Urinary Biomarkers of Aminoglycoside-Induced Nephrotoxicity in Cystic Fibrosis: Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin

Abstract

Aminoglycosides are commonly used for the treatment of pulmonary exacerbations in patients with cystic fibrosis (CF). However, they are potentially nephrotoxic. This prospective observational cohort study aimed to investigate the potential validity of two urinary renal biomarkers, Kidney Injury Molecule-1 (KIM-1) and Neutrophil Gelatinase-associated Lipocalin (NGAL), in identifying aminoglycoside-induced nephrotoxicity in children with CF. Children and young adults up to 20 years of age with a confirmed diagnosis of CF were recruited from ten United Kingdom hospitals. Participants provided urine samples for measurement of KIM-1 and NGAL concentrations, at baseline, at regular outpatient appointments, and before, during and after exposure to clinically-indicated treatment with the aminoglycoside tobramycin. 37/158 patients recruited (23.4%) received at least one course of IV tobramycin during the study. The median peak fold-change during tobramycin exposure for KIM-1 was 2.28 (IQR 2.69) and 4.02 (IQR 7.29) for NGAL, in the absence of serum creatinine changes. Baseline KIM-1 was positively associated with cumulative courses of IV aminoglycosides (R2 = 0.11; β = 0.03; p < 0.0001). KIM-1, in particular, may be a useful, non-invasive, biomarker of acute and chronic proximal tubular injury associated with exposure to aminoglycosides in patients with CF, but its clinical utility needs to be further evaluated in prospective studies.

Sepsis associated acute kidney injury

“…Data have been inconsistent in SA-AKI 7475. Multiple studies have shown that plasma NGAL is elevated in patients with sepsis even in the absence of AKI 76.…”

Could urinary kidney injury molecule-1 be a good marker in subclinical acute kidney injury in mild to moderate COVID-19 infection?

“…One of these markers is uKIM-1. Various studies provide data showing that the uKIM-1 level measured in patients that have not developed AKI could be a marker indicating early kidney injury, as well as a parameter that predicts both the need for renal replacement therapy and mortality in the long term [27][28][29]. In the current study, the patients with mild/moderate COVID-19 were evaluated, and it was determined that there was a group that could be interpreted as subclinical AKI despite not meeting the KDIGO-AKI criteria, which presented with significantly increased proteinuria accompanying high uKIM-1 levels.…”

Evaluation of colistin nephrotoxicity and urinary level of kidney injury molecule-1 in hospitalized adult ICU patients

“…In addition, the sensitivity and specificity (and overall, accuracy) of KIM-1 levels on days 0, 3rd, 5th, and 7th of colistin treatment was significantly lower than the serum creatinine level in the detection of colistin nephrotoxicity. So far, six clinical studies have examined the role of urinary levels of KIM-1 in detecting nephrotoxicity of drugs including cisplatin, gentamicin, amphotericin B, and vancomycin (21)(22)(23)(24)(25)(26). Accordingly, in two studies in pediatric patients, KIM-1 was superior to n-acetyl-beta-glucose amines (NAG), urinary neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 in detecting nephrotoxicity caused by cisplatin, ifosfamide, and aminoglycosides (17,21).…”