Abstract
Objective: We investigate the mechanism of neutrophil/lymphocyte ratio (NLR) elevation, a useful prognostic marker in patients with cardiovascular diseases (CVDs).Methods: In this clinical study, we retrospectively searched for factors associated with NLR elevation in cardiovascular outpatients. In animal experiments using mice with adenine-induced nephropathy, we further examined the hematopoietic process in bone marrow and explored the mechanism of NLR elevation.Result: In patients with CVDs or their risk factors, multiple regression analysis revealed that decrease in estimated glemerular filtration rate and increase in white blood cell count were significantly associated with increase in NLR. In mice with adenine-induced nephropathy, NLR and serum indoxyl sulfate (IS) levels were increased. Fluorescence-activated cell sorting revealed the increase in the number of myeloid progenitors and decrease in the number of common lymphoid progenitors, suggesting biased granulocyte side in the hematopoietic process in bone marrow. Treatment with oral charcoal adsorbent AST-120 decreased serum concentration of IS and normalized NLR and bone marrow abnormalities in mice with adenine-induced nephropathy.Conclusion: Renal function was a strong determinant of NLR in cardiovascular outpatients. NLR elevation due to renal impairment is caused by distortion of the hematopoietic process in bone marrow. IS plays a significant role in these processes.
Highlights
In patients with chronic kidney disease (CKD), the morbidity and mortality of cardiovascular disease (CVD) such as heart failure, stroke, and myocardial infarction are increased
Our clinical research has revealed that reduced renal function and increased leukocytes were significantly associated with Neutrophil/lymphocyte ratio (NLR) elevation in patients with CVD or their risk factors
NLR elevation has been shown to be associated with CKD in patients with chronic heart failure [15]
Summary
In patients with chronic kidney disease (CKD), the morbidity and mortality of cardiovascular disease (CVD) such as heart failure, stroke, and myocardial infarction are increased. Elucidation of molecular mechanisms of crosstalk between CKD and CVD is an important key for developing new treatment strategy of cardio-renal syndrome. Chronic inflammation has recently drawn attention as a new risk factor of CVD and CKD. Chronic inflammation is suggested to be an important key that links CKD and CVD [10]. NLR has attracted attention since NLR is elevated in patients with various malignant tumors and CVD and a strong prognostic marker in them [12,13,14,15,16]. As NLR elevation is a disease condition common to various diseases, clarifying its mechanism may lead to the development of a new treatment method common to each disease
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