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A bidirectional Mendelian randomization study supports causal effects of kidney function on blood pressure
Open accessAbstract
Blood pressure and kidney function have a bidirectional relation. Hypertension has long been considered as a risk factor for kidney function decline. However, whether intensive blood pressure control could promote kidney health has been uncertain. The kidney is known to have a major role in affecting blood pressure through sodium extraction and regulating electrolyte balance. This bidirectional relation makes causal inference between these two traits difficult. Therefore, to examine the causal relations between these two traits, we performed two-sample Mendelian randomization analyses using summary statistics of large-scale genome-wide association studies. We selected genetic instruments more likely to be specific for kidney function using meta-analyses of complementary kidney function biomarkers (glomerular filtration rate estimated from serum creatinine [eGFRcr], and blood urea nitrogen from the CKDGen Consortium). Systolic and diastolic blood pressure summary statistics were from the International Consortium for Blood Pressure and UK Biobank. Significant evidence supported the causal effects of higher kidney function on lower blood pressure. Based on the mode-based Mendelian randomization method, the effect estimates for one standard deviation (SD) higher in log-transformed eGFRcr was -0.17 SD unit (95 % confidence interval: -0.09 to -0.24) in systolic blood pressure and -0.15 SD unit (95% confidence interval: -0.07 to -0.22) in diastolic blood pressure. In contrast, the causal effects of blood pressure on kidney function were not statistically significant. Thus, our results support causal effects of higher kidney function on lower blood pressure and suggest preventing kidney function decline can reduce the public health burden of hypertension.
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“An important distinction is that unlike other BP lowering agents, 24 there appears to be no association between baseline values and the magnitude of BP reduction, an observation which we have extended to people with CKD.”
From Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial (2021) · cites this paper as [24]
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Metadata
- Authors
- Yu, Z., Coresh, J., Qi, G., Grams, M., Boerwinkle, E., Snieder, H., Teumer, A., Pattaro, C., Köttgen, A., Chatterjee, N., & Tin, A.
- Affiliations
- Johns Hopkins University (US)
- Baylor College of Medicine (US)
- University Medical Center Groningen (NL)
- Universitätsmedizin Greifswald (DE)
- Eurac Research (IT)
- Corresponding author
- Tin, Adrienne
- ORCID
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 98
- Issue
- 3
- Pages
- 708-716
- ISSN
- 0085-2538 (ISSN-L)
- PMC
- PMC7784392
- OpenAlex
- W3028085141
- Cited by
- 135
- References
- 61
- Citations by year
- 2026: 8 · 2025: 25 · 2024: 29 · 2023: 17 · 2022: 24 · 2021: 26 · 2020: 6
- FWCI
- 10.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion, other-oa)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Open Research (University of Surrey) (submittedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- National Human Genome Research Institute (R01 HG010480-01)
- Deutsche Forschungsgemeinschaft
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR073178-01A1, HHSN268201100009C)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- renal function, blood pressure, bidirectional causality, estimated glomerular filtration rate, blood urea nitrogen, hypertension, renal function decline, intensive blood pressure control, systolic blood pressure, diastolic blood pressure, genetic instruments
- MeSH terms
- Blood Pressure, Humans, Hypertension, Kidney, Genome-Wide Association Study, Mendelian Randomization Analysis
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