Active Kidney Injury Biomarkers in the Diagnosis of Kidney Diseases

Early diagnosis of kidney diseases is very important to initiate timely management; however, it is hampered by the low sensitivity of the traditional markers of kidney function. The most commonly used markers to evaluate kidney function include serum creatinine, urea nitrogen, and SDMA concentrations as well as urine specific gravity. All of these are markers indicate changes in kidney function, but cannot identify active or ongoing subclinical injury or disease that is not associated with concurrent changes in kidney function, regardless of its severity. Functional filtration markers also are insensitive predictors of the early decline in kidney function due to the nonlinear (exponential) relationship between these markers and the glomerular filtration rate. Specifically, a substantial decrease in GFR at an early stage of the disease may results only in a mild increase of the functional markers. For these reasons the diagnosis of both AKI and stable or progressive CKD may be delayed. The diagnostic utility of novel active kidney injury biomarkers is of growing interest due to the historical limitations of these functional markers. A biomarker, or a group of biomarkers, that can identify the presence of active and persistent renal parenchymal damage, inflammation, oxidative stress, or fibrosis would be extremely useful for the early diagnosis and characterization of kidney diseases.

In recent years there is growing investigation on active injury biomarkers. These are released from stressed, damaged or ruptured canine kidney cells, and their presence in the urine becomes a sensitive predictor of acute or sustained renal tubular cell injury. It has been demonstrated that epithelial damage is present in animals with AKI prior to any increase in functional markers, as well as in animals with apparently stable CKD on the basis of functional markers. It also has been suggested that the degree of epithelial damage is associated with disease progression and survival. Rigorous evaluation of these markers in longitudinal studies of clinical patients to define their true predictive potential is currently an unmet need and IRIS encourages more studies to be initiated and ultimately published in peer-reviewed journals to provide the evidence for their use in clinical practice.

IRIS expects that the availability of real-time biomarkers with potential to identify active or ongoing kidney injury in animals with kidney disease has potential to alter the way practitioners diagnose, monitor, and treat kidney diseases in the future. Novel active injury biomarkers are not intended to replace the use of traditional markers of kidney function, but rather used diagnostically in conjunction with traditional functional markers to reveal occult or subclinical kidney disease which is otherwise undetectable. As nephrologists, we anxiously await this new era of early disease discovery and management.

The IRIS Board June 2023