Assessment of Some Biochemical and Inflammatory Markers in Diabetic Patient with Renal Impairment

Daroon Essam Raffik; Amina Hamed Ahmed; Abdullah Adil Raoof

Authors

Daroon Essam Raffik University of Kirkuk
Amina Hamed Ahmed University College of Medicine
Abdullah Adil Raoof Kirkuk University College of Medicine

Keywords:

Diabetic Kidney Disease (DKD), Glomerular Filtration Rate (GFR). α-Klotho, Glycated Albumin, HOMA-IR, Inflammatory Biomarkers

Abstract

Background: Diabetes mellitus (D M) is a chronic metabolic disorder associated with persistent hyperglycemia, insulin resistance, and systemic inflammation. One of its most serious complications is diabetic kidney disease (DKD), which evolves silently and is often underdiagnosed during its early stages despite detectable biochemical changes.

Objective: This study objective to evaluate the diagnostic and prognostic significance of selected biochemical, hormonal, and inflammatory biomarkers in patients with type 2 DM, both with and without renal impairment, to identify early indicators of DKD.

Materials and Methods: A total of 150 participants were enrolled and equally divided into 3 groups: 50 patients with type 2 DM, 50 with DKD, and 50 healthy controls. FBS, HbA1c, creatinine, urea, albumin, insulin, HOMA-IR, eGFR , microalbuminuria, and inflammatory markers such as CRP, TNF-α, IGF-1, α-Klotho, glycated albumin, and fructosamine were all measured in blood samples. One-way ANOVA (Tukey post hoc) and Pearson correlation (SPSS v26). Results: DKD patients exhibited significantly elevated FBS (301.49 ± 207.36 mg/dL), HbA1c (10.67 ± 4.38%), creatinine (3.93 ± 0.81 mg/dL), microalbuminuria (71.19 ± 11.91 mg/day), CRP (8.65 ± 3.97 mg/L), TNF-α (12.4 ± 3.2 pg/mL), and glycated albumin (1248 ± 873.3 mg/dL), alongside reduced eGFR (42.5 ± 15.2 mL/min) and α-Klotho (120 ± 450 pg/mL) compared to other groups (P<0.001).

Conclusion: Glycated albumin, microalbuminuria, TNF-α, and α-Klotho alterations could all be markers for the early identification of DKD. Including these indicators in routine diagnostic procedures may enhance early risk assessment. longitudinal research is required to validate these initial findings.

References

P. Saeedi, I. Petersohn, P. Salpea, B. Malanda, S. Karuranga, N. Unwin, et al., "Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition," Diabetes Res. Clin. Pract., vol. 157, p. 107843, 2019.

International Diabetes Federation, IDF Diabetes Atlas, 10th ed., Brussels: International Diabetes Federation, 2021.

M. C. Thomas, M. Brownlee, K. Susztak, K. Sharma, K. A. Jandeleit-Dahm, S. Zoungas, et al., "Diabetic kidney disease," Nat. Rev. Dis. Primers, vol. 1, p. 15018, 2015.

S. Mir, A. Ozdemir, F. G. Girgin, "Biomarkers in diabetic nephropathy: Present and future," World J. Diabetes, vol. 6, no. 6, pp. 1046–1056, 2015.

A. Abd-Alsalam, I. G. Zainal, G. A. Taqa, "Estimation of protein oxidation parameters in patients with diabetic nephropathy," AIP Conf. Proc., vol. 2394, no. 1, 2022.

H. Zhao, T. Sun, S. Li, X. Shao, J. Guo, X. Wang, "α-Klotho as a novel biomarker in chronic diabetic nephropathy," Int. J. Clin. Exp. Med., vol. 10, no. 3, pp. 4943–4950, 2017.

Y. Kang, Q. Jin, M. Zhou, L. Sun, X. Wang, H. Zhang, et al., "Association between serum α klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: Evidence from a Chinese cohort and the NHANES database," Diabetol. Metab. Syndr., vol. 17, p. 148, 2025.

J. Malyszko, M. Bolanowski, J. S. Malyszko, "Soluble α Klotho as a novel biomarker in the early stage of diabetic nephropathy," PLoS One, vol. 9, no. 4, p. e102984, 2014.

X. He, W. Shen, C. Xu, M. Lu, H. Ma, K. Song, et al., "Novel biomarkers of diabetic kidney disease," Biomolecules, vol. 13, no. 4, p. 633, 2023.

S. Doi, Y. Zou, O. Togao, J. V. Pastor, G. B. John, L. Wang, et al., "Klotho inhibits transforming growth factor-beta1 (TGF-β1) signaling and suppresses renal fibrosis and cancer metastasis in mice," J. Biol. Chem., vol. 286, no. 10, pp. 8655–8665, 2011.

M. Kuro-O, "Klotho and aging," Biochim. Biophys. Acta, vol. 1790, no. 10, pp. 1049–1058, 2009.

K. Lim, A. Groen, G. Molostvov, T. Lu, K. S. Lilley, D. Snead, et al., "α-Klotho expression in human tissues," J. Clin. Endocrinol. Metab., vol. 100, no. 10, pp. E1308–E1318, 2015.

