[en] We report a multicenter, prospective, randomized, open-label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients. Adult patients with good renal function undergoing primary liver transplant were randomized to either: group A (standard-dose tacrolimus [target trough levels >10 ng/mL] and corticosteroids; n = 183); group B (mycophenolate mofetil [MMF] 2g/day, reduced-dose tacrolimus [target trough levels </=8 ng/mL], and corticosteroids; n = 170); group C (daclizumab induction, MMF, reduced-dose tacrolimus delayed until the fifth day posttransplant and corticosteroids, n = 172). The primary endpoint was change from baseline in estimated glomerular filtration rate (eGFR) at 52 weeks. The eGFR decreased by 23.61, 21.22 and 13.63 mL/min in groups A, B and C, respectively (A vs C, p = 0.012; A vs B, p = 0.199). Renal dialysis was required less frequently in group C versus group A (4.2% vs. 9.9%; p = 0.037). Biopsy-proven acute rejection rates were 27.6%, 29.2% and 19.0%, respectively. Patient and graft survival was similar. In conclusion, daclizumab induction, MMF, corticosteroids and delayed reduced-dose tacrolimus was associated with less nephrotoxicity than therapy with standard-dose tacrolimus and corticosteroids without compromising efficacy or tolerability.
Disciplines :
Surgery Gastroenterology & hepatology
Author, co-author :
Neuberger, J. M.
Mamelok, R. D.
Neuhaus, P.
Pirenne, J.
Samuel, D.
Isoniemi, H.
Rostaing, L.
Rimola, A.
Marshall, S.
Mayer, A. D.
Fabregat-Prous, J.
Durand, F.
Friman, S.
Bechstein, W.
Schmidt, J.
Schemmer, P.
Hauss, J. P.
Clavien, P. A.
Broelsch, C. E.
Bernados, A.
Detry, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > Chirurgie abdominale- endocrinienne et de transplantation
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
European Liver Transplant Registry. 2007 [cited 2008 May 20]; Available from : http://www.eltr.org/publi/index-rv.php3.
U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients. 2007 OPTN/SRTR Annual Report: Transplant data 1997-2006. 2007 [cited 2008 May 1]; Available from : http://www.ustransplant. org/annual-reports/current/906d-li.html.
Ojo AO, Held PJ, Port FK et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003 349 : 931 940.
Cohen AJ, Stegall MD, Rosen CB et al. Chronic renal dysfunction late after liver transplantation. Liver Transpl 2002 8 : 916 921.
Wilkinson A, Pham PT. Kidney dysfunction in the recipients of liver transplants. Liver Transpl 2005 11 (11 Suppl 2 S47 S51.
Fisher NC, Nightingale PG, Gunson BK, Lipkin GW, Neuberger JM. Chronic renal failure following liver transplantation: A retrospective analysis. Transplantation 1998 66 : 59 66.
Morard I, Mentha G, Spahr L et al. Long-term renal function after liver transplantation is related to calcineurin inhibitors blood levels. Clin Transplant 2006 20 : 96 101.
Velidedeoglu E, Bloom RD, Crawford MD et al. Early kidney dysfunction post liver transplantation predicts late chronic kidney disease. Transplantation 2004 77 : 553 556.
Gonwa TA, Mai ML, Melton LB et al. End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: Risk of development and treatment. Transplantation 2001 72 : 1934 1939.
Pawarode A, Fine DM, Thuluvath PJ. Independent risk factors and natural history of renal dysfunction in liver transplant recipients. Liver Transpl 2003 9 : 741 747.
Kniepeiss D, Iberer F, Schaffellner S et al. Nonnephrotoxic immunosuppression in patients after liver transplantation. Int Immunopharmacol 2005 5 : 133 136.
Kornberg A, Küpper B, Hommann M, Scheele J. Introduction of MMF in conjunction with stepwise reduction of calcineurin inhibitor in stable liver transplant patients with renal dysfunction. Int Immunopharmacol 2005 5 : 141 146.
Pageaux GP, Rostaing L, Calmus Y et al. Mycophenolate mofetil in combination with reduction of calcineurin inhibitors for chronic renal dysfunction after liver transplantation. Liver Transpl 2006 12 : 1755 1760.
Reich DJ, Clavien PA, Hodge EE. Mycophenolate mofetil for renal dysfunction in liver transplant recipients on cyclosporine or tacrolimus: Randomized, prospective, multicenter pilot study results. Transplantation 2005 80 : 8 25.
