The genetics of kidney stone disease and nephrocalcinosis

Singh, Prince; Harris, Peter C.; Sas, David J.; Lieske, John C.

doi:10.1038/s41581-021-00513-4

Cited by 104 publications

(60 citation statements)

References 210 publications

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“…Urolithiasis is a common disease in urology, affecting approximately 10% of people worldwide, and increasing yearly ( Singh et al, 2021 ). The 5-year recurrence rate of urolithiasis is up to 67% ( D’Costa et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

CAV1 alleviated CaOx stones formation via suppressing autophagy-dependent ferroptosis

Yang

Hong

et al. 2022

PeerJ

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Background Calcium oxalate (CaOx) is the most common type of kidney stone, but the mechanism of CaOx stones formation remains unclear. The injury of renal cells such as ferroptosis and autophagy has been considered a basis for stones formation. Methods We conducted transmission electron microscope (TEM), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and C11-BODIPY analysis to explore whether CaOx could induce autophagy-dependent ferroptosis in vivo and in vitro . To explore the possible mechanism, we conducted bioinformatic analysis of patients with or without CaOx stones, Western blot and qPCR were used to identify the different genes we found in bioinformatic analysis. Results In our study, we found that CaOx could induce autophagy-dependent ferroptosis no matter in vivo or in vitro , which might finally lead to urolithiasis. Bioinformatic analysis of the dataset indicated that the expression of caveolin-1 (CAV1) was higher in control patients than CaOx stone patients, the STRING database indicated that CAV1 might interact with low density lipoprotein receptro-related protein 6 (LRP6), Gene Set Enrichment Analysis (GSEA) showed that the WNT pathway positively associated with the control group while negatively related to the stone group, and LRP6 was the core gene of the WNT pathway. Western blot found that CAV1, LRP6, and Wnt/β-Catenin were decreased in Human Kidney2 (HK2) cells stimulated with CaOx. Furthermore, the WNT pathway was considered to be involved in autophagy and ferroptosis. Conclusions We presumed that CAV1 could ameliorate autophagy-dependent ferroptosis through the LRP6/Wnt/β-Catenin axis, and finally alleviate CaOx stone formation.

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Section: Introductionmentioning

confidence: 99%

CAV1 alleviated CaOx stones formation via suppressing autophagy-dependent ferroptosis

Yang

Hong

et al. 2022

PeerJ

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“…Kidney stones are stones in the junction of renal calyces, renal pelvis or pelvic ureter and are one of the most common urological diseases, accounting for 40-50% of all urinary stone diseases (1,2). Hematuria and back pain are the main clinical manifestations, which can cause urological infection, urinary tract obstruction and even uremia (3,4).…”

Section: Introductionmentioning

confidence: 99%

Physical Activity Reduces the Effect of High Body Mass Index on Kidney Stones in Diabetes Participants From the 2007–2018 NHANES Cycles: A Cross-Sectional Study

Mao

Zhang

Sun

et al. 2022

Front. Public Health

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BackgroundBody mass index (BMI) is a vital risk factor for kidney stones, but physical activity may reduce the incidence of kidney stones. However, it remains unknown whether physical activity reduces the effect of high BMI on kidney stones in diabetes participants.MethodsWe included clinical information from 4,008 adult participants with diabetes from the National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2018. Univariate and multivariate logistic regression analyses were used to analyze the relationship between BMI and kidney stones, as well as the risk of BMI and kidney stones in different physical activity subgroups.ResultsA total of 4,008 diabetic participants were included in this study, of whom 652 (16.3%) self-reported a history of kidney stones. Logistic regression analysis showed a positive association between BMI and kidney stones. After adjusting for other confounders, the adjusted ORs for the risk of kidney stones was 1.514 (95% CI, 1.134–2.022, p = 0.005) for participants with BMI ≥30 kg/m2 among all participants; the risk of kidney stones was elevated (OR = 1.572, 95% CI, 1.134–2.022, p = 0.005) in group without physical activity, and a reduced risk (OR = 1.421, 95% CI, 0.847–2.382, p = 0.183) in the group with physical activity. Furthermore, similar results were found in most subgroups.ConclusionOur study suggests that high BMI is a risk factor for diabetes kidney stone participants and that physical activity may moderate this relationship to some extent.

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“…They appear almost once in every 1,000 nucleotides, meaning roughly 4 to 5 million SNPs in a person’s genome. In particular, genetic variants in the population may contribute significant risk for manifesting such multifactorial disorders, including kidney stone formation and recurrence ( Howles and Thakker, 2020 ; Singh et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms and Kidney Stones Around the Globe: A Systematic Review and Meta-Analysis

et al. 2022

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Objective: This study explores associations between recurrent kidney stones and genetic polymorphisms.Methods: Meta-analysis of polymorphisms in renal stone cases versus control groups. Four electronic databases (PubMed, SCOPUS, EMBASE, and Web of Science) were searched up to 30 May 2021, using the keywords: “kidney stone” or “kidney calculi,” or “urolithiasis” or “nephrolithiasis” or “urinary calculi” and “genome” or “genetic” or “mutation” or “single nucleotide polymorphism.” Forrest plots, ORs, 95% CI, Chi-square (χ2)-test, and index of heterogeneity (I2) were calculated. Only studies with Newcastle–Ottawa scale (NOS) ≥ 6 were included for quality control, and Funnel, Begg’s, and Eager’s plots assessed publication bias. PROSPERO: CRD42022250427.Results: Among 7,671 searched articles, 72 were included. Polymorphisms in VDR (OR: 1.20; 95% CI: 1.06–1.36), CASR (OR = 1.24; 95% CI: 1.01–1.52), Osteopontin (OR = 1.38; 95% CI: 1.09–1.74), and Urokinase genes (OR = 1.52; 95% CI: 1.02–2.28) showed a significant association with risk of urinary stone formation, while Klotho gene showed a protective effect (OR = 0.75; 95% CI: 0.57–0.99). The VDR gene polymorphism was frequent in Asians, whereas CASR polymorphism was frequent in European and North American populations.Conclusion: Multifactorial nature of the stone formation, emphasizing the role of environmental factors, might explain contradictory results in the literature. While polymorphisms in VDR, CASR, Osteopontin, and Urokinase genes were associated with urinary stone formation, the Klotho gene showed a protective effect.

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The genetics of kidney stone disease and nephrocalcinosis

Cited by 104 publications

References 210 publications

CAV1 alleviated CaOx stones formation via suppressing autophagy-dependent ferroptosis

CAV1 alleviated CaOx stones formation via suppressing autophagy-dependent ferroptosis

Physical Activity Reduces the Effect of High Body Mass Index on Kidney Stones in Diabetes Participants From the 2007–2018 NHANES Cycles: A Cross-Sectional Study

Genetic Polymorphisms and Kidney Stones Around the Globe: A Systematic Review and Meta-Analysis

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