Treatment with plasmapheresis, immunoglobulins and rituximab for chronic-active antibody-mediated rejection in kidney transplantation: Clinical, immunological and pathological results

Table 1 Clinical and demographical data of PE-IVIG-RTX and control group n (%)

	PE-IVIG-RTX group (n = 9)	Control group (n = 12)	P-value
Recipient age at diagnosis, yr	47 (24-65)	52 (26-67)	0.234
Gender (M/F ratio)	5/4	8/4	0.604
Donor age, yr	58 (37-80)	49 (18-82)	0.203
Living donor transplantation	2/9 (22.2)	0/12 (0)	0.086
Previous transplants	1/9 (11.1)	3/12 (25)	0.422
Maximum PRA	0% (0-89)	27.5% (0-95)	0.061
Mismatches HLA A-B-DR, n	2 (1-4)	3 (1-4)	0.639
Previous episodes of acute rejection
(acute AMR – ACR)	1/9 (11.1)-1/9 (11.1)	1/12 (8.3)-1/12 (8.3)	0.586
Immunosuppression: Induction1	9/9 (100)	10/12 (83.3)	0.198
Clinical data at diagnosis
Time between transplantation and diagnosis of cAMR, mo	51 (21-108)	79 (20-258)	0.201
Serum creatinine, mg/dL	1.9 (1.2-3)	1.9 (0.9-3.7)	0.477
GFR2, mL/min	55,4 (23.9-65.4)	42.35 (18.9-88.1)	0.887
Proteinuria, g/d	1.6 (1-4)	1.55 (0.3-7.3)	0.886

¹All patients in both groups were treated with basiliximab except the two patients in control group who received only steroid induction.

²GFR estimated by Cockroft-Gault formula. Data are expressed as median (min-max). GFR: Glomerular filtration rate; PRA: Panel reactive lymphocytotoxicity assay; AMR: Antibody-mediated rejection; ACR: Acute cellular rejection.

Table 2 Donor-specific HLA antibody specificity and C1q-fixing assessment in PE-IVIG-RTX and control groups at diagnosis n (%)

	PE-IVIG-RTX group (n = 9)	Control group (n = 12)	P-value
Class I	2/9 (22.2)	6/12 (50)
Class II	5/9 (55.6)	2/12 (16.7)	0.166
Class I + II	2/9 (22.2)	4/12 (33.3)
MFI at diagnosis1	9800 (2700 – 24400)	4500 (900-24700)	0.327
C1q-fixing DSA1	4/9 (44.4)	4/102 (40)	0.845

¹Considering immunodominant antibody;

²Two patients were not tested for serum unavailability. DSA: Donor-specific antibodies.

Table 3 Analysis of Banff scores at diagnosis

	PE-IVIG-RTX group (n = 9)	Control group (n = 12)	P-value
Chronic glomerulopathy (cg)	2 (1-3)	1.5 (0-3)	0.792
Glomerulitis (g)	2 (1-3)	2 (0-3)	0.23
Peritubular capillaritis (ptc)	1 (0-2)	0.5 (0-3)	0.122
Microvascular inflammation (g + ptc)	3 (2-5)	2.5 (2-3)	0.219
Interstitial inflammation (ci)	1 (0-3)	1 (0-2)	0.624
Tubular atrophy (ct)	0 (0-1)	1 (0-1)	0.04
Chronicity score (ci + ct)	1 (0-3)	2 (0-3)	0.497
Arteriolar hyaline thickening (ah)	2 (0-3)	2 (0-3)	0.075
C4d+, n (%)	7/9 (77.8)	7/12 (58.3)	0.35
C4d score	2 (0-3)	1 (0-3)	0.831

Data are expressed as median (min-max).

Table 4 Analysis of Banff score changes in PE-IVIG-RTX group

	Pre PE-IVIG-RTX (n = 9)	Post PE-IVIG-RTX (n = 8)	P-value
Chronic glomerulopathy (cg)	2 (1-3)	2 (1-3)	0.705
Glomerulitis (g)	2 (1-3)	0.5 (0-2)	0.054
Peritubular capillaritis (ptc)	1 (0-2)	0.5 (0-2)	0.160
Microvascular inflammation (g + ptc)	3 (2-5)	1.5 (0-4)	0.047
Interstitial inflammation (ci)	1 (0-3)	1 (1-3)	0.480
Tubular atrophy (ct)	0 (0-1)	1 (0-2)	0.059
Chronicity score (ci + ct)	1 (0-3)	2 (1-5)	0.084
C4d+, n (%)	7/9 (77.8)	3/8 (37.5)	0.083
C4d score	2 (0-3)	0 (0-3)	0.102

Data are expressed as median (min-max).

