Kidney stone disease and cardiovascular events: a study on bidirectional causality based on mendelian randomization

Abstract

Background: Kidney stone disease (KSD) has been reported to be associated with several cardiovascular diseases. However, the causality between the conditions remains unknown. In the study, we performed a study on bidirectional causality by two-sample Mendelian randomization (MR) to investigate the causality between KSD and cardiovascular diseases including coronary atherosclerosis, hypertension, and cardiomyopathy.Methods: In the recent study, we performed a bidirectional two-sample MR study using available genomewide association summary data from the online database MRBASE. We identified genetic variants associated with KSD in one European population from UK Biobank (version 2, n=462,933). Two phenotypes of samples were chosen from the population to define our genetic instrumental variables: (I) samples with the phenotype of kidney stone/ureter stone/bladder stone (ukb-b-8297), and (II) samples with the phenotype of kidney stone surgery/lithotripsy (ukb-b-13537). For cardiovascular diseases, we picked up another independent European population from FinnGen Biobank (n=93,421). We selected the exposure and outcome SNPs and then performed the two-sample MR using R package.Results: After bidirectional causality by two-sample MR, we verified that genetic predisposition to KSD could increase the risk of coronary atherosclerosis (OR: 4.45×1037; SE=±7.80×10 14 , P for MR-Egger =0.024) and cardiomyopathy (OR: 5.35×10 13 ; SE=±7.18×10 6 , P for IVW=0.045 for finn-a-I9_CARDMYO, and OR: 3.60×10 25 ; SE=±3.26×10 12 , P for IVW=0.041 for finn-a-I9_CARDMYOOTH) when we used ukb-b-13537 as exposure group. Furthermore, hypertension could increase the risk of KSD (OR: 1.001; SE=±1.00, P for IVW=0.003) when we used ukb-b-8297 as exposure group, without detected pleiotropy bias (P>0.05). Conclusions:We confirmed KSD may trigger causal pathological processes including coronary atherosclerosis and cardiomyopathy. Furthermore, hypertension may causally affect KSD.

Causal effects of modifiable risk factors on kidney stones: a bidirectional mendelian randomization study

“…Reversely, Madore et al found that hypertension did not affect nephrolithiasis risk in men and wemon [ 37 , 38 ]. A previous MR analysis reported that kidney stone disease could unidirectionally increase the risk of hypertension with little impact (OR = 1.001) [ 11 ]. On the contrary, we verified that the presence of kidney stones was causally connected with high systolic and diastolic blood pressure (OR = 1.51, P = 0.0005; OR = 1.28, P = 0.0001, respectively), but not vice versa.…”

“…By taking advantage of the random assortment of SNPs at conception, MR studies are less vulnerable to confounding and reverse causation bias than conventional observational studies [ 9 ]. Several MR analyses have explored the associations between single modifiable risk factors and kidney stones, such as obesity [ 10 ], T2D [ 10 ], cardiovascular events [ 11 ], coffee and caffeine consumption [ 12 ], education [ 13 ], serum urate [ 14 ], 25(OH)D [ 15 ], and calcium [ 16 ]. Here we aimed to extend our analysis to comprehensively estimate the causal effects of 47 potentially modifiable risk factors on the risk of kidney stones by using a bidirectional MR approach.…”

Sex disparities and the risk of urolithiasis: a large cross-sectional study

“…In addition, HBP, FL, and UpH presented a positive correlation with a higher risk for urolithiasis in both genders. Hypertension was reported to be associated with an increased risk of urolithiasis from epidemiological and genetic perspectives [ 28 ]. Federico et al.…”

Association between body fat distribution and kidney stones: Evidence from a US population

“…However, the correlation between A/G ratio and KSD was more significant in the hypertensive group. This may be because hypertension itself is a risk factor for KSD (53), so it enhances this correlation. Interestingly, diabetes itself is also a risk factor for KSD.…”