M. C. Hu, M. Shi, J. Zhang, J. Pastor, T. Nakatani, B. Lanske, et al., "Klotho deficiency causes vascular calcification in chronic kidney disease," J. Am. Soc. Nephrol., vol. 22, no. 1, pp. 124–136, 2011.

S. Tanaka, T. Tanaka, M. Nangaku, "Hypoxia as a key player in the AKI-to-CKD transition," Am. J. Physiol. Renal Physiol., vol. 307, no. 11, pp. F1187–F1195, 2014.

J. L. Alge, N. Karakala, B. A. Neely, M. G. Janech, J. A. Tumlin, L. S. Chawla, et al., "Urinary angiotensinogen and transforming growth factor-β1 levels predict adverse outcomes in patients with acute kidney injury," Kidney Int. Rep., vol. 5, no. 9, pp. 1394–1403, 2020.

T. Akimoto, E. Kusano, Y. Matsumoto, T. Hashimoto, T. Yokoyama, K. Shibuya, et al., "Persistent inflammation as a key factor for progression of chronic kidney disease: Role of acute phase reactants," Nephrology (Carlton), vol. 18, no. 7, pp. 389–396, 2013.

S. Kundu, M. Ahammed, Y. Ouyang, X. Zhong, H. Xu, Z. Dong, et al., "Inflammation and oxidative stress in diabetic nephropathy: Role of Nrf2 signaling," Int. J. Mol. Sci., vol. 24, no. 2, p. 1102, 2023.

J. M. Forbes, M. E. Cooper, "Mechanisms of diabetic complications," Physiol. Rev., vol. 93, no. 1, pp. 137–188, 2013.

H. J. L. Heerspink, R. T. Gansevoort, B. M. Brenner, M. E. Cooper, H. H. Parving, S. Shahinfar, et al., "Comparison of different measures of urinary protein excretion for prediction of renal events," J. Am. Soc. Nephrol., vol. 21, no. 8, pp. 1355–1360, 2010.

S. Copur, K. Turkmen, O. Gungor, T. Yildirim, Z. Tonbul, "Serum glycated albumin predicts all-cause mortality in dialysis patients: a systematic review and meta-analysis," Acta Diabetol., vol. 58, no. 12, pp. 1591–1601, 2021.

M. Olivieri, M. Rosetti, G. Poletti, et al., "Ability of the Capillary Electrophoresis-based HbA1c Assay to Detect Rare Hemoglobin Variants," Ann. Lab. Med., vol. 45, no. 1, pp. 101–104, 2025.

N. Zotova, Y. Zhuravleva, V. Chereshnev, E. Gusev, "Acute and chronic systemic inflammation: features and differences in the pathogenesis, and integral criteria for verification and differentiation," Int. J. Mol. Sci., vol. 24, no. 2, p. 1144, 2023.

G. Aktas, "Serum C-reactive protein to albumin ratio as a reliable marker of diabetic neuropathy in type 2 diabetes mellitus," Biomol. Biomed., vol. 24, no. 5, p. 1380, 2024.

J. M. Tocados, A. P. Gómez, J. D. Coral, J. M. Valdivielso, "The multiple functions of Insulin-like Growth Factor 1 in kidney disease," Nefrología, 2025, p. 501337.

A. D. Hajare, N. Dagar, A. B. Gaikwad, "Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases," Mol. Biomed., vol. 6, no. 1, p. 19, 2025.

L. X. Yu, S. S. Li, M. Y. Sha, J. W. Kong, J. M. Ye, Q. F. Liu, "The controversy of klotho as a potential biomarker in chronic kidney disease," Front. Pharmacol., vol. 13, p. 931746, 2022.

A. Serbis, V. Giapros, E. P. Kotanidou, A. Galli-Tsinopoulou, E. Siomou, "Diagnosis, treatment and prevention of type 2 diabetes mellitus in children and adolescents," World J. Diabetes, vol. 12, no. 4, p. 344, 2021.

Y. Z. Hani, I. G. Zainal, "Estimate the Correlation Between Some Antioxidant Biomarkers and Pseudo Peroxidase Activity of Hemoglobin in Patients With Chronic Kidney Disease," J. Pioneering Med. Sci., vol. 13, pp. 28–35, 2024.

R. Agarwal, "Pathogenesis of diabetic nephropathy," ADA Clin. Compendia, vol. 2021, no. 1, pp. 2–7, 2021.

W. Kriz, J. Löwen, H. J. Gröne, "The complex pathology of diabetic nephropathy in humans," Nephrol. Dial. Transplant., vol. 38, no. 10, pp. 2109–2119, 2023.

N. Bowker, R. L. Shah, S. J. Sharp, et al., "Meta Analysis Investigating the Role of Interleukin 6 Mediated Inflammation in Type 2 Diabetes," eBioMedicine, vol. 61, p. 103062, 2020.

T. E. Wu, Y. W. Su, H. S. Chen, "Mean HbA1c and HbA1c variability are associated with differing diabetes-related complications in patients with type 2 diabetes mellitus," Diabetes Res. Clin. Pract., vol. 192, p. 110069, 2022.

S. Kume, H. Maegawa, "Lipotoxicity and autophagy in diabetic kidney disease," JMA J., vol. 3, no. 1, pp. 6–12, 2020.