Novel test for antibiotic associated kidney damage in children with cystic fibrosis identified
Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by a mutation in the CFTR gene, leading to the production of defective CFTR proteins. CFTR is located in the epithelial cells of several organs, particularly the lungs, pancreas, liver, skin, reproductive organs and intestine, controlling the flow of ions in and out of cells. In CF, the abnormal CFTR causes ionic and osmotic imbalances which leads to thick, sticky mucus that can obstruct airways and glands, affecting bodily processes such as sweating and digestive enzyme production, and trapping bacteria in the lungs which leads to chronic infection.
These chronic infections are often caused by the resistant bacterium Pseudomonas aeruginosa, with aminoglycoside antibiotics showing good efficacy against the bacterium and are therefore commonly used to treat these infections. Their use, however, is potentially nephrotoxic and has been associated with acute kidney injury (AKI) in children.
Current methods for the assessment of AKI rely on the measurement of serum creatine, with higher than normal levels indicating poor renal function as the kidneys are less able to filter creatine from the blood. This method, however, only indicates injury once significant kidney damage has occurred, something that is especially detrimental to children.
New research from the University of Liverpool, by a team led by Dr Steve McWilliam, has identified two other proteins, KIM-1 and NGAL, that may be suitable biomarkers for kidney injury in children treated with aminoglycosides.
The researchers recruited over 150 children and young adults with CF to take part in the study. Urine samples were provided at regular intervals before, during and after treatment with aminoglycosides and were tested for KIM-1 and NGAL proteins. They found that the concentration of these proteins in urine was significantly increased during treatment with aminoglycosides. This occurred in the absence of serum creatine, suggesting that KIM-1 and NGAL indicate subclinical AKI. KIM-1 also exhibited an cumulative increase in concentration following successive rounds of aminoglycoside treatment, suggestive of chronic renal damage.
Dr McWilliam said, "Our research shows that KIM-1 may be a useful, non-invasive, biomarker of acute and chronic kidney damage associated with exposure to aminoglycosides in patients with CF, but its clinical utility needs to be further evaluated in prospective studies."
The authors state that KIM-1 shows particular promise in this setting as a biomarker for acute and chronic kidney injury, however, further study will be required to properly evaluate its clinical utility.