Fairbanks KD, Eustace JA, Fine D, Thuluvath PJ. Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus. Liver Transpl 2003 9 : 1079 1085.
Schlitt HJ, Barkmann A, Böker KH et al. Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction: A randomised controlled study. Lancet 2001 357 : 587 591.
Heffron TG, Smallwood GA, de Vera ME et al. Daclizumab induction in liver transplant recipients. Transplant Proc 2001 33 : 1527.
Heffron TG, Smallwood GA, Pillen T et al. Liver transplant induction trial of daclizumab to spare calcineurin inhibition. Transplant Proc 2002 34 : 1514 1515.
Yoshida EM, Marotta PJ, Greig PD et al. Evaluation of renal function in liver transplant recipients receiving daclizumab Zenapax, mycophenolate mofetil, and a delayed, low-dose tacrolimus regimen vs a standard-dose tacrolimus and mycophenolate mofetil regimen: A multicenter randomized clinical trial. Liver Transpl 2005 11 : 1064 1072.
Brunet M, Cirera I, Martorell J et al. Sequential determination of pharmacokinetics and pharmacodynamics of mycophenolic acid in liver transplant patients treated with mycophenolate mofetil.[see comment]. Transplantation 2006 81 : 541 546.
Jain A, Venkataramanan R, Kwong T et al. Pharmacokinetics of mycophenolic acid in liver transplant patients after intravenous and oral administration of mycophenolate mofetil. Liver Transpl 2007 13 : 791 796.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976 16 : 31 41.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999 130 : 461 470.
Astellas Pharma US Inc. Prograf (tacrolimus capsules) product information. 2006.
Montini G, Murer L, Ghio L et al. One-year results of basiliximab induction and tacrolimus associated with sequential steroid and MMF treatment in pediatric kidney transplant recipient. Transpl Int 2005 18 : 36 42.
Eckhoff DE, McGuire B, Sellers M et al. The safety and efficacy of a two-dose daclizumab (zenapax) induction therapy in liver transplant recipients. Transplantation 2000 69 : 1867 1872.
Fahlke J, Wolff S, Mantke R et al. Staggered immunosuppression with the interleukin-2 receptor antagonist daclizumab combined with tacrolimus, prednisolone, and mycophenolate mofetil after orthotopic liver transplantation: A pilot efficacy and safety study. Transplant Proc 2002 34 : 1242 1244.
Vincenti F, Pace D, Birnbaum J et al. Pharmacokinetic and pharmacodynamic studies of one or two doses of daclizumab in renal transplantation. Am J Transplant 2003 3 : 50 52.
Eckhoff DE, McGuire BM, Frenette LR, Contreras JL, Hudson SL, Bynon JS. Tacrolimus (FK506) and mycophenolate mofetil combination therapy versus tacrolimus in adult liver transplantation. Transplantation 1998 65 : 180 187.
Fisher RA, Ham JM, Marcos A et al. A prospective randomized trial of mycophenolate mofetil with neoral or tacrolimus after orthotopic liver transplantation. Transplantation 1998 66 : 1616 1621.
Jain AB, Hamad I, Rakela J et al. A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients: An interim report. Transplantation 1998 66 : 1395 1398.
Lake JR, David KM, Steffen BJ, Chu AH, Gordon RD, Wiesner RH. Addition of MMF to dual immunosuppression does not increase the risk of malignant short-term death after liver transplantation. Am J Transplant 2005 5 : 2961 2967.
Wiesner RH, Shorr JS, Steffen BJ, Chu AH, Gordon RD, Lake JR. Mycophenolate mofetil combination therapy improves long-term outcomes after liver transplantation in patients with and without hepatitis C. Liver Transpl 2005 11 : 750 759.
National Kidney Foundation. NKF K/DOQI clinical practice guidelines for chronic kidney disease. 2002 [cited 29 Nov 2007]; Available from : http://www.kidney.org.
Scott LJ, McKeage K, Keam SJ, Plosker GL. Tacrolimus: A further update of its use in the management of organ transplantation. Drugs 2003 63 : 1247 1297.
Paramesh AS, Roayaie S, Doan Y et al. Post-liver transplant acute renal failure: Factors predicting development of end-stage renal disease. Clin Transplant 2004 18 : 94 99.
Aberg F, Koivusalo AM, Höckerstedt K, Isoniemi H. Renal dysfunction in liver transplant patients: Comparing patients transplanted for liver tumor or acute or chronic disease. Transpl Int 2007 20 : 591 599.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.