Mediators of vascular inflammation and tertiary lymphoid organ formation in chronic kidney disease

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Patients with chronic kidney disease (CKD) suffer from increased cardiovascular morbidity and mortality compared to individuals with normal renal function but otherwise similar risk factors. Chronic inflammation can initiate tertiary lymphoid organs (TLO) with differential effects on kidney disease progression as we have delineated in a cohort with renal inflammation in IgA nephropathy. Our previous investigations have elucidated a mechanistic role of the cytokine interleukin (IL)-17A in enhancing vascular inflammation in CKD. Both, renal and vascular inflammation are usually diagnosed in established disease, thus the mechanisms maintaining inflammation are critical for therapeutic success in patients with CKD. Using a combination of clinical cohort studies and specific gene deficient mouse models established at the collaborating sites, the current project aims at 1) delineating the role of IL-17A in TLO formation in atherosclerosis and the kidney and 2) the role of fractalkine receptor in chronic inflammation in human kidney and murine atherosclerosis in CKD. Results of this study will enhance pathophysiologic understanding to enable specific anti-inflammatory strategies in patients with chronic kidney disease