Table 2.
Immunosuppression and rejection
| Study | Follow-up days [mean ± SD or median (range)] | Induction | Maintenance | Type of rejection | Treatment of rejection |
|---|---|---|---|---|---|
| Roland 2008) | 1520 ± 593 days | Anti-CD25 | CSA, Steroids ± MMF |
Acute cellular 14 (78%) Acute vascular 1 (6%) Acute cellular and vascular 2 (11%) |
Not specified |
| Touzot (2010) | 29 months (range 12–48 months) | Antiinterleukin 2 receptor antibody (Basiliximab, Novartis, 20 mg at day 0 and day 4) (26) and polyclonal antithymocyte globulins (1) (Thymoglobuline, Genzyme, 1.5 mg/kg/day during 4 days) | CSA or D29, Steroids ± MMF. MMF was given at 1000 mg twice a day. Methylprednisolone was given as followed: 500 mg intravenously at day 0 and 125 mg at day 1. From day 2, 20 mg/day of oral prednisone was given and tapered progressively to 10 mg/day at 6 months and 5 mg/day at 9 months | Acute cellular rejection | Steroid pulses |
| Mazuecos (2006) | 489 ± 468 days | ATG(1); Anti-CD25(3) | TAC, MMF and steroids | Not specified | Mpred (250 mg) Rituximab (for AMR) |
| Stock (2003) | 480 ± 300 days | Not used | CSA, MMF and steroids | Not specified | Mild rejection was treated with bolus steroids and a switch in maintenance immunosuppression from CSA to tacrolimus. Vascular (type II) rejection was treated with the polyclonal anti-T-cell agent Thymoglobulin, bolus steroids, and a switch in maintenance immunosuppression from + D15 to tacrolimus |
| Stock (2010) | 1.7 years | An induction therapy by a monoclonal antiinterleukin 2 receptor antibody, antithymocyte globulin (ATG), or both was permitted | Initial immunosuppressive therapy included glucocorticoids, CSA or TAC, and MMF. Sirolimus was used in patients with calcineurin-inhibitor-associated nephrotoxicity |
Acute cellular rejection episodes(42) Acute vascular rejection episodes(4) Acute cellular and vascular rejection episodes combined(7) Chronic and acute rejection episodes(4) |
Not specified |
| Kumar (2004) | 730 days | Antiinterleukin 2 receptor antibody | Cyclosporine, sirolimus, and Steroids. | Cell and antibody mediated rejection (2/9) |
Methylprednisolone(9) Intravenous immune globulin and rituximab(2) |
| Qiu (2006) | 1825 days | Anti-CD25 (23) | CSA(20); Tac(13); Sir(14); Steroid-sparing(1) | Not specified | Not specified |
| Tan (2004) | 1485 ± 425 days; 246 ± 87 days |
None (42%) (deceased donor) Alemtuzumab (57%) (living-related donor) |
TAC, MMF and Steroids | Not specified | Not specified |
| Carter (2006) | 854 days | Induction therapy with lymphocyte-depleting agents was avoided. IL-2 receptor inhibitor induction was used | All patients received perioperative steroids, MMF (2–3 g/day), a calcineurin inhibitor (either cyclosporine or TAC), and/or sirolimus | Treatment for acute rejection consisted of 3 days of high-dose methylprednisolone, followed by a prednisone taper, and increased maintenance immunosuppression, which frequently meant switching the recipient from cyclosporine to tacrolimus. Additionally, moderate-to-severe cases of rejection were treated with thymoglobulin on an individualized basis | |
| Gruber (2008) | 15 months | All patients received induction therapy with antiinterleukin 2 receptor antibody (basiliximab 20 mg on postoperative days 0 and 4) or daclizumab (1.5 mg/kg on days 0 and 7) | CSA, MMF and Steroids | Not specified | Borderline or grade I rejection episodes were treated with methylprednisolone 500 mg IV for 3 days, followed by a steroid taper. Steroid-resistant grade I, and grade II rejections were treated with 5 to 7 daily doses of Thymoglobulin with target absolute CD3 counts less than or equal to 10 |
| Gómez (2013) | 16.0 months (range 3.0 to 96.6 months) | Iinduction therapy used antiinterleukin 2 receptor antibody (baxiliximab) (3/7) | TAC, MMF and Steroids | Not specified | Patients were treated with steroid pulses, which reversed acute rejection and improved renal function |
| Izzo (2017) | 126.1 weeks | The patients received an induction therapy with antiinterleukin 2 receptor antibody (basiliximab) in two doses. Intravenous methylprednisolone was given in tapering doses and discontinued on day 5 after transplantation,or received basiliximab, methylprednisolone and antilymphocyte serum as induction therapy | TAC, MMF and Steroids | Not specified | Not specified |
| Roland (2004) | 314 days (3–1696) | Not specified | CSA, MMF and Steroids | Not specified | Not specified |
| Gasser (2009) | Not specified | Ten of the 27 transplant recipients received antithymocyte globulin (ATG) perioperatively (i.e. immediately prior to transplantation [n = 9], or within the first 12 weeks posttransplantation [n = 1]) | Twenty-five of the 27 [92.6%] individuals were initiated on a standard triple IS regimen consisting of steroids (Prednisone), a calcineurin inhibitor (Cyclosporine A or TAC) and a nucleotide/DNA synthesis inhibitor (MMF or Azathioprine) | Not specified | Not specified |
