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   2010| January-March  | Volume 4 | Issue 1  
    Online since December 6, 2017

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Pharmacogenetic analysis of calcineurin inhibitors in renal transplant patients: Towards personalized immunosuppressive therapy?
Ranjana Singh, Aneesh Srivastava, Rama Devi Mittal
January-March 2010, 4(1):5-14
Summary The calcineurin inhibitors (CNIs), cyclosporine (CsA) and tacrolimus (Tac), have had a revolutionary effect on the overall success of renal transplantation through reduction in early immunologic injury and acute rejection rates. Both CsA and Tac are well known for highly variable dose requirement in individuals. Although therapeutic drug monitoring, by measuring whole blood C2 level for CsA and T0 level for Tac, is routinely performed to maintain therapeutic blood concentrations, both, allograft rejection due to underimmunosuppression and chronic CNI toxicity due to over-dose occur in day to day clinical practice. Moreover, some patients do not reach target concentrations with recommended starting doses and therefore have an increased risk of under-immunosuppression and acute rejection. The poor correlation between dose, blood concentration and therapeutic response provided the rationale for searching complementary strategies to manage immunosuppressants beyond therapeutic drug monitoring. In recent years, the field of pharmacogenetics with an aim to identify the inherited basis for inter-individual differences in drug response has provided important information concerning the role of drug metabolizing and drug transporter gene variants in response to immunosuppressive therapy in transplant recipients. The key proteins involved in metabolism and transport of CsA and Tac include cytochome P450IIIA (CYP3A), encoded by CYP3A4 and CYP3A5 genes and P-glycoprotein (P-gp), encoded by ABCB1 gene, also known as multidrug resistance 1 gene (MDR1). Pglycoprotein acts as transporter on the surface of enterocytes, hepatocytes and lymohocytes and CYP3A influence pharmacokinetics of drugs by metabolism in the small intestine and liver. Several polymorphisms with a significant impact on protein expression and function have been described. An attractive hypothesis has emerged that such inter-individual differences in CsA/Tac pharmacokinetics may partly result from genetic polymorphisms in genes for drug metabolism and drug transport. The present review therefore, highlights the importance of performing pharmacogenetic analysis of CNIs in renal transplant recipients, taking into account different studies conducted till date, with the ultimate aim of personalized immunosuppressive therapy.
[ABSTRACT]   Full text not available  [PDF]
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A two-year retrospective analysis of renal transplant patients in sri lanka
Chaturaka Rodrigo, Ricaz Sheriff, Senaka Rajapakse, Rushika D Lanerolle, Rezvi Sheriff
January-March 2010, 4(1):15-19
This retrospective analytical study aimed at establishing a database of patients who underwent renal transplant under the Faculty of Medicine (Colombo) renal transplant programme. Patients who underwent renal transplant under the programme from 31st December 2004 to 31st December 2006 were included in the study. The objective was to build a profile of renal transplant patient with focus on post KT infections and complications of renal transplants. An interviewer administered questionnaire was used. N=72, government sector 46 (62.5 %) and private sector 26 (37.5 %). Eighteen (25%) had died by February 2007. Forty three patients (58.3%) were interviewed and twelve patients could not be contacted. Of the interviewed, 28 (38.9%) were on azathioprine, prednisolone and cyclosporin while 15 (20.8%) were on prednisolone, cyclosporin and mycophenolate mofetil. Four patients had symptomatic cytomegalovirus infection and 5 had tuberculosis post transplant. Of all infections, the most commonly reported was urinary tract infection (11 cases). Out of the total sample, 33 (45.8 %) had received induction therapy with either basiliximab (8) or daclizumab (25). There was no significant benefit in protection against acute rejection in those who took induction therapy. Acute rejection was the most commonly encountered complication with 9 cases (12.5 %) being reported over the study period. Of late complications, most were due to immunosuppression. Overall 2 year survival was 75%, with no significant difference depending on the center of transplant.
[ABSTRACT]   Full text not available  [PDF]
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Srivastava Aneesh
January-March 2010, 4(1):1-1
Full text not available  [PDF]
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An overview of banff classification of renal transplant pathology
Manoj Jain
January-March 2010, 4(1):20-25
Full text not available  [PDF]
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Gene expression analysis in predicting rejection and its outcome
Alok Srivastava, Aneesh Srivastava
January-March 2010, 4(1):2-4
Full text not available  [PDF]
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XXth Annual conference of indian society of organ transplantation (ISOT), Department of nephrology, institute of medical sciences, Banaras hindu university, Varanasi, India October 8th to 10th 2009

January-March 2010, 4(1):26-42
Full text not available  [PDF]
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