Role of novel biomarkers in kidney transplantation

Table 9 Summary of biomarkers associated with infectious outcomes

Ref.	n	Sample	Biomarkers	Outcome	Study conclusion
Fernández-Ruiz et al[73], 2017	100	Plasma	sCD30	Bacterial infection	sCD30 correlates to bacterial infection at baselinea and 1 moa, 3 moa, and 6 moa after KT. Patients with sCD30 ≥ 13.5 ng/mL had lower 12-mo bacterial infection-free survivalb (35.0% vs 80.0%) Baseline sCD30 levels ≥ 13.5 ng/mL is a risk factor for infectionc (HR: 4.65; 2.05-10.53)
Sadeghi et al[74], 2016	70	Plasma	IL-23	CMV infection	Patients with post-KT CMV disease (n = 13; 150 ± 106 d post-KT range 41–363 d) had higher pre-KT IL-23d (8.6 ± 4.4 vs 8.0 ± 17) and IL-23/Cr ratiosd than patients w/o CMV disease post-KT (n = 57). Pre-KT IL-23 plasma level of > 7 pg/mL is a risk factor for post-KT CMV infection/reactivation and symptomatic infectione (RR = 4.50, 95%CI: 1.23 to 16.52) ROC curve analysis post-KT CMV disease showed a sensitivity of 69% and a specificity of 67%
Leone et al[75], 2019	189	Plasma	94ins/delE37delATTG NFKB1 polymorphism	CMV infection	65% of CMV infections occurred in ins/ins group. Survival free from CMV was 54.7% for ins/ins group and 79.4% for del carriers one-year post-KT. A multivariate regression for del carriers showed a ↓ risk of CMV infectionf and recurrence for ins/ins KTRsg (HR = 0.224, 0.307)
Kim et al[77], 2017	385	Urine	Urine microRNA bkv-miR-B1-5p and bkv-miR-B1-3p	BKVN	↑ bkv-miR-B1-5p and bkv-miR-B1-3p in KTRs w biopsy proven BKVN distinguished them from disease free recipients (AUC = 0.989, 0.985). Only 13 KTRs with BKVN
Abend et al[78], 2017	116	Plasma	Donor BK virus antibody, recipient BK virus antibody	Post-transplant BK viremia	Donor BK virus antibody seropositivity correlated to post-transplant BK viremiah (OR = 5.0; 95%CI: 1.9-12.7). The authors did not examine for BKVN however
Ho et al[79], 2018	107	Urine	CXCL10	BKVN	↑CXCL10 correlated with t+ii (uCXCL10/creatinine, 1.23 ng/mmol vs 0.46 ng/mmol; AUC = 0.69) and mvi, specifically ptci (uCXCL10/creatinine, 1.72 ng/mmol vs 0.46 ng/mmol; AUC = 0.69) compared to normal histology. Urinary CXCL10i corresponded with BKV, but not CMV viremia. These urine CXCL10 findings were confirmed in the independent validation set

^aP < 0.05 vs kidney transplant recipients without bacterial infection.

^bP < 0.0001 vs kidney transplant recipients with sCD30 < 13.5 ng/mL.

^cP < 0.001 vs kidney transplant recipients with sCD30 < 13.5 ng/mL.

^dP < 0.05 vs kidney transplant recipients w/o CMV disease.

^eP < 0.05 vs kidney transplant recipients with pre-Tx IL 23 < 7 pg/mL.

^fP < 0.005 vs ins/ins carriers.

^gP < 0.05 vs del carriers.

^hP < 0.0001 vs seronegative BK virus antibody donors.

ⁱP < 0.05 vs low CXCL10 KTRs. sCD30: Soluble cluster of differentiation 30; KT: Kidney transplant; HR: Hazard ratio; IL-23: Interleukin twenty three; CMV: Cytomegalovirus; RR: Relative risk; Cr: Creatinine; ROC: Receiver operating characteristic; ins: Insertion; del: Deletion; NFKB1: Nuclear Factor kappa-light-chain-enhancer of activated B cells; KTRs: Kidney transplant recipients; bkv: BK viral; RNA: Ribonucleic acid; miR: Mature form of micro RNA; BKVN: BK virus nephropathy; AUC: Area under the curve; OR: Odds ratio; CI: Confidence interval; C-X-C: C-terminal amino acid sequence Cystine-X-Cystine; CXCL10: C-X-C motif chemokine ligand ten; t: Tubulitis; i: Interstitial inflammation; mvi: Microvascular inflammation; ptc: Peritubular capillaritis.