Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study

Abstract

Background: The ability of urinary biomarkers to complement established clinical risk prediction models for postoperative adverse kidney events is unclear. We assessed the effect of urinary biomarkers linked to suspected pathogenesis of cardiac surgery-induced acute kidney injury (AKI) on the performance of the Cleveland Score, a risk assessment model for postoperative adverse kidney events.Methods: This pilot study included 100 patients who underwent open-heart surgery. We determined improvements to the Cleveland Score when adding urinary biomarkers measured using clinical laboratory platforms (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-6) and those in the preclinical stage (hepcidin-25, midkine, alpha-1 microglobulin), all sampled immediately post-surgery. The primary endpoint was major adverse kidney events (MAKE), and the secondary endpoint was AKI. We performed ROC curve analysis, assessed baseline model performance (odds ratios [OR], 95% CI), and carried out statistical reclassification analyses to assess model improvement.Results: NGAL (OR [95% CI] per 20 concentration-units wherever applicable): (1.

Thirty-Eight-Negative Kinase 1 Is a Mediator of Acute Kidney Injury in Experimental and Clinical Traumatic Hemorrhagic Shock

“…Whether IL-6 functions only as a monitoring marker or is also causatively involved in driving the pathophysiology of AKI development is the objective of current research. Both IL-6 and NGAL determined shortly after surgical tissue injury inflicted by major cardiac surgery were independent predictors of AKI in the postoperative course ( 32 ). In murine kidney ischemia and reperfusion injury, anti-IL-6 therapy by gene delivery was capable of improving renal function and of decreasing NGAL concentrations, indicating some causal involvement of IL-6 ( 33 ).…”

Biomarker-Guided Risk Assessment for Acute Kidney Injury: Time for Clinical Implementation?

“…These findings may indicate that different pathophysiological mechanisms of tubular injury may be present, and, on the other hand, patients may be in different phases of tubular injury and repair. Various data have demonstrated that septic AKI has different predominant underlying pathophysiologic processes compared with cardiac surgery-associated AKI [ 79 , 80 ]. The existence of single-biomarker positive subclinical AKI needs to be verified and the prognosis of such patients needs to be investigated.…”

“…However, a candidate biomarker should be able to improve an established clinical reference model to be of diagnostic or prognostic benefit [ 103 ]. Previous studies have shown that the predictive ability of a risk prediction model may improve following the addition of candidate biomarkers, such as NGAL and interleukin-6 [ 79 ], hepcidin-25 [ 79 , 104 ], or [TIMP-2]•[IGFBP7] [ 58 , 105 ]. The combination of kidney injury biomarkers and hepcidin-25, previously described as a biomarker with renal protective ability [ 47 , 65 ], was able to further improve diagnostic discrimination [ 79 ].…”

“…Previous studies have shown that the predictive ability of a risk prediction model may improve following the addition of candidate biomarkers, such as NGAL and interleukin-6 [ 79 ], hepcidin-25 [ 79 , 104 ], or [TIMP-2]•[IGFBP7] [ 58 , 105 ]. The combination of kidney injury biomarkers and hepcidin-25, previously described as a biomarker with renal protective ability [ 47 , 65 ], was able to further improve diagnostic discrimination [ 79 ]. The latter is of particular interest [ 79 ]; higher plasma catalytic iron concentrations were shown to be associated with a significantly greater risk of mortality, as were lower hepcidin concentrations in patients with severe AKI stages requiring RRT [ 106 ].…”

“…The combination of kidney injury biomarkers and hepcidin-25, previously described as a biomarker with renal protective ability [ 47 , 65 ], was able to further improve diagnostic discrimination [ 79 ]. The latter is of particular interest [ 79 ]; higher plasma catalytic iron concentrations were shown to be associated with a significantly greater risk of mortality, as were lower hepcidin concentrations in patients with severe AKI stages requiring RRT [ 106 ].…”