Skip to main content
SpringerLink
Log in

Increased renal uptake and urine excretion of oxidized LDL is possibly associated with formation of large calcium oxalate nephrolithiasis: a preliminary study

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

Growing evidence have suggested an association between nephrolithiasis and cardiovascular disease (CVD) with unclear mechanism. Oxidized low-density lipoproteins (oxLDL) induces atherosclerosis and was found to be the possible link between these two diseases. Our study aimed to examine the serum, urine and kidney expression of oxLDL in relation to large calcium oxalate (CaOx) renal stone disease.

Methods

A total of 67 large CaOx dominant renal stone patients and 31 stone-free controls were enrolled in the prospective case–control study. All participants were without known CVD history. Serum, urine, and kidney biopsy were collected before and during percutaneous nephrolithotomy, respectively. Enzyme-linked immunosorbent assays were used to assess serum and urine oxLDL, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and high-sensitivity C-reactive protein (hsCRP).

Results

There was no significantly difference in circulating oxLDL, but serum hsCRP was significantly near two-fold higher in nephrolithiasis patients. Serum hsCRP was also correlated with stone maximal length. Urine oxLDL was significantly higher in the nephrolithiasis group and correlated with serum hsCRP and stone maximal length. Increased oxLDL uptake in kidney was found in nephrolithiasis patients, whereas no significantly renal expression of oxLDL was observed in controls.

Conclusions

The renal uptake of oxLDL with increased oxLDL excretion from large CaOx renal stone formers, independent of increased circulating oxLDL, is a novel pathological finding in kidney stone disease and brings attention to the possible involvement of renal steatosis in the process of urolithiasis formation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Chewcharat A, Curhan G (2021) Trends in the prevalence of kidney stones in the United States from 2007 to 2016. Urolithiasis 49:27–39

    Article  CAS  PubMed  Google Scholar 

  2. Alexander RT, Hemmelgarn BR, Wiebe N et al (2014) Kidney stones and cardiovascular events: a cohort study. Clin J Am Soc Nephrol 9:506–512

    Article  PubMed  Google Scholar 

  3. Lara-Guzman OJ, Gil-Izquierdo A, Medina S et al (2018) Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages. Redox Biol 15:1–11

    Article  CAS  PubMed  Google Scholar 

  4. Ghattas A, Griffiths HR, Devitt A et al (2013) Monocytes in coronary artery disease and atherosclerosis: where are we now? J Am Coll Cardiol 62:1541–1551

    Article  CAS  PubMed  Google Scholar 

  5. Trpkovic A, Resanovic I, Stanimirovic J et al (2015) Oxidized low-density lipoprotein as a biomarker of cardiovascular diseases. Crit Rev Clin Lab Sci 52:70–85

    Article  CAS  PubMed  Google Scholar 

  6. de Freitas ACP, Torres LC, Duarte M et al (2019) Is oxidized low-density lipoprotein the connection between atherosclerosis, cardiovascular risk and nephrolithiasis? Urolithiasis 47:347–356

    Article  PubMed  Google Scholar 

  7. Gai Z, Wang T, Visentin M et al (2019) Lipid accumulation and chronic kidney disease. Nutrients 11:2

    Article  Google Scholar 

  8. Abdelhafez MF, Bedke J, Amend B et al (2012) Minimally invasive percutaneous nephrolitholapaxy (PCNL) as an effective and safe procedure for large renal stones. BJU Int 110:E1022-1026

    Article  PubMed  Google Scholar 

  9. Wang X, Krambeck AE, Williams JC Jr et al (2014) Distinguishing characteristics of idiopathic calcium oxalate kidney stone formers with low amounts of Randall’s plaque. Clin J Am Soc Nephrol 9:1757–1763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ticinesi A, Milani C, Guerra A et al (2018) Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers. Gut 67:2097–2106

    Article  CAS  PubMed  Google Scholar 

  11. Taguchi K, Hamamoto S, Okada A et al (2017) Genome-wide gene expression profiling of Randall’s plaques in calcium oxalate stone formers. J Am Soc Nephrol 28:333–347

    Article  CAS  PubMed  Google Scholar 

  12. Chaiyarit S, Thongboonkerd V (2020) Mitochondrial dysfunction and kidney stone disease. Front Physiol 11:566506

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hsi RS, Spieker AJ, Stoller ML et al (2016) Coronary artery calcium score and association with recurrent nephrolithiasis: the multi-ethnic study of atherosclerosis. J Urol 195:971–976

    Article  CAS  PubMed  Google Scholar 

  14. Devarajan A (2018) Cross-talk between renal lithogenesis and atherosclerosis: an unveiled link between kidney stone formation and cardiovascular diseases. Clin Sci (Lond) 132:615–626

    Article  CAS  PubMed  Google Scholar 

  15. Ma MC, Chen YS, Huang HS (2014) Erythrocyte oxidative stress in patients with calcium oxalate stones correlates with stone size and renal tubular damage. Urology 83(510):e519–e517

    Google Scholar 

  16. Heidari F, Rabizadeh S, Mansournia MA et al (2019) Inflammatory, oxidative stress and anti-oxidative markers in patients with endometrial carcinoma and diabetes. Cytokine 120:186–190

