Abstract
Diabetic kidney disease (DKD) is the main microvascular complication in patients with diabetes mellitus; it is an entity that generates a significant increase in mortality of cardiovascular origin in this group of patients, although its early diagnosis has a significant impact on the evolution to end-stage kidney disease and, therefore, on mortality. The detection of albuminuria in urine and the deterioration of the estimated glomerular filtration rate are the main diagnostic techniques that are used in clinical practice to establish the presence of DKD; however, they have limitations and therefore it is important to note that kidney damage is usually irreversible once they are present. Over the last few years, numerous studies have focused on the discovery of new biomarkers to detect DKD and this is where the urinary proteomics appears as a new tool, an emerging technology that allows the identification of proteins in a urine sample that strongly suggest the early presence of this disease. Likewise, the discovery of proteomic-based biomarkers represents a novel strategy to improve the diagnosis, prognosis, and treatment of diabetic nephropathy; however, proteomics-based approaches are not yet available in the majority of clinical chemistry laboratories.
References
American Diabetes Association. Standars of Medical Care in Diabetes - 2020. Diabetes Care J Clin Appl Res Educ. Published online 2020.
Chan GCW, Tang SCW. Diabetic nephropathy: Landmark clinical trials and tribulations. Nephrol Dial Transplant. Published online 2016. doi:10.1093/ndt/gfu411
Anders HJ, Huber TB, Isermann B, Schiffer M. CKD in diabetes: Diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. Published online 2018. doi:10.1038/s41581-018-0001-y
Umanath K, Lewis JB. Update on Diabetic Nephropathy: Core Curriculum 2018. Am J Kidney Dis. Published online 2018. doi:10.1053/j.ajkd.2017.10.026
Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci. Published online 2013. doi:10.1042/CS20120198
Duran-Salgado MB. Diabetic nephropathy and inflammation. World J Diabetes. Published online 2014. doi:10.4239/wjd.v5.i3.393
Peti-Peterdi J, Kang JJ, Toma I. Activation of the renal renin-angiotensin system in diabetes - New concepts. Nephrol Dial Transplant. Published online 2008. doi:10.1093/ndt/gfn377
Musante L, Tataruch D, Gu D, et al. Proteases and protease inhibitors of urinary extracellular vesicles in diabetic nephropathy. J Diabetes Res. Published online 2015. doi:10.1155/2015/289734
Livingstone SJ, Levin D, Looker HC, et al. Estimated life expectancy in a scottish cohort with type 1 diabetes, 2008-2010. JAMA - J Am Med Assoc. Published online 2015. doi:10.1001/jama.2014.16425
Tonneijck L, Muskiet MHA, Smits MM, et al. Glomerular hyperfiltration in diabetes: Mechanisms, clinical significance, and treatment. J Am Soc Nephrol. Published online 2017. doi:10.1681/ASN.2016060666
Porrini E, Ruggenenti P, Luis-Lima S, et al. Estimated GFR: time for a critical appraisal. Nat Rev Nephrol. Published online 2019. doi:10.1038/s41581-018-0080-9
Mansour I, Thajudeen B. Overview of diabetic nephropathy. In: Managing Diabetic Nephropathies in Clinical Practice. ; 2017. doi:10.1007/978-3-319-08873-0
Berhane AM, Weil EJ, Knowler WC, Nelson RG, Hanson RL. Albuminuria and estimated glomerular filtration rate as predictors of diabetic end-stage renal disease and death. Clin J Am Soc Nephrol. Published online 2011. https://dx.doi.org/10.2215/CJN.00580111
Zeni L, Norden AGW, Cancarini G, Unwin RJ. A more tubulocentric view of diabetic kidney disease. J Nephrol. Published online 2017. doi:10.1007/s40620-017-0423-9
Ruggenenti P, Porrini EL, Gaspari F, et al. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care. Published online 2012. doi:10.2337/dc11-2189
Schalkwijk CG, Stehouwer CDA. Vascular complications in diabetes mellitus: The role of endothelial dysfunction. Clin Sci. Published online 2005. doi:10.1042/CS20050025
Toth-Manikowski S, Atta MG. Diabetic kidney disease: Pathophysiology and therapeutic targets. J Diabetes Res. Published online 2015. doi:10.1155/2015/697010
Restrepo-Valencia CA, Buitrago-Villa CA, Torres-Saltarín JJ, Serna-Flórez J, editores. Ne-frología básica 2. Bogotá D.C.: Asociacxión Colombiana de Nefrología e Hipertención Ar-terial; 2019.
