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Clonal myelopoiesis promotes adverse outcomes in chronic kidney disease

Leukemia, 2022-02, Vol.36 (2), p.507-515 [Peer Reviewed Journal]

2021. The Author(s). ;The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2021 ;ISSN: 0887-6924 ;EISSN: 1476-5551 ;DOI: 10.1038/s41375-021-01382-3 ;PMID: 34413458

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Title:
Clonal myelopoiesis promotes adverse outcomes in chronic kidney disease
Author: Dawoud, Ahmed A Z ; Gilbert, Rodney D ; Tapper, William J ; Cross, Nicholas C P
Subjects: Abnormalities ; Age ; Cardiovascular diseases ; Chromosome Aberrations ; Chromosomes ; Clonal Evolution ; Creatinine ; Creatinine - metabolism ; Cystatin ; Cystatin C - genetics ; Cystatin C - metabolism ; Epidermal growth factor receptors ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Health risks ; Hematopoiesis ; Hemopoiesis ; Humans ; Janus kinase 2 ; Kidney diseases ; Kidneys ; Male ; Mendelian Randomization Analysis ; Middle Aged ; Mutation ; Myelopoiesis ; Neoplasms ; Prognosis ; Prospective Studies ; Renal Insufficiency, Chronic - etiology ; Renal Insufficiency, Chronic - metabolism ; Renal Insufficiency, Chronic - pathology ; Tumors
Is Part Of: Leukemia, 2022-02, Vol.36 (2), p.507-515
Description: We sought to determine the relationship between age-related clonal hematopoiesis (CH) and chronic kidney disease (CKD). CH, defined as mosaic chromosome abnormalities (mCA) and/or driver mutations was identified in 5449 (2.9%) eligible UK Biobank participants (n = 190,487 median age = 58 years). CH was negatively associated with glomerular filtration rate estimated from cystatin-C (eGFR.cys; β = -0.75, P = 2.37 × 10 ), but not with eGFR estimated from creatinine, and was specifically associated with CKD defined by eGFR.cys < 60 (OR = 1.02, P = 8.44 × 10 ). In participants without prevalent myeloid neoplasms, eGFR.cys was associated with myeloid mCA (n = 148, β = -3.36, P = 0.01) and somatic driver mutations (n = 3241, β = -1.08, P = 6.25 × 10 ) associated with myeloid neoplasia (myeloid CH), specifically mutations in CBL, TET2, JAK2, PPM1D and GNB1 but not DNMT3A or ASXL1. In participants with no history of cardiovascular disease or myeloid neoplasms, myeloid CH increased the risk of adverse outcomes in CKD (HR = 1.6, P = 0.002) compared to those without myeloid CH. Mendelian randomisation analysis provided suggestive evidence for a causal relationship between CH and CKD (P = 0.03). We conclude that CH, and specifically myeloid CH, is associated with CKD defined by eGFR.cys. Myeloid CH promotes adverse outcomes in CKD, highlighting the importance of the interaction between intrinsic and extrinsic factors to define the health risk associated with CH.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 0887-6924
EISSN: 1476-5551
DOI: 10.1038/s41375-021-01382-3
PMID: 34413458
Source: AUTh Library subscriptions: ProQuest Central
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Clonal myelopoiesis promotes adverse outcomes in chronic kidney disease

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