    Article  CAS  PubMed  Google Scholar 

  17. Diri A, Diri B (2018) Management of staghorn renal stones. Ren Fail 40:357–362

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bobulescu IA, Dubree M, Zhang J et al (2008) Effect of renal lipid accumulation on proximal tubule Na+/H+ exchange and ammonium secretion. Am J Physiol Renal Physiol 294:F1315-1322

    Article  CAS  PubMed  Google Scholar 

  19. Yokoo T, Clark HR, Pedrosa I et al (2016) Quantification of renal steatosis in type II diabetes mellitus using dixon-based MRI. J Magn Reson Imaging 44:1312–1319

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yang W, Luo Y, Yang S et al (2018) Ectopic lipid accumulation: potential role in tubular injury and inflammation in diabetic kidney disease. Clin Sci (Lond) 132:2407–2422

    Article  CAS  PubMed  Google Scholar 

  21. Okamura DM, Pennathur S, Pasichnyk K et al (2009) CD36 regulates oxidative stress and inflammation in hypercholesterolemic CKD. J Am Soc Nephrol 20:495–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jung JH, Choi JE, Song JH et al (2018) Human CD36 overexpression in renal tubules accelerates the progression of renal diseases in a mouse model of folic acid-induced acute kidney injury. Kidney Res Clin Pract 37:30–40

    Article  PubMed  PubMed Central  Google Scholar 

  23. Souza AC, Bocharov AV, Baranova IN et al (2016) Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation. Kidney Int 89:809–822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Torricelli FC, De SK, Gebreselassie S et al (2014) Dyslipidemia and kidney stone risk. J Urol 191:667–672

    Article  CAS  PubMed  Google Scholar 

  25. Kohjimoto Y, Sasaki Y, Iguchi M et al (2013) Association of metabolic syndrome traits and severity of kidney stones: results from a nationwide survey on urolithiasis in Japan. Am J Kidney Dis 61:923–929

    Article  PubMed  Google Scholar 

  26. Gambaro G, Croppi E, Bushinsky D et al (2017) The risk of chronic kidney disease associated with urolithiasis and its urological treatments: a review. J Urol 198:268–273

    Article  PubMed  Google Scholar 

  27. Shang W, Li L, Ren Y et al (2017) History of kidney stones and risk of chronic kidney disease: a meta-analysis. PeerJ 5:e2907

    Article  PubMed  PubMed Central  Google Scholar 

  28. D’Costa MR, Haley WE, Mara KC et al (2019) Symptomatic and radiographic manifestations of kidney stone recurrence and their prediction by risk factors: a prospective cohort study. J Am Soc Nephrol 30:1251–1260

    Article  PubMed  PubMed Central  Google Scholar 

  29. Okamura DM, Lopez-Guisa JM, Koelsch K et al (2007) Atherogenic scavenger receptor modulation in the tubulointerstitium in response to chronic renal injury. Am J Physiol Renal Physiol 293:F575-585

    Article  CAS  PubMed  Google Scholar 

  30. Bosmans JL, Holvoet P, Dauwe SE et al (2001) Oxidative modification of low-density lipoproteins and the outcome of renal allografts at 1 1/2 years. Kidney Int 59:2346–2356

    Article  CAS  PubMed  Google Scholar 

  31. Yang X, Okamura DM, Lu X et al (2017) CD36 in chronic kidney disease: novel insights and therapeutic opportunities. Nat Rev Nephrol 13:769–781

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research received the grant from National Cheng Kung University Hospital (Grant Nos: NCKUH-10804026 and NCKUH-10904017). None of the authors reported a conflict of interest related to the study.

Author information

Authors and Affiliations

  1. Department of Urology, National Cheng Kung University Hospital, Tainan, Taiwan

    Chan-Jung Liu & Ho-Shiang Huang

  2. Department of Urology, College of Medicine, National Cheng Kung University, Tainan, 704302, Taiwan

    Chan-Jung Liu, Kuan-Ta Ho & Ho-Shiang Huang

  3. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 704302, Taiwan

    Kuan-Ta Ho

  4. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 704302, Taiwan

    Kuan-Ta Ho & Yau-Sheng Tsai

  5. Clinical Medicine Research Center, National Cheng Kung University Hospital, Tainan, 704302, Taiwan

    Yau-Sheng Tsai

Authors
  1. Chan-Jung Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kuan-Ta Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yau-Sheng Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ho-Shiang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yau-Sheng Tsai or Ho-Shiang Huang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human/animal participants

The Ethical Committee for Human Research at the National Cheng Kung University Hospital approved the study protocol used in this work (A-ER-107-291 and A-ER-108-425).

Informed consent

The participants’ informed consent was collected in all participants.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, CJ., Ho, KT., Tsai, YS. et al. Increased renal uptake and urine excretion of oxidized LDL is possibly associated with formation of large calcium oxalate nephrolithiasis: a preliminary study. World J Urol 41, 1423–1430 (2023). https://doi.org/10.1007/s00345-023-04360-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-023-04360-9

Keywords

Search

Navigation