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肾功能障碍中的中性粒细胞/淋巴细胞比值升高是由骨髓中白细胞造血的扭曲引起的。

Neutrophil/lymphocyte ratio elevation in renal dysfunction is caused by distortion of leukocyte hematopoiesis in bone marrow.

机构信息

a Division of Pharmaceutical Therapeutics, Department of Pharmacy, School of Pharmacy , Hyogo University of Health Sciences , Kobe , Japan.

b Division of Immunobiology, Department of Pharmacy, School of Pharmacy , Hyogo University of Health Sciences , Kobe , Japan.

出版信息

Ren Fail. 2019 Nov;41(1):284-293. doi: 10.1080/0886022X.2019.1597736.

DOI:10.1080/0886022X.2019.1597736
PMID:31014150
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6493297/
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.

摘要

目的

我们研究中性粒细胞/淋巴细胞比值（NLR）升高的机制，NLR 是心血管疾病（CVDs）患者有用的预后标志物。

方法

在这项临床研究中，我们回顾性地搜索了心血管门诊患者 NLR 升高相关的因素。在使用腺嘌呤诱导肾病的小鼠的动物实验中，我们进一步研究了骨髓中的造血过程，并探讨了 NLR 升高的机制。

结果

在患有 CVDs 或其危险因素的患者中，多元回归分析显示，估算肾小球滤过率的降低和白细胞计数的增加与 NLR 的升高显著相关。在腺嘌呤诱导肾病的小鼠中，NLR 和血清吲哚硫酸（IS）水平升高。荧光激活细胞分选显示髓系祖细胞数量增加，共同淋巴祖细胞数量减少，提示骨髓中的造血过程偏向于粒细胞侧。用口服活性炭吸附剂 AST-120 治疗可降低血清 IS 浓度，并使腺嘌呤诱导肾病小鼠的 NLR 和骨髓异常正常化。

结论

肾功能是心血管门诊患者 NLR 的一个重要决定因素。由于肾功能损害导致的 NLR 升高是由骨髓造血过程的扭曲引起的。IS 在这些过程中起着重要的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/881764316d16/IRNF_A_1597736_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/24cc87bf54dd/IRNF_A_1597736_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/50185db748c9/IRNF_A_1597736_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/b7455293b85c/IRNF_A_1597736_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/87eb2d65bdb2/IRNF_A_1597736_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/881764316d16/IRNF_A_1597736_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/24cc87bf54dd/IRNF_A_1597736_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/50185db748c9/IRNF_A_1597736_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/b7455293b85c/IRNF_A_1597736_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/87eb2d65bdb2/IRNF_A_1597736_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d15/6493297/881764316d16/IRNF_A_1597736_F0005_B.jpg

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