Leukocyte-endothelial interaction in CKD

Chronic kidney disease (CKD) represents an independent risk factor for cardiovascular diseases (CVD). Accordingly, CKD patients show a substantial increased risk of cardiovascular mortality. Inflammation represents an important link between CKD and CVD. The interaction between endothelial cells and effector cells of the innate immune system plays a central role in the development and progression of inflammation. Vascular injury causes endothelial dysfunction, leading to augmented oxidative stress, increased expression of leukocyte adhesion molecules and chronic inflammation. CKD induces numerous metabolic changes, creating a uremic milieu resulting in the accumulation of various uremic toxins. These toxins lead to vascular injury, endothelial dysfunction and activation of the innate immune system. Recent studies describe CKD-dependent changes in monocytes that promote endothelial dysfunction and thus CKD progression and CKD-associated CVD. The NLR family pyrin domain containing 3-interleukin-1 & beta;-interleukin-6 (NLRP3-IL-1 & beta;-IL-6) signaling pathway plays a pivotal role in the development and progression of CVD and CKD alike. Several clinical trials are investigating targeted inhibition of this pathway indicating that anti-inflammatory therapeutic strategies may emerge as novel approaches in patients at high cardiovascular risk and nonresolving inflammation. CKD patients in particular would benefit from targeted anti-inflammatory therapy, since conventional therapeutic regimens have limited efficacy in this population. Lay Summary Sterile inflammation, which refers to inflammation not caused by infections, plays an important role in the development and progression of chronic kidney disease and cardiovascular disease alike. Thereby, white blood cells circulating in the blood adhere to the wall of the blood vessels and transmigrate into the tissue. There, they release a plethora of substances, which further maintain an inflammatory response and which finally lead to irreversible tissue damage. Recently, anti-inflammatory therapies have emerged as novel therapeutic approaches in kidney and cardiovascular diseases.