Corticosteroid minimization in renal transplantation: Careful patient selection enables feasibility

Table 1 Characteristics of the multi-center, randomized Astellas Corticosteroid Withdrawal Study with a follow-up time of 5 years[8]

	CS withdrawal at day 7 arm (n = 191)	Standard CS arm (n = 195)	P-value
Baseline demographic, immunological risk and immunosuppressive therapy data
Age (mean ± SD, yr)	46.6 ± 12.2	46.2 ± 12.7	NS
Female gender (%)	30.9	36.4	NS
African American (%)	17.8	21.5	NS
Deceased donor (%)	43.5	42.6	NS
Cold ischemic time (mean ± SD, h)	18.4 ± 5.7	17.2 ± 7.3	NS
HLA mismatch (mean)	3.5	3.5	NS
Current PRA (mean ± SD)	1.6 ± 5.3	1.8 ± 5.5	NS
Induction immunosuppression (%)			NS
Thymoglobulin	65.4	69.7
Basiliximab	31.4	27.2
Daclizumab	3.1	3.1
Maintenance immunosuppression	TAC, MMF	TAC, MMF
Main outcomes
Biopsy-proven acute rejection (%)	17.8	10.8	0.04 (with Kaplan-Meier analysis)
Allograft survival (%)	94.2	93.3	NS
Patient survival (%)	94.2	96.4	NS
Creatinine clearance (Cockroft-Gault equation, mean ± SD, mL/min)	58.6 ± 19.7	59.8 ± 20.5	NS

CS: Corticosteroid; HLA: Human leukocyte antigens; MMF: Mycophenolate mofetil; NS: Not significant; PRA: Panel-reactive antibodies; SD: Standard deviation; TAC: Tacrolimus.

Table 2 Characteristics of major randomized corticosteroid avoidance trials (the trial by Woodle et al[8] is described separately in table 1); P > 0.05 for all comparisons unless otherwise stated

Ref.	Patient number	Immunological risk	Timing of CS withdrawal	Induction immunosuppression	Maintenance immunosuppression	Biopsy-proven acute rejection (%)	Allograf/patient survival (%)	Follow-up (mo)
Vítko et al[10]	151	Low/moderate	Day 1	No	TAC, MMF	30.5f	97/99	6
	147	(PRA < 50%, first transplant)	Standard CS			8.2f	96/100
Laftavi et al[13]	30	Low (PRA < 30%, first transplant)	Day 7	rALG	TAC, MMF	13	NR	12
	30		Standard CS			11
Kumar et al[12]	150	Low	Day 2	Basiliximab	TAC or CsA, MMF or sirolimus	16	78/91	36
	150	(PRA < 10%)	Standard CS			14	79/89
Vincenti et al[11]	112	Low (PRA < 20%, first transplant)	No CS	Basiliximab	CsA, EC-MPS	31.5a	96/95	12
	115		Day 7			26.1b	98/98
	109		Standard CS			14.7ba	97/98
Hanaway et al[17]	164	Low	Day 5	Alemtuzumab	TAC, MMF	10d	93/95	36
	171	(PRA < 20%, first transplant)	Day 5	Basiliximab		22d	92/98
Haynes et al[16]	426	Unselected	No CS	Alemtuzumab	Low-dose TAC-MMF/ Standard TAC-MMF	7h	96/97	6
	426	patients	Standard CS	Basiliximab		16h	97/99

^aP = 0.046,

^bP = 0.004,

^dP = 0.003,

^fP < 0.001,

^hP = 0.0001. CS: Corticosteroids; CsA: Cyclosporine; EC-MPS: Enteric-coated mycophenolate sodium; MMF: Mycophenolate mofetil; NR: Not reported; PRA: Panel-reactive antibodies; rALG: Rabbit antilymphocyte globulin; TAC: Tacrolimus.

Table 3 Characteristics of major randomized corticosteroid withdrawal trials

Ref.	Patient number	Immunological risk	Timing of CS withdrawal	Induction immunosuppression	Maintenance immunosuppression	Biopsy-proven acute rejection (%)	Allograft/patient survival (%)	Follow-up (mo)
Vanrenterghem et al[20]	252	Low	At month 3	No	CsA, MMF	23b	95/99	12
	248		Standard CS			14b	96/98
Smak Gregoor et al[24]	76	Low	After month 6	No	CsA, MMF	4.0a	98/97	24
	73		Standard CS			1.4	97/97
Vanrenterghem et al[21]	279	Low	After month 3	No	TAC, MMF	5.9ad	93/99	6
	277		Standard CS			0.9d	94/98

P > 0.05 for all comparisons unless otherwise stated.

^aAfter CS discontinuation,

^bP = 0.008,

^dP = 0.004. CS: Corticosteroids; CsA: Cyclosporine; MMF: Mycophenolate mofetil; TAC: Tacrolimus.

Table 4 Characteristics of corticosteroid avoidance/withdrawal trials in immunologically high-risk and in pediatric patients

Ref.	Patient number	Immunological risk	Timing of CS withdrawal	Induction immunosuppression	Maintenance immunosuppression	Acute rejection (%)	Allograft/patient survival (%)	Follow-up (mo)
Immunologically high-risk patients
Thomas et al[26]	11	PRA > 20%, or	No CS	Alemtuzumab	TAC	18.2	86/100	12
	10	repeat transplant	Day 5	ATG	TAC, MMF	37.5	88/88
Hanaway et al[17]	164	PRA > 20%, or	Day 5	Alemtuzumab	TAC, MMF	18	91/99	36
	171	black race, or repeat transplant	Day 5	ATG		15	84/91
Pediatric patients
Grenda et al[28]	98	Low/moderate	Day 4	Daclizumab	TAC, MMF	10.2	97/99	6
	98	(PRA < 50%)	Standard CS	No induction		7.1	97/100
Höcker et al[29]	23	Moderate/high (PRA < 80%)	After year 1	No	CsA, MMF	4	100/100	24
	19		Standard CS			10	100/100

ATG: Antithymocyte globulin; CS: Corticosteroids; CsA: Cyclosporine; MMF: Mycophenolate mofetil; PRA: Panel-reactive antibodies; TAC: Tacrolimus.