Table 1.
Therapeutic strategies for focal segmental glomerulosclerosis in renal transplantation
| Treatment schedule | Patients | Outcome | Adjunctive information | |
| Plasma exchange | ||||
| Ponticelli et al[4] | Analysis of PE response in 22 studies | 144 patients (70 < 18 yr, 77 ≥ 18 yr) | Partial/complete remission of proteinuria in 49/70 (70%) children and 49/77 (63%) adults | Analysis also includes Canaud et al[33] 10 patients |
| Gohh et al[31] | Prophylactic course of 8 PE sessions in the peri-operative period in patients at high risk of recurrence | 10 patients (1 < 18 yr, 9 ≥ 18 yr) | 7/10 free of recurrence | |
| Chikamoto et al[32] | Prophylactic course of 4 PE sessions 12 d before transplantation in a high risk patient | 1 patient (< 18 yr) | No recurrence after 8 mo | Patient also received Rituximab® (375 mg/m2; 2 doses), methylprednisolone (1 mg/kg per day), tacrolimus (10 ng/mL) and mycophenolate mofetil (600 mg/m2 per day) 2 wk before transplantation |
| Glucocorticoids | ||||
| Shishido et al[41] | Methylprednisolone pulses (20 mg/kg on three consecutive days in weeks 1, 3 and 5) and increasing CyA target levels | 10 patients (8 < 18 yr, 2 ≥ 18 yr) | Complete remission in 7/10 | |
| CyA | ||||
| Canaud et al[33] | Intravenous CyA (C0 levels between 200-400 ng/mL), followed by oral CyA (C2 levels 1200-1400 ng/mL), high dose oral steroids (1 mg/kg per day for the first 4 wk, then progressively tapered) and a course of PE sessions for 9 mo | 10 patients (≥ 18 yr) | Complete remission of proteinuria in 10/10; proteinuria relapse in 1/10 successfully treated with Rituximab® (2 doses) | |
| Ingulli et al[44] | Progressive up-titration of CyA oral doses | 2 patients (< 18 yr) | Complete remission in 1; partial remission in 1 | |
| Salomon et al[45] | Intravenous CyA (through levels: 250-350 ng/mL) | 16 patients (< 18 yr; 1 re-grafted with a subsequent recurrence) | Complete remission in 14/17 (82%); partial remission in 2/17 (12%) | |
| Raafat et al[46] | Progressive up-titration of CyA oral doses until proteinuria reduction/serum creatinine elevation (CyA doses from 6 to 25 mg/kg per day) | 16 patients (< 18 yr) | Complete remission in 11/16 (69%); partial remission in 2/16 (12%) | |
| CYC/MMF | ||||
| Kershaw et al[53] | CYC (1-2 mg/kg per day, adjusted for white blood cell count) for 8-12 wk | 3 patients (< 18 yr) | Complete remission in 2/3; partial remission in 1/3 | |
| Cheong et al[54] | CYC (2 mg/kg per day) + PE (10 sessions over 2 wk followed by one session per week for 2 mo) | 6 patients (< 18 yr) | Complete remission in 3/6; partial remission in 3/6 | |
| Dall’Amico et al[55] | CYC (2-mo course, 2 mg/kg per day) and PE sessions | 11 patients (< 18 yr) | Complete remission in 9/11 (persistent remission in 7/9) | |
| Gipson et al[57] | 12-mo course of CYC vs MMF + dexamethasone | 138 patients [93/168 (67%) < 18 yr] | CyA arm: complete remission in 14/72 (19%), partial remission in 19/72 (26%) | |
| MMF + dexamethasone arm: complete remission in 6/66 (9%), partial remission in 16/66 (24%) | ||||
| Renin angiotensin system blockers | ||||
| Freiberger et al[62] | Ramipril (10 mg) + candesartan (64 mg) + aliskiren (300 mg) | 1 patient (≥ 18 yr) | Partial remission | Patient was previously treated with Rituximab® (375 mg/m2; 3 doses) and PE without response |
| Galactose | ||||
| Jhaveri et al[64] | High galactose diet + supplemental powder galactose (0.2 g/kg orally 2 times per day) one month later | 1 patient (≥ 18 yr) | Complete remission | No apparent response with previous treatments including Rituximab® (1 g, 2 doses), PE (15 sessions) and IgEv (2 doses) |
| Robson et al[65] | High galactose diet (14 g twice daily in patient 1, 10 g twice daily in patient 2) | 2 patients (≥ 18 yr) | Complete remission in 1; partial remission in 1 | |
