Dysmetabolic nephropathies in persons with bone and joint pathology

Abstract

Objective: Dysmetabolic nephropathies are characterized by disturbances in oxalate, urate and phosphate metabolism and have been suggested as triggering factors for bone and joint pathology. The aim of this study was determine the frequency of dysmetabolic nephropathies in patients with bone and joint pathology and to compare the laboratory parameters between patients with dysmetabolic nephropathy and controls. Patients and Methods: Patients with bone and joint pathology (coxarthrosis, gonarthrosis, ligamentum ruptures, and bone fractures) were enrolled in the study. Dysmetabolic nephropathy (characterized by hyperoxaluria, uraturia or phosphaturia) was revealed in 9% of patients with bone and joint pathology. Sixty-one patients without dysmetabolic nephropathy served as a control group. The patients underwent general clinical and biochemical examinations. Results: The persons with bone and joint pathology and the presence of dysmetabolic nephropathy demonstrated a prevalence of hyperoxaluria (59%) with less frequency of uraturia (25.7%) and phosphaturia (15.1%). Hyperoxaluria was associated with a high incidence of ligamentum ruptures and bone fractures (21.6%). The persons with hyperoxaluria demonstrated higher levels of eosinophils, platelets, white blood cells (WBCs), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), thymol probe, and serum alkaline phosphatase. The persons with dysmetabolic nephropathy showed higher levels of WBCs, ESR, alkaline phosphatase, creatinine, thymol probe, and CRP (P<0.05). Patients with bone fractures demonstrated higher serum levels of glucose, creatinine, CRP and thymol probe and lower levels of serum calcium compared to the controls (P<0.05). Conclusion: Hyperoxaluria was associated with increased frequency of ligamentum ruptures and bone fractures. The physicians should monitor the studied parameters in patients with dysmetabolic nephropathy during the treatment of bone and joint pathology.

Keywords

• Oxalates
• Calcium
• Dysmetabolic nephropathy
• Bones
• Urea

References

1. Colaci C, Gambardella ML, Scarlata GGM, et al. Dysmetabolic comorbidities and non-alcoholic fatty liver disease: a stairway to metabolic dysfunction-associated steatotic liver disease. Hepatoma Res 2024;10:16. doi.org/10.20517/2394- 5079.2023.134.
2. Shastri S, Patel J, Sambandam KK, Lederer ED. Kidney Stone Pathophysiology, Evaluation and Management: Core Curriculum. Am J Kidney Dis 2023;82:617-34. doi: 10.1053/j. ajkd.2023.03.017.
3. Kouri, Timo T, Hofmann, et al. The EFLM European Urinalysis Guideline 2023. CCLM 2024. doi.org/10.1515/ cclm-2024-0070.
4. Qian X, Wan J, Xu J, et al. Epidemiological trends of urolithiasis at the global, regional, and national levels: A population-based study. Int J Clin Pract 2022;2022:6807203. doi: 10.1155/2022/6807203.
5. Verdesca S, Fogazzi GB, Garigali G, Messa P, Daudon M. Crystalluria: prevalence, different types of crystals and the role of infrared spectroscopy. Clin Chem Lab Med 2011;49:515-20. doi: 10.1515/CCLM.2011.078.
6. Moya FJ, Rodríguez-Perales S, García-Escudero R, et al. Restored glyoxylate metabolism after AGXT gene correction and direct reprogramming of primary hyperoxaluria type 1 fibroblasts. iScience 2024;27:109530. doi: 10.1016/j. isci.2024.109530.
7. Grover PK, Ryall RL. Inhibition of calcium oxalate crystal growth and aggregation by prothrombin and its fragments in vitro: relationship between protein structure and inhibitory activity. Eur J Biochem 1999;263:50-6. doi: 10.1046/j.1432- 1327.1999.00448.x.
8. A. Hesse, H. Wuzel, W. Vahlensieck. Significance of glycosaminoglycans for the formation of calcium oxalate stones. Am J Kidney Dis 1991;17:414-9. doi.org/10.1016/ S0272-6386(12)80634-2.

