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Evaluation of any relationship between serum calcium and uric acid levels with Computed Tomography (CT scan) Stone Densit

KHAFFAJI, ALI TALIB JASSIM AL; ALBUMOHAMMED, ALI HASAN

Abstract

Both of Calcium & uric acid are important in stone formation, There are multiple risk factors for stone formation such as: low fluid intake,hypercalciuria,primary hyperparathyroidism, high salt diet, high animal protein intake. Computed tomography CT is currently used most commonly to predict the type and opacity of stone (stone density) measured in HU. (Hounsfield unit) A total of 100 adult patients with renal stone, discovered by abdominal ultrasound examination, were chosen, there was no significant difference in the mean stone density in terms of patients’ age, gender, and BMI, the patients with high uric acid levels had significantly higher mean stone density when compared to the patients with low or normal levels of uric acid, Patients with high serum calcium levels may have high CT stone density.

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 Corresponding author: ALI TALIB JASSIM AL-KHAFFAJI Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Evaluation of any relationship between serum calcium and uric acid levels with Computed Tomography (CT scan) Stone Density ALI TALIB JASSIM AL-KHAFFAJI 1, * and ALI HASAN ALBUMOHAMMED 2 1 Senior Radiologist, Head of Department of Radiology, AL Shaheed AL Sader hospital, Resafa Healthcare Directorate, Baghdad, Iraq. 2 Senior Radiologist, Department of Radiology, AL Shaheed AL Sader hospital, Resafa Healthcare Directorate, Baghdad, Iraq. World Journal of Advanced Research and Reviews, 2025, 26(03), 2656-2661 Publication history: Received on 13 May 2025; revised on 18 June 2025; accepted on 21 June 2025 Article DOI: https://doi.org/10.30574/wjarr.2025.26.3.2407 Abstract Both of Calcium & uric acid are important in stone formation, There are multiple risk factors for stone formation such as: low fluid intake,hypercalciuria,primary hyperparathyroidism, high salt diet, high animal protein intake. Computed tomography CT is currently used most commonly to predict the type and opacity of stone (stone density) measured in HU. (Hounsfield unit) A total of 100 adult patients with renal stone, discovered by abdominal ultrasound examination, were chosen, there was no significant difference in the mean stone density in terms of patients’ age, gender, and BMI, the patients with high uric acid levels had significantly higher mean stone density when compared to the patients with low or normal levels of uric acid, Patients with high serum calcium levels may have high CT stone density. Keywords: Computed tomography CT; Hounsfield unit HU; Urinary stones 1. Introduction Kidney stone disease typically presents between the ages of 20 and 60 and is more prevalent in hot climates1, It affects about 10% of people over their lifetime, incidence increasing with age; 50% will have a recurrence within 5–10 years and 75% within 20 years.2, Developed countries have seen rapid increases over the last 30 years, especially in women in whom incidence is now almost equal to that of men 3, Computed tomography CT is currently used most commonly to predict the type of stone and assess the potential efficacy of extracorporeal shock wave lithotripsy treatment. However, it might also assist urologists to decide which of percutaneous nephrolithotomy, ureterorenoscopic ureterolithotripsy, and medical expulsive treatment should be used to treat a patient.4 Objective Both of Calciumanduric acid is important in stone formation, our study to detect any relationship between serum calcium and uric acid levels with CT scan stone density. 2. Material and methods A study was done in period from 1st of march 2023 to the end of December 2023, A hundred adult from both sexes between (18-76) year with renal stone (discovered by abdominal ultrasound examination) were chosen, informed World Journal of Advanced Research and Reviews, 2025, 26(03), 2656-2661 2657 consent was obtained from all participants, all send to lab. for serum calcium and uric acid levels and also GUE, Also all done abdominal CT scan with UH. stone density measurement. 