TABLE 6.

Summary of studies on outcome of subclinical ABMR with or without treatment.

Study	Type of study	Total patients (n)	Total subclinical ABMR (n) or (%)	Type 1 or type 2 ABMR	Time of biopsy	Treatment of subclinical ABMR	Outcome
Parajuli et al. [102]	Retrospective single center	220	25 (all treated)	Type 1 and 2	Detection of dnDSA	≤3 months post-transplant: Pulse steroids, IVIG, PP	No significant difference in 5 years post-biopsy DCGS between treated subclinical ABMR and no rejection
					Protocol biopsies in case of pretranplant DSA		Significantly better 5 years post-biopsy DCGS in treated subclinical ABMR than clinical ABMR and than DSA- indication biopsies
					50% rise in MFI	≥3 months post-transplant: Pulse steroids, IVIG, situationally RTX	(92% vs. 54%, proportion of DSA- indication biopsies with DCGS not provided)
					Graft dysfunction		No significant difference in post-biopsy DCGS between type 1 or type 2 subclinical ABMR.
Orandi et al. [175]	Retrospective single center	2097	77 (41 treated)	Uncertain Mostly type 1	Protocol biopsies at 1,3,6, 12 months post-transplant in HLA or ABOi incompatible transplants	PP + Situationally RTX or eculizumab	No significant difference in DCGS between treated subclinical ABMR and ABMR free matched controls. HR 1.73; 95% CI: 0.73–4.05; p = 0.21
							Significantly worse DCGS in untreated subclinical ABMR vs. ABMR free matched controls. HR 3.34; 95% CI: 1.37–8.11; p = 0.008
Yamamoto et al. [79]	Retrospective single center	43	18 (all treated)	Type 2	At dnDSA detection	Plasmapheresis and RTX	Significant decrease of MFI in 6 out of 18 patients
							Within 10 patients with rebiopsy, 4 had improvement or no change in graft histology
Bertrand et al. [77]	Retrospective Multicenter	123	51 (19 treated)	Type 2	At dnDSA detection	A combination of IVIG/PP/RTX	Significantly worse 8 years biopsy DCGS in subclinical ABMR patients vs. no rejection. (78% vs. 97%, p < 0.01)
							No significant difference in 8 years post-biopsy DCGS between treated and untreated subclinical ABMR
Loupy et al. [57]	Retrospective single center + External validation	1,001	142 (56 treated)	Type 1 and 2	Protocol biopsy at 1 year post-transplant	IVIG, PP, RTX	Significantly worse 8 years graft survival probability in subclinical ABMR vs. no rejection (56% vs. 90%, p < 0.0001
							Significantly faster decline of eGFR over 8 years in subclinical ABMR vs. no rejection (p not provided)
							No analysis in regards to treated vs. untreated subclinical ABMR

ABMR, Antibody-mediated rejection; DCGS, Death-censored graft survival; DSA, Donor-specific antibody; dnDSA, de novo DSA; eGFR, Estimated glomerular filtration rate; IVIG, Intravenous immunoglobulins; MFI, Mean fluorescence intensity; PP, Plasmapheresis; RTX, Rituximab.