Circulating and Urinary CCL20 in Human Kidney Disease

CC motif chemokine ligand 20 (CCL20), a chemokine involved in immune cell migration through its receptor CCR6, has been implicated in kidney inflammation in crescentic glomerulonephritis and acute kidney injury. However, clinical information for other kidney diseases is scarce. We have analysed CCL20 levels in plasma and urine from patients with diabetic kidney disease (DKD, n = 98) and autosomal dominant polycystic kidney disease (ADPKD, n = 85) treated according to the guidelines and studied their association with baseline characteristics and long-term (median follow-up 4.9 and 7.1 years, respectively) clinical outcomes. Single-cell kidney transcriptomics were mined to identify CCL20-expressing cells. Plasma CCL20 was higher in DKD and ADPKD than in a reference group: median 12.8 (3.5-33.2), 6.0 (1.2-19.2), and 0.0 (0.0-9.0) pg/mL, respectively. Urinary CCL20 was quantifiable in 48% of patients with DKD but not in the reference group. Transcriptomics data support a local kidney source of CCL20. In DKD, plasma CCL20 was higher in early compared to advanced CKD. Urinary CCL20 was higher in patients with A2 albuminuria than in those with other albuminuria categories. In ADPKD, higher plasma and urinary CCL20 levels tended to be associated with lower eGFR, higher albuminuria, and larger kidneys. However, no significant association was found between CCL20 levels and progression to kidney failure or death. In conclusion, CCL20 is increased in biological fluids and locally produced in CKD. While this may point to a potential role in risk stratification, further studies are necessary.