Table 2 Immunosuppression and 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