3. Results A total of 100 adult patients with renal stones were recruited in this study. The age range was 18 to 76, with a mean of 45.97 ± 14.63 years. The highest proportion of the studied patients aged > 55 years (31%), followed by 27% who aged < 35 years. Regarding gender, there were 60% males versus 40% females with a male-to-female ratio of 1.5:1. The calculated BMI had a mean of 27.25 ± 4. 88 kg/m2, 33% had normal weight while 43% and 24% were overweight and obese, respectively. According to the CT scan, the mean stone density was 767.3 ± 236.7 HU. There was no significant difference in the mean stone density in terms of patients’ age, gender, and BMI (P ≥ 0.05). As shown in (Table 1). Table 1 Comparison of CT stone density according to age, gender, and BMI Stone Density (HU) Mean ± SD Test Value PValue* Age Group (Years) < 35 757.1 ± 238.3 0.722 0.539 35 – 44 837.6 ± 287.3 45 – 54 803.4 ± 223.1 ≥ 55 705.4 ± 236.7 Gender Male 774.4 ± 251.1 0.255 0.799 Female 756.8 ± 218.1 BMI (kg/m2) Normal 787.7 ± 214.5 0.805 0.450 Overweight 794.1 ± 251.1 Obese 691.3 ± 242.6 * Significant difference between two means using the Students-t-test, and more than two means using ANOVA test at 0.05 level. This study found a statistically significant difference in the mean stone density according to the uric acid levels. Multiple comparisons showed that the patients with high uric acid levels had significantly higher mean stone density when compared to the patients with low or normal levels of uric acid (923.7 mg/dl vs 494.1 mg/dl and 775.1 mg/dl, P= 0.001) respectively. Although the mean stone density was higher in the patients with high calcium concentrations than those with low or normal levels, this difference was not significant. Further, no significant difference was detected in the stone density according to findings of general urine examination. As illustrated in (Table 2). Table 2 Comparison of CT stone density according to biochemical parameters Biochemical Parameters Stone Density (HU) Mean ± SD Test Value PValue* Uric Acid (mg/dl) Low 494.1 ± 227.4 3.342 0.039 Normal 775.1 ± 233.1 High 923.7 ± 252.8 Serum Calcium (mg/dl) Low 647.3 ± 283.4 0.896 0.412 World Journal of Advanced Research and Reviews, 2025, 26(03), 2656-2661 2658 Normal 781.1 ± 248.2 High 814.4 ± 270.6 General Urine Examination Urate 759.8 ± 236.5 - 0.886 0.378 Others 885.67 ± 248.5 In the Pearson correlation analysis, there was a significant, positive correlation between stone density and uric acid levels (r= 0.403, P= 0.001) while the stone density was not significantly correlated with the other variables. As shown in (Figure 1) and (Table 3). Figure 1 Correlation of stone density with uric acid levels Table 3 Correlations of stone density with clinical characteristics Variable Stone Density (HU) r P - Value* Age (Years) - 0.128 0.205 BMI (kg/m2) - 0.042 0.682 Uric Acid (mg/dl) 0.403 0.001 Serum Calcium (mg/dl) 0.079 0.432 *Correlation is significant at the 0.05 level. 3.1. Statistical analysis All analyses were performed using SPSS version 25.0 (IBM Corp.). Kolmogorov–Smirnov and Shapiro–Wilk tests were used to determine the presence of a parametric distribution and they confirmed that the data were normally distributed. Therefore, the significance of the difference between different means (quantitative data) was tested using the Studentst-test for the difference between two independent means, or the ANOVA test for the difference between more than two means. Pearson correlation was calculated for the correlation between two quantitative variables with its t-test for testing the significance of correlation. Pearson correlation was calculated for the correlation between two quantitative variables with its t-test for testing the significance of correlation. The correlation coefficient value (r) is either positive (direct correlation) or negative (inverse correlation) with values <0.3 representing no correlation, 0.3-<0.5 representing weak correlation, 0.5-<0.7 moderate strength, and>0.7 strong correlation. A level of P-value less than 0.05 was considered significant. 