Diagnostic value of renal tubular and glomerular markers in different stages of renal injury in patients with type 2 diabetes

doi:10.3969/j.issn.1006-7795.2024.03.009

Abstract

Abstract: Objective To investigate the diagnostic value of renal tubular and glomerular markers in type 2 diabetes patients at different stages of renal injury. Methods Totally 272 patients with type 2 diabetes mellitus (T2DM) admitted to the Department of Endocrinology, Beijing Tongren Hospital，Capital Medical University, from April 1, 2018 to October 31, 2019 were enrolled, to improve the clinical biochemical indicators and four items of urine protein: urinary microalbumin/creatinine (ACR), α1-microglobulin/creatinine (UA1CR), urinary immunoglobulin G to creatinine ratio (UIGG), transferrin/creatinine (UTRF); Perform fundus photography, nuclear medicine 99mTc-EC to measure renal effective plasma flow (ERPF), and 99mTc-DTPA to measure glomerular filtration rate (GFR). According to ACR, there were 164 cases in the normal proteinuria group, 78 cases in the microalbuminuria group, and 30 cases in the macroproteinuria group. The normal proteinuria group was divided into control group ［132 cases without diabetes retinopathy (DR)］ and diabetic kidney disease (DKD） early stage group (32 cases with DR) according to fundus examination. Compare the levels of urinary protein, ERPF, and GFR among four groups, and evaluate the diagnostic value of the above indicators in different stages of renal injury through ROC curves. Results There were statistical differences (P<0.05) in the levels of urinary protein, ERPF, and GFR among different groups. In the normal urine protein group, the markers representing renal tubular function in the DR group were significantly higher in UA1CR compared to the control group (P<0.01); The markers representing glomerular function, ACR, UTRF, and GFR, showed no significant statistical difference between the two groups (P>0.05), while UIGG increased compared to the control group (P<0.01). In the group of microalbuminuria and the group of macroproteinuria, the four urinary protein levels increased with the degree of renal injury, while ERPF and GFR decreased with the degree of renal injury. ROC curve analysis showed that the area under curve (AUC) of UA1CR and ERPF, the markers reflecting renal tubular function, in type 2 diabetes patients with DR who had normal urinary protein excretion, were 68.2% (P<0.01) and 60.5% (P<0.05), respectively, while the AUC of classic ACR and GFR reflecting glomerular function were less than 60% (P>0.05) without statistical significance. The AUC of urinary protein and GFR in both trace and high proteinuria groups was greater than 60% (P<0.05), while the AUC of ERPF in high proteinuria group was 67.2% (P<0.05). Conclusion In the very early stage of T2DM, when ACR is normal and only DR is present, renal tubular markers UA1CR and ERPF undergo changes before glomerular markers ACR and GFR. In the early stage of renal injury, the diagnostic efficacy of renal tubular markers is superior to that of glomeruli; In the later stage of renal injury, the diagnostic efficacy of glomerular markers is due to the renal tubules. The changes in renal tubular function in DKD may occur earlier than in the glomerulus.

Key words: renal tubular biomarkers, diabetes nephropathy, α1-microglobulin, renal effective plasma flow, area under the receiver operating characteristic curve

CLC Number:

R587.1

Zhang Lin, Xie Rongrong, Yang Fangyuan, Li Mei, Luo Sha, Wan Xiaohua, Tian Wei, Yang Jinkui. Diagnostic value of renal tubular and glomerular markers in different stages of renal injury in patients with type 2 diabetes[J]. Journal of Capital Medical University, 2024, 45(3): 429-437.

