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

Li, Wen; Wang, Miaomiao; Liu, Jianyong; Yan, Qiuxia; Liu, Ming

doi:10.1186/s12920-023-01520-z

Cited by 13 publications

(6 citation statements)

References 53 publications

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“…In this study, we have used two-sample MR to evaluate the causal relationship between a variety of food intakes and the risk of urolithiasis. In line with previous publications, our study supported a protective role of tea intake in calculus of kidney and ureter, but not in calculus of lower urinary tract [ 25 , 26 ]. Furthermore, we have identified fresh fruit intake, instead of dry fruit intake, as a reverse causal factor for urolithiasis.…”

Section: Discussionsupporting

confidence: 92%

Mendelian randomization analysis reveals fresh fruit intake as a protective factor for urolithiasis

Lin,

Zhou,

et al. 2023

Hum Genomics

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Objective Previous studies have proposed that food intakes are associated with the risk of urolithiasis. Here, we conducted a two-sample Mendelian randomization (MR) study to evaluate the causal effects of different food intakes on urolithiasis. Methods Independent genetic variants associated with different food intakes at a genome-wide significant level were selected from summary-level statistics of genome-wide association studies from the UK Biobank. The association of these instrumental variables with urolithiasis was studied in a cohort from FinnGen Consortium. Results Among the 15 studied food intake exposures, tea intake (odds ratio [OR] = 0.433, 95% confidence interval [CI] = 0.281–0.667, p value = 1.470 × 10–4) and fresh fruit intake (OR = 0.358, 95% CI = 0.185–0.694, p value = 0.002) were found to significantly reduce the risk of the calculus of kidney and ureter. The association remained consistent in the sensitivity analyses. After adjusting for the effects of vitamin D and vitamin C, fresh fruit intake remained the reverse causal association with the calculus of kidney and ureter. Conclusions Genetically proxied fresh fruit intake is causally associated with a reduced risk of the calculus of kidney and ureter.

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Section: Discussionsupporting

confidence: 92%

Mendelian randomization analysis reveals fresh fruit intake as a protective factor for urolithiasis

Lin,

Zhou,

et al. 2023

Hum Genomics

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“…4,5 Our results, that are based on optimized outcome data, differ from recent studies in finding limited evidence that genetic liability to T2D increases risk of kidney stones and no evidence to support causal effects of dyslipidemias associated with metabolic syndrome on risk of kidney stone formation. 14,15 Considering the results of our multivariable MR analyses, we propose that the effects of T2D on increasing risk of kidney stone disease are confounded by coexisting adiposity. This study indicates that hypertension does not have a causal effect on risk of nephrolithiasis.…”

Section: Discussionmentioning

confidence: 98%

“…12,13 Furthermore, multivariable and mediation MR facilitate the identification of independent causal effects and estimation of the relative importance of multiple exposures. 12,13 Recent studies have used MR techniques to increase understanding of the pathogenesis of kidney stone disease and its relation to adiposity and metabolic syndrome 14,15 ; however, the relative contributions of central and general adiposity have not been assessed using multivariable techniques, nor have mediators of effects of adiposity on risk of kidney stone disease been identified. In this study, we use both conventional and genetic epidemiological approaches to demonstrate that increased central adiposity is causally associated with kidney stone disease, independent of general adiposity, and that the influence of central adiposity on kidney stone risk is due, in part, to increasing serum calcium concentrations.…”

Section: Introductionmentioning

confidence: 99%

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Central Adiposity Increases Risk of Kidney Stone Disease through Effects on Serum Calcium Concentrations

Lovegrove,

Bešević,

Wiberg

et al. 2023

JASN

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Background: Kidney stone disease affects approximately 10% of individuals in their lifetime and is frequently recurrent. The disease is linked to obesity, but the mechanisms mediating this association are uncertain. Methods: Associations of adiposity and incident kidney stone disease were assessed in the UK Biobank over a mean of 11.6 years/person. Genome-wide association studies and Mendelian randomization (MR) analyses were undertaken in the UK Biobank, FinnGen, and in meta-analysed cohorts to identify factors that affect kidney stone disease risk. Results: Observational analyses on UK Biobank data demonstrated that increasing central and general adiposity are independently associated with incident kidney stone formation. Multivariable MR, using meta-analysed UK Biobank and FinnGen data, established that risk of kidney stone disease increases by ∼22% per one standard deviation increase in body mass index (BMI, a marker of general adiposity) independent of waist-to-hip ratio (WHR, a marker of central adiposity) and per one standard deviation increase of WHR independent of BMI. Genetic analyses indicate that higher WHR, but not higher BMI, increases risk of kidney stone disease by elevating adjusted serum calcium concentrations (β=0.12mmol/L); WHR mediates 14-19% of its effect on kidney stone risk in this way. Conclusions: Our study indicates that visceral adipose depots elevate serum calcium concentrations, resulting in increased risk of kidney stone disease. These findings highlight the importance of weight loss in individuals with recurrent kidney stones and suggest that therapies targeting adipose depots may affect calcium homeostasis and contribute to prevention of kidney stone disease.

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“…KSD is a multifactorial systemic disease with diverse triggers. Based on epidemiological studies, metabolic syndrome, hypertension, inflammatory bowel disease, microbiome dysbiosis, parathyroid hormone disorder, and vitamin D deficiency can induce KSD, and they are related to a disrupted circadian clock ( 50 – 52 ) ( Figure 2 ).…”

Section: Epidemiological Evidence Of Circadian Rhythm Disruption In Ksdmentioning

confidence: 99%

Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review

He,

Wang,

et al. 2023

Front. Endocrinol.

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The circadian rhythm generated by circadian clock genes functions as an internal timing system. Since the circadian rhythm controls abundant physiological processes, the circadian rhythm evolved in organisms is salient for adaptation to environmental change. A disturbed circadian rhythm is a trigger for numerous pathological events. Recently, accumulated data have indicated that kidney stone disease (KSD) is related to circadian rhythm disturbance. However, the mechanism between them has not been fully elucidated. In this narrative review, we summarized existing evidence to illustrate the possible association between circadian rhythm disturbance and KSD based on the epidemiological studies and risk factors that are linked to circadian rhythm disturbance and discuss some chronotherapies for KSD. In summary, KSD is associated with systemic disorders. Metabolic syndrome, inflammatory bowel disease, and microbiome dysbiosis are the major risk factors supported by sufficient data to cause KSD in patients with circadian rhythm disturbance, while others including hypertension, vitamin D deficiency, parathyroid gland dysfunction, and renal tubular damage/dysfunction need further investigation. Then, some chronotherapies for KSD were confirmed to be effective, but the molecular mechanism is still unclear.

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

Cited by 13 publications

References 53 publications

Mendelian randomization analysis reveals fresh fruit intake as a protective factor for urolithiasis

Mendelian randomization analysis reveals fresh fruit intake as a protective factor for urolithiasis

Central Adiposity Increases Risk of Kidney Stone Disease through Effects on Serum Calcium Concentrations

Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review

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