Table 1.
Characteristics of included randomized studies (ciclosporin levels, C0 or C2 are shown in milligrams per millilitre)
| Boissonnat et al. (2011) [25] | Gullestad et al. (2010) [21] | Potena et al. (2010) [23] | Groetzner et al. (2009) [20] | Lehmkuhl et al. (2009) [22] | Wang et al. (2010) [24] | Cantarovich et al. (2008) [18] | Gleissner et al. (2006) [19] | |
|---|---|---|---|---|---|---|---|---|
| Participants (n) | 95 | 282 | 34 | 63 | 176 | 25 | 76 (cohort A) | 36 |
| Low dose/standard | 48/47 | 140/142 | 17/17 | 19/14 | 92/84 | 12/13 | 25/51 | 16/20 |
| Follow-up duration (months) | 12 | 12 | 12 | 12 | 12 | 6 | 12 | 6 |
| Intervention = low CNI | CsA | CNI | CsA | CNI-free + mTOR (Siro) + MMF | CsA C0 50–100 (7–12 months) + mTOR (Eve) | CsA | CsA 12 month C0 183 (A3) | CNI-free + mTOR (Siro) + MMF |
| C0 130–200 + MMF | C0 30–70% of baseline + mTOR (Eve) + MMF or AZA | C0 40–90 + mTOR (Eve) | C2 300–500 (day 150–180) + mTOR (Eve) | 197 (A2) + MMF | ||||
| Standard | CsA | CsA or Tacro + MMF or AZA | CsA | CNI | CsA C0 100–250 (7–12 months) + MMF | CsA C2 600–1000 (days 150–180) + Eve | C2 1600–1800 (A1 group) + MMF | CsA C0 < 80 + MMF |
| C0 200–300 + MMF | C0 100–150 + MMF | C0 reduced by 40% + MMF | ||||||
| Additional immunosuppressive treatment (control and experimental groups) | MMF + corticosteroids | MMF or AZA + corticosteroids | Eve (experimental group) | MMF + corticosteroids | Eve (experimental group) | CsA and Eve + corticosteroids | MMF + corticosteroids | MMF + corticosteroids |
| MMF (control group) + corticosteroids | MMF (control group) + corticosteroids | |||||||
| Renal function inclusion criteria | Creatinine ≤250 μmol l−1 | GFR 20–90 ml min−1 | GFR 20–60 ml min−1 | GFR <60 ml min−1 | GFR ≥ 50 ml min−1 | Creatinine ≤ 246.4 μmol l−1 | Creatinine ≤ 170 μmol l−1 | Patients with renal failure |
| Renal function calculation | Cockroft, MDRD | Measured glomerular filtration rate, MDRD | Cockroft | ? calculated creatinine clearance | Cockroft | Cockroft | Cockroft | Cockroft |
| Baseline mean age (years) | 49 (SD 11) | 58 (SD 8) | 63 (SD 6) | 60.9 | 51 (SD 11) | 44 | 49 (SD 12) | 64 |
| Percentage of men | 65 | 72 | 79 | 95.2 | 81 | 84 | 86 | 86 |
| Time post-transplant | <96 h | >1 year | 1–4 years | >6 months | ≤72 h | ≤72 h | 4–6 h | >6 months |
| Mean time from transplant (years) | De novo | 6 | 2.5 | De novo | De novo | De novo | De novo | 8.2 |
| Baseline renal function* | 126 mmol l−1 | 50 (SD 14) ml min−1 | 43.5 (SD 9.1) ml min−1 | 39 (SD 15) ml min−1 | 72.5 (SD 28) ml min−1 | 85 (SD 18) ml min−1 | 72.37 (SD 25.64) ml min−1 | 48.28 (SD 13) ml min−1 |
| CsA C0 level achieved in intervention group | 161 (SD 40.7) | 60 (SD 35) | 60 (SD 32) | CNI withdrawal | 110 (SD 50) | 505.5 (SD 187.8) | 190 (SD 190.5) | CNI withdrawal 6 months |
| C2 | ||||||||
| CsA C0 level in control group | 176.2 (SD 42) | 115 (SD 50) | 136 (SD 34) | 75 (SD 19) | 180 (SD 55) | 644.4 (SD 167.9) | 269 (SD 96) | 62.9 (SD 20.6) |
| C2 | 6 months | |||||||
| Percentage decrease in intervention group | −8.63 | −47.83 | −55.88 | −100.00 | −38.89 | −21.55 | −29.37 | −100.00 |
| Jadad score | 3 | 3 | 3 | 3 | 3 | 1 | 1 | 1 |
Abbreviations are as follows: AZA, azathiprine; CNI, calcineurin inhibitor; CsA, ciclosporin; C0, CsA dosage before CsA administration; C2, CsA concentration 2 h after administration; Eve, everolimus; GFR, glomerular filtration rate; MDRD, Modification of Diet in Renal Disease; MMF, mycofenolate mofetil; mTOR, mammalian target of rapamycin; Siro, sirolimus; and Tacro, tacrolimus.
*
Baseline renal function was measured using either serum creatinine or creatinine clearance.