American Diabetes Association. 11. Microvascular complications and foot care: Standardsof Medical Care in Diabete-2020. Diabetes Care. 2020;43(Suppl 1):S135-S151. https://dx.doi.org/10.2337/dc20-S011.
Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease: A report from an ADA consensus conference. Diabetes Care. Published online 2014. doi:10.2337/dc14-1296
National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD:2012 update. Am J Kidney Dis. 2012;60(5):850-86. https://dx.doi.org/10.1053/j.ajkd.2012.07.005
Wang L, Wu J, Cheng JF, et al. Diagnostic value of quantitative contrast-enhanced ultrasound (CEUS) for early detection of renal hyperperfusion in diabetic kidney disease. J Nephrol. Published online 2015. doi:10.1007/s40620-015-0183-3
Filip S, Zoidakis J, Vlahou A, Mischak H. Advances in urinary proteome analysis and applications in systems biology. Bioanalysis. Published online 2014. doi:10.4155/bio.14.210
Merchant ML, Klein JB. Proteomic Discovery of Diabetic Nephropathy Biomarkers. Adv Chronic Kidney Dis. Published online 2010. doi:10.1053/j.ackd.2010.09.001
Moresco RN, Sangoi MB, De Carvalho JAM, Tatsch E, Bochi G V. Diabetic nephropathy: Traditional to proteomic markers. Clin Chim Acta. Published online 2013. doi:10.1016/j.cca.2013.02.019
Wu J, Chen YD, Gu W. Urinary proteomics as a novel tool for biomarker discovery in kidney diseases. J Zhejiang Univ Sci B. Published online 2010. doi:10.1631/jzus.B0900327
Gao YH. Urine-an untapped goldmine for biomarker discovery? Sci China Life Sci. Published online 2013. doi:10.1007/s11427-013-4574-1
Weissinger EM, Wittke S, Kaiser T, et al. Proteomic patterns established with capillary electrophoresis and mass spectrometry for diagnostic purposes. Kidney Int. Published online 2004. doi:10.1111/j.1523-1755.2004.00659.x
Haubitz M, Wittke S, Weissinger EM, et al. Urine protein patterns can serve as diagnostic tools in patients with IgA nephropathy. Kidney Int. Published online 2005. doi:10.1111/j.1523-1755.2005.00335.x
Julian BA, Wittke S, Novak J, et al. Electrophoretic methods for analysis of urinary polypeptides in lgA-associated renal diseases. Electrophoresis. Published online 2007. doi:10.1002/elps.200700237
Rossing K, Mischak H, Dakna M, et al. Urinary proteomics in diabetes and CKD. J Am Soc Nephrol. Published online 2008. doi:10.1681/ASN.2007091025
Haubitz M, Good DM, Woywodt A, et al. Identification and validation of urinary biomarkers for differential diagnosis and evaluation of therapeutic intervention in anti-neutrophil cytoplasmic antibody-associated vasculitis. Mol Cell Proteomics. Published online 2009. doi:10.1074/mcp.M800529-MCP200
Zou L, Sun W. Human urine proteome: A powerful source for clinical research. Adv Exp Med Biol. Published online 2015. doi:10.1007/978-94-017-9523-4_4
Jun M, Ohkuma T, Zoungas S, et al. Changes in albuminuria and the risk of major clinical outcomes in diabetes: Results from ADVANCE-ON. Diabetes Care. Published online 2018. doi:10.2337/dc17-1467
Thongboonkerd V. Study of diabetic nephropathy in the proteomic era. Contrib Nephrol. Published online 2011. doi:10.1159/000325657
Zürbig P, Jerums G, Hovind P, et al. Urinary proteomics for early diagnosis in diabetic nephropathy. Diabetes. Published online 2012. doi:10.2337/db12-0348
Papale M, Di Paolo S, Magistroni R, et al. Urine proteome analysis may allow noninvasive differential diagnosis of diabetic nephropathy. Diabetes Care. Published online 2010. doi:10.2337/dc10-0345
Roscioni SS, De Zeeuw D, Hellemons ME, et al. A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus. Diabetologia. Published online 2013. doi:10.1007/s00125-012-2755-2
Nielsen SE, Schjoedt KJ, Astrup AS, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM1) in patients with diabetic nephropathy: A cross-sectional study and the effects of lisinopril. Diabet Med. Published online 2010. doi:10.1111/j.1464-5491.2010.03083.x

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