4. Discussion Stone growth starts with the formation of crystals in supersaturated urine which then adhere to urothelium, thus creating the nidus for subsequent stone growth, recent theories focus on the role of cell surface molecules which favour World Journal of Advanced Research and Reviews, 2025, 26(03), 2656-2661 2659 or inhibit crystal adhesion .(5,6), Urothelial injury and repair after a stone episode may increase surface expression of these molecules to favour further crystal adhesion (7,8) There is multiple risk factors for stone formation such as: Low fluid intake, Hypercalciuria(9) primary hyperparathyroidism(10),deactivating vitamin D receptor (VDR) polymorphisms (11) and activating fibroblast growth factor (FGF) 23 polymorphism(12,13), A high salt diet increases urinary calcium output(14,15), oxaluria (16,17), low calcium intake (18,19,20,21),Hypocitraturia(22),High animal protein intake(23,24),Enteric hyperoxaluria(25), Primary hyperoxaluria(26,27) Abdominal CT can assess the density of the stone in Hounsfield units (HU). The HU, or Hounsfield density have been used to predict the type and opacity of stones during diagnosis, and the efficacy has been assessed using methods including extracorporeal shock wave lithotripsy (ESWL)(28,29,30,31,32,33), percutaneous nephrolithotomy (PCNL) (34,35,36 ),ureterorenoscopic ureterolithotripsy (URSL)37, and medical expulsive treatment (MET) 38, Sir Godfrey Newbold Hounsfield first introduced the principle to quantify the amount of X-rays that pass through or are absorbed by tissues, and developed the resulting radiodensity scale. CT images are made up of pixels, each of which has a gray scale value from 1 (black) to 256 (white). This value corresponds to the amount of X-rays that pass through the structure, and can be measured and expressed in Hounsfield units (HU). HU have since been used to evaluate and quantify tissues and fluids. When the radiodensity of water is defined as 0, fat has a negative HU, and blood and other tissues have a positive HU. Using this method it is possible to differentiate 256 shades of gray that are indistinguishable to the naked eye,39. Our study show incidence of stone more in age group more than 55yr old and more on male than female, goes with similar study, Fadhil Y.S.(2022)40, also show high renal stone incidence on over weight and obese patients similar to study done by Michelle J. Semins, Andrew D. Shore, Martin A. Makary, Thomas Magnuson, Roger Johns, and Brian R. Matlaga, 2009, (41) Our study showing high CT stone density on patient with high serum uric acid goes with other study done Jong Chan Kim,(1) Kang Su Cho,(2) Do Kyung Kim,2 Doo Yong Chung,1 Hae Do Jung,3 and Joo Yong Lee(1,*42) Also high calcium goes with high CT stone density similar to study done by Abdallah Saud Alharb Assessment of Hounsfield Units and Factors Associated with Fragmentation of Renal Stones by Extracorporeal Shock Wave Lithotripsy: A Computerized Tomography Study 5. Conclusion • Patients with high serum uric acid levels showing high CT stone density • Patients with high serum calcium levels may have high CT stone density • Age, genderand BMI have no any relationship to CT stone density Compliance with ethical standards Acknowledgments Acknowledged to MR. Mohammd Hmood and MR. Husam Jabbar, CT SCAN operators at AL Shaheed AL Sader hospital. Disclosure of conflict of interest No conflict of interest to be disclosed. Statement of informed consent Informed consent was obtained from all individual participants that were included in the study. References [1] Fakheri RJ, Goldfarb DS. Ambient temperature as a contributor to kidney stone formation: implications of global warming. Kidney Int 2011; 79:1178–85. [2] Moe