Role of novel biomarkers in kidney transplantation

Table 2 Summary of micro-ribonucleic acid-related novel biomarker studies associated with immunologic outcomes

Ref.	n	Sample	Biomarkers	Outcome	Study conclusion
Matz et al[17], 2016	160	Plasma	miR-15B, miR-103A, miR-106A	TCMR	miR-15Ba,b, miR-103Aa,b and miR-106Aa,b discriminated patients with stable graft function from patients with TCMR and UTI
Matz et al[18], 2018	111	Plasma	miR-223-3p; miR-424-3p; miR-145-5p; miR-15b-5p	ABMR, TCMR, IFTA	miR-223-3p, miR-424-3p and miR-145-5p distinguished TCMR and ABMR from stable graft function; mir-145-5P decreased in IFTA (AUC 0.891) compared to stable graft function
Millán et al[19], 2017	80	Urine	miR-142-3p, miR-210-3p and miR-155-5p, CXCL10	Rejection	↑miR-142-3p, ↑miR-155-5p, ↑CXCL10 + ↓miR-210-3p (AUC = 0.875) and CXCL10 (AUC = 0.865) discriminate rejectors and nonrejectors (sensitivity 85%, 84% and specificity 86% and 80% respectively)
Halloran et al[20], 2017	519	Allograft biopsy	Molecular Microscope® Diagnostic System (MMDx™)/microRNA	TCMR, ABMR	Agreement between MMDx™ and histology = 77% for TCMR, 77% for ABMR, and 76% for no rejection with blinding to histology, HLA. MMDx™c agreed with clinical judgment (87%) more than histology (80%)
Ledeganck et al[21], 2019	11 studies	Allograft biopsy	microRNA	TCMR, ABMR, cABMR	↑miR-142, miR-155, miR-223 and ↓miR-125, miR-30, miR-204 predict TCMR, ABMR, cABMR
Lorenzen et al[23], 2015	93	Urine	lcRNA; RP11-354P17.15-001 (L328)	TCMR	RP11-354P17.15-001d (L328) was associated with acute TCMR (AUC = 0.76) sensitivity 49%, specificity 95%; L328 can detect subclinical TCMR

^aP < 0.001 for TCMR vs controls.

^bP < 0.001 for UTI vs controls.

^cP < 0.005 vs histology.

^dP <0.001 vs controls. miR: Mature form of microribonucleic acid; RNA: Ribonucleic acid; TCMR: T cell-mediated rejection; HLA: Human leukocyte antigen; UTI: Urinary tract infection; ABMR: Antibody-mediated rejection; IFTA: Interstitial fibrosis tubular atrophy; AUC: Area under the curve; C-X-C: C-terminal amino acid sequence Cystine-X-Cystine; CXCL10: C-X-C motif chemokine ligand ten; MMDx™: Molecular Microscope^® Diagnostic System; cABMR: Chronic antibody-mediated rejection; lcRNA: Long noncoding RNAs.