| Sgambat et al[66] | High galactose diet (0.2 g/kg per dose twice daily orally) | 7 patients (< 18 yr) with steroid-resistant nephrotic syndrome (2/7 with recurrent FSGS) | Reduction in permeability factor without effect on proteinuria values | |
| Anti-TNF-α agents | ||||
| Leroy et al[69] | Infliximab (3 mg/kg twice monthly) | 1 patient (< 18 yr) | Complete remission | No apparent response with previous treatments including reinforced immunosuppression, CyA (5 mg/kg per day in continuous i.v. perfusion) followed by oral high dose CyA (10 mg/kg per day), methylprednisolone pulses followed by high dose oral prednisone (60 mg/1.73 m2 per day), MMF (600 mg/1.73 m2 per day) switch to cyclophosphamide (100 mg/d, interrupted for hematologic toxicity) and PE (15 sessions within 1 mo) |
| Bitzan et al[70] | Etanercept (twice weekly) | 1 patient (< 18 yr) | Partial remission | |
| Rituximab® | ||||
| Pescovitz et al[28] | Rituximab® (6 doses, 375 mg/m2) | 1 patient (< 18 yr) | Complete remission | |
| Hristea et al[74] | Rituximab® (2 doses, 375 mg/m2) | 1 patient (≥ 18 yr) | Complete remission | Patient also received a short course of oral cyclophosphamide (100 mg/d, days 22-40) and 3 additional PE sessions (days 34, 39, 49) |
| Gossmann et al[75] | Rituximab® (2 doses, 375 mg/m2) | 1 patient (≥ 18 yr) | Complete remission | |
| Fornoni et al[21] | Rituximab® within 24 h after surgery (1 dose, 375 mg/m2) in patients at high risk of recurrence | 41 patients (14 controls vs 27 treated) | Nephrotic proteinuria within 1 mo in 7/27 patients in Rituximab® group vs 9/14 patients in control group (P < 0.005) | Patient mean age: 12.3 ± 5.2 yr (control group), 15.0 ± 5.5 yr (Rituximab® group) |
| Audard et al[76] | Rituximab® induction in patients at high risk of recurrence (first graft lost due to recurrence) | 4 patients (≥ 18 yr) | No evidence of significant proteinuria at the end of follow-up | Single dose of 75 mg/m2 in 2/4 patients, repeated dose of 375 mg/m2 on day 7 in the remaining 2 patients; associated PE sessions (6 and 15, respectively) in 2/4 patients |
| Hickson et al[77] | Rituximab® (375 mg/m2; 2-4 doses) + PE | 4 patients (3 < 18 yr, 1 ≥ 18 yr) | Complete remissions in 4/4 patients | Early Rituximab® treatment in 3/4 (7–63 d post-transplantation), late treatment in 1/4 (982 d post-transplantation during a prolonged PE-dependent remission) |
| Dello Strologo et al[78] | Rituximab® (375 mg/m2; 1-4 doses) + PE | 6 patients (4 < 18 yr; 2 ≥ 18 yr) | Complete remission in 3; partial remission in 2; no response in 1 | 1/7 patients received one dose, 4/7 patients received 2 doses, and 1/7 received 4 doses; 1/7 patients experienced a severe reaction during first infusion and was excluded from the analysis |
| Tsagalis et al[79] | Rituximab® (1 g, 2 doses) + PE | 4 patients (2 < 18 yr; 2 ≥ 18 yr) | Complete remission in 2; partial remission in 2 | |
| Cho et al[80] | Rituximab® (100 mg, 1 dose) | 1 patient (≥ 18 yr) | Complete remission | |
| Yabu et al[87] | Rituximab® + PE | 4 patients (≥ 18 yr) | No response or proteinuria relapse after Rituximab® | Rituximab® schedule: 1 g, 2 doses in 1/4; 375 mg/m2, 4 doses in 1/4; 375 mg/m2, 6 doses in 2/4 |
| Kumar et al[117] | Rituximab® + PE | 8 patients (< 18 yr) | Complete remission in 2/8; partial remission in 4/8; no response in 2/8 | Rituximab® schedule: 375 mg/m2, 4 doses in 4/8; 375 mg/m2, 1 doses in 1/8; 375 mg/m2, 3 doses in 1/8; 375 mg/m2, 8 doses in 1/8; 375 mg/m2, 10 doses in 1/8 |
| Park et al[88] | Rituximab® (375 mg/m2, 1 or 2 doses) before transplantation with or without PE | 9 patients PE ± Rituximab® treated (Rituximab® group) vs 18 patients (control group) | No statistical difference in the prevention of recurrence between PE ± Rituximab® group (2/9, 22%) vs control group (5/18, 28%) | Rituximab® schedule: 375 mg/m2, 1 dose for desensitization in high risk patients; 375 mg/m2, 2 doses in ABO-incompatible transplantation; data not shown for recurrence prevention |
