EVALUATION OF SERUM PROTEINS (CTRP12 AND ADIPSIN) AS BIOMARKERS OF CHRONIC KIDNEY DISEASE AMONG INDIAN POPULATION

Mohammed M  Abdulkadhm; Aws Rassul  Hussain; Abbas Abdulhasan  Jebur; Rakesh M.  Rawal; Rushikesh Joshi

doi:10.47413/k3qh6f62

Authors

Mohammed M Abdulkadhm Gujarat University
Aws Rassul Hussain University of Al-Qadisiyah
Abbas Abdulhasan Jebur Gujarat University
Rakesh M. Rawal Gujarat University
Rushikesh Joshi Gujarat University

DOI:

https://doi.org/10.47413/k3qh6f62

Abstract

Background: Chronic kidney disease (CKD) is a progressive disorder marked by a gradual decline in renal function, often associated with systemic inflammation and metabolic dysregulation. Adipokines such as Adipsin and C1q/TNF-related protein 12 (CTRP12) have been implicated in metabolic and inflammatory pathways, but their roles in CKD remain underexplored. Methods: A case-control study was conducted involving 90 CKD patients and 90 healthy controls from the Indian population. Serum levels of CTRP12 and Adipsin were quantified using ELISA. Standard biochemical parameters, including serum creatinine, blood urea nitrogen (BUN), uric acid, calcium, C-reactive protein (CRP), and estimated glomerular filtration rate (eGFR), were measured using spectrophotometric methods. Statistical analyses included independent t-tests, Mann-Whitney U-tests, correlation analysis, and Bonferroni correction for multiple comparisons. Results: CKD patients exhibited significantly elevated levels of serum creatinine (7.519 ± 2.023 mg/dL), BUN (94.226 ± 19.647 mg/dL), uric acid (17.060 ± 5.848 mg/dL), and CRP (42.560 ± 15.169 mg/dL), alongside reduced eGFR (26.149 ± 6.337 mL/min/1.73 m²) and calcium levels (6.526 ± 1.058 mg/dL) compared to controls (p < 0.001). CTRP12 levels were significantly lower in CKD patients (0.985 ± 0.252 ng/mL) versus controls (1.390 ± 0.701 ng/mL), while Adipsin levels were significantly elevated (28.233 ± 6.532 ng/mL vs. 12.928 ± 4.612 ng/mL, p < 0.001). A weak but positive correlation was observed between CTRP12 and Adipsin levels (r = 0.204, p = 0.046). Conclusion: This study highlights significant alterations in CTRP12 and Adipsin levels among CKD patients, supporting their potential roles as supplementary biomarkers for early detection and monitoring of CKD. Further large-scale, longitudinal studies are necessary to validate these findings and explore their mechanistic roles in CKD progression.

References

1. Achari, A.E.; Jain, S.K., 2017. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int. J. Mol. Sci. 18, 1321.

2. Avinash Krishnegowda, Nagaraja Padmarajaiah, Shivakumar Anantharaman, Krishna Honnur., 2017. Spectrophotometric assay of creatinine in human serum sample, Arabian Journal of Chemistry. Volume 10, Supplement 2, Pages S2018-S2024. https://doi.org/10.1016/j.arabjc.2013.07.030.

3. Cañadas-Garre, M.; Anderson, K.; Cappa, R.; Skelly, R.; Smyth, L.J.; McKnight, A.J.; Maxwell, A.P., 2019. Genetic Susceptibility to Chronic Kidney Disease—Some More Pieces for the Heritability Puzzle. Front. Genet. 10, 453.

4. Choi, H.M.; Doss, H.M.; Kim, K.S. et al., 2020. Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases. Int. J. Mol. Sci. 21, 1219.

5. Coimbra, S.; Reis, F.; Nunes, S.R.R.P.; Viana, S.; Valente, M.J.; Rocha, S.; Catarino, C.; Rocha-Pereira, P.; Bronze-Da-Rocha, E.; Sameiro-Faria, M.; et al., 2019. The Protective Role of Adiponectin for Lipoproteins in End-Stage Renal Disease Patients: Relationship with Diabetes and Body Mass Index. Oxidative Med. Cell. Longev. 3021785.

6. Du J, Xu J, Wang X, Liu Y, Zhao X, Zhang H., 2020. Reduced serum CTRP12 levels in type 2 diabetes are associated with renal dysfunction. Int Urol Nephrol. 52(12):2321-2327. doi: 10.1007/s11255-020-02591-y. Epub 2020 Jul 30. PMID: 32734505.

7. Duan, J.; Wang, C.; Liu, D.; Qiao, Y.; Pan, S.; Jiang, D.; Zhao, Z.; Liang, L.; Tian, F.; Yu, P.; et al., 2019. Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in Chinese rural residents: A cross-sectional survey. Sci. Rep. 9, 10408.

