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©The Author(s) 2017.
World J Transplant. Apr 24, 2017; 7(2): 144-151
Published online Apr 24, 2017. doi: 10.5500/wjt.v7.i2.144
Published online Apr 24, 2017. doi: 10.5500/wjt.v7.i2.144
Table 1 Criteria for the inclusion of early mammalian target of rapamycin inhibitor conversion studies
| Study design | Prospective cohort design with a well-defined study population |
| Study group | Post renal transplant |
| Conversion time | Period of 2 wk to 6 mo post-transplant |
| Study size | > 30 patients |
| Length of follow-up | Any |
| Source | Peer-reviewed journals |
| Language | English |
| Outcome measure | Patient safety, exposure-response relationships, adverse events, and graft functioning and long-term survival |
Table 2 Summary of Different Early Conversion Clinical Trials
| Ref. | Study design | Time of conversion | Group 1 | Group 2 |
| Everolimus | ||||
| Budde et al[23], 2011 (ZEUS Study) | Multicentre, Prospective, Randomized Study (n = 300), 12 mo | 4.5th month | EVR (C0, 6-10 ng/mL) Induction: Basiliximab (n = 155) | CsA (C0, 120-180 ng/mL till 4.5-6 mo then decreased to 100-150 ng/mL) Induction: Basiliximab (n = 145) |
| Mjörnstedt et al[24], 2012 (CENTRAL trial) | Multicentre, Prospective, Randomized Study, (n = 269), 12 mo | 7th week | EVR (C0, 6-10 ng/mL) + MMF (1.4 g/d till 2 wk then decreased to 1.08 g/d) + S (n = 92) | Low CsA (C0, 75-200 ng/mL till 2 wk then decreased to 50-150 ng/mL) + MMF (1.4 g/d) + S (n = 90) |
| Sirolimus | ||||
| Lebranchu et al[25], 2009 (CONCEPT Study) | Multicentre Prospective, Randomized Study, (n = 193), 12 mo | 3rd month | SRL (C0, 8-15 ng/mL till 39 wk then decreased to 5-10 ng/mL) + MMF + S (Induction: Daclizumab) (n = 95) | CsA (C0, 500-800 ng/mL) + MMF + S (Induction: Daclizumab) (n = 97) |
| Guba et al[26], 2010 (SMART Trial) | Multicentre Prospective, Randomized Study, (n = 140), 12 mo | 10-24th day | SRL (C0, 8-12 ng/mL then decreased to 5-10 ng/mL) + MMF (1.5 g/d) + S (Induction: ATG) (n = 69) | CsA (C0, 150-200 ng/mL then decreased to 100-150 ng/mL) + MMF (2 g/d) + S (Induction: ATG) (n = 71) |
| Weir et al[27], 2010 (Spare the Nephron Trial) | Multicentre, Prospective, Randomized Study, (n = 299), 12 mo | Within 115 d | MMF + SRL (n = 148) | MMF + CNI (n = 151) |
| Heilman et al[28], 2011 | Multicentre Prospective, Randomized Study, (n = 122), 12 mo | 1 mo | SRL (C0, 9.8 ± 3.6 ng/mL) + MMF + S (Induction: Basiliximab) (n = 62) | TAC (C0, 6.9 ± 4.6 ng/mL) + MMF + S (Induction: Basiliximab) (n = 60) |
Table 3 Summary of outcomes in Different Early Conversion Clinical Trials
| Ref. | Renal function (Gp1 vs Gp 2) | BPAR (Gp1 vs Gp 2) | Adverse event (Gp1 vs Gp 2) | Remarks |
| Everolimus | ||||
