A bidirectional Mendelian randomization study supports causal effects of kidney function on blood pressure.

TitleA bidirectional Mendelian randomization study supports causal effects of kidney function on blood pressure.
Publication TypeJournal Article
Year of Publication2020
AuthorsYu, Z, Coresh, J, Qi, G, Grams, M, Boerwinkle, E, Snieder, H, Teumer, A, Pattaro, C, Köttgen, A, Chatterjee, N, Tin, A
JournalKidney Int
Volume98
Issue3
Pagination708-716
Date Published2020 Sep
ISSN1523-1755
KeywordsBlood Pressure, Genome-Wide Association Study, Humans, Hypertension, Kidney, Mendelian Randomization Analysis
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.

DOI10.1016/j.kint.2020.04.044
Alternate JournalKidney Int
PubMed ID32454124
PubMed Central IDPMC7784392
Grant ListHHSN268201100009I / HL / NHLBI NIH HHS / United States
R01 HG010480 / HG / NHGRI NIH HHS / United States
R01 AR073178 / AR / NIAMS NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States

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