Urinary Smad1 as a New Biomarker for Diabetic Nephropathy in Patients with
Type 1 Diabetes Mellitus
Mohamed Mohamed Ismail
*
and Sally kamal Ibrahim
Cairo University Kasr Alainy, Cairo, Egypt
*
Corresponding authors: Mohamed Mohamed Ismail, Faculty of Medicine, Cairo University Kasr Alainy, Cairo, Egypt, Tel: 0201144479999; E-mail:
mohamed_i_smail@yahoo.com
Received date: July 25, 2017; Accepted date: August 16, 2017; Published date: August 20, 2017
Copyright: © 2017 Ismail MM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Introduction: Type 1 diabetes mellitus is an autoimmune disease affecting children worldwide with many
consequences disturbing their quality of life. Diabetic nephropathy is among the most important complications of
T1DM. The reliability of albuminuria as a predictor and prognosticator for renal injury has been frequently
questioned. Many markers were investigated to replace urinary albumin. The current study aimed to assess the
potential value of urinary Smad1 as a new biomarker for the early diagnosis and assessment of severity of diabetic
nephropathy in children with.
Material and method: A case control cross sectional study with 53 patients with type 1 diabetes mellitus. 30
patients with diabetic nephropathy including 19 patients with microalbuminuria (urinary albumin creatinine ratio:
30-300 mg/gm) and 11 patients with macroalbuminuria (urinary albumin creatinine ratio: >300 mg/gm). The
remainder 23 patients had normal urinary albumin levels. In addition, there were 20 healthy age and sex matched
children who served as control group. In all subjects we assessed urinary albumin, urinary creatinine and urinary
albumin creatinine ratio and urinary Smad1 levels
Results: Urinary Smad1 levels and urinary Smad1 creatinine ratio show good sensitivity and specificity in
detection of DN as compared to urinary albumin. The performance of SCR was better than urinary Smad1 with
sensitivity and specificity of 100.0% and 96.0% for SCR, compared to sensitivity and specificity of 90.0% and 91.0%
for urinary Smad1.
Conclusion: Urinary Smad1 is a promising new biomarker for detection of diabetic nephropathy in patients with
type 1 diabetes mellitus with high sensitivity and specificity.
Keywords: Urinary Smad1; Biomarkers; Diabetic nephropathy
Introduction
Diabetes mellitus type 1 (T1DM) is an autoimmune disease
afecting children worldwide with many consequences disturbing their
quality of life. Diabetic nephropathy (DN) is among the most
important complications of T1DM with signifcant association to
patients’ morbidity and mortality [1].
Currently, albuminuria is generally accepted as an early marker for
detection of DN. However, reliability of albuminuria as a predictor and
prognosticator for renal injury has been ofen questioned due to the
fact that even patients with normal urinary albumin levels can sufer
substantial pathological injury [2] or reduced glomerular fltration rate
(GFR) [3]. In addition micro albuminuria, as an early marker for
diabetic nephropathy, has numerous confusing concerns related to the
efect of exercise, urinary tract infection, acute illness and cardiac
failure. Also, it is known that micro albuminuria and macro
albuminuria can occur in non-diabetic subjects, signifying the non-
specifcity of albuminuria as a predictor designed for early diagnosis of
diabetic nephropathy [4]. Tis led to a continuous pursuit for other
biomarkers to overcome this essential faw.
In this context, many markers were investigated. Mehta et al.
classifed urinary biomarkers according to the mechanism of their
secretion in urine into markers of increased glomerular permeability
including albumin, Cystatin C, immunoglobulins and transferrin;
markers of extracellular matrix including transforming growth factor-
beta (TGF-β), connective tissue growth factor (CTGF), Type IV
collagen and Fibronectin; markers of epithelial-mesenchymal
transition including fbronectin, matrix metalloproteinase and α-
smooth muscle actin; markers of tubulointerstitial damage including
kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated
lipocalin (NGAL), Liver-type fatty acid-binding protein (L-FABP),
retinol binding protein and monocyte chemoattractant protein-1
(MCP-1) [5]. In addition many other urinary biomarkers including
urinary γ-glutamyl transferase, urinary alkaline phosphatase, urinary
peptidome-based classifer and osteoinductive factor are being
investigated [6-8].
Smad1 in human was known for the 1st time in human the TGF-β/
Smads signaling pathway. TGF-β is an eminent factor the pathway of
fbrous tissue formation in many tissues. It is greatly expressed in
glomerular epithelium. It is also expressed in the renal tubular
epithelium [7]. Multiple animal studies provided evidence that
Smad1 play a pivotal role in the development of DN. Tis is mediated
by increasing synthesis of extracellular matrix via diferent pathways
Ismail et al., J Diabetes Metab 2017, 8:8
DOI: 10.4172/2155-6156.1000756
Open Access
J Diabetes Metab, an open access journal
ISSN:2155-6156
Volume 8 • Issue 8 • 1000756
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ISSN: 2155-6156
Journal of Diabetes and Metabolism
Research Article