Update on the treatment of focal segmental glomerulosclerosis in renal transplantation

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.