Ann Lab Med.  2021 Jan;41(1):1-15. 10.3343/alm.2021.41.1.1.

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

• Albert C
• Haase M
• Albert A
• Zapf A
• Braun-Dullaeus RC
• Haase-Fielitz A

• KMID: 2512729
• DOI: http://doi.org/10.3343/alm.2021.41.1.1

Abstract

Acute kidney injury (AKI) is a common and serious complication in hospitalized patients, which continues to pose a clinical challenge for treating physicians. The most recent Kidney Disease Improving Global Outcomes practice guidelines for AKI have restated the importance of earliest possible detection of AKI and adjusting treatment accordingly. Since the emergence of initial studies examining the use of neutrophil gelatinase-associated lipocalin (NGAL) and cycle arrest biomarkers, tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein (IGFBP7), for early diagnosis of AKI, a vast number of studies have investigated the accuracy and additional clinical benefits of these biomarkers. As proposed by the Acute Dialysis Quality Initiative, new AKI diagnostic criteria should equally utilize glomerular function and tubular injury markers for AKI diagnosis. In addition to refining our capabilities in kidney risk prediction with kidney injury biomarkers, structural disorder phenotypes referred to as “preclinical-” and “subclinical AKI” have been described and are increasingly recognized. Additionally, positive biomarker test findings were found to provide prognostic information regardless of an acute decline in renal function (positive serum creatinine criteria). We summarize and discuss the recent findings focusing on two of the most promising and clinically available kidney injury biomarkers, NGAL and cell cycle arrest markers, in the context of AKI phenotypes. Finally, we draw conclusions regarding the clinical implications for kidney risk prediction.

Keyword

Acute kidney injury; AKI phenotypes; Neutrophil gelatinase-associated lipocalin; Subclinical AKI; Preclinical AKI; Kidney biomarker; Serum creatinine; Kidney risk prediction; Cell cycle arrest biomarker

Figure

• 

  Fig. 1 Entities within the AKI spectrum. AKI phenotypes derived from a 2×2 table of four scenarios essentially differentiating changes in glomerular filtration function and structural tubular kidney injury. Abbreviations: AKI, acute kidney injury; BM, biomarker; SCr, serum creatinine; RFR, renal functional reserve.

• 

  Fig. 2 Revised conceptual model for AKI. White and light grey circles represent antecedents of AKI, i.e. patients at risk with suspected sepsis or those undergoing cardiac surgery. Acute kidney stress is defined as the preinjury phase that may transition into AKI. Sustained kidney stress will mitigate renal functional reserve and eventually transition into any variation of structural and functional kidney impairment (BM+/SCr-, BM-/SCr+, BM+/SCr+, and AKI-RRT). Structural kidney injury is indicated by a positive BM (+) finding. Arrows between the circles show potential transitions between AKI stages. AKI requiring RRT or patient death are associated adverse outcomes. Grey variations of the circles for kidney risk, kidney stress, and structural or functional kidney injury reflect increasing risk of adverse events [75, 93]. Abbreviations: AKI, acute kidney injury; SCr, serum creatinine; GFR, glomerular filtration rate; RFR, renal functional reserve; RRT, renal replacement therapy; BM, biomarker. Low risk for event Risk for event (observation zone), potential “kidney-stress”, “preclinical” or “subclinical” AKI Severe risk for event Critical risk for event

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  Fig. 3 Risk assessment chart for severe AKI. Consideration of NGAL cutoff concentrations provides the possibility of delineating a diagnostic “grey-zone” in clinical kidney risk assessment into an “Observational Zone” with the risk of kidney stress and preclinical or subclinical AKI. Severe AKI defined as RIFLE AKI stage injury or failure. Derived from data reported in [35]. Abbreviations: AKI, acute kidney injury; NGAL, neutrophil gelatinase-associated lipocalin; RIFLE, risk injury, failure, loss of kidney function, end-stage renal disease classification [70].

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