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Re-Examining the Association Between Vascular Calcification and Urinary Stone Disease: Results from a Large, Multiethnic, Case-Control Study - Beyond the Abstract

Urinary stone disease refers to the deposition of crystals, most commonly calcium oxalate and calcium phosphate, within the kidneys and urinary system. While urinary stone disease is not classically thought of as a metabolic disorder, a positive association between urinary stone disease and adverse cardiovascular events (e.g., myocardial infarction) has been reported, with vascular calcifications suggested as the pathological link between the two disorders.1


Vascular calcification is the pathological deposition of minerals within the vascular system; it has been directly associated with diabetes mellitus, chronic kidney disease, and hyperlipidemia.2,3  A marker of the degree of vascular calcifications is the presence and amount of abdominal aortic calcification (AAC), which is assessed using non-contrast computed tomography (NCCT) of the abdomen.4  Given that both vascular calcifications and urinary stone disease represent extra-osseous sites of calcification, it has been hypothesized that worsened cardiovascular disease health in urinary stone disease patients is due to increased vascular calcification burden in these patients.5,6

Several studies have reported a positive association between vascular calcifications and urinary stone disease via the severity score of AAC on abdominal NCCT, but the relationship has not been consistently demonstrated. Some studies have reported a higher AAC severity score among urinary stone disease patients,6-8  while others have not reported an association,9 or that associations were limited to subgroups of patients.10  Most of the studies published to date on this topic have been relatively small in the number of patients included, and have not reported whether the associations varied by race/ethnicity.

In this study, we examined the relationship between AAC severity score and urinary stone disease in a large case-control study conducted in a single tertiary care hospital serving a multiethnic population in the Bronx, New York.11  A total of 672 patients with urinary stone disease confirmed using abdominal NCCT were matched to 672 controls (i.e. patients who had abdominal NCCT for unrelated gastrointestinal pathologies and who did not have urinary stone disease) on age, gender, and race/ethnicity. Abdominal NCCT images were reviewed to assess the degree of AAC severity among cases and controls.4 Associations between the presence and severity of AAC and risk of urinary stone disease were examined via logistic regression models. Overall, there were no association between AAC prevalence (OR = 0.98, 95% CI 0.78-1.23, p=0.86) or AAC severity score quartile (OR 0.96, 0.87, 1.07, 1.03 for increasing AAC quartile, p-for-trend=0.54) between urinary stone disease cases and controls. There were also no associations when analyses were stratified by sex, by race/ethnicity, or by stone type.

The strengths of our study include the large multiethnic representation of both cases and controls. Additionally, we carefully matched cases and controls by age, sex, and race/ethnicity in order to limit confounding and that could potentially affect the underlying relationship between urinary stone disease and AAC. Some limitations include its observational, cross-sectional design, and the use of the AAC severity score, which may have a lower sensitivity for vascular calcification compared to higher resolution protocols such as automated Agatston scoring of coronary artery calcifications and other arteries.7,12

Our findings from this large, multiethnic study population indicate that there is no association between urinary stone disease and vascular calcification. Rather, it suggests that urinary stone disease and vascular calcification are driven by different pathophysiological processes, such as the microenvironments of the vascular endothelium13,14  and the renal papilla.15,16  Larger, prospective cohort studies are warranted to examine further this relationship and determine whether an association between urinary stone disease and vascular calcification exists. Furthermore, we call for more basic science research into the underlying mechanisms of urinary stone disease and vascular calcification to better elucidate their respective mechanisms.

Written by: Denzel Zhu, BS & Ilir Agalliu, MD, ScD, Albert Einstein College of Medicine, Bronx, NY

References:

  1. Alexander RT, Hemmelgarn BR, Wiebe N, et al. Kidney stones and cardiovascular events: a cohort study. Clin J Am Soc Nephrol. 2014;9(3):506-512.
  2. Schulz E, Arfai K, Liu X, Sayre J, Gilsanz V. Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab. 2004;89(9):4246-4253.
  3. Wilson PW, Kauppila LI, O'Donnell CJ, et al. Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality. Circulation. 2001;103(11):1529-1534.
  4. Leckstroem DC, Bhuvanakrishna T, McGrath A, Goldsmith DJ. Prevalence and predictors of abdominal aortic calcification in healthy living kidney donors. Int Urol Nephrol. 2014;46(1):63-70.
  5. Reiner AP, Kahn A, Eisner BH, et al. Kidney stones and subclinical atherosclerosis in young adults: the CARDIA study. J Urol. 2011;185(3):920-925.
  6. Shavit L, Girfoglio D, Vijay V, et al. Vascular calcification and bone mineral density in recurrent kidney stone formers. Clin J Am Soc Nephrol. 2015;10(2):278-285.
  7. Hsi RS, Spieker AJ, Stoller ML, et al. Coronary Artery Calcium Score and Association with Recurrent Nephrolithiasis: The Multi-Ethnic Study of Atherosclerosis. J Urol. 2016;195(4 Pt 1):971-976.
  8. Ferraro PM, Marano R, Primiano A, et al. Stone composition and vascular calcifications in patients with nephrolithiasis. J Nephrol. 2019;32(4):589-594.
  9. Tanaka T, Hatakeyama S, Yamamoto H, et al. Clinical relevance of aortic calcification in urolithiasis patients. BMC Urol. 2017;17(1):25.
  10. Yasui T, Itoh Y, Bing G, Okada A, Tozawa K, Kohri K. Aortic calcification in urolithiasis patients. Scand J Urol Nephrol. 2007;41(5):419-421.
  11. Schoenfeld D, Zhu D, Mohn L, Di Vito J, Agalliu I, Stern JM. The relationship between vascular calcifications and urolithiasis in a large, multiethnic patient population. Urolithiasis. 2021. doi: 1007/s00240-021-01268-0.
  12. Stern KL, Ward RD, Li J, Remer EM, Stoller ML, Monga M. Nonrenal Systemic Arterial Calcification Predicts the Formation of Kidney Stones. J Endourol. 2019;33(12):1032-1034.
  13. Yiu AJ, Callaghan D, Sultana R, Bandyopadhyay BC. Vascular Calcification and Stone Disease: A New Look towards the Mechanism. J Cardiovasc Dev Dis. 2015;2(3):141-164.
  14. Demer LL, Tintut Y. Vascular calcification: pathobiology of a multifaceted disease. Circulation. 2008;117(22):2938-2948.
  15. Evan AP, Worcester EM, Coe FL, Williams J, Jr., Lingeman JE. Mechanisms of human kidney stone formation. Urolithiasis. 2015;43 Suppl 1(0 1):19-32.
  16. Taylor ER, Stoller ML. Vascular theory of the formation of Randall plaques. Urolithiasis. 2015;43 Suppl 1:41-45.

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