9. Han T, Chen W, Qiu X, Wang W. Epidemiology of gout – Global burden of disease research from 1990 to 2019 and future trend predictions. Ther Adv Endocrinol Metab 2024;15:204.201.88241227295. doi: 10.1177/20420188241227295.
10. Chen S, Guo X, Yu S, et al. Association between serum uric acid and elevated alanine aminotransferase in the general population. Int J Environ Res Public Health 2016;13:841. doi: 10.3390/ijerph13090841.
11. Liu Li , Shao Y, Xiaojing Li, Sun J, Xing D. Individual and combined relationship of serum uric acid and alanine aminotransferase on metabolic syndrome in adults in Qingdao, China. Nutr Metab Cardiovasc Dis 2022;32:2822-9. doi: 10.1016/j.numecd.2022.08.014.
12. Wardhana W, Rudijanto A. Effect of uric acid on blood glucose levels. Acta Med Indonesn 2018 ;50:253-6.
13. Wang X, Zhong S, Guo X. The associations between fasting glucose, lipids and uric acid levels strengthen with the decile of uric acid increase and differ by sex. Nutr Metab Cardiovasc Dis 2022;32:2786-93. doi: 10.1016/j.numecd.2022.09.004.
14. Zechner C, Adams-Huet B, Gregory B, Neyra JA, Rule JA, Li X, Rakela J, Moe OW, Lee WM; Acute Liver Failure Study Group. Hypophosphatemia in acute liver failure of a broad range of etiologies is associated with phosphaturia without kidney damage or phosphatonin elevation. Transl Res 2021;238:1-11. doi: 10.1016/j.trsl.2021.07.003.
15. Mossman, D. M., Kooser, R. G., & Welch, L. E. (1996). The complexometric determination of calcium and magnesium in limestone using a laser photometer for endpoint identification. J Chem Edu 199;73:82. doi:10.1021/ed073p82
16. Morozenko DV, Leontieva FS. Metody doslidzhennia markeriv metabolizmu spoluchnoyi tkanyny u klinichniy tа eksperymentalniy medytsyni. Molodyi vchenyi. 2016; 2: 168-72. Available from: http://nbuv.gov.ua/UJRN/ molv_2016_2_43.
17. Ji D, Roman M, Zhou J, Hildreth J. Determination of chondroitin sulfate content in raw materials and dietary supplements by high-performance liquid chromatography with ultraviolet detection after enzymatic hydrolysis: singlelaboratory validation. J AOAC Int 2007;90:659-69.
18. Reitman S, Frrankel SA. A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56-63. doi:10.1093/ajcp/28.1.56.
19. Kirsztajn GM, Silva Junior GBD, Silva AQBD, Abensur H, Romão Junior JE, Bastos MG, Calice-Silva V, Carmo LPFD, Sandes-Freitas TV, Abreu PF, Andreguetto BD, Cortes LGF, Oliveira MGL, Vieira LMF, Moura-Neto JA, Andriolo A. Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML). J Bras Nefrol 2024;46:e20230193. doi: 10.1590/2175-8239-JBN- 2023-0193en.
20. Sarısoy Ö, Arıcı Ş, Demirci Bodur E, et al. Is aortic elasticity associated with hydration status in stage of chronic renal disease in children? Marmara Med J 2024;37:311-7. doi. org/10.5472/marumj.1573657
21. Seker A, Gogas Yavuz D. Bone mineral density in patients with Cushing’s syndrome. Marmara Med J 2024;37:185-91. doi: 10.5472/marumj.1485351
22. Büscher R, Pape L, Büscher AK. Bone health in children with primary hyperoxaluria type 1 following liver and kidney transplantation. Front Pediatr 2024;12:1353880. doi: 10.3389/ fped.2024.1353880.
