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Abstract
Background
Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens.
Methods
We assigned 299 renal-transplant recipients to receive group A (standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids), group B (low-dose cyclosporine, basiliximab induction, mycophenolate mofetil, and corticosteroids), group C (standard-dose tacrolimus, mycophenolate mofetil, and corticosteroids), or group D (low-dose tacrolimus, basiliximab induction, mycophenolate mofetil, and corticosteroids) regimens. We compared the groups according to graft function through estimated glomerular filtration rate (GFR), acute rejection, and allograft survival.
Results
The mean calculated GFR in patients receiving low-dose tacrolimus (76.4 mL per minute) was higher than in the other three groups (range, 66.3 to 73.8 mL per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (14.3%) than in those receiving standard-dose cyclosporine (29.6%), low-dose cyclosporine (19.8%), or standard-dose tacrolimus (23.8%). Allograft survival rates differed significantly among the four groups (P=0.006) and were highest in the low-dose tacrolimus group (99.9%). Serious adverse events were more common in the standard-dose tacrolimus group than in the other groups (51.2% vs a range of 41.4 to 42.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (81.1 to 90.5%).
Conclusions
A regimen of basiliximab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, compared with regimens containing basiliximab induction plus either low-dose cyclosporine or standard-dose tacrolimus or with standard-dose cyclosporine without induction.
References
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Table 1.
Baseline characteristics of the patients
| Variable | Group A a (n=95) | Group B b (n=132) | Group C c (n=42) | Group D d (n=30) |
|---|---|---|---|---|
| Age (yr) | 40.1±10.8 | 40.2±11.3 | 39.8±10.0 | 44.9±9.3 |
| Male sex (%) | 74.7 | 56.8 | 64.3 | 47.6 |
| Cause of ESRD (%) | ||||
| Glomerulonephritis | 17.9 | 16.7 | 19.0 | 9.5 |
| Diabetes mellitus | 5.3 | 5.3 | 2.4 | 0 |
| Pyelonephritis or interstitial nephritis | 21.1 | 25.0 | 4.8 | 0 |
| Polycystic kidney disease | 0 | 2.3 | 9.5 | 0 |
| Uncertain | 57.9 | 50.8 | 30.9 | 85.7 |
| Other | 19.1 | 11.3 | 30.1 | 4.8 |
| Missing data | 30.6 | 11.3 | 2.4 | 0 |
| Type of donor (%) | ||||
| Deceased | 1.1 | 1.5 | 1.2 | 2.9 |
| Living related | 29.5 | 58.3 | 52.4 | 42.9 |
| Living unrelated | 69.5 | 40.2 | 35.7 | 28.6 |
| Donor age (yr) | 39.5±10.3 | 47.3±10.9 | 40.1±10.2 | 38.4±13.7 |
| Matched HLA-A, -B and -DR (no.) | 2.5±1.5 | 1.9±1.5 | 1.4±1.5 | 1.9±1.4 |
| CMV – D (+), R (−) (%) | 13.6 | 13.5 | 12.7 | 15.5 |
Table 2.
Primary end points and selected secondary end points
| Group A a (n=95) | Group B b (n=132) | Group C c (n=42) | Group D d (n=30) | P | |
|---|---|---|---|---|---|
| End Point | |||||
| At 1 mo (mL/min) | 60.9±24.4 | 55.0±28.3 | 58.7±25.5 | 55.4±25.7 | ＜0.001 |
| At 12 mo (mL/min) | 66.3±21.0 | 73.8±24.9 | 66.8±28.2 | 76.4±28.5 | ＜0.001 |
| Biopsy-proven AR | |||||
| At 1 mo (%) | 29.6 | 19.8 | 23.8 | 14.3 | ＜0.001 |
| At 12 mo (%) | 38.9 | 20.6 | 26.2 | 14.3 | ＜0.001 |
| Allograft survival (%) | 90.5 | 97.0 | 92.9 | 99.9 | 0.53 |
| Treatment failure (%) | 34.7 | 20.5 | 45.2 | 14.3 | ＜0.001 |
Table 3.
Adverse events and serious adverse events
| Event | Group A a (n=95) | Group B b (n=132) | Group C c (n=42) | Group D d (n=30) |
|---|---|---|---|---|
| Blood or lymphatic (%) | 10.5 | 9.1 | 4.8 | 4.8 |
| Anemia | 4.2 | 4.5 | 2.4 | 0 |
| Leukopenia | 5.3 | 5.3 | 2.4 | 2.4 |
| Gastrointestinal (%) | 57.9 | 47.7 | 45.2 | 56.7 |
| Erosive gastritis | 30.5 | 28.8 | 31.0 | 21.4 |
| Diarrhea | 10.9 | 9.8 | 9.5 | 9.0 |
| Opportunistic infection (%) | 23.3 | 23.5 | 16.7 | 16.2 |
| Candida | 3.2 | 3.0 | 4.8 | 2.4 |
| Cytomegalovirus | 12.2 | 12.1 | 14.3 | 12.0 |
| Herpes simplex virus | 5.8 | 4.5 | 4.8 | 4.8 |
| Other infection (%) | 20.5 | 22.0 | 23.8 | 14.3 |
| Nasopharyngitis | 2.1 | 3.0 | 2.4 | 2.4 |
| Pneumonia | 7.4 | 3.0 | 9.5 | 4.2 |
| Urinary tract infection | 7.4 | 6.1 | 4.8 | 2.4 |
| Lymphocele (%) | 1.1 | 1.5 | 2.4 | 0 |
| Diabetes mellitus (%) | 12.7 | 10.8 | 13.3 | 10.1 |
| Hyperuricemia (%) | 5.7 | 5.6 | 4.5 | 1.6 |
| Renal or urinary infection (%) | 15.8 | 27.3 | 23.8 | 9.5 |
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