Emerging role of cell-free DNA in kidney transplantation

Table 1 Biomarkers studied in the field of transplantation

Ref.	Biomarker name	Biomarker assay method	Sample size	Rejection type	Sensitivity/ specificity	PPV/NPV	Comments
Patel et al[56]	CDC crossmatch	Micro-cytotoxicity assay	225	Hyper acute rejection/ early graft loss	0.75/0.97	0.80/0.97	FDA approved
Mahoney et al[57]	Flow crossmatch	Flow cytometry	90	Early graft loss	0.71/0.74	0.33/0.93	FDA approved
Pei et al[58]	Luminex	HLA beads; flow cytometry	10	Anti HLA Ab	-	-	FDA approved
Ashokkumar et al[59]	Pleximmune	T cytotoxicmemory cell	32	Acute rejection	0.88/0.94	0.93/0.88	FDA approved
He et al[60]	Cylex-Immuknow	Lymphocyte ATPgeneration	42	CD4 T cell function	-	-	FDA approved
Loupy et al[61]	C1q bindingassay	Flow cytometric C1q binding	1016	TCMR/ABMR/graft loss	-	-	FDA approved
Hricik et al[62]	IFN-γ ELISPOT	Donor-reactive memory T cell	21	De novo DSA/ rejection	1.0/0.67	0.67/1.0	Not FDA approved
Roedder et al[63]	KSORT	PBLRNA by qPCR	143	AR	0.83/0.91	0.81/0.91	Not FDA approved
Bloom et al[33]	dd-cfDNA	PBL single gene sequencing	102 (107 samples)	ABMR and I b or higher TCMR	0.59/0.85	0.61/0.84	FDA approved
Acquino–Dias et al[64]	FOXP3	PBL, urine (PCR)	65 (78 sample)	AR vs DGF	0.94/0.95	0.94/0.95
Li et al[65]	Granzyme B, perforin	Urine mRNA (PCR)	85 (151 samples)	AR	0.79-0.83 /0.77-0.83	-
Hricik et al[66]	Urine CXCL9	Urine ELISA	258	TCMR	0.85/0.81	0.68/0.92	Not FDA approved
Suthanthiran et al[67]	Urine 3 gene; CD3E, CXCL10, 18SrRna	Urine RNA by PCR	485 pts (4300 samples)	Diagnosis AR 20 d early	0.79/0.78	-	Not FDA approved
Renesto et al[68]	TIM-3	PBL, urine mRNA PCR	115 (160 samples)	Diagnose AR, values normal post treatment	0.87/0.95	0.87/0.93
Valujskikh et al[69]	miRNA-210	Urine miR-210 PCR	81 (88 samples)	Diagnose AR, values normal post treatment	0.52/0.74	-

ABMR: Antibody-mediated rejection; AR: Acute rejection; CDC: Complement dependent cell cytotoxicity; dd-cfDNA: Donor-derived cell-free DNA; ELISA: Enzyme-linked immunosorbent assay; FDA: Food and Drug Administration; HLA: Human leukocyte antigen; IFN: Interferon; PBL: Peripheral blood lymphocyte; PCR: Polymerase chain reaction; TCMR: T cell-mediated rejection.