| Kamar et al[89] | Rituximab® (2-4 doses, 375 mg/m2) | 2 patients (≥ 18 yr) | Complete remission in 1 patient; no response in 1 patient | Rituximab® schedule: 75 mg/m2, 2 doses in the first patient (a supplemental dose was repeated after proteinuria relapse in association with PE sessions, achieving a new complete remission); 375 mg/m2, 4 doses in the second patient |
| El-Firjani et al[90] | Rituximab® (6 doses, 375 mg/m2) | 1 patient (≥ 18 yr) | No response | |
| Apeland et al[81] | Rituximab® (3 doses, 375 mg/m2) | 1 patient (≥ 18 yr) | Complete remission | |
| Grenda et al[82] | Rituximab® (4 doses, 375 mg/m2) | 1 patient (< 18 yr) | Complete remission | |
| Sethna et al[83] | Rituximab® (4 doses, 375 mg/m2) + PE | 4 patients (< 18 yr) | Complete remission in 3/4; partial and unsustained response in 1/4 | Proteinuria relapse in 1/3 patients with complete remission response to PE sessions intensification + an adjunctive dose of Rituximab® |
| Prytula et al[91] | Rituximab® (1-5 doses, 375 mg/m2) | 14 patients (< 18 yr) | Complete remission in 6/14; partial remission in 3/14; no response in 5/14 | |
| Stewart et al[92] | Rituximab® (4 doses, 375 mg/m2) | 1 patient (< 18 yr) | Complete remission | |
| Nozu et al[84] | Rituximab® (4 doses, 375 mg/m2) | 1 patient (< 18 yr) | Complete remission | Treatment was adopted after a diagnosis of post-transplant lymphoproliferative disorder |
| Nakayama et al[85] | Rituximab® (1-2 doses, 375 mg/m2) | 2 patients (< 18 yr) | Complete remission in 2 patients | One patient received a single dose; the other patient, after achieving a complete remission with the first dose, experienced a proteinuria relapse and rapidly responded to a second Rituximab® dose |
| Marks and McGraw[93] | Rituximab® (4 doses, 375 mg/m2 in one case; 2 doses 750 mg/m2 in the other one) | 2 patients (< 18 yr) | No response | |
| Bayrakci et al[86] | Rituximab® (4 doses, 375 mg/m2) | 1 patient (< 18 yr) | Complete remission | |
| Rodríguez-Ferrero et al[94] | Rituximab® (4 doses, 375 mg/m2) | 3 patients (≥ 18 yr) | Partial remission in 2/3; no response in 1/3 | |
| CTLA4-Ig (considered as the prevalent treatment) | ||||
| Yu et al[103] | Abatacept | 4 patients (2/4 < 18 yr, 2/4 ≥ 18 yr) with FSGS recurrence; 1 patient (≥ 18 yr) with FSGS on native kidneys | Complete remission in 2/5; partial remission in 3/5 | Patients 1 and 2 received a single dose; patients 3 and 4 received 2 doses; patient 5 (the only one with FSGS on native kidneys) received 3 doses (days 1, 15, 30) and a dose monthly thereafter |
| Alachkar et al[104] | Abatacept (1 dose; 10 mg/kg) in patient 1; belatacept (3 doses 10 mg/kg or continuative treatment) in patients 2-5 | 5 patients (≥ 18 yr) | No response | |
| Garin et al[105] | Abatacept (1 or 2 doses; 10 mg/kg) or belatacept (16 doses 5 mg/kg) | 5 patients (2/5 < 18 yr with minimal change in disease or FSGS on native kidneys; 3/5 with FSGS recurrence (1/3 < 18 yr, 2/3 ≥ 18 yr) | Partial response in minimal change disease patient; no response in primary FSGS patient; partial remission in 1/3 with FSGS recurrence (abatacept treated); no response in 2/3 (abatacept/ belatacept treated respectively) | Patients 1, 2 and 4 received 2 abatacept doses: patient 3 received 1 abatacept dose; patient 5 was treated with belatacept |
| Alkandari et al[106] | Abatacept (3 doses; 10 mg/kg) | 1 patient (< 18 yr) | No response | |
| Grellier et al[107] | Belatacept (days 1, 15, 30 and monthly thereafter, 5 mg/kg) | 5 patients (≥ 18 yr) | Partial response in 2/5; no response in 3/5 (no worsening in proteinuria values pre- and post-belatacept therapy in 1/3) | |
PE: Plasma exchange; CyA: Cyclosporine; CYC: Cyclophosphamide; FSGS: Focal segmental glomerulosclerosis; TNF-α: Tumor necrosis factor-alpha; MMF: Mycophenolate mofetil.