| Budde et al[23], 2011, (ZEUS Study) | 12 mo Sr. Cr: 141.7 ± 44 μmol/L vs 137.0 ± 43 μmol/L (P = NS) eGFR: 71.8 ± 18 mL/min vs 61.2 ± 16 mL/min (P = 0.000) | 9.7% vs 3.4% (P = 0.03) | SAE/Infection: 61% vs 59% (P = NS) UTI: 57.0% vs 53% (P = NS) Diarrhoea: 36% vs 27% (P = NS) HPL: 14% vs 10% (P = NS) | Graft survival: 100% vs 100% (P = NS) Patient survival 100% vs 99% (P = NS) |
| Mjornstedt et al[24], 2012 (CENTRAL trial) | 12 mo Sr. Cr: 122.0 ± 35 μmol/L vs 132.0 ± 45 μmol/L (P = NS) eGFR: 68.1 ± 21.5 mL/min vs 69.4 ± 22.9 mL/min (P = NS) | 27.5% vs 11.0% (P = 0.004) | SAE/Infection: 53.9% vs 38.0% (P = 0.025) CMV infection: 8.8% vs 13.0% (P = NS) Edema: 29.4% vs 21.0% (P = NS) Anaemia: 16.7% vs 6.0% (P = 0.02) HPL: 12.7% vs 9.0% (P = NS) Proteinuria: 4.9% vs 0% (P = 0.06) Acne: 12.7% vs 2.0% (P = 0.006) Mouth Ulceration: 12.7% vs 2.0 % (P = 0.001) | Graft survival: 100% vs 100% (P = NS) Patient survival 98% vs 98% (P = NS) |
| Sirolimus | ||||
| Lebranchu et al[25], 2009 (CONCEPT Study) | 12 mo: Sr. Cr: 117.4 μmol/L vs 132.3 μmol/L (P < 0.001) eGFR: 68.9 mL/min vs 64.4 mL/min (P = 0.017) | 16.8% vs 8.2% (P = NS) | Peripheral Edema: 28.1% vs 22.6% (P = NS) SAE/infection: 60% vs 44% (P = 0.025) Diarrhoea: 30.2% vs 9.2% (P < 0.001) Dyslipidemia: 5.20% vs 4.12% (P = NS) Proteinuria: 9.3% vs 3.09 % (P = NS) NODAT: 3.1% vs 2.06% (P = NS) Apthous Stomatitis: 45.8% vs 5.15% (P < 0.001) | Graft Survival: 99% (P = NS) Patient Survival 97% (P = NS) |
| Guba et al[26], 2010, (SMART Trial) | 12 mo: Sr Cr: 111.5 ± 45 mg/dL vs 142.6 ± 74 mg/dL (P = 0.004) eGFR: 64.5 ± 25.2 mL/min vs 53.4 ± 18.0 mL/min (P = 0.001) | 17.4% vs 15.5% (P = NS) | Wound Healing Disorder: 10.1% vs 11.3%, (P = NS) Infection: 52.2% vs 60.6% (P = NS) CMV: 7.3% vs 28.2% (P < 0.001) HPL: 20.3% vs 7.0% (P = 0.02) Diarrhoea: 13.0% vs 9.9% (P = NS) Lymphocele: 27.5% vs 23.9% (P = NS) | Graft Survival: 99% vs 97% (P = NS) Patient Survival 99% vs 99% (P = NS) |
| Weir et al[27], 2010 (Spare the Nephron Trial) | 12 mo Sr. Cr: 126.2 ± 82.8 μmol/L vs 145.0 ± 96.5 μmol/L (P = NS) eGFR: 74.6 ± 17.9 mL/min vs 71.5 ± 21.2 mL/min (P = 0.06) | 7.4% vs 6.0% (P = NS) | Infection: 16.2% vs 18.3% (P = NS) HPL: 24.3% vs 10.5% (P = 0.000) CMV: 4.7% vs 9.2% (P = NS) Polyoma virus: 2% vs 4% (P = NS) Diarrhoea: 29.7% vs 9.8% (P = 0.001) Malignancy: 4.7% vs 6.5% (P = NS) | Graft Survival: 98% vs 97.4% (P = NS) Patient Survival 100% vs 98% (P = NS) |
| Heilman et al[28], 2011 | 12 mo Sr. Cr: 96.1 ± 28 μmol/L vs 106.1 ± 61 μmol/L (P = NS) eGFR: 63.0 ± 19.1 mL/min vs 59.8 ± 18.9 mL/min (P = NS) | 13% vs 5% (P = NS) | CMV: 13% vs 13% (P = NS) Polyoma virus: 2% vs 4% (P = NS) | NA |
- Citation: Kumar J, Reccia I, Kusano T, Julie BM, Sharma A, Halawa A. Systemic meta-analysis assessing the short term applicability of early conversion to mammalian target of rapamycin inhibitors in kidney transplant. World J Transplant 2017; 7(2): 144-151
- URL: https://www.wjgnet.com/2220-3230/full/v7/i2/144.htm
- DOI: https://dx.doi.org/10.5500/wjt.v7.i2.144