Table 1.
renal transplant studies utilizing mycophenolic acid to withdraw calcineurin inhibitor beyond 6 mo post-transplant (“Late”)[83-93]
| Ref. | Design | Population (n) | Baseline Regimen | n | Strategy | Follow-up | Renal function | Acute rejection | Graft survival | Patient survival |
| Kosch et al[83] | Prospective, randomized, single-center | 6-mo of deteriorating renal function, BP-CAN | CsA, Prednisolone | 12 | MMF added, target 2 g per day; CsA withdrawn over 4 wk | 6 mo | SCr + 0.03 mg/dL vs baseline (P = NS) | NA | NA | NA |
| 12 | MMF added, target 2 g; CsA continued | SCr + 0.07 mg/dL vs baseline (P = NS) | NA | NA | NA | |||||
| Suwelack et al[84] | Prospective, randomized, single-center | > 1-yr post transplant, SCr < 4 mg/dL, BP-CAN, deteriorating renal function | CsA or TAC, Prednisolone | 18 | MMF added, target 2 g; CsA withdrawn over 6 wk | 35 wk | Slope 1/SCr 0.00585 ± 0.01122; 67% responders; Proteinuria 0.5 ± 0.55 g/24 h | 0% | 100% | NA |
| 20 | MMF added, target 2 g; CsA continued | Slope 1/SCr -0.00728 ± 0.01105 (P = 0.0018); 25% responders (P = 0.021); Proteinuria 1.5 ± 0.48 g/24 h (P = 0.01) | 0% | 85% | NA | |||||
| McGrath et al[85] | Prospective, randomized, single-center | > 1-yr post transplant, BP-CAN, deteriorating renal function | CsA, azathioprine, prednisolone | 15 | MMF added, target 2 g; CsA withdrawn by 14 wk | 6 mo | SCr - 58 μmol/L vs baseline (P < 0.001); isotope GFR + 8.5 mL/min vs baseline (P < 0.01) | 0% | NA | NA |
| 15 | CsA switch to TAC | SCr + 15 μmol/L vs baseline (P = NS); isotope GFR -2.1 mL/min vs baseline (P = NS) | 0% | NA | NA | |||||
| Hanvesakul et al[86] | Retrospective, consecutive patients, single-center | > 1-yr post transplant, CAN | CsA or TAC, azathioprine, prednisolone | 30 | MMF added, target 1.5-2 g; azathioprine stopped; CNI withdrawn over 4 wk | 1 yr | eGFR + 2 mL/min vs baseline | 3.30% | 86.70% | 96.70% |
| Dudley et al[87] | Randomized, open, multicenter | > 6-mo post transplant, deteriorating renal function, no recent ACR | CsA monotherapy, or CsA/corticosteroid, or CsA/azathioprine/ corticosteroids | 73 | MMF added, target 2 g; azathioprine discontinued, if applicable; CsA withdrawn over 6 wk, if needed corticosteroid added | 1 yr | Response rate (6 mo): 58% stabilized or reduced SCr; Response rate (1 yr): 48%; Least squares mean SCr -24.9 μmol/L; Least squares mean CrCL +5 mL/min | 0% | 93.20% | 95.90% |
| CsA monotherapy, or CsA/corticosteroid, or CsA/azathioprine/ corticosteroids | 70 | Continued regimen | Response rate (6 mo): 32% stabilized or reduced SCr (P = 0.006); Response rate (1 yr): 35% (P = 0.1885); Least squares mean SCr +22.2 μmol/L (P < 0.01); Least squares mean CrCL -0.7 mL/min (P < 0.01) | 0% | 94.3% | 100% | ||||