8. Elshamaa MF, Sabry SM, El-Sonbaty MM, Elghoroury EA, Emara N, Raafat M. et al., 2012. Adiponectin: an adipocyte-derived hormone, and its gene encoding in children with chronic kidney disease. BMC Res Notes. 5:174. doi: 10.1186/1756-0500-5-174.

9. Ene-Iordache, B.; Perico, N.; Bikbov, B.; Carminati, S.; Remuzzi, A.; Perna, A.; Islam, N.; Bravo, R.F.; Aleckovic-Halilovic, M.; Zou, H.; et al., 2016. Chronic kidney disease and cardiovascular risk in six regions of the world (ISN-KDDC): A cross-sectional study. Lancet Glob. Health. 4, e307–e319.

10. Fadaei R, Moradi N, Kazemi T et al., 2019. Decreased serum levels of CTRP12/adipolin in patients with coronary artery disease in relation to inflammatory cytokines and insulin resistance. Cytokine. 113:326–331

11. Farhan, Layla & Abed, Baydaa & Dawood, Ashganslman., 2023. Comparison Study between Adipsin Levels in Sera of Iraqi Patients with Diabetes and Neuropathy. Baghdad Science Journal. 10.21123/bsj.2022.7408.

12. Hill, N.R.; Fatoba, S.T.; Oke, J.L.; Hirst, J.; O’Callaghan, C.A.; Lasserson, D.; Hobbs, R., 2016. Global Prevalence of Chronic Kidney Disease—A Systematic Review and Meta-Analysis. PLoS ONE. 11, e0158765.

13. Inker LA, Mondal H, Greene T, Masaschi T, Locatelli F, Schena FP, Katafuchi R, Appel GB, Maes BD, Li PK, Praga M, Del Vecchio L, Andrulli S, Manno C, Gutierrez E, Mercer A, Carroll KJ, Schmid CH, Levey AS., 2016. Early Change in Urine Protein as a Surrogate End Point in Studies of IgA Nephropathy: An Individual-Patient Meta-analysis. Am J Kidney Dis. 68(3):392-401. doi: 10.1053/j.ajkd.2016.02.042. Epub 2016 Mar 29. PMID: 27032886.

14. Jha, V.; Garcia-Garcia, G.; Iseki, K.; Li, Z.; Naicker, S.; Plattner, B.; Saran, R.; Wang, A.Y.-M.; Yang, C.-W., 2013. Chronic kidney disease: Global dimension and perspectives. Lancet. 382, 260–272.

15. Kamimura MA, Canziani ME, Sanches FR, Velludo CM, Carrero JJ, Bazanelli AP. et al., 2012. Variations in adiponectin levels in patients with chronic kidney disease: a prospective study of 12 months. J Bras Nefrol. 34:259–65. doi: 10.5935/0101-2800.20120007.

16. Kir HM, Eraldemir C, Dervisoglu E, Caglayan C, Kalender B., 2012. Effects of chronic kidney disease and type of dialysis on serum levels of adiponectin, TNF-alpha and high sensitive C-reactive protein. Clin Lab. 58:495–500.

17. Koziolek, Michael & Mueller, Gerhard & Dihazi, Gry Helene & Jung, Klaus & Altubar, Constanze & Wallbach, Manuel & Markovic, Ivana & Raddatz, Dirk & Jahn, Olaf & Karaköse, Hülya & Lenz, Christof & Urlaub, Henning & Dihazi, Abdelhi & El Meziane, Abdellatif & Dihazi, Hassan., 2020. Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients. Journal of Clinical Medicine. 9. 639. 10.3390/jcm9030639.

18. Li J, Chen J, Lan HY, Tang Y., 2022. Role of C-Reactive Protein in Kidney Diseases. Kidney Dis (Basel). 14; 9(2):73-81. doi: 10.1159/000528693. PMID: 37065607; PMCID: PMC10090978.

19. Li ZI, Chung AC, Zhou L, Huang XR, Liu F, Fu P, et al., 2011. C-reactive protein promotes acute renal inflammation and fibrosis in unilateral ureteral obstructive nephropathy in mice. Lab Invest. 91((6)):837–851. doi: 10.1038/labinvest.2011.42.

20. Libby P, Buring JE, Badimon L, Hansson GK, Deanfield J, Bittencourt MS, et al., 2019. Atherosclerosis. Nat Rev Dis Primers. 5:56. doi: 10.1038/s41572-019-0106-z

21. Liu, K. Z. et al., 2020. Detection of renal biomarkers in chronic kidney disease using microfluidics: progress, challenges and opportunities. Biomed. Microdevices. 22, 29.

