephrology, Department of Medicine, 3Division of Molecular Genetics, Department of Research and Development, Faculty of Medicine Siriraj Hospital, 4Department of Pharmacology, Faculty of Pharmacy, Mahidol University, 5Department of Medicine, Faculty of Medicine, Thammasat University, Bangkok, Thailand Background: Despite use of a lower mycophenolate dose in Thai kidney transplant patients, acceptable graft and patient outcomes can be achieved. We therefore examined the pharmacokinetics of mycophenolic acid (MPA) by area under the curve (AUC) and investigated genetic contribution in mycophenolate metabolism in this population. Methods: Kidney transplant recipients with stable graft function who were receiving mycophenolate mofetil 1,000 mg/d in combination with either cyclosporine or tacrolimus, and prednisolone were studied. The MPA concentration was measured by fluorescence polarization immunoassay (FPIA), at predose and 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing. Genetic polymorphisms in UGT1A8, UGT1A9, and UGT2B7 were examined by denaturing high-performance liquid chromatography (DHPLC)-based single-base extension (SBE) analysis. Results: A total 138 patients were included in study. The mean AUC was 39.49 mg-h/L (28.39–89.58 mg-h/L), which was in the therapeutic range. The correlation between the predose MPA concentration and AUC was poor. The mean AUC in the tacrolimus group was higher than that in the cyclosporine group. Polymorphisms in UGT2B7 showed significant association with AUC. Conclusion: Most of our patients with reduced mycophenolate dose had the AUC within the therapeutic range. Genetic polymorphisms in UGT2B7 may play a role in MPA metabolism in Thai kidney transplant patients. Keywords: UGT, MPA, pharmacokinetic, immunosuppressiv