4.7 Article

The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population

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SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-021-88107-9

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  1. Netherlands Heart Foundation (CVON Predict2) [2018-30]
  2. Foundation Leducq (CurePLaN)
  3. European Research Council [ERC CoG 818715]
  4. Netherlands Heart Foundation (CVON DOSIS) [2014-40]

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Plasma levels of DKK3 are associated with cardiovascular risk factors, but are generally not independently associated with prevalent and new-onset CVD and CKD, and only predicted for new-onset CKD in those subjects with the lowest UAE values.
Dickkopf-3 (DKK3) is an emerging biomarker for cardiovascular disease (CVD) and chronic kidney disease (CKD). Herein, baseline DKK3 plasma levels were measured in 8420 subjects from the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort, a large general population cohort, using enzyme-linked immunosorbent assays. Associations with clinical variables and outcomes were analysed. Median DKK3 level was 32.8 ng/ml (28.0-39.0). In multivariable linear regression analysis, the strongest correlates for plasma DKK3 were age, body mass index and estimated glomerular filtration rate (eGFR). At baseline, 564 (6.7%) subjects had CVD (defined as a myocardial infarction and/or cerebrovascular accident) and 1361 (16.2%) subjects had CKD (defined as eGFR <60 ml/min/1.73m(2) and/or urinary albumin excretion (UAE)>30 mg/24 h). Of subjects with known CVD and CKD follow-up status (respectively 7828 and 5548), 669 (8.5%) developed CVD and 951 (17.1%) developed CKD (median follow-up respectively 12.5 and 10.2 years). Crude logistic regression analysis revealed that DKK3 levels were associated with prevalent CVD (Odds ratio: 2.14 [1.76-2.61] per DKK3 doubling, P<0.001) and CKD (Odds ratio: 1.84 [1.59-2.13] per DKK3 doubling, P<0.001). In crude Cox proportional hazard regression analysis, higher DKK3 levels were associated with higher risk for new-onset CVD (Hazard ratio: 1.47 [1.13-1.91] per DKK3 doubling, P=0.004) and CKD (Hazard ratio: 1.45, [1.25-1.69] per DKK3 doubling, P<0.001). However, these associations remained no longer significant after correction for common clinical variables and risk factors, though independently predicted for new-onset CKD in a subgroup of subjects with the lowest UAE values. Together, DKK3 plasma levels are associated with cardiovascular risk factors, but are generally not independently associated with prevalent and new-onset CVD and CKD and only predicted for new-onset CKD in those subjects with the lowest UAE values.

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