A bidirectional Mendelian randomization study supports causal effects of kidney function on blood pressure
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 affectin...
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| Published in: | Kidney international Vol. 98; no. 3; p. 708 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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01.09.2020
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| ISSN: | 1523-1755, 1523-1755 |
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| Abstract | 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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| AbstractList | 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. 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.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. |
| Author | Boerwinkle, Eric Teumer, Alexander Chatterjee, Nilanjan Yu, Zhi Pattaro, Cristian Qi, Guanghao Coresh, Josef Grams, Morgan Snieder, Harold Köttgen, Anna Tin, Adrienne |
| Author_xml | – sequence: 1 givenname: Zhi surname: Yu fullname: Yu, Zhi organization: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 2 givenname: Josef surname: Coresh fullname: Coresh, Josef organization: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 3 givenname: Guanghao surname: Qi fullname: Qi, Guanghao organization: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA – sequence: 4 givenname: Morgan surname: Grams fullname: Grams, Morgan organization: Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA – sequence: 5 givenname: Eric surname: Boerwinkle fullname: Boerwinkle, Eric organization: Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA – sequence: 6 givenname: Harold surname: Snieder fullname: Snieder, Harold organization: Department of Epidemiology, University Medical Centre Groningen, Groningen, The Netherlands – sequence: 7 givenname: Alexander surname: Teumer fullname: Teumer, Alexander organization: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany – sequence: 8 givenname: Cristian surname: Pattaro fullname: Pattaro, Cristian organization: Eurac Research, Institute for Biomedicine (affiliated to the University of Lübeck), Bolzano, Italy – sequence: 9 givenname: Anna surname: Köttgen fullname: Köttgen, Anna organization: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and Medical Bioinformatics, Faculty of Medicine and Medical Centre - University of Freiburg, Freiburg, Germany – sequence: 10 givenname: Nilanjan surname: Chatterjee fullname: Chatterjee, Nilanjan organization: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA – sequence: 11 givenname: Adrienne surname: Tin fullname: Tin, Adrienne email: atin1@jhu.edu organization: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA; Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA. Electronic address: atin1@jhu.edu |
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| Keywords | blood pressure chronic kidney disease kidney function Mendelian randomization biomarkers genome-wide association study |
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