Arterial and Cellular Inflammation in Patients with CKD

Abstract

CKD associates with a 1.5- to 3.5-fold increased risk for cardiovascular disease. Both diseases are characterized by increased inflammation, and in patients with CKD, elevated C-reactive protein level predicts cardiovascular risk. In addition to systemic inflammation, local arterial inflammation, driven by monocyte-derived macrophages, predicts future cardiovascular events in the general population. We hypothesized that subjects with CKD have increased arterial and cellular inflammation, reflected by F-fluorodeoxyglucose (F-FDG) positron emission tomography computed tomography (PET/CT) of the arterial wall and a migratory phenotype of monocytes. We assessed F-FDG uptake in the arterial wall in 14 patients with CKD (mean±SD age: 59±5 years, mean±SD eGFR: 37±12 ml/min per 1.73 m) but without cardiovascular diseases, diabetes, or inflammatory conditions and in 14 control subjects (mean age: 60±11 years, mean eGFR: 86±16 ml/min per 1.73 m). Compared with controls, patients with CKD showed increased arterial inflammation, quantified as target-to-background ratio (TBR) in the aorta (TBR: CKD, 3.14±0.70 versus control, 2.12±0.27; =0.001) and the carotid arteries (TBR: CKD, 2.45±0.65 versus control, 1.66±0.27; <0.001). Characterization of circulating monocytes using flow cytometry revealed increased chemokine receptor expression and enhanced transendothelial migration capacity in patients with CKD compared with controls. In conclusion, this increased arterial wall inflammation, observed in patients with CKD but without overt atherosclerotic disease and with few traditional risk factors, may contribute to the increased cardiovascular risk associated with CKD. The concomitant elevation of monocyte activity may provide novel therapeutic targets for attenuating this inflammation and thereby preventing CKD-associated cardiovascular disease.

Salt increases monocyte CCR2 expression and inflammatory responses in humans

“…Furthermore, proinflammatory activation and CCR2 have been implicated in acute and chronic kidney disease (9,40,41) and cardiovascular disease (6,42,43), underlining the relevance of our findings for kidney and cardiovascular patients. Patients with chronic kidney disease show increased arterial inflammation and increased proinflammatory phenotype of monocytes, as displayed by increased CCR7 and CCR2 expression (9). Reduction of CCR2-expressing monocytes by inhibition of MCP-1 has been shown to reduce proinflammatory priming of renal macrophages and reduced albuminuria in diabetic nephropathy (41).…”

“…However, knowledge of potential explaining mechanisms remains incomplete. There might be a role for inflammation with regard to these mechanisms, since it has been suggested by several authors that inflammation plays a role in the previously mentioned diseases (4)(5)(6)(7)(8)(9). Recent animal studies propose a role for specific phenotypes of circulating monocytes and macrophages, as well as their infiltration in various tissues such as the skin interstitium and the vessel wall (6,10,11).…”

Plasma Leucine-Rich α-2-Glycoprotein 1 Predicts Cardiovascular Disease Risk in End-Stage Renal Disease

“…Chronic inflammation is a hallmark of CKD and ESRD [26][27][28] . In ulcerative colitis, LRG1 level is elevated and parallel to disease activity.…”

Risk of Retinal Vein Occlusion in Patients With End-Stage Renal Disease: A 12-Year, Retrospective, Nationwide Cohort Study in South Korea

“…33,34 Chronic inflammation can induce atherosclerosis and thrombosis, which contributes to increased cardiovascular risk. 33,35 In addition, ESRD patients also exhibit an elevated plasma homocysteine level, which is associated with thrombosis and cardiovascular disease. [36][37][38] Dysregulation of coagulation and anticoagulation is reported as a major risk factor for RVO.…”