Update on diagnostic and therapeutic strategies for antibody-mediated rejection in kidney transplantation

Table 6 The Transplantation Society 2019 consensus-based treatment recommendations in alignment with the Kidney Disease: Improving Global Outcomes 2023 guidelines for the treatment of antibody-mediated rejection

2019 consensus	DSA	Banff 2017 phenotypes	Standard of care	Consider adjunctive therapies	KDIGO 2023 updates
Early acute (< 30 days)	Preexisting DSA (or nonimmunologically naive)	Active AMR	PP/IVIG1 glucocorticoids	Complement	Eculizumab use is restricted to select cases with complement activation; not routine. KDIGO recommends early biopsy confirmation, dd-cfDNA and GEP monitoring, and tailored immunosuppression
				Inhibitor (e.g., eculizumab)
				Rituximab3
				Splenectomy
	Preexisting DSA	Active AMR	PP/IVIG1 glucocorticoids	Rituximab3	KDIGO advises against routine complement blockade unless complement-mediated injury is proven
Late (> 30 days)	De novo DSA	Chronic AMR	Optimize baseline immunosuppression2	-	KDIGO supports noninvasive monitoring (e.g., dd-cfDNA, GEP), and individualized therapy based on graft function
		Active AMR	Optimize baseline immunosuppression2	PP, IVIG	KDIGO encourages molecular diagnostics (e.g., MMDx) and consideration of adherence issues
				Rituximab
		Chronic AMR	Evaluate and manage nonadherence	IVIG	KDIGO highlights importance of patient education, adherence tracking, and long-term graft surveillance

¹Daily or alternate day plasmapheresis sessions × 6 based on donor-specific antibody titer; intravenous immunoglobulin 100 mg/kg after each plasmapheresis treatment or intravenous immunoglobulin 2/kg at the end of plasmapheresis treatments.

²Includes the use of tacrolimus with the goal through levels of > 5 ng/mL and use of maintenance steroid equivalent to prednisone 5 mg/day.

³If age < 70 years, estimated glomerular filtration rate ≥ 20 mL/minute/1.73 m³, lower chronicity scores on biopsy (interstitial fibrosis + tubular atrophy + fibrous intimal thickening + allograft glomerulopathy < 8) and evidence of severe disease [higher donor-specific antibody, diffuse C4d staining, or more extensive microvascular inflammation (i.e., glomerulitis score + peritubular capillary score ≥ 4) on biopsy].

AMR: Antibody-mediated rejection; DSA: Donor-specific antibody; IVIG: Intravenous immunoglobulin; PP: Plasmapheresis; KDIGO: Kidney Disease: Improving Global Outcomes; dd-cfDNA: Donor-derived cell-free DNA; GEP: Gene expression profiling; MMDx: Molecular Microscope Diagnostic System.