BACKGROUNDLongitudinal investigations of murine
acute kidney injury (AKI) suggest that injury and
inflammation may persist long after the initial insult. However, the evolution of these processes and their prognostic values are unknown in patients with AKI.METHODSIn a prospective cohort of 656 participants hospitalized with AKI, we measured 7 urine and 2 plasma
biomarkers of kidney injury,
inflammation, and tubular health at multiple time points from the diagnosis to 12 months after AKI. We used linear mixed-effect models to estimate
biomarker changes over time, and we used Cox proportional hazard regressions to determine their associations with a composite outcome of
chronic kidney disease (CKD) incidence and progression. We compared the gene expression kinetics of
biomarkers in murine models of repair and
atrophy after ischemic
reperfusion injury (IRI).RESULTSAfter 4.3 years, 106 and 52 participants developed incident CKD and CKD progression, respectively. Each SD increase in the change of urine KIM-1, MCP-1, and plasma
TNFR1 from baseline to 12 months was associated with 2- to 3-fold increased risk for CKD, while the increase in urine
uromodulin was associated with 40% reduced risk for CKD. The trajectories of these biological processes were associated with progression to kidney
atrophy in mice after IRI.CONCLUSIONSustained tissue injury and
inflammation, and slower restoration of tubular health, are associated with higher risk of
kidney disease progression. Further investigation into these ongoing biological processes may help researchers understand and prevent the AKI-to-CKD transition.FUNDINGNIH and NIDDK (grants U01DK082223, U01DK082185, U01DK082192, U01DK082183, R01DK098233, R01DK101507, R01DK114014, K23DK100468, R03DK111881, K01DK120783, and R01DK093771).