Novel Biomarkers and Imaging Tests for AKI Diagnosis in Patients with Cancer.

Abstract

The lack of non-invasive urine and blood-based biomarkers for the diagnosis of acute kidney injury (AKI) in patients with cancer is an area of significant unmet clinical need. Traditional non-invasive diagnostic tools that are currently utilized in the clinic, such as creatinine and cystatin C-based eGFR measurements, urinalysis, urine sediment exam, urine protein quantification, and urine electrolyte measurement, lack the sensitivity and specificity to distinguish between the various underlying etiologies of AKI in patients with cancer. Imaging-based diagnostics can be helpful to rule out urinary obstruction, but also lack sensitivity and specificity to diagnose the etiology of AKI. Kidney biopsy is often required for definitive diagnosis. As our scientific understanding of the biological pathways that are dysregulated in AKI has advanced, there has been considerable interest in developing new biomarkers for AKI. For example, the diagnosis of acute interstitial nephritis (AIN), which can occur in patients treated with immune checkpoint inhibitors (ICIs), promises to be revolutionized by the incorporation of urinary testing for inflammatory biomarkers such as C-X-C motif ligand 9 (CXCL9), tumor necrosis factor alpha (TNF-α), and interleukin 9 (IL-9). In the case of cisplatin administration, biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) may improve prognostication, differentiating between persistent AKI resulting from acute tubular injury versus pre-renal azotemia. The development and validation of blood, urine and imaging biomarkers into widely utilized diagnostic tests will require a concerted effort, but could improve diagnosis, management and prognostication for a growing group of patients who are at high risk of developing AKI during the course of their illness.