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.

Table 2 Trials of donor-derived cell-free DNA in kidney transplantation

NCT02424227	Noninvasive blood test to diagnose acute rejection after kidney transplantation (DART)	Completed
NCT03765203	Utility of a novel dd-cfDNA test to detect injury in renal posttransplant patients (QIDNEY)	Completed
NCT03326076	Evaluation of patient outcomes from the kidney allograft outcomes allosure registry (KOAR)	Recruiting
NCT04091984	The Prospera kidney transplant active rejection assessment registry (ProActive)	Recruiting
NCT04057742	Allosure for the monitoring of antibody-mediated processes after kidney transplantation (All-MAP)	Recruiting
NCT03759535	Study in detection cfDNA for the early stage diagnosis of acute rejection post-renal transplantation	Not yet recruiting
NCT03984747	Study for the prediction of active rejection in organs using donor-derived cell-free DNA detection (SPARO)	Recruiting
NCT04130685	Donor-derived cell-free DNA for surveillance in simultaneous pancreas and kidney transplant recipients	Recruiting
NCT04166149	Eliminating the need for pancreas biopsy using peripheral blood cell-free DNA (PancDX)	Recruiting
NCT03859388	Longitudinal changes in donor-derived cell-free DNA with tocilizumab treatment for chronic antibody-mediated rejection	Enrolling
NCT04225988	Comparison of tacrolimus extended-release (envarsus xr) to tacrolimus immediate-release in HLA sensitized kidney transplant recipients	Recruiting
NCT04177095	Immune monitoring to facilitate belatacept monotherapy	Recruiting
NCT04239703	Intercomex donor-derived cell-free DNA study	Recruiting

dd-cfDNA: Donor-derived cell-free DNA; HLA: Human leukocyte antigen.