Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac Surgery

Abstract

Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed via national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes.

Keywords: acute renal failure; cardiovascular disease; mortality risk.

Graphical abstract

Figure 1.

Flow diagram of patient selection into the study cohort.

Figure 2.

Increased Risk for CV events or death by increasing AKI stage or duration of AKI. Differently dashed lines indicate different AKI stages or duration, as explained in the figure.

Figure 3.

AKI stage and duration are independently associated wtih CV events or death. Adjusted hazard ratios are displayed here by AKI stage (A) and duration (B). 95% CIs are shown, with vertical dashed gray lines indicating hazard ratios of 1. n represents the number of events for each category.

Figure 4.

Peak post-operative plasma biomarkers are independently associated with CV events and mortality, while peak post-operative urine biomarkers are not independently associated with the outcome. Adjusted hazard ratios are displayed here by log-transformed urine biomarkers (A) and plasma biomarkers (B). 95% CIs are shown, with vertical dashed gray lines indicating hazard ratios of 1. n represents the number of patients.

Figure 5.

Schematic displaying that CVD risk in not significantly associated with urine biomarkers but is significantly associated with plasma biomarkers. Solid lines represent associations presented in Figure 3 (AKI to composite outcome of CV events and death) and Figure 3 (biomarkers to composite outcome of CV events and death). Dashed lines represent models explored in mediation analyses and reported in Table 2. CV, cardiovascular; Cr, creatinine.