Table 5 Analysis of MFI and C1q-fixing ability changes in PE-IVIG-RTX group

	Immunodominant DSA specificity	Pre PE-IVIG-RTX (n = 9)		Post PE-IVIG-RTX (n = 8)
		MFI	C1q-fixing	MFI	C1q-fixing
Patient 1	DPw3	13400	No	8200	Yes
Patient 2	DQ9	3000	No	10300	No
Patient 3	A24	9800	Yes	21200	No
Patient 4	DR4	2700	No	0	No
Patient 5	B35	10300	No	2500	No
Patient 6	DQ5	7000	Yes	0	No
Patient 7	DR53	15000	Yes	24000	Yes
Patient 8	DQ7	24400	Yes	9000	Yes
Patient 9	DR51	7400	No	3400	No
Median (min-max)		9800 (2700-24400)1	4/92	8200 (0-24000)1	3/92

¹P = 0.767 for difference in pre- and post-PE-IVIG-RTX MFI;

²P = 1 for difference in pre- and post-PE-IVIG-RTX C1q-fixing ability.

Table 6 Analysis of Banff scores at diagnosis in functioning and non-functioning grafts at 24 mo

	PE-IVIG-RTX group(n = 9)		P-value	Control group(n = 12)		P-value
	Functioninggraft(n = 6)	Non-functioning graft(n = 3)		Functioninggraft(n = 8)	Non-functioning graft(n = 4)
Chronic glomerulopathy (cg)	2.5 (1-3)	1 (1-3)	0.57	2.5 (1-3)	1 (0-2)	0.226
Glomerulitis (g)	2 (1-3)	1 (1-3)	0.472	2 (2-3)	1 (0-2)	0.043
Peritubular capillaritis (ptc)	1 (0-2)	1 (0-2)	0.829	0 (0-1)	1 (1-3)	0.037
Microvascular inflammation (g + ptc)	2.5 (2-5)	3 (2-3)	0.269	2.5 (2-3)	2.5 (2-3)	0.727
Interstitial inflammation (ci)	0.5 (0-2)	2 (1-2)	0.131	1 (0-1)	1 (1-2)	0.852
Tubular atrophy (ct)	0 (0-1)	0 (0-0)	0.667	1 (0-1)	1 (1-1)	0.255
Chronicity score (ci + ct)	0.5 (0-2)	2 (1-3)	0.29	1.5 (0-3)	2 (1-3)	0.807
C4d+, n (%)	5/7 (71.4)	2/3 (66.7)	0.583	3/8 (37.5)	4/4 (100)	0.071

Data are expressed as median (min-max).

Table 7 Analysis of kidney functional tests, proteinuria, MFI and DSAs-C1q fixing ability at diagnosis in functioning and non-functioning grafts at 24 mo

	PE-IVIG-RTX group(n = 9)		P-value	Control group(n = 12)		P-value
	Functioninggraft(n = 6)	Non-functioning graft(n = 3)		Functioninggraft(n = 8)	Non-functioninggraft(n = 4)
Creatinine, mg/dL	1.75 (1.2-2.7)	2 (1.9-3)	0.167	1.4 (0.9-2.3)	2.9 (2.4-3.7)	0.04
GFR, mL/min	47.9 (31-65.4)	55.4 (23.9-63.8)	0.905	52 (34.5-88.1)	30.5 (18.9-33.6)	0.04
Proteinuria, g/d	1.55 (1.3-2.5)	1.8 (1-4)	0.905	1.7 (0.8-7.3)	1.1 (0.3-2.6)	0.154
Donor age, yr	61 (37-63)	44 (43-80)	0.796	50.5 (18-82)	48 (25-55)	0.799
MFI	11600 (2700-24400)	7400 (7000-10300)	0.714	4500 (900-19300)	13200 (1700-24700)	0.533
C1q-fixing DSA, n (%)	3/6 (50)	1/3 (33.3)	0.595	2/7(28.6)	2/3(66.7)	0.333

DSA: Donor-specific antibodies.

Table 8 Adverse events after cAMR diagnosis in the 24 mo follow-up (number of total events)

	PE-IVIG-RTX group (n = 9)	Control group (n = 12)
Infections
Pyelonephritis and urinary tract infections	1	0
Gastrointestinal (diarrhea, ileitis)	2	0
Respiratory infection (bronchiolitis)	1	0
Acute cholecystitis	1	0
Cancers	0	2
Death	1	1