Early Urinary Markers of Kidney Injury in Adult People with Cystic Fibrosis Correlate with Neutrophil Activation and Lung Infection

Abstract

AbstractBackgroundAdult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF.MethodsUrinary total protein, albumin, and markers of kidney injury and neutrophil activation, normalized to creatinine, as well as urinary immune cells, were quantified in CF (n = 48) and healthy (n = 33) cohorts. Infection burden and chronicity were defined by sputum culture and serum titers of anti-bacterial antibodies.ResultsPwCF had increased urinary protein levels, consisting of low-molecular-weight tubular injury markers, independent of glomerular filtration rate (eGFR). This finding suggests subclinical renal injury processes. Urinary analysis of the CF cohort identified two renal tubular injury signatures: one associated with aminoglycoside exposure and one associated with increased urinary levels of neutrophil activation. High urinary KIM-1 levels and increased prevalence of neutrophils among urine immune cells correlated with decreased lung function in PwCF. The relationship between tubular injury and neutrophil activation was most prominent in patients harboring chronicPseudomonas aeruginosainfection.ConclusionsIncreased urinary tubular injury markers in PwCF suggest early subclinical renal injury not readily detected by eGFR. The strong association of high urinary KIM-1 and neutrophils with diminished lung function and highPseudomonas aeruginosaburden suggests that pulmonary disease may contribute to renal injury in CF.