title: Combination therapy with diltiazem plus CsA/MMF/Pred or CsA/Aza/Pred triple immunosuppressive regimens for use in clinical kidney transplantation in Northwestern China.
abstract: OBJECTIVE
  The effects of diltiazem on 1692 kidney transplant recipients under the immunosuppressive regimen of cyclosporine A (CsA) in combination with either mycophenolate mofetil or azothioprine were assessed. The two treatment groups were compared for blood concentrations of CsA, the extent of acceptable dosage reduction for the maintenance of immunotherapy, potential effects of kidney protection, and promotion of graft function.
  
  
  METHODS
  We monitored changes of blood concentrations of CsA in the two different patient treatment groups for post-transplant graft function, episodes of acute rejection, and hepatic and renal toxicity in 1640 renal transplant recipients after treatment with diltiazem.
  
  
  RESULTS
  In patients treated with the triple immunosuppressive regimen consisting of CsA, azothioprine, and prednisolone (Pred), the sub-group of patients receiving the diltiazem treatment saw a significantly reduced CsA dosage in comparison to the non-diltiazem group (control group 1) (P < 0.05), but the blood concentrations of CsA of the diltiazem group were higher than those of control group 1 (P < 0.01). Of the patients treated with CsA, mycophenolate mofetil, and Pred, the sub-group of patients also treated with diltiazem showed similar effects: CsA dosage was reduced (P < 0.01) and the blood concentrations of CsA significantly increased (P < 0.01) in comparison with those of control group 2. In addition, recovery time of graft function decreased to 4.7 ± 1.8 days and 3.9 ± 1.4 days in the two diltiazem treatment groups, respectively (P < 0.05), and the rate of acute rejection decreased to 21 (p < 0.05) and 7.9% (P < 0.01), respectively.
  
  
  CONCLUSIONS
  In our cohort of renal transplantation patients, co-administration of CsA and diltiazem increased CsA blood concentration, thereby resulting in a reduction in its required dosage treatment, which lightened the patients' economic burden while improving primary and long-term kidney function by promoting the recovery of graft function and decreasing hepatic and renal toxicity. The co-administration of diltiazem may also reduce the rate of acute rejection, especially in patients who also receive the triple immunosuppressive regimen consisting of CsA, mycophenolate mofetil, and Pred.
authors.affiliation: Department of Hepatobiliary Surgery, Third Affiliated Hospital (Shanxi Provincial People's Hospital), Medical School of Xi'an Jiaotong University, Xi'an, Shanxi Province, China, songyongbetter@gmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
authors.forename: Wujun
authors.initials: W
authors.lastname: Xue
authors.forename: Puxun
authors.initials: P
authors.lastname: Tian
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ding
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Pan
authors.forename: Hang
authors.initials: H
authors.lastname: Yan
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.forename: Xinshun
authors.initials: X
authors.lastname: Feng
authors.forename: Heli
authors.initials: H
authors.lastname: Xiang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Tian
authors.forename: Gaoping
authors.initials: G
authors.lastname: Qin
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood / Q000191:economics / Q000627:therapeutic use*; D004110:Diltiazem / Q000009:adverse effects / Q000097:blood / Q000191:economics / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000191:economics / Q000627:therapeutic use*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000379:methods; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D004110:Diltiazem; D009173:Mycophenolic Acid; D001379:Azathioprine