| Gathogo (2014) | Not specified | Of the 32 patients with available data, 30 (88%) received induction immunosuppressive therapy consisting of basiliximab (73%) or daclizumab (27%) with methylprednisolone, and two patients received methylprednisolone only. 30 (88%) received induction immunosuppressive therapy consisting of basiliximab (73%) or daclizumab (27%) with methylprednisolone, and two patients received methylprednisolone only | All patients received triple maintenance immunosuppressive therapy consisting of a CNI, mycophenolate or azathioprine, and Steroids | Not specified | Six patients responded to pulsed corticosteroid; other or additional treatment interventions to combat AR included intravenous immunoglobulin (IVIG, 1⁄44), plasma exchange (1/41), ATG (1/41), rituximab (1/42) and augmentation of baseline immunosuppression (1/48) |
| Baisi (2016) | 3.1 years | Two recipients received induction therapy with a standard dose of basiliximab; 500 mg intravenous (IV) methylprednisolone (MP) was given intra-operatively, followed by oral prednisolone progressively tapered from 16 mg to complete withdrawal within the 3rd month | Immunosuppression protocol included a delayed CSA (2.5 mg/kg bid when creatinine was < 3.0 mg/dL) targeted to maintain CSA (C2 level) at initial value of 1000 ng/mL. At post-operative day (pod) 21, everolimus (EVL) 0.75 mg bid was introduced (EVL 0.75 mg bid; target EVL trough blood levels [TLC]: 8e10 ng/mL and CsAC2: 400e500 ng/mL); steroid was tapered to 4 mg/day within 45 days. After 6 months, EVL and CsA blood levels were targeted to EVLTLC 6 to 8 ng/mL and CsAC2, 250 to 350 ng/mL. After the first 6 case, mycophenolic acid (MPA) 720 mg bid was added until pod 21 | Not specified | Not specified |
| Xia (2014) | Not specified | Not specified | Not specified | Not specified | Not specified |
| Locke (2015) | 3.8 years | Not specified | Not specified | Not specified | Not specified |
| Abbott (2004) | 2.62 ± 1.32 years | Induction antibody use(22) |
Cyclosporine(30) TAC(19) MMF(38) AZA(7) |
Not specified | Not specified |
| Cristelli (2017) Brazil | 2.8 years ± 2.51 |
No induction(17) ATG(11) Antiinterleukin 2 receptor antibody (basiliximab)(11) |
TAC, MMF and Steroids(23) CSA, MMF and Steroids(2) TAC, AZA and Steroids(12) Other(2) |
Borderline changes(5), IA(6), IB(7), IIA(1), IIB(3) | Not specified |
| Cristelli (2017) Spain | 4.6 years ± 2.85 |
No induction(2) ATG(6) antiinterleukin 2 receptor antibody (basiliximab)(7) |
TAC, MMF and Steroids(12) MTOR,MMF and SteroidsF(3) |
Borderline changes(2), IA(1), IB(0), IIA(1) | Not specified |
| Mazuecos (2013) | 33.6 months | Not specified | Not specified | Borderline/IA(3), IB(2), IIA(4), Antibody-mediated(2) | Not specified |
| Rosa (2016) | 1028 ± 813 days | All of the patients received anti–thymocyte globulin, basiliximab and methylprednisolone for induction. | Prednisone(52), IVIG(5), Rituximab(7), TAC(57), MMF(57), Sirolimus(3), Cyclosporine(2) | Not specified | Not specified |
| Vicari (2016) | Not specified |
No induction(26) ATG(5) antiinterleukin 2 receptor antibody (basiliximab)(22) |
Steroids(53), TAC(40), Cyclosporine(10), MMF(41), AZA(9), mTOR inhibitors(1) |
Antibody-mediated AR(2) Antibody-mediated AR(3) |
Not specified |
| Bossini (2014) | 50 ± 22.0 months | Antiinterleukin 2 receptor antibody (basiliximab) and methylprednisolone | TAC or cyclosporine and MMF | CMR(4), AMR(4), and both CMR and AMR (mixed)(4). Overall, indicators of AMR were present in eight of 12 episodes (66.6%) | Acute cellular-mediated rejections (CMR) were treated with methylprednisolone (MP) at high doses (800–1000 mg divided into 4 days) and subsequently tapered to a daily dose between 8 and 4 mg/day to be maintained indefinitely. Treatment of antibody-mediated rejection (AMR) involved a combination of multiple modalities, including high doses of steroids, plasma exchange, intravenous immunoglobulins (IVIg), and thymoglobulin |
| Mazuecos (2011) | 39.98 ± 36.51 months | Anti-CD25(6), Thymoglobulin(1) |
TAC(18) MMF(2) Mycophenolate(20) |
Antibody mediated acute rejection | |
| Gathogo (2016) | Not specified |
Antiinterleukin 2 receptor antibody (basiliximab)(68) Alemtuzumab(2) Rituximab + plasma exchange(1) Pulsed corticosteroids only(2) |
Calcineurin inhibitor + MMF or AZA +Steroids(76) TAC monotherapy(2) |
Not specified | Not specified |
| Malat (2018) | 16 years | Antiinterleukin 2 receptor antibody (basiliximab) |
Calcineurin inhibitors (CNIs), sirolimus, and Steroids TAC, MMF, and low-dose Steriods Belatacept(3) |
Not specified | Not specified |