Role of novel biomarkers in kidney transplantation

Table 8 Summary of biomarkers associated with cardiovascular events and cardiovascular mortality

Ref.	n	Sample	Biomarkers	Outcome	Study conclusion
Foster et al[68], 2017	508	Urine and plasma	Cystatin C, B2M, Cr	CV events, Mortality, Kidney failure	HR eGFRcys and HR eGFRB2M < 30 vs 60+ were 2.02a (95%CI: 1.09 to 3.76) and 2.56b (95%CI: 1.35 to 4.88) for CV events; 3.92c (95%CI: 2.11 to 7.31) and 4.09b (95%CI: 2.21 to 7.54) for mortality; and 9.49c (95%CI: 4.28 to 21.00) and 15.53b (95%CI 6.99 to 34.51) for kidney failure
Bansal et al[69], 2016	1027	Urine	uNGAL, uKIM-1, IL-18, L-FABP, UCr	CV events, Graft failure, mortality	Each ↑ log in uNGAL/Cr associated with a 24% ↑ risk of CV events (aHR = 1.24 (95%CI: 1.06 to 1.45), graft failure (1.40; 1.16 to 1.68), and risk of death (1.44; 1.26 to 1.65). uKIM-1/Cr and IL-18/Cr associated with higher risk of death (1.29; 1.03 to 1.61 and 1.25; 1.04 to 1.49 per log increase)
Park et al[70], 2017	1184 (300 CVD, 371 death, 513 random sub-cohort)	Urine	urine alpha 1 microglobulin [A1M], monocyte chemoattractant protein-1 [MCP-1], procollagen type I [PINP] and type III [PIIINP] N-terminal amino peptide)	CV events, Death	↑uA1M (HR per doubling of biomarker = 1.40 (95%CI: 1.21 to 1.62), MCP-1 [HR 1.18 (1.03 to 1.36)], and PINP [HR = 1.13 (1.03 to 1.23)]were associated with CVD events and death (HR per doubling α1m = 1.51 (95%CI: 1.32 to 1.72); MCP-1 = 1.31 (1.13 to 1.51); PINP = 1.11 (1.03 to 1.20)
Devine et al[71], 2020	367	Plasma	ST2	CV events, CV mortality, All-cause mortality	↑ ST2 was associated with CV events (aHR = 1.31 (95% CI: 1.00 to 1.73); significantly for CV mortalityd (aHR = 1.61; (95%CI: 1.07 to 2.41; P = 0.022), The addition of ST2, to risk prediction models for CV mortality/events failed to improve their predictive accuracy
Yepes- Calderón et al[72], 2020	604	Plasma	Malondialdehyde	CV mortality	During a follow-up period, 110 KTRs died, with 40% CV death. MDA was significantly associated with the risk for CV mortality. The association between MDA concentration and the risk for CV mortality was stronger in KTRs with ↓ eGFR [HR 2.09 (95%CI: 1.45-3.00) per 1-SD increment]

^aP < 0.05 vs eGFR_cys > 60.

^bP < 0.005 vs eGFR_B2M > 60.

^cP < 0.005 vs eGFR_cys > 60.

^dP < 0.05 vs low ST2 group. B2M: Beta-2-microglobulin; Cr: Creatinine; CV: Cardiovascular; HR: Hazard ratio; eGFR: Estimated glomerular filtration rate; eGFR_cys: Estimated glomerular filtration rate based on cysteine; eGFR_B2M: Estimated glomerular filtration rate based on beta-2-microglobulin; uNGAL: Urinary neutrophil gelatinase-associated lipocalin; KIM-1: Kidney injury molecule 1; IL-18: Interleukin eighteen; L-FABP: Liver fatty acid binding protein; UCr: Urine creatinine; aHR: Adjusted hazard ratio; A1M: Alpha 1 microglobulin; MCP-1: Monocyte chemoattractant protein-1; PINP: Procollagen type I intact N-terminal peptide; PIIINP: Procollagen type III intact N-terminal peptide; ST2: Cardiac biomarker; MDA: Malondialdehyde; SD: Standard deviation.