Association Between Glycemic Control and Complications With Concentration of Urinary Exfoliated Proximal Tubule Kidney Cells in People With Diabetes Mellitus

Overview

Journal J Diabetes Res

Publisher Wiley

Date 2025 Jan 24

PMID 39850513

Authors

Henry H L Wu

Venkatesha Bhagavath

Long The Nguyen

Rajkumar Chinnadurai

Ewa M Goldys

Carol A Pollock

Sonia Saad

Affiliations

Soon will be listed here.

Abstract

Emerging evidence suggests cell exfoliation could be operating under the control of cell metabolism. It is unclear if there are associations between the concentration of exfoliated kidney proximal tubule cells (PTCs) in urine with glycemic control and complications. Our study is aimed at exploring this. Urine samples were collected from 122 adult study participants and stored at -80°C. Exfoliated PTCs were extracted from thawed urine using a validated specific immunomagnetic separation method based on anti-CD13 and anti-SGLT-2 antibodies. The number of PTCs was assessed using brightfield microscopy. Study participants were grouped into those with no diabetes mellitus (DM) and those with DM. Individuals with DM were further subgrouped into those with and without retinopathy. Adjusted Poisson regression analysis was conducted for the DM cohort, investigating associations between demographic, clinical, and biochemical parameters with mean urinary exfoliated PTCs. The adjusted Poisson regression analysis noted sex to have a significant association with mean number of urinary exfoliated PTCs, with a lower incidence rate in males compared to females (incidence rate ratio (IRR) 0.56, 95% CI 0.35-0.89, = 0.014). Each 1% increase in glycated haemoglobin (HbA1c) was associated with an increase of 1.03 times in mean exfoliated PTCs (IRR 1.03, 95% CI 1.01-1.04, = 0.007), and DM patients with retinopathy had an increase of 1.68 times in mean exfoliated PTCs compared to those without retinopathy (IRR 1.68, 95% CI 1.07-2.62, = 0.024). No significant associations were observed with albuminuria or estimated glomerular filtration rate (eGFR). Our results indicate increased shedding of PTCs into the urinary tract in patients with poorer glycemic control, particularly those with diabetic retinopathy and in females.

References

Lu Y, Liu D, Feng Q, Liu Z . Diabetic Nephropathy: Perspective on Extracellular Vesicles. Front Immunol. 2020; 11:943. PMC: 7283536. DOI: 10.3389/fimmu.2020.00943. View

Mahbub S, Nguyen L, Habibalahi A, Campbell J, Anwer A, Qadri U . Non-invasive assessment of exfoliated kidney cells extracted from urine using multispectral autofluorescence features. Sci Rep. 2021; 11(1):10655. PMC: 8138006. DOI: 10.1038/s41598-021-89758-4. View

Petermann A, Pippin J, Krofft R, Blonski M, Griffin S, Durvasula R . Viable podocytes detach in experimental diabetic nephropathy: potential mechanism underlying glomerulosclerosis. Nephron Exp Nephrol. 2005; 98(4):e114-23. DOI: 10.1159/000081555. View

Detrisac C, Mayfield R, Colwell J, Garvin A, Sens D . In vitro culture of cells exfoliated in the urine by patients with diabetes mellitus. J Clin Invest. 1983; 71(1):170-3. PMC: 436850. DOI: 10.1172/jci110747. View

Curtis T, Gardiner T, Stitt A . Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?. Eye (Lond). 2009; 23(7):1496-508. DOI: 10.1038/eye.2009.108. View

Wei H, Liu S, Liao Y, Ma C, Wang D, Tong J . A Systematic Review of the Medicinal Potential of Mulberry in Treating Diabetes Mellitus. Am J Chin Med. 2018; 46(8):1743-1770. DOI: 10.1142/S0192415X1850088X. View

Levine B, Klionsky D . Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004; 6(4):463-77. DOI: 10.1016/s1534-5807(04)00099-1. View

Huebschmann A, Regensteiner J, Vlassara H, Reusch J . Diabetes and advanced glycoxidation end products. Diabetes Care. 2006; 29(6):1420-32. DOI: 10.2337/dc05-2096. View

Wu H, Goldys E, Pollock C, Saad S . Exfoliated Kidney Cells from Urine for Early Diagnosis and Prognostication of CKD: The Way of the Future?. Int J Mol Sci. 2022; 23(14). PMC: 9324667. DOI: 10.3390/ijms23147610. View

10.

Ng K, Cao Z, Chen H, Zhao Z, Zhu L, Yi T . Oolong tea: A critical review of processing methods, chemical composition, health effects, and risk. Crit Rev Food Sci Nutr. 2017; 58(17):2957-2980. DOI: 10.1080/10408398.2017.1347556. View

11.

Cockcroft D, GAULT M . Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16(1):31-41. DOI: 10.1159/000180580. View

12.

Bertrand K . Survival of exfoliated epithelial cells: a delicate balance between anoikis and apoptosis. J Biomed Biotechnol. 2011; 2011:534139. PMC: 3205804. DOI: 10.1155/2011/534139. View

13.

Horton W, Barrett E . Microvascular Dysfunction in Diabetes Mellitus and Cardiometabolic Disease. Endocr Rev. 2020; 42(1):29-55. PMC: 7846151. DOI: 10.1210/endrev/bnaa025. View

14.

Lytvyn Y, Xiao F, Kennedy C, Perkins B, Reich H, Scholey J . Assessment of urinary microparticles in normotensive patients with type 1 diabetes. Diabetologia. 2016; 60(3):581-584. DOI: 10.1007/s00125-016-4190-2. View

15.

Coughlan M, Cooper M, Forbes J . Renal microvascular injury in diabetes: RAGE and redox signaling. Antioxid Redox Signal. 2006; 9(3):331-42. DOI: 10.1089/ars.2006.1469. View

16.

Gailit J, Colflesh D, Rabiner I, Simone J, Goligorsky M . Redistribution and dysfunction of integrins in cultured renal epithelial cells exposed to oxidative stress. Am J Physiol. 1993; 264(1 Pt 2):F149-57. DOI: 10.1152/ajprenal.1993.264.1.F149. View

17.

Pereira-Moreira R, Muscelli E . Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review. J Diabetes Res. 2020; 2020:8492467. PMC: 7180501. DOI: 10.1155/2020/8492467. View

18.

Inker L, Eneanya N, Coresh J, Tighiouart H, Wang D, Sang Y . New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021; 385(19):1737-1749. PMC: 8822996. DOI: 10.1056/NEJMoa2102953. View

19.

Liang X, Wang P, Chen B, Ge Y, Gong A, Flickinger B . Glycogen synthase kinase 3β hyperactivity in urinary exfoliated cells predicts progression of diabetic kidney disease. Kidney Int. 2019; 97(1):175-192. DOI: 10.1016/j.kint.2019.08.036. View

20.

Lee D, Huang E, Ward H . Tight junction biology and kidney dysfunction. Am J Physiol Renal Physiol. 2005; 290(1):F20-34. DOI: 10.1152/ajprenal.00052.2005. View