| Weir et al[88] | Prospective, non-randomized, single-center | Mean 853.3 d post transplant, BP-CAN, deteriorating renal function, no ACR | CsA or TAC, prednisone, azathioprine or MMF | 18 | Azathioprine stopped; MMF added, target 2 g; CNI withdrawn | Mean 651 d | Response rate: 91.7% improved or lack of deterioration in renal function using least squares method slope 1/SCr (P = 0.038) | NCR | 100% | NA |
| CsA, prednisone, azathioprine or MMF | 67 | CsA dose reduced approximately 50%; azathioprine withdrawn; MMF added, target 2 g | Response rate: 51.7% improved or lack of deterioration | NCR | 100% | NA | ||||
| TAC, prednisone, azathioprine or MMF | 33 | TAC dose reduced approximately 50%; azathioprine withdrawn; MMF added, target 2 g | 59.3% improved or lack of deterioration | NCR | 100% | NA | ||||
| Weir et al[89] | Continuation of above trial | 13 | CNI withdrawn | 76 mo | 2.7 ± 0.2 mg/dL | 7.7% | 92.3% | 100% | ||
| 64 | CsA dose reduced | 54 mo | 3 ± 0.1 mg/dL | 4.7% | 62.5% | 92.2% | ||||
| 28 | TAC dose reduced | 42 mo | 3 ± 0.2 mg/dL | 7.1% | 67.8% | 100% | ||||
| Abramowicz et al[90] | Randomized, controlled, multicenter | No recent ACR, ≤ 1 ACR overall, 12 to 30 mo post-transplant, stable renal function | CsA, prednisone, ± azathioprine or MMF | 85 | MMF added over 3 mo, target 2 g; CsA withdrawn over 3 mo | 12 mo | CrCL improved 10% in 46%; SCr -1 μmol/L; CrCL + 4.5 mL/min vs control group (P = 0.16), eGFR + 2.3 mL/min vs control group (P = 0.24) | 10.6% | 100% | NA |
| 85 | MMF added over 3 mo, target 2 g; continued triple therapy | SCr + 4 μmol/L | 2.4% (P = 0.03) | 100% | ||||||
| Abramowicz et al[91] | Continuation of above trial | 74 | CsA withdrawn | 60 mo | CrCL 67.4 mL/min | 10% | 88% | 93% | ||
| 77 | Triple therapy | CrCL 61.7 mL/min (P = 0.05) | 1% (P = 0.028) | 92% | 95% | |||||
| Heeg et al[92] | Retrospective | BP-CNI toxicity, deteriorating renal function, mean 11.2 mo post-transplant | CsA or TAC, Prednisolone, ± MMF or MPS | 17 | MPS added; CNI withdrawn; MMF withdrawn | 48 mo | All vs Baseline. SCr at 6 mo -0.5 mg/dL (P < 0.05); eGFR at 6 mo + 11 mL/min; SCr at 36 mo -0.5 mg/dL (P = 0.063); eGFR at 36 mo +11 mL/min P = 0.022); SCr at 48 mo + 0.6 mg/dL (P = 0.27); eGFR at 48 mo +1 mL/min (P = 0.91) | NA | NA | NA |
| Mourer et al[93] | Prospective, randomized, single-center | No recent ACR, ≤ 2 ACR overall, at least 12 mo post-transplant, stable renal function | CsA or TAC, Prednisone, MMF | 79 | CNI withdrawn, MMF concentration controlled | 36 mo | eGFR 59.5 ± 2.1 mL/min | 5.1% | 98.7% | 94.9% |
| 79 | MMF withdrawn, CNI concentration controlled | eGFR 51.1 ± 2.1 mL/min (P = 0.006) | 2.5% | 98.7% | 92.4% |
ACR: Acute cellular rejection; BP-CAN: Biopsy-proven chronic allograft nephropathy; CAN: Chronic allograft nephropathy; CNI: Calcineurin inhibitor; CsA: Cyclosporine; eGFR: Estimated glomerular filtration rate; GFR: Glomerular filtration rate; MMF: Mycophenolate mofetil; MPS: Mycophenolate sodium; NA: not assessed/applicable; NCR: Not clearly reported by group; NS: Not significant; SCr: Serum creatinine; TAC: Tacrolimus.