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References

［1］中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版)［J］. 中华糖尿病杂志, 2021, 13(4): 315-409.
［2］ Alicic R Z, Rooney M T, Tuttle K R. Diabetic kidney disease: challenges, progress, and possibilities［J］. Clin J Am Soc Nephrol, 2017, 12(12): 2032-2045.
［3］ Afkarian M, Zelnick L R, Hall Y N, et al. Clinical manifestations of kidney disease among US adults with diabetes, 1988—2014［J］. JAMA, 2016, 316(6): 602-610.
［4］ Wan X H, Zhang L, Gu H T, et al. The association of serum hsCRP and urinary alpha1-microglobulin in patients with type 2 diabetes mellitus［J］. Biomed Res Int, 2019, 2019: 6364390.
［5］ Zhou Y K, Zhang Y D, Chen J J, et al. Diagnostic value of α1—MG and URBP in early diabetic renal impairment［J］. Front Physiol, 2023, 14: 1173982.
［6］ Scilletta S, Di M M, Miano N, et al. Update on diabetic kidney disease (DKD): focus on non-albuminuric DKD and cardiovascular risk［J］. Biomolecules, 2023, 13(5): 752.
［7］ Tan R J, Zhou D, Liu Y H. Signaling crosstalk between tubular epithelial cells and interstitial fibroblasts after kidney injury［J］. Kidney Dis (Basel), 2016, 2(3): 136-144.
［8］姚立新, 李昨非, 刘波, 等. 糖尿病患者肾小球滤过率和肾有效血浆流量的改变及影响因素分析［J］. 国际放射医学核医学杂志, 2010, 34(5): 281-284.
［9］ Jiang X, Zhang Q, Wang H B, et al. Associations of urinary, glomerular, and tubular markers with the development of diabetic kidney disease in type 2 diabetes patients［J］. J Clin Lab Anal, 2018, 32(1): e22191.
［10］ Zhao L J, Ren H H, Zhang J L, et al. Diabetic retinopathy, classified using the lesion-aware deep learning system, predicts diabetic end-stage renal disease in Chinese patients［J］. Endocr Pract, 2020, 26(4): 429-443.
［11］ Cankurtaran V, Inanc M, Tekin K, et al. Retinal microcirculation in predicting diabetic nephropathy in type 2 diabetic patients without retinopathy［J］. Ophthalmologica, 2020, 243(4): 271-279.
［12］ Alberti K G, Zimmet P Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation［J］. Diabet Med, 1998, 15(7): 539-553.
［13］ Wilkinson C P, Ferris F L, Klein R E, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales［J］. Ophthalmology, 2003, 110(9): 1677-1682.
［14］ Martínez C A, Navarro G J F, Górriz J L, et al. The concept and the epidemiology of diabetic nephropathy have changed in recent years［J］. J Clin Med, 2015, 4(6): 1207-1216.
［15］ Yao L, Liang X H, Qiao Y J, et al. Mitochondrial dysfunction in diabetic tubulopathy［J］. Metabolism, 2022, 131: 155195.
［16］ Lee K, He J C. AKI-to-CKD transition is a potential mechanism for non-albuminuric diabetic kidney disease［J］. Fac Rev. 2022, 11: 21.
［17］中华医学会内分泌学分会. 中国成人糖尿病肾脏病临床诊断的专家共识［J］. 中华内分泌代谢杂志, 2015, 31(5): 379-385.
［18］ Shore N, Khurshid R, Saleem M. Alpha-1 microglobulin: a marker for early detection of tubular disorders in diabetic nephropathy［J］. J Ayub Med Coll Abbottabad, 2010, 22(4): 53-55.
［19］ Petrica L, Petrica M, Vlad A, et al. Proximal tubule dysfunction is dissociated from endothelial dysfunction in normoalbuminuric patients with type 2 diabetes mellitus: a cross-sectional study［J］. Nephron Clin Pract, 2011, 118(2): c155-c164.
［20］ Narita T K A, Hosoba M, Kakei M, et al. Increased urinary excretions of immunoglobulin G, ceruloplasmin, and transferrin predict development of microalbuminuria in patients with type 2 diabetes［J］. Diabetes Care, 2006, 29(1): 142-144.
［21］ Mohan S, Kalia K, Mannari J. Association between urinary IgG and relative risk for factors affecting proteinuria in type 2 diabetic patients［J］. Indian J Clin Biochem, 2012, 27(4): 333-339.
［22］ Kazumi T, Hozumi T, Ishida Y, et al. Increased urinary transferrin excretion predicts microalbuminuria in patients with type 2 diabetes［J］. Diabetes Care, 1999, 22(7): 1176-1180.
［23］ Xu X Y, Gao B, Ding W X, et al. Retinal image measurements and their association with chronic kidney disease in Chinese patients with type 2 diabetes: the NCD study［J］. Acta Diabetol, 2021, 58(3): 363-370.

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