title: Sustained renal response to mycophenolate mofetil and CNI taper promotes survival in liver transplant patients with CNI-related renal dysfunction.
abstract: OBJECTIVE
  The aim of this trial was to evaluate the impact of conversion from a calcineurin-inhibitor (CNI)-based immunosuppressive regimen to mycophenolate mofetil (MMF) and reduced-dose CNI on long-term renal function and survival in a series of 63 liver transplant patients with CNI-induced renal dysfunction.
  
  
  METHODS
  CNI dosage was significantly tapered after introduction of 2,000 mg MMF per day. Renal function was assessed by determination of serum creatinine levels and calculated creatinine clearance (CCl). The impact of relevant clinical parameters on renal function and survival post-conversion was analyzed by univariate and multivariate analysis.
  
  
  RESULTS
  At 60 months post-conversion, mean creatinine level had significantly declined from 197.2±58.3 μmol/l at baseline to 160.0±76.5 μmol/l, and mean CCl has significantly increased from 38.4±13.4 ml/min at baseline to 47.9±21.1 ml/min (p<0.001), respectively. Forty-six patients (73.1%) demonstrated sustained renal response to modified immunosuppression. Full-dose MMF medication (p=0.006) and the early conversion (p=0.02) were identified as independent predictors of persistent renal function improvement. Sustained renal response to MMF plus reduced-dose CNI was identified as the most relevant independent promoter of long-term survival (hazard ratio 6.9). Five-year survival rate post-conversion was 93.9% in renal responders and 64.3% in renal non-responders (log rank<0.001).
  
  
  CONCLUSIONS
  Sustained renal response to MMF and CNI dose reduction promotes long-term survival in liver transplant patients with CNI-induced renal dysfunction.
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany. ArnoKornberg@aol.com
authors.forename: A
authors.initials: A
authors.lastname: Kornberg
authors.forename: B
authors.initials: B
authors.lastname: Küpper
authors.forename: K
authors.initials: K
authors.lastname: Thrum
authors.forename: B
authors.initials: B
authors.lastname: Krause
authors.forename: P
authors.initials: P
authors.lastname: Büchler
authors.forename: J
authors.initials: J
authors.lastname: Kornberg
authors.forename: A
authors.initials: A
authors.lastname: Sappler
authors.forename: A
authors.initials: A
authors.lastname: Altendorf-Hofmann
authors.forename: J
authors.initials: J
authors.lastname: Wilberg
authors.forename: H
authors.initials: H
authors.lastname: Friess
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000401:mortality*; D007677:Kidney Function Tests; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011183:Postoperative Complications; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D016559:Tacrolimus / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus
references.citation: Liver Transpl. 2008 May;14(5):651-9
references.pmid: 18433069
references.citation: Aliment Pharmacol Ther. 2007 Nov 1;26(9):1195-208
references.pmid: 17944734
references.citation: Drugs. 2004;64(12):1325-38
references.pmid: 15200347
references.citation: Ther Drug Monit. 2005 Aug;27(4):442-50
references.pmid: 16044100
references.citation: Transplantation. 1998 Jul 15;66(1):59-66
references.pmid: 9679823
references.citation: Transplantation. 2005 Oct 15;80(2 Suppl):S181-90
references.pmid: 16251851
references.citation: Liver Transpl. 2007 Jun;13(6):791-6
references.pmid: 17538999
references.citation: N Engl J Med. 2003 Sep 4;349(10):931-40
references.pmid: 12954741
references.citation: Am J Transplant. 2006 Jul;6(7):1609-16
references.pmid: 16827861
references.citation: Nephrol Dial Transplant. 2000 Feb;15(2):184-90
references.pmid: 10648663
references.citation: Transplantation. 2000 Jun 27;69(12 Suppl):SS5-10
references.pmid: 10910256
references.citation: Transplantation. 2000 Jun 27;69(12 Suppl):SS11-3
references.pmid: 10910257
references.citation: Clin Transplant. 2009 Mar-Apr;23(2):191-8
references.pmid: 19210525
references.citation: Transplantation. 2005 Jul 15;80(1):18-25
references.pmid: 16003228
references.citation: Transplant Proc. 2004 Nov;36(9):2671-4
references.pmid: 15621120
references.citation: Transplantation. 2005 Sep 27;80(6):859-64
references.pmid: 16210976
references.citation: Liver Transpl. 2006 Dec;12(12):1755-60
references.pmid: 17133564
references.citation: Curr Med Res Opin. 2006 Dec;22(12):2355-64
references.pmid: 17257450
references.citation: Cardiovasc Res. 2006 Feb 1;69(2):341-7
references.pmid: 16289002
references.citation: Lancet. 2001 Feb 24;357(9256):609-10
references.pmid: 11558493
references.citation: Transplantation. 2003 Jul 15;76(1):98-102
references.pmid: 12865793
references.citation: Am J Transplant. 2007 Feb;7(2):366-76
references.pmid: 17283486
references.citation: Transplantation. 2005 Oct 15;80(2 Suppl):S221-34
references.pmid: 16251855
references.citation: Int Immunopharmacol. 2005 Jan;5(1):141-6
references.pmid: 15589474
references.citation: Lancet. 2001 Feb 24;357(9256):587-91
references.pmid: 11558484
references.citation: Immunopharmacology. 2000 May;47(2-3):85-118
references.pmid: 10878285
references.citation: Liver Transpl. 2005 Jul;11(7):750-759
references.pmid: 15973716
references.citation: Transplantation. 2001 Dec 27;72(12):1934-9
references.pmid: 11773892
references.citation: Clin Transplant. 2008 Jan-Feb;22(1):1-15
references.pmid: 18217899
references.citation: Kidney Int. 2002 Sep;62(3):857-67
references.pmid: 12164867
references.citation: Clin Transplant. 2005 Apr;19(2):193-8
references.pmid: 15740554
references.citation: J Pharmacol Exp Ther. 2007 May;321(2):583-9
references.pmid: 17272676
references.citation: Transplantation. 2003 Jan 27;75(2):186-90
references.pmid: 12548120
references.citation: N Engl J Med. 1994 Oct 27;331(17):1110-5
references.pmid: 7523946
references.citation: Liver Transpl. 2005 Nov;(11 Suppl 2):S47-51
references.pmid: 16237714
references.citation: Liver Transpl. 2004 Sep;10(9):1189-94
references.pmid: 15350013
references.citation: Drugs. 2004;64(18):2047-73
references.pmid: 15341497
references.citation: Transplant Proc. 2005 Nov;37(9):3729-32
references.pmid: 16386520
references.citation: Transpl Int. 1994 May;7(3):172-6
references.pmid: 8060465
references.citation: Clin Transplant. 2001 Dec;15(6):402-9
references.pmid: 11737117
references.citation: Liver Transpl. 2004 Apr;10(4):492-502
references.pmid: 15048791