Novel Markers in Diabetic Kidney Disease-Current State and Perspectives

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2022 May 28

PMID 35626360

Authors

Agnieszka Piwkowska

Lukasz Zdrojewski

Zbigniew Heleniak

Alicja Debska-Slizien

Affiliations

Soon will be listed here.

Abstract

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Along with the increasing prevalence of diabetes, DKD is expected to affect a higher number of patients. Despite the major progress in the therapy of DKD and diabetes mellitus (DM), the classic clinical diagnostic tools in DKD remain insufficient, delaying proper diagnosis and therapeutic interventions. We put forward a thesis that there is a need for novel markers that will be early, specific, and non-invasively obtained. The ongoing investigations uncover new molecules that may potentially become new markers of DKD-among those are: soluble α-Klotho and proteases (ADAM10, ADAM17, cathepsin, dipeptidyl peptidase 4, caspase, thrombin, and circulating microRNAs). This review summarizes the current clinical state-of-the-art in the diagnosis of DKD and a selection of potential novel markers, based on up-to-date literature.

Citing Articles

Mechanisms, Biomarkers, and Treatment Approaches for Diabetic Kidney Disease: Current Insights and Future Perspectives.

Joumaa J, Raffoul A, Sarkis C, Chatrieh E, Zaidan S, Attieh P J Clin Med. 2025; 14(3).

PMID: 39941397 PMC: 11818458. DOI: 10.3390/jcm14030727.

Association Between Serum α-Klotho Levels and Diabetic Kidney Disease Prevalence in Middle-Aged and Elderly US Patients with Diabetes: A Cross-Sectional Study Using NHANES 2007-2016 Data.

Ding S, Sun J, Wang L, Wu L, Liu W Diabetes Ther. 2025; 16(3):499-511.

PMID: 39928222 PMC: 11868003. DOI: 10.1007/s13300-024-01683-7.

Predictive value of bone metabolism markers in the progression of diabetic kidney disease: a cross-sectional study.

Kang Y, Jin Q, Zhou M, Li Z, Zheng H, Li D Front Endocrinol (Lausanne). 2024; 15:1489676.

PMID: 39558979 PMC: 11570274. DOI: 10.3389/fendo.2024.1489676.

Associations between the TyG index and the ɑ-Klotho protein in middle-aged and older population relevant to diabetes mellitus in NHANES 2007-2016.

Qiu S, Li C, Zhu J, Guo Z Lipids Health Dis. 2024; 23(1):188.

PMID: 38907289 PMC: 11191244. DOI: 10.1186/s12944-024-02172-3.

Association between Albumin Alterations and Renal Function in Patients with Type 2 Diabetes Mellitus.

Nugnes M, Baldassarre M, Ribichini D, Tedesco D, Capelli I, Vetrano D Int J Mol Sci. 2024; 25(6).

PMID: 38542146 PMC: 10970212. DOI: 10.3390/ijms25063168.

References

McGuire D, Shih W, Cosentino F, Charbonnel B, Cherney D, Dagogo-Jack S . Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis. JAMA Cardiol. 2020; 6(2):148-158. PMC: 7542529. DOI: 10.1001/jamacardio.2020.4511. View

Mogensen C, Christensen C, Vittinghus E . The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983; 32 Suppl 2:64-78. DOI: 10.2337/diab.32.2.s64. View

Ford B, Eid A, Gooz M, Barnes J, Gorin Y, Abboud H . ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice. Am J Physiol Renal Physiol. 2013; 305(3):F323-32. PMC: 3742865. DOI: 10.1152/ajprenal.00522.2012. View

Mundel P, Reiser J . Proteinuria: an enzymatic disease of the podocyte?. Kidney Int. 2009; 77(7):571-80. PMC: 4109304. DOI: 10.1038/ki.2009.424. View

Kim H, Nam B, Kim D, Kang M, Han J, Lee M . Circulating α-klotho levels in CKD and relationship to progression. Am J Kidney Dis. 2013; 61(6):899-909. DOI: 10.1053/j.ajkd.2013.01.024. View

