Abstract
Objective
To investigate the relationship between plasma levels of sKL and Nrf2 and calcium oxalate calculi.
Methods
The clinical data of 135 patients with calcium oxalate calculi treated in the Department of Urology of the second affiliated Hospital of Xinjiang Medical University from February 2019 to December 2022, and 125 healthy persons who underwent physical examination in the same period were collected and divided into healthy group and stone group. The levels of sKL and Nrf2 were measured by ELISA. Correlation test was used to analyze the risk factors of calcium oxalate stones, logistic regression analysis was used to analyze the risk factors of calcium oxalate stones, and ROC curve was used to evaluate the sensitivity and specificity of sKL and Nrf2 in predicting urinary calculi.
Results
Compared with the healthy group, the plasma sKL level in the stone group decreased (111.53 ± 27.89 vs 130.68 ± 32.51), while the plasma Nrf2 level increased (300.74 ± 114.31 vs 246.74 ± 108.22). There was no significant difference in the distribution of age and sex between the healthy group and the stone group, but there were significant differences in plasma levels of WBC, NEUT, CRP, BUN, BUA, SCr, BMI, and eating habits. The results of correlation test showed that the level of plasma Nrf2 was positively correlated with SCr (r = 0.181, P < 0.05) and NEUT (r = 0.144 P < 0.05). Plasma sKL was not significantly correlated with Nrf2 (r = 0.047, P > 0.05), WBC (r = 0.108, P > 0.05), CRP (r = − 0.022, P > 0.05), BUN (r = − 0.115, P > 0.05), BUA (r = − 0.139, P > 0.05), SCr (r = 0.049, P > 0.05), and NEUT (r = 0.027, P > 0.05). Plasma Nrf2 was not significantly correlated with WBC (r = 0.097, P > 0.05), CRP (r = 0.045, P > 0.05), BUN (r = 0.122, P > 0.05), and BUA (r = 0.122, P > 0.05); (r = 0.078, P > 0.05) had no significant correlation. Logistic regression showed that elevated plasma sKL (OR 0.978, 95% CI 0.969 ~ 0.988, P < 0.05) was a protective factor for the occurrence of calcium oxalate stones, BMI (OR 1.122, 95% CI 1.045 ~ 1.206, P < 0.05), dietary habit score (OR 1.571, 95% CI 1.221 ~ 2.020, P < 0.05), and WBC (OR 1.551, 95% CI 1.423 ~ 1.424, P < 0.05). Increased NEUT (OR 1.539, 95% CI 1.391 ~ 1.395, P < 0.05) and CRP (OR 1.118, 95% CI: 1.066 ~ 1.098, P < 0.05) are risk factors for the occurrence of calcium oxalate stones.
Conclusion
Plasma sKL level decreased and Nrf2 level increased in patients with calcium oxalate calculi. Plasma sKL may play an antioxidant role in the pathogenesis of calcium oxalate stones through Nrf2 antioxidant pathway.
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Data availability
The data used to support the findings of this study are included within the article.
References
Liu Y, Chen Y, Liao B et al (2018) Epidemiology of urolithiasis in Asia[J]. Asian J Urol 5(4):205–214
Maihemuti M, Du heng, Tuerhong D, et al (2017) Effect of Klotho protein on renal oxidative stress in rats with calcium oxalate nephrolithiasis. Chinese J Urol. 38(12):941–945
Makoto K-O (2019) The Klotho proteins in health and disease. J Nat Rev Nephrol. 15:27–44
Jian X, Joonho Y, Sung-Wan An et al (2015) Soluble Klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate. J Am Soc Nephrol 26:1150–1160
Navarro-González Juan F, Dolores S-N, Javier D-C et al (2018) Effects of Pentoxifylline on soluble Klotho concentrations and renal tubular cell expression in diabetic kidney disease. J Diabetes Care 41:1817–1820
Sivandzade F, Prasad S, Bhalerao A et al (2019) NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: Molecular mechanisms and possible therapeutic approaches[J]. Redox Biol 21:101059
Meng X, Feng Y, Ying Le et al (2021) Klotho protects against diabetic kidney disease via AMPK- and ERK-mediated autophagy. Acta Diabetol. https://doi.org/10.1007/s00592-021-01736-4
Bishop K, Momah T, Ricks J (2020) Nephrolithiasis[J]. Prim Care 47(4):661–671
Wagner CA (2021) Etiopathogenic factors of urolithiasis. Factores etiopatogénicos de la urolitiasis. Arch Esp Urol 74(1):16–23
Gao X, Sun Z, Ma G et al (2021) Reduced plasma levels of α-klotho and their correlation with klotho polymorphisms in elderly patients with major depressive disorders. Front Psychiatry. 12:682691
He Q, Babcook MA, Shukla S et al (2016) Obesity-initiated metabolic syndrome promotes urinary voiding dysfunction in a mouse model. Prostate 76(11):964–976
Drew DA, Katz R, Kritchevsky S et al (2017) Association between Soluble Klotho and change in kidney function: the health aging and body composition study. J Am Soc of Nephrol. https://doi.org/10.1681/ASN.2016080828
Ahmatjan B, Ruotian L, Rahman A et al (2023) Klotho inhibits the formation of calcium oxalate stones by regulating the Keap1-Nrf2-ARE signaling pathway. Int Urol Nephrol 55(2):263–276
Chen WY (2020) Soluble Alpha-Klotho alleviates cardiac fibrosis without altering cardiomyocytes renewal. Int J Mol Sci 21(6):2186
Maltese G, Psefteli PM, Rizzo B et al (2017) The anti-ageing hormone klotho induces Nrf2-mediated antioxidant defences in human aortic smooth muscle cells. J Cell Mole Med. https://doi.org/10.1111/jcmm.12996
Wei C, Bin, et al (2018) Klotho protein inhibits H2O2-induced oxidative injury in endothelial Cells via regulation of PI3K/Akt/Nrf2/HO-1 Pathways. Can J Physiol Pharmacol. https://doi.org/10.1139/cjpp-2018-0277
Lindberg K, Amin R, Moe OW et al (2014) The kidney is the principal organ mediating klotho effects. J Am Soc Nephrol 25(10):2169–2175
Wolf M, An SW, Nie M et al (2014) Klotho Up-regulates Renal Calcium Channel Transient Receptor Potential Vanilloid 5 (TRPV5) by Intra- and Extracellular N-glycosylation-dependent Mechanisms. J Biol Chem. https://doi.org/10.1074/jbc.M114.616649
Acknowledgements
This study is supported by the Natural Science Foundation of Xinjiang Uyghur Autonomous region (No. 81760128).
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BA: experimental operation and paper writing; MM: data collation and statistical analysis; BA, LR, and MM: research guidance, paper revision, and financial support.
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Aihemaitijiang, B., Ruotian, L., Qi, Y. et al. Correlation between sKL and Nrf2 plasma levels and calcium oxalate urolithiasis. Int Urol Nephrol 55, 1671–1676 (2023). https://doi.org/10.1007/s11255-023-03615-z
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DOI: https://doi.org/10.1007/s11255-023-03615-z