OW. Kidney stones: pathophysiology and medical management. Review. Lancet 2006; 367:333–44. World Journal of Advanced Research and Reviews, 2025, 26(03), 2656-2661 2660 [3] Lieske JC, Pena de la Vega LS, Slezak JM et al. Renal stone epidemiology in Rochester, Minnesota: an update. Kidney Int 2006; 69:760–4. [4] Gücük A,Üyetürk U. Usefulness of hounsfield unit and density in the assessment and treatment of urinary stones. World J Nephrol 2014; 3(4): 282-286 Available from: URL: http://www. wjgnet.com/22206124/full/v3/i4/282.htm DOI: http://dx.doi. org/10.5527/wjn.v3.i4.28 [5] Asselman M, Verhulst A, De Broe ME, Verkoelen CF. Calcium oxalate crystal adherence to hyaluronan–, osteopontin–, and CD44–expressing injured/regenerating tubular epithelial cells in rat kidneys. J Am SocNephrol 2003; 14:3155–66. [6] Randall A. Recent Advances in Knowledge Relating to the Formation, Recognition and Treatment of Kidney Calculi. Bull N Y Acad Med 1944; 20:473–84. [7] Asselman M, Verhulst A, Van Ballegooijen ES et al. Hyaluronan is apically secreted and expressed by proliferating or regenerating renal tubular cells. Kidney Int 2005; 68:71–83. [8] Parks JH, Coe FL. An increasing number of calcium oxalate stone events worsens treatment outcome. Kidney Int 1994; 45:1722–30. [9] Tomson CR. Prevention of recurrent calcium stones: a rational approach. Review. Br J Urol 1995; 76:419–24. [10] Vezzoli G, Terranegra A, Arcidiacono T et al. Calcium kidney stones are associated with a haplotype of the calcium–sensing receptor gene regulatory region. Nephrol Dial Transplant 2010; 25:2245–52. [11] Sugiyama T, Wang JC, Scott DK, Granner DK. Transcription activation by the orphan nuclear receptor, chicken ovalbumin upstream promoter–transcription factor I (COUP–TFI). Definition of the domain involved in the glucocorticoid response othephosphoenolpyruvatecarboxykinase gene. J BiolChem 2000; 275:3446–54. [12] Rendina D, Esposito T, Mossetti G et al. A functional allelic variant of the FGF23 gene is associated with renal phosphate leak in calcium nephrolithiasis. ClinEndocrinol Metab 2012;97:E840–4. [13] Morrison NA, Qi JC, Tokita A et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994; 367:284–7. [14] Silver J, Rubinger D, Friedlaender MM, Popovtzer MM. Sodium–dependent idiopathic hypercalciuria in renal– stone formers. Lancet 1983; 2:484–6. [15] Muldowney FP, Freaney R, Barnes E. Dietary chloride and urinary calcium in stone disease. QJM 1994; 87:501– 9. [16] Robijn S, Hoppe B, Vervaet BA et al. Hyperoxaluria: a gut–kidney axis? Kidney Int 2011; 80:1146–58. [17] Robertson WG, peacock. The cause of idiopathic calcium stone disease:hypercaliuria? Nephron 1980,26:105-10 [18] Borghi L, Schianchi T, Meschi T et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med 2002; 346:77–84. [19] Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med 1993; 328:833–8. [20] Curhan GC,Willett WC,Speizer FE et al comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women.Ann intern Med 1997:126:497-504 [21] Asplin JR. Uric acid stones.SeminNephrol 1996;16:412–24. [22] Zuckerman JM, Assimos DG. Hypocitraturia: pathophysiology and medical management. Rev Urol 2009; 11:134– 44. [23] Nguyen QV, Kälin A, Drouve U et al. Sensitivity to meat protein intake and hyperoxaluria in idiopathic calcium stone formers. Kidney Int 2001; 59:2273–81. [24] Reddy ST, Wang CY, Sakhaee K et al. Effect of low–carbohydrate high–protein diets on acid–base balance, stone– forming propensity, and calcium metabolism. Am J Kidney Dis 2002; 40:265–74. [25] Park C, Ha YS, Kim YJ et al. Comparison of Metabolic Risk Factors in Urolithiasis Patients according to Family History. Korean J Urol 2010; 51:50–3. [26] Resnick M, Pridgen DB, Goodman HO. Genetic predisposition to formation of calcium oxalate renal calculi. N Engl J Med 1968; 278:1313–8. World Journal of Advanced Research and Reviews, 2025, 26(03), 2656-2661 2661 [27] Goldfarb DS, Fischer ME, Keich Y, Goldberg J. A twin study of genetic and dietary influences on