Urinary miRNA-377 and miRNA-216a as biomarkers of nephropathy and subclinical atherosclerotic risk in pediatric patients with type 1 diabetes Mona Hussein El-Samahy a , Amira AbdelMoneam Adly a, ⁎, Yasmine Ibrahim Elhenawy a , Eman AbdelRahman Ismail b , Shaimaa Abdelmalik Pessar b , Mohamed El-Sayed Mowafy a , Mohammed Salah Saad a , Hossam Hassan Mohammed a a Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt b Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt abstract article info Article history: Received 11 February 2017 Received in revised form 23 October 2017 Accepted 28 October 2017 Available online xxxx Keywords: Type 1 diabetes Nephropathy Urinary micorRNA CIMT Atherosclerosis Background: Urinary microRNAs (miRNAs) play a role in the pathogenesis of chronic kidney disease (CKD). Aim: To identify the expression of urinary miR-377 and miR-216a in 50 children and adolescents with type 1 di- abetes (T1DM) compared with 50 healthy controls and assess their relation to the degree of albuminuria, glyce- mic control and carotid intimal thickness (CIMT) as an index of atherosclerosis. Methods: Diabetic subjects were divided into normoalbuminuric and microalbuminuric groups according to uri- nary albumin creatinine ration (UACR). Urinary miRNAs were assessed using real time polymerase chain reac- tion. CIMT was measured using high resolution carotid ultrasound. Results: The expression of urinary miR-377 was significantly higher in patients with microalbumiuria (median, 3.8) compared with 2.65 and 0.98 in normoalbuminic patients and healthy controls, respectively (p b 0.05). Uri- nary miR-216a was significantly lower in all patients with type 1 diabetes and the lowest levels were among the microalbumiuric group. Significant positive correlations were found between urinary miR-377 and HbA1C, UACR and CIMT while urinary miR-216a was negatively correlated to these variables. Conclusions: Urinary miR-377 and miR-216a can be considered early biomarkers of nephropathy in pediatric type 1 diabetes. Their correlation with CIMT provides insights on the subclinical atherosclerotic process that occurs in diabetic nephropathy. © 2017 Elsevier Inc. All rights reserved. 1. Introduction Diabetic nephropathy (DN) is characterized by excessive accumulation of extracellular matrix (ECM) with thickening of glomer- ular and tubular basement membranes and increased amount of mesangial matrix, which ultimately progresses to glomerulosclerosis and tubulointerstitial fibrosis. 1,2 DN is a leading cause of end stage renal disease (ESRD). 3,4 Patients with type 1 diabetes mellitus (T1DM) are at risk of DN. Hence, a better understanding of the factors affecting disease from hyperfiltration to microalbuminuria, dipstick positive macroalbuminuria, impaired filtration and ESRD in patients with T1DM is urgently needed. 5,6 Early identification of patients who are prone to develop renal com- plications would be an important step for their better management dur- ing the clinical course of this disease process. 7 There are no suitable biomarkers for the diagnosis of early stages of DN. 8 Albuminuria both reflects and results from nephropathy. Testing for albuminuria among people with diabetes identifies people at higher risk of subsequent com- plications and identifies people to whom to offer treatment. 9 Elevated urinary albumin excretion (UAE) has been linked with in- creased cardiovascular disease mortality in individuals with and with- out diabetes. 10 Therefore, children with T1DM have the risk of cardiovascular diseases that may appear later. Thus, defining factors re- sponsible for atherosclerosis is of great importance. The most significant changes in early subclinical period of atherosclerotic disease are endo- thelial dysfunction and increase in intima-media thickness observed in all arterial beds. 11 A noninvasive ultrasound measurement of carotid Journal of Diabetes and Its Complications xxx (2017) xxx–xxx All the authors equally contributed in this article. Contributors: All authors were involved in concept, design, data collection, analysis and drafting of the manuscript. The authors have no disclosures to declare. Financial disclosure: None Competing interest: None ⁎ Corresponding author at: 6 A ElSheshini Street, Shoubra, Soudia Buildings, Cairo, Egypt. E-mail address: amiraadly73@med.asu.edu.eg (A.A. Adly). https://doi.org/10.1016/j.jdiacomp.2017.10.014 1056-8727/© 2017 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Journal of Diabetes and Its Complications journal homepage: www.jdcjournal.com Please cite this article as: El-Samahy MH, et al. Urinary miRNA-377 and miRNA-216a as biomarkers of nephropathy and subclinical atherosclerotic risk in pediatric patients with type.... Journal of Diabetes and Its Complications (2017), https://doi.org/10.1016/j.jdiacomp.2017.10.014