Kurosu H, Yamamoto M, Clark J, Pastor J, Nandi A, Gurnani P . Suppression of aging in mice by the hormone Klotho. Science. 2005; 309(5742):1829-33. PMC: 2536606. DOI: 10.1126/science.1112766. View

Kramer H, Nguyen Q, Curhan G, Hsu C . Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA. 2003; 289(24):3273-7. DOI: 10.1001/jama.289.24.3273. View

Holthofer H, Ahola H, Solin M, Wang S, Palmen T, Luimula P . Nephrin localizes at the podocyte filtration slit area and is characteristically spliced in the human kidney. Am J Pathol. 1999; 155(5):1681-7. PMC: 1866978. DOI: 10.1016/S0002-9440(10)65483-1. View

Krochmal M, Kontostathi G, Magalhaes P, Makridakis M, Klein J, Husi H . Urinary peptidomics analysis reveals proteases involved in diabetic nephropathy. Sci Rep. 2017; 7(1):15160. PMC: 5680307. DOI: 10.1038/s41598-017-15359-9. View

10.

Bell H, Gooz M . ADAM-17 is activated by the mitogenic protein kinase ERK in a model of kidney fibrosis. Am J Med Sci. 2010; 339(2):105-7. PMC: 2834474. DOI: 10.1097/MAJ.0b013e3181cb4487. View

11.

Petrica L, Ursoniu S, Gadalean F, Vlad A, Gluhovschi G, Dumitrascu V . Urinary podocyte-associated mRNA levels correlate with proximal tubule dysfunction in early diabetic nephropathy of type 2 diabetes mellitus. Diabetol Metab Syndr. 2017; 9:31. PMC: 5420400. DOI: 10.1186/s13098-017-0228-y. View

12.

Akimoto T, Yoshizawa H, Watanabe Y, Numata A, Yamazaki T, Takeshima E . Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease. BMC Nephrol. 2012; 13:155. PMC: 3519712. DOI: 10.1186/1471-2369-13-155. View

13.

Gooz P, Dang Y, Higashiyama S, Twal W, Haycraft C, Gooz M . A disintegrin and metalloenzyme (ADAM) 17 activation is regulated by α5β1 integrin in kidney mesangial cells. PLoS One. 2012; 7(3):e33350. PMC: 3297637. DOI: 10.1371/journal.pone.0033350. View

14.

Sharkovska Y, Reichetzeder C, Alter M, Tsuprykov O, Bachmann S, Secher T . Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy. J Hypertens. 2014; 32(11):2211-23. DOI: 10.1097/HJH.0000000000000328. View

15.

. 11. Chronic Kidney Disease and Risk Management: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2021; 45(Suppl 1):S175-S184. DOI: 10.2337/dc22-S011. View

16.

Qi C, Mao X, Zhang Z, Wu H . Classification and Differential Diagnosis of Diabetic Nephropathy. J Diabetes Res. 2017; 2017:8637138. PMC: 5337846. DOI: 10.1155/2017/8637138. View

17.

Zelniker T, Wiviott S, Raz I, Im K, Goodrich E, Furtado R . Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus. Circulation. 2019; 139(17):2022-2031. DOI: 10.1161/CIRCULATIONAHA.118.038868. View

18.

Rinschen M, Huesgen P, Koch R . The podocyte protease web: uncovering the gatekeepers of glomerular disease. Am J Physiol Renal Physiol. 2018; 315(6):F1812-F1816. DOI: 10.1152/ajprenal.00380.2018. View

19.

Yokoyama H, Araki S, Honjo J, Okizaki S, Yamada D, Shudo R . Association between remission of macroalbuminuria and preservation of renal function in patients with type 2 diabetes with overt proteinuria. Diabetes Care. 2013; 36(10):3227-33. PMC: 3781501. DOI: 10.2337/dc13-0281. View

20.

Rondeau E, Vigneau C, Berrou J . Role of thrombin receptors in the kidney: lessons from PAR1 knock-out mice. Nephrol Dial Transplant. 2001; 16(8):1529-31. DOI: 10.1093/ndt/16.8.1529. View