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Dietary vinegar prevents kidney stone recurrence via epigenetic regulations.
EBioMedicine 2019; 45:231-250E

Abstract

BACKGROUND

Epidemiological evidence of over 9000 people suggests that daily intake of vinegar whose principal bioactive component is acetic acid is associated with a reduced risk of nephrolithiasis. The underlying mechanism, however, remains largely unknown.

METHODS

We examined the in vitro and in vivo anti-nephrolithiasis effects of vinegar and acetate. A randomized study was performed to confirm the effects of vinegar in humans.

FINDINGS

We found individuals with daily consumption of vinegar compared to those without have a higher citrate and a lower calcium excretion in urine, two critical molecules for calcium oxalate (CaOx) kidney stone in humans. We observed that oral administration of vinegar or 5% acetate increased citrate and reduced calcium in urinary excretion, and finally suppressed renal CaOx crystal formation in a rat model. Mechanism dissection suggested that acetate enhanced acetylation of Histone H3 in renal tubular cells and promoted expression of microRNAs-130a-3p, -148b-3p and -374b-5p by increasing H3K9, H3K27 acetylation at their promoter regions. These miRNAs can suppress the expression of Nadc1 and Cldn14, thus enhancing urinary citrate excretion and reducing urinary calcium excretion. Significantly these mechanistic findings were confirmed in human kidney tissues, suggesting similar mechanistic relationships exist in humans. Results from a pilot clinical study indicated that daily intake of vinegar reduced stone recurrence, increased citrate and reduced calcium in urinary excretion in CaOx stone formers without adverse side effects.

INTERPRETATION

Vinegar prevents renal CaOx crystal formation through influencing urinary citrate and calcium excretion via epigenetic regulations. Vinegar consumption is a promising strategy to prevent CaOx nephrolithiasis occurrence and recurrence. FUND: National Natural Science Foundations of China and National Natural Science Foundation of Guangdong Province.

Authors+Show Affiliations

Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology, People's Hospital of Changzhi, Shanxi 046000, China.Department of Urology, People's Hospital of Changzhi, Shanxi 046000, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China; Department of Radiation Oncology, University of Rochester Medical Center, Rochester 14646, NY, USA. Electronic address: Yin_Sun@URMC.Rochester.edu.Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, Guangdong, China. Electronic address: gzgyzgh@vip.sina.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31202812

Citation

Zhu, Wei, et al. "Dietary Vinegar Prevents Kidney Stone Recurrence Via Epigenetic Regulations." EBioMedicine, vol. 45, 2019, pp. 231-250.
Zhu W, Liu Y, Lan Y, et al. Dietary vinegar prevents kidney stone recurrence via epigenetic regulations. EBioMedicine. 2019;45:231-250.
Zhu, W., Liu, Y., Lan, Y., Li, X., Luo, L., Duan, X., ... Zeng, G. (2019). Dietary vinegar prevents kidney stone recurrence via epigenetic regulations. EBioMedicine, 45, pp. 231-250. doi:10.1016/j.ebiom.2019.06.004.
Zhu W, et al. Dietary Vinegar Prevents Kidney Stone Recurrence Via Epigenetic Regulations. EBioMedicine. 2019;45:231-250. PubMed PMID: 31202812.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary vinegar prevents kidney stone recurrence via epigenetic regulations. AU - Zhu,Wei, AU - Liu,Yang, AU - Lan,Yu, AU - Li,Xiaohang, AU - Luo,Lianmin, AU - Duan,Xiaolu, AU - Lei,Ming, AU - Liu,Guanzhao, AU - Yang,Zhou, AU - Mai,Xin, AU - Sun,Yan, AU - Wang,Li, AU - Lu,Suilin, AU - Ou,Lili, AU - Wu,Wenqi, AU - Mai,Zanlin, AU - Zhong,Dongliang, AU - Cai,Chao, AU - Zhao,Zhijian, AU - Zhong,Wen, AU - Liu,Yongda, AU - Sun,Yin, AU - Zeng,Guohua, Y1 - 2019/06/13/ PY - 2019/04/24/received PY - 2019/05/19/revised PY - 2019/06/03/accepted PY - 2019/6/17/pubmed PY - 2019/6/17/medline PY - 2019/6/17/entrez KW - Acetate KW - Calcium KW - Citrate KW - Epigenetic regulation KW - Nephrolithiasis KW - Vinegar KW - microRNA SP - 231 EP - 250 JF - EBioMedicine JO - EBioMedicine VL - 45 N2 - BACKGROUND: Epidemiological evidence of over 9000 people suggests that daily intake of vinegar whose principal bioactive component is acetic acid is associated with a reduced risk of nephrolithiasis. The underlying mechanism, however, remains largely unknown. METHODS: We examined the in vitro and in vivo anti-nephrolithiasis effects of vinegar and acetate. A randomized study was performed to confirm the effects of vinegar in humans. FINDINGS: We found individuals with daily consumption of vinegar compared to those without have a higher citrate and a lower calcium excretion in urine, two critical molecules for calcium oxalate (CaOx) kidney stone in humans. We observed that oral administration of vinegar or 5% acetate increased citrate and reduced calcium in urinary excretion, and finally suppressed renal CaOx crystal formation in a rat model. Mechanism dissection suggested that acetate enhanced acetylation of Histone H3 in renal tubular cells and promoted expression of microRNAs-130a-3p, -148b-3p and -374b-5p by increasing H3K9, H3K27 acetylation at their promoter regions. These miRNAs can suppress the expression of Nadc1 and Cldn14, thus enhancing urinary citrate excretion and reducing urinary calcium excretion. Significantly these mechanistic findings were confirmed in human kidney tissues, suggesting similar mechanistic relationships exist in humans. Results from a pilot clinical study indicated that daily intake of vinegar reduced stone recurrence, increased citrate and reduced calcium in urinary excretion in CaOx stone formers without adverse side effects. INTERPRETATION: Vinegar prevents renal CaOx crystal formation through influencing urinary citrate and calcium excretion via epigenetic regulations. Vinegar consumption is a promising strategy to prevent CaOx nephrolithiasis occurrence and recurrence. FUND: National Natural Science Foundations of China and National Natural Science Foundation of Guangdong Province. SN - 2352-3964 UR - https://www.unboundmedicine.com/medline/citation/31202812/Dietary_vinegar_prevents_kidney_stone_recurrence_via_epigenetic_regulations L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-3964(19)30379-2 DB - PRIME DP - Unbound Medicine ER -