Improving Mortality in Subclinical Acute Kidney Injury after Cardiac Surgery by Composite Biomarker Panel

We read with great interest the study of Bouma et al (1) demonstrating the increase in long-term mortality of patients experiencing cardiac surgery associated acute kidney injury (CSA-AKI) stage 1 or higher not only after coronary artery bypass but also after cardiac valve operations. Even more, the mortality risk increased already substantially far below the threshold of AKI definition for stage 1(1). By consistently showing increased mortality also in (combined) valve operations this study closes the missing gap and carries therewith several important implications. First, the study justifies the endeavors for improved AKI definition, very early AKI detection as well as targeted interventions limited to high-risk subgroups in the hope of reducing incidence and severity of CSA-AKI. Second, the present study invariably shows, that the abovementioned endeavors should not be based upon creatinine-derived definitions, because important proportion of patients with potentially deleterious short- and longer-term outcomes could be missed in this way. Essentially, the study of Bouma et al. supports the concept of subclinical CSA-AKI, defined as being not always clinically expressed as per standard creatinine-based criteria but nevertheless strongly predicting adverse acute and late clinical outcomes (1). With the purpose of timely detecting subclinical AKI and forms of its potential (ir-)reversible progression towards more severe forms, we recently proposed a combination of conventional creatinine, relative delta (post-preoperative) creatinine dynamic changes, Neutrophil gelatinase-associated lipocalin to depict acute tubular injury and Cystatin C as a Glomerular Filtration Rate marker (2). While acknowledging that also minimal (up to 10%) creatinine changes could identify patients at higher risk of CSA-AKI, it has been till now unknown that even subclinical increase of creatinine after cardiac surgery in the range of 10-25% translates into substantially higher long-term mortality (1). Mizuguchi et al have recently identified patients at increased risk of AKI to acute kidney disease (AKD) progression by acute kidney injury severity determination (3). On the other hand, it has been reported that applying care bundles could reverse the kidney disease progression, namely by reducing the frequency as well as severity of AKI after cardiac surgery compared to standard postoperative care (4). We strongly believe that a proposed composite biomarker panel, with respect to other available novel biomarkers also costly efficient, could help us overcoming the gap, presented in the current manuscript whereby 10-25% patients with initially subclinical and undetected AKI present with substantially higher mortality (1). Finally, we once again congratulate the authors for the carefully executed study, underlying the inadequacy of the present CSA-AKI creatinine-based definition to reliably assess long-term mortality after cardiac operations therewith further supporting the view that future development of evidence-based Composite Biomarker Panel with reference values for early detection of (ir-)reversible CSA-AKI and CSA-AKD corresponds to putting additional horse before the cart rather than putting a cart before the horse