Abstract
BackgroundMonocyte chemoattractant protein-1 (MCP-1) plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD) were assessed in African Americans (AAs) with type 2 diabetes (T2D).MethodsSerum MCP-1 concentration, urine albumin:creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and atherosclerotic calcified plaque (CP) in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP.ResultsParticipants were 57% female, with mean ± SD (median) age 55.6±9.5 (55.0) years, diabetes duration 10.3±8.2 (8.0) years, urine ACR 149.7±566.7 (14.0) mg/g, CKD-EPI eGFR 92.4±23.3 (92.0) ml/min/1.73m2, MCP-1 262.9±239.1 (224.4) pg/ml, coronary artery CP 280.1±633.8 (13.5), carotid artery CP 47.1±132.9 (0), and aorta CP 1616.0±2864.0 (319.0). Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04) and negatively associated with eGFR (parameter estimate −0.0003, P=0.001). MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes.ConclusionsSerum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.
Highlights
Monocyte chemoattractant protein-1 (MCP-1) plays important roles in kidney disease susceptibility and atherogenesis in experimental models
Interaction effects were evaluated by testing for the direct interaction effect by including the centered product of body mass index (BMI) by MCP-1 and performing the association analysis between MCP-1 and the kidney function measures stratified by BMI where the sample was stratified into two subgroups
CAC was present in 62.7% of participants, 48.5% had detectable Carotid artery calcified plaque (CarCP), and 77.9% detectable Infrarenal aorta calcified plaque (AorCP)
Summary
Monocyte chemoattractant protein-1 (MCP-1) plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD) were assessed in African Americans (AAs) with type 2 diabetes (T2D). Inflammation, influx of circulating inflammatory cells, synthesis and secretion of chemokines and cytokines play important roles in diabetic kidney disease and atherosclerosis [1,2]. The relationship between serum chemokine monocyte chemoattractant protein-1 (MCP-1, or CCL2) levels with kidney disease and subclinical cardiovascular disease (CVD) has not been evaluated in the African American (AA) population. In experimental and human DN, macrophages are the principal infiltrating leukocyte population and the degree of macrophage influx and MCP-1 expression in the glomerular and interstitial compartments correlate with albuminuria and kidney function outcome [4,6,7,8]. MCP-1 suppression ameliorated albuminuria and kidney interstitial disease [7]
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