Correlation Between Acute Phase Proteins and Oxidative Stress Markers in Patients with Kidney Stones

Authors

  • Mayada Nazar Al-khafaji Department of Biology, College of Science, University of Diyala, Iraq
  • Hadeel Maan Rashied Department of Medical Laboratory Techniques, College of Medical Technology, Islamic University of Najaf, Iraq
  • Hala R. Mohammed College of Pharmacy, University of Babylon, Iraq

Keywords:

Kidney Stone, GSH, SAA, CRP, SOD, CAT, MDA

Abstract

Biomarkers of acute-phase protein and oxidative stress have been recognized as important pathophysiological alterations that may underlie stone formation. This case-control study investigated the correlation between the main oxidative stress indicators (malondialdehyde (MDA), catalase (CAT), and glutathione (GSH)) and the acute-phase proteins (C-reactive protein (CRP), serum amyloid A (SAA), and ceruloplasmin in stone-formers. In total, 140 individuals were invited to participate including 80 patients with confirmed kidney stones and 60 healthy controls. It reported a highly oxidative stress profile in patients with much higher levels of MDA (P = 0.002), and much lower levels of CAT (P = 0.001) and GSH (P = 0.003) levels, respectively. Moreover, acute-phase proteins were markedly higher among the patients with abnormal concentrations versus those that remained within the normal physiological ranges such as CRP (P = 0.034), SAA (P = 0.028), and ceruloplasmin (P = 0.012). Moreover, correlation analyses showed that MDA was positively associated with CRP (r = 0.41), SAA (r = 0.38), and ceruloplasmin (r = 0.29). Meanwhile, CAT and GSH expressed significant negative correlation with all acute-phase proteins, It has bee suggested that kidney stone patients have increased oxidative stress and increased acute-phase proteins, indicative of an enhanced systemic inflammatory response. The strong correlations between markers of oxidative stress and other inflammatory proteins underscore the dual contribution of oxidative stress and inflammation in the pathobiology of kidney stones. These results suggest that therapeutic approaches that simultaneously target oxidative load and inflammation should be explored to mitigate disease progression and recurrence.

References

Chaiyarit, S., & Thongboonkerd, V. (2020). Mitochondrial dysfunction and kidney stone disease. Frontiers in Physiology, 11, 566506. https://doi.org/10.3389/fphys.2020.566506

Gabay, C., & Kushner, I. (1999). Acute-phase proteins and other systemic responses to inflammation. The New England journal of medicine, 340(6), 448–454. https://doi.org/10.1056/NEJM199902113400607

Khan S. R. (2014). Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis. Translational andrology and urology, 3(3), 256–276. https://doi.org/10.3978/j.issn.2223-4683.2014.06.04

Khan, S.R. (2025) Oxidative stress, inflammation and kidney stones. Urolithiasis 53, 137. https://doi.org/10.1007/s00240-025-01808-y

Lasota, A., Wasilewska, A., & Rybi-Szumińska, A. (2023). Current status of protein biomarkers in urolithiasis — A review of the recent literature. Journal of Clinical Medicine, 12(22), 7135. https://doi.org/10.3390/jcm12227135

Liu, H., Xiang, X., Shi, C., Guo, J., Ran, T., Lin, J., Dong, F., Yang, J., & Miao, H. (2025). Oxidative stress and inflammation in renal fibrosis: Novel molecular mechanisms and therapeutic targets. Chemico-biological interactions, 421, 111784. https://doi.org/10.1016/j.cbi.2025.111784

Liu, Y., Chen, Y., Liao, B., Luo, D., Wang, K., Li, H., & Zeng, G. (2018). Epidemiology of urolithiasis in Asia. Asian journal of urology, 5(4), 205–214. https://doi.org/10.1016/j.ajur.2018.08.007

Lobo, S. M., Lobo, F. R., Bota, D. P., Lopes-Ferreira, F., Soliman, H. M., Mélot, C., & Vincent, J. L. (2003). C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest, 123(6), 2043–2049. https://doi.org/10.1378/chest.123.6.2043

Ming, S., Tian, J., Ma, K., Liu, R., & Zhang, X. (2022). Oxalate-induced apoptosis through ERS–ROS–NF-κB signalling pathway in renal tubular epithelial cells. Molecular Medicine, 28, 88. https://doi.org/10.1186/s10020-022-00494-5

Rostampour, F., Ghasemi, H., Mousavi-bahar, S.H., Ranjbar, A., Shayesteh, T.H., & Tayebinia, H. (2017). Total antioxidant capacity, lipid peroxidation, thiol group and catalase activity in patients with kidney stone. https://doi.org/10.15171/ajmb.2017.11

Stielow, M., Fijałkowski, Ł., Alaburda, A., Grześk, G., Grześk, E., Nowaczyk, J., & Nowaczyk, A. (2025). SGLT2 inhibitors: From molecular mechanisms to clinical outcomes in cardiology and diabetology. Molecules, 30(15), 3112. https://doi.org/10.3390/molecules30153112

Sun, Y., Sun, H., Zhang, Z., Tan, F., Qu, Y., Lei, X., Xu, Q., Wang, J., Shu, L., Xiao, H., Yang, Z., & Liu, H. (2024). New insight into oxidative stress and inflammatory responses to kidney stones: Potential therapeutic strategies with natural active ingredients. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 179, 117333. https://doi.org/10.1016/j.biopha.2024.117333

Tarigopula, V., Devana, S. K., Sharma, A. P., & Zohmangaihi, D. (2025). Evaluation of change in oxidative stress in urolithiasis patients following complete stone clearance: A prospective observational study. Indian journal of urology : IJU : journal of the Urological Society of India, 41(3), 210–215. https://doi.org/10.4103/iju.iju_53_25

Uhlar, C. M., & Whitehead, A. S. (1999). Serum amyloid A, the major vertebrate acute-phase reactant. European journal of biochemistry, 265(2), 501–523. https://doi.org/10.1046/j.1432-1327.1999.00657.x

Wigner, P., Grębowski, R., Bijak, M., Szemraj, J., & Saluk-Bijak, J. (2021). The molecular aspect of nephrolithiasis development. Cells, 10(8), 1926. https://doi.org/10.3390/cells10081926

Wigner, P., Grębowski, R., Bijak, M., Szemraj, J., & Saluk-Bijak, J. (2021). The molecular aspect of nephrolithiasis development. Cells, 10(8), 1926. https://doi.org/10.3390/cells10081926.

Worcester, E. M., & Coe, F. L. (2010). Clinical practice. Calcium kidney stones. The New England journal of medicine, 363(10), 954–963. https://doi.org/10.1056/NEJMcp1001011

Yang, X., Ding, H., Qin, Z., Zhang, C., Qi, S., Zhang, H., Yang, T., He, Z., Yang, K., Du, E., Liu, C., Xu, Y., & Zhang, Z. (2016). Metformin Prevents Renal Stone Formation through an Antioxidant Mechanism In Vitro and In Vivo. Oxidative medicine and cellular longevity, 2016, 4156075. https://doi.org/10.1155/2016/4156075

Downloads

Published

2025-12-18