Strong Associations Between Early Tubular Damage and Urinary Cytokine, Chemokine, and Growth Factor Levels in Elderly Males and Females

Acute tubular necrosis is associated with high mortality rates and it is important to develop new biomarkers for tubular damage. The aim of this study was to investigate the effect of early tubular damage on a large number of urinary cytokines, chemokines, and growth factors. We selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The tubular damage markers cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were analyzed in the urine samples and urinary cytokine levels were analyzed with 2 multiplex assays (proximity extension assay). After adjustment for sex, body mass index, estimated glomerular filtration rate, smoking, and multiplicity testing using the false discovery rate approach, there remained 26 cytokines that correlated significantly with urine cystatin C, 27 cytokines that correlated with NGAL, and 66 cytokines that correlated with KIM-1. Tubular damage shows a strong association with urinary cytokines, chemokines, and growth factors. Our findings indicate that multiplex proteomics could be a promising new approach to explore the complex effects of tubular damage.