23. El Hage S, Ghanem I, Baradhi A. Skeletal features of primary hyperoxaluria type 1, revisited. J Child Orthop. 2008 Jun;2(3):205-10. doi: 10.1007/s11832.008.0082-4. Epub 2008 Feb 15. PMID: 19308578; PMCID: PMC2656805.
24. Hassona Y, Hassan S, Atef A, et al. Primary hyperoxaluria: Description of a new oral finding and review of literature. Spec Care Dentist 2024;44:1041-1048. doi: 10.1111/scd.12968.
25. Horta-Baas G, Vargas-Gutiérrez C, Barile-Fabris L. Large joint destructive arthropathy and tumoral calcinosis associated to primary oxalosis: case report and literature review. Rheumatol Clin 2013;9:181-5. doi: 10.1016/j.reuma.2012.09.009. 23570963.
26. Bacchetta J, Boivin G, Cochat P. Bone impairment in primary hyperoxaluria: a review. Pediatr Nephrol 2016;31:1-6. doi: 10.1007/s00467-015-3048-z.
27. Demoulin N, Aydin S, Gillion V, Morelle J, Jadoul M. Pathophysiology and Management of Hyperoxaluria and Oxalate Nephropathy: A Review. Am J Kidney Dis 2022;79:717-27. doi: 10.1053/j.ajkd.2021.07.018.
28. Nazzal L, Francois F, Henderson N. et al. Effect of antibiotic treatment on Oxalobacter formigenes colonization of the gut microbiome and urinary oxalate excretion. Sci Rep 2021; 11:16428. hdoi: 10.1038/s41598-021-95992-7.
29. Liu Y, Zhao Y, Shukha Y, et al. Dysregulated oxalate metabolism is a driver and therapeutic target in atherosclerosis. Cell Rep 2021;27;36:109420. doi: 10.1016/j.celrep.2021.109420.
30. Guo S, Wang M, Yu Y, et al. The association of erythrocyte sedimentation rate, high-sensitivity C-reactive protein and diabetic kidney disease in patients with type 2 diabetes. BMC Endocr Disord 2020;20:103. doi: 10.1186/s12902-020-00584-7.
31. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ 2008; 7 (336,7656):1298-302. doi: 10.1136/bmj.39582.589433.BE.
32. Bernd H, Bodo B. Beck, Dawn S. M. The primary hyperoxalurias. Kidney International 2009;75:1264-1271. doi:10.1038/ki.2009.32.
33. Lalayiannis AD, Soeiro EMD, Moysés RMA, Shroff R. Chronic kidney disease mineral bone disorder in childhood and young adulthood: a ‘growing’ understanding. Pediatr Nephrol 2024;39:723-39. doi: 10.1007/s00467-023-06109-3.
34. Joshi S, Clapp WL, Wang W, Khan SR. Osteogenic changes in kidneys of hyperoxaluric rats. Biochim Biophy Acta (BBA) – Mol Basis Dis 2015;1852:2000-12.
35. Yang R, Ding N, Qin J, Peng H. The relationship between uric acid and bone mineral density in the intermediate stage of CKD 1-3. BMC Nephrol 2024;25:219. doi: 10.1186/s12882- 024-03650-7.
36. Kim S, Lee S, Kwon H. Association between serum uric acid level and bone mineral density in men more than 50 years of age. Front Endocrinol (Lausanne) 2023;30:1259077. doi: 10.3389/fendo.2023.125.9077.
37. Ibrahim WN, Younes N, Shi Z, Abu-Madi MA. Serum uric acid level is positively associated with higher bone mineral density at multiple skeletal sites among healthy Qataris. Front Endocrinol (Lausanne) 2021;12:653685. doi: 10.3389/ fendo.2021.653685.
38. Li Y, Tan J, Tian J, et al. Cross-sectional analysis of the correlation between serum uric acid and trabecular bone score: NHANES 2005-2008. Sci Rep 2023;13:21546. doi: 10.1038/s41598-023-48739-5.