nephrolithiasis:areport from the Vietnam Era Twin (VET) Registry. Kidney Int 2005; 67:1053–61. [28] Gupta NP, Ansari MS, Kesarvani P, Kapoor A, Mukhopadhyay S. Role of computed tomography with no contrast medium enhancement in predicting the outcome of extracorporeal shock wave lithotripsy for urinary calculi. BJU Int 2005; 95: 1285-1288 [PMID: 15892818 DOI: 10.1111/j.1464410X.2005.05520.x] [29] Pareek G, Hedican SP, Lee FT, Nakada SY. Shock wave lithotripsy success determined by skin-to-stone distance on computed tomography. Urology 2005; 66: 941-944 [PMID: 16286099 DOI: 10.1016/j.urology.2005.05.011] [30] Hameed DA, Elgammal MA, ElGanainy EO, Hageb A, Mohammed K, El-Taher AM, Mostafa MM, Ahmed AI. Comparing non contrast computerized tomography criteria versus dual X-ray absorptiometry as predictors of radioopaque upper urinary tract stone fragmentation after electromagnetic shockwave lithotripsy. Urolithiasis 2013; 41: 511-515 [PMID: 23907170 DOI: 10.1007/s00240-013-0596-1] [31] el-Assmy A, Abou-el-Ghar ME, el-Nahas AR, Refaie HF, Sheir KZ. Multidetector computed tomography: role in determination of urinary stones composition and disintegration with extracorporeal shock wave lithotripsy--an in vitro study. Urology 2011; 77: 286-290 [PMID: 20719366 DOI: 10.1016/j.urology.2010.05.021] 32 El-Assmy A, [32] El-Nahas AR, Abou-El-Ghar ME, Awad BA, Sheir KZ. Kidney stone size and hounsfield units predict successful shockwave lithotripsy in children.Urology 2013; 81: 880-884 [PMID: 23395121 DOI: 10.1016/ j.urology.2012.12.012] [33] Ouzaid I, Al-qahtani S, Dominique S, Hupertan V, Fernandez P, Hermieu JF, Delmas V, Ravery V. A 970 Hounsfield units (HU) threshold of kidney stone density on non-contrast computed tomography (NCCT) improves patients’ selection for extracorporeal shockwave lithotripsy (ESWL): evidence from a prospective study. BJU Int 2012; 110: E438-E442 [PMID: 22372937 DOI: 10.1111/j.1464-410X.2012.10964.x] [34] Gücük A, Uyetürk U, Oztürk U, Kemahli E, Yildiz M, Metin A. Does the Hounsfield unit value determined by computed tomography predict the outcome of percutaneous nephrolithotomy? J Endourol 2012; 26: 792-796 [PMID: 22201298 DOI: 10.1089/end.2011.0518] [35] Gücük A, Kemahlı E, Üyetürk U, Tuygun C, Yıldız M, Metin A. Routine flexible nephroscopy for percutaneous nephrolithotomy for renal stones with low density: a prospective, randomized study. J Urol 2013; 190: 144-148 [PMID: 23313202 DOI: 10.1016/j.juro.2013.01.009] [36] Gücük A, Uyetürk U, Oztürk U, Kemahli E, Yildiz M, Metin A. Does the Hounsfield unit value determined by computed tomography predict the outcome of percutaneous nephrolithotomy? J Endourol 2012; 26: 792-796 [PMID: 22201298 DOI: 10.1089/end.2011.0518] [37] Kim JW, Chae JY, Kim JW, Oh MM, Park HS, Moon du G, Yoon CY. Computed tomography-based novel prediction model for the stone-free rate of ureteroscopic lithotripsy. Urolithiasis 2014; 42: 75-79 [PMID: 24162952 DOI: 10.1007/ s00240-013-0609-0] [38] Foda K, Abdeldaeim H, Youssif M, Assem A. Calculating the number of shock waves, expulsion time, and optimum stone parameters based on noncontrast computerized tomography characteristics. Urology 2013; 82: 1026-1031 [PMID: 24044913 DOI: 10.1016/j.urology.2013.06.061] [39] CT Teaching Manual. Edited by Hoffer M. Verlog, Berlin: Springer; 2007 [40] Fadhil, Y. S. (2022). A study on renal stones incidence with regard to age, gender and chemicalcomposition of stones in Western Iraq. International Journal of Health Sciences, 6(S1), 9814²9818.https://doi.org/10.53730/ijhs.v6nS1.7291 [41] Michelle J. Semins, Andrew D. Shore, Martin A. Makary, Thomas Magnuson, Roger Johns, and Brian R. Matlaga The Association of Increasing Body Mass Index and Kidney Stone Disease [42] Predictors of Uric Acid Stones: Mean Stone Density, Stone Heterogeneity Index, and Variation Coefficient of Stone Density by Single-Energy Non-Contrast Computed Tomography and Urinary pH, 2019 Jong Chan Kim,1 Kang Su Cho,2 Do Kyung Kim,2 Doo Yong Chung,1 Hae Do Jung,3 and Joo Yong Lee1,*