22. Liu, M.; Liu, S.-W.; Wang, L.-J.; Bai, Y.-M.; Zeng, X.-Y.; Guo, H.-B.; Liu, Y.-N.; Jiang, Y.-Y.; Dong, W.-L.; He, G.-X.; et al., 2018. Burden of diabetes, hyperglycaemia in China from to 2016: Findings from the 1990 to 2016, global burden of disease study. Diabetes Metab. 45, 286–293.

23. Martinez Cantarin MP, Waldman SA, Doria C, Frank AM, Maley WR, Ramirez CB. et al., 2013. The adipose tissue production of adiponectin is increased in end-stage renal disease. Kidney Int. 83:487–94. doi: 10.1038/ki.2012.421.

24. Martinez Cantarin, M.P.; Keith, S.W.; Waldman, S.A.; Falkner, B., 2014. Adiponectin receptor and adiponectin signaling in human tissue among patients with end-stage renal disease. Nephrol. Dial. Transplant. 29, 2268–2277.

25. Messias BA, Botelho RV, Saad SS, Mocchetti ER, Turke KC, Waisberg J., 2020. Serum C-reactive protein is a useful marker to exclude anastomotic leakage after colorectal surgery. Sci Rep. 3;10((1)):1687. doi: 10.1038/s41598-020-58780-3.

26. Murton, M.; Goff-Leggett, D.; Bobrowska, A.; Garcia Sanchez, J.J.; James, G.; Wittbrodt, E.; Nolan, S.; Sörstadius, E.; Pecoits-Filho, R.; Tuttle, K., 2021. Burden of Chronic Kidney Disease by KDIGO Categories of Glomerular Filtration Rate and Albuminuria: A Systematic Review. Adv. Ther. 38, 180–200.

27. Nakagawa N, Yao N, Hirayama T, Ishida M, Ishida H, Wada A. et al., 2011. Potential impact of renin-angiotensin system inhibitors and calcium channel blockers on plasma high-molecular-weight adiponectin levels in hemodialysis patients. Hypertens Res. 34:592–8. doi: 10.1038/hr.2010.282.

28. Redmon, J.H.; Elledge, M.F.; Womack, D.S.; Wickremashinghe, R.; Wanigasuriya, K.P.; Peiris-John, R.J.; Lunyera, J.; Smith, K.; Raymer, J.H.; Levine, K.E., 2014. Additional perspectives on chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka—Lessons learned from the WHO CKDu population prevalence study. BMC Nephrol. 15, 125.

29. Ruiz-Ortega, M.; Rayego-Mateos, S.; Lamas, S.; Ortiz, A.; Rodrigues-Diez, R.R., 2020. Targeting the progression of chronic kidney disease. Nat. Rev. Nephrol. 16, 269–288.

30. Schrauben SJ, Jepson C, Hsu JY, Wilson FP, Zhang X, Lash JP, Robinson BM, Townsend RR, Chen J, Fogelfeld L, Kao P, Landis JR, Rader DJ, Hamm LL, Anderson AH, Feldman HI., 2019. Insulin resistance and chronic kidney disease progression, cardiovascular events, and death: findings from the chronic renal insufficiency cohort study. BMC Nephrol. 20; 20(1):60.

31. Si Y, Fan W, Sun L, A., 2020. Review of the relationship between ctrp family and coronary artery disease. Curr Atheroscler Rep. 22:22. doi: 10.1007/s11883-020-00840-0

32. Song, S.H.; Oh, T.R.; Choi, H.S.; Kim, C.S.; Ma, S.K.; Oh, K.H.; Ahn, C.; Kim, S.W.; Bae, E.H., 2020. High serum adiponectin as a biomarker of renal dysfunction: Results from the KNOW-CKD study. Sci. Rep. 10, 5598.

33. Steubl D, Block M, Herbst V, Nockher WA, Schlumberger W, Satanovskij R, Angermann S, Hasenau AL, Stecher L, Heemann U, Renders L, Scherberich J., 2016. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients. Medicine (Baltimore). 95(10):e3011. doi: 10.1097/MD.0000000000003011. PMID: 26962815; PMCID: PMC4998896.

34. Stevens, L.A.; Viswanathan, G.; Weiner, G.E., 2010. Chronic kidney disease and end-stage renal disease in the elderly population: Current prevalence, future projections, and clinical significance. Adv. Chronic Kidney Dis. 17, 293–301.

35. Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, et al., 2022. Heart disease and stroke statistics-2022 update: a report from the american heart association. Circulation. 145:e153–639. doi: 10.1161/CIR.0000000000001052

36. Wang, G., Chen, JJ., Deng, WY. et al., 2021. CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway. Cell Death Dis. 12, 254. https://doi.org/10.1038/s41419-021-03544-8

37. Zoccali C., 2000. Cardiovascular risk in uraemic patients—is it fully explained by classical risk factors? Nephrol Dial Transplant. 15:454–7. doi: 10.1093/ndt/15.4.454.