Table 1 Data extraction chart for IRI, fibrosis, and long-term complications-related studies

Mehta et al. [41]

USA

CS OBS

To find changes in urine epigenetics suitable as biomarkers in early KT injury and repair

N = 88

KTRs cohort: 23 patients (13 DD, 10 LD) on day 2

HC: 65

Differential DNAm in urine of loci like CALCA promoter of KTRs compared to HC and DDs compared to LDs. No significant correlation between patients undergoing ATN vs. AR and between patients undergoing DGF vs. HCs

Bontha et al. [42]

USA

CS OBS

To understand oxidative stress and inflammatory setting trigger changes in DNAm patterns of the KA leading to fibrosis development and graft dysfunction

N = 95

Patients: 95 KTR of DD grafts, 99 biopsies

59 Post-KT (30 IFTA, 29 NFA)

40 Pre-KT (20 IFTA, 20 NFA)

A relationship between DNAm pattern alterations and IFTA has been found, with specific patterns involving fibrosis-related pathways, mostly acting on transcription factors and homeobox genes

McGuinness et al. [43]

UK

R OBS

To identify molecular signatures associated with DGF, to adjust for the effects of IRI, and to validate by comparison with publicly available data sets

N = 55

55 KTRs: PPPs

from DD

23 extreme DGF phenotype or IGF phenotype

Specific transcript promoter’s differential DNAm upon perfusion state and DGF occurrence has been found, identifying molecular signatures associated with DGF

Heylen et al. [44]

Belgium

CS OBS

To investigate whether ischemia induces DNA HrM and contributes to chronic injury

N = ?

Biopsies, 3 cohorts

13 PPPs + 2 × 5 in a subgroup at 3 or 12 months;

82 biopsies immediately before KT;

46 postreperfusion biopsies;

Validation cohort: 10 postreperfusion biopsies

DNAm pattern alterations involving genes suppressing kidney injury and fibrosis were found, linking ischemia at the time of KT with progressive chronic allograft injury at 1 year after KT. Ischemia seemed to reduce TET enzymes activity

Heylen et al. [45]

Belgium

CS OBS

To understand kidney-associated DNAm changes in the context of aging, trying to find out which specific genes are affected

N = ?

Biopsies

Discovery cohort: 95 prior to KT (82 BDDs, 13 LDs)

Validation cohort: 67 immediately after KT and reperfusion (58 BDDs, 9 LDs)

Age-associated changes in DNAm at the time of KT predicted future injury of the KA and epigenetic renal aging is implicated in progressive fibrosis in both the glomerulus and the interstitium. No association was found between the methylation patterns, arteriosclerosis, and tubular atrophy

Schaenman et al. [46]

USA

P OBS

To prove the potential benefit of DNAmAge analysis in the context of KT, trying to associate DNAmAge and infection occurrence

N = 60

Old cohort: 24

Young cohort: 36

DNAmAge analysis holds promise for improving clinical outcomes and has been associated with post-KT infections. DNAmAge may be higher or lower than chronological age