By: Mohamed M. Omran ^1,*, Rasha A. Youssef ², Fathy M. Eltaweel², Ashraf A. Tabll^3, Ahmed A. Eldeeb⁴

¹ Chemistry Department, Faculty of Science, Helwan University, Cairo, Egypt

² Chemistry Department,Faculty of Science, Damietta University, Egypt

³ Microbial Biotechnology Department, National Research Centre, Giza, Egypt

⁴Nephrology Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Abstract

Background: Albuminuria is used to screen early stages of diabetic nephropathy (DN) but it is limited by the fact that structural damage may precede albumin excretion. This necessitates identifying better biomarkers that diagnose or predict diabetic nephropathy.  The aim of the study was  to evaluate tissue inhibitor metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor 1 (PAI-1) and neutrophil/lymphocyte ratio (NLR) as potential biomarkers for early detection of diabetic nephropathy and its progression in patients with type 2 diabetes.

Materials and Methods: A total of 88 subjects were included in this cross-sectional hospital based study, healthy individuals (N=10) and diabetic patients (n= 78). Diabetic patients were classified according to an albumin creatinine ratio (ACR) into normoalbuminuria (A1=30), microalbuminuria (A2=14) and macroalbuminuria  (A3 =34). TIMP-1, PAI-1 levels, NLR were measured in all subjects. Multivariate discriminant analysis (MDA) was used to develop a novel index. The diagnostic value of TIMP-1, PAI-1 and NLR was assessed by the area under the receiver operating characteristic (ROC). Results: The mean ± SD of NLR, PAI-1 (ng/ml) and TIMP-1  (ng/ml) in healthy were (1.9±0.30; 6.8 ±2.4 and 76.8±15.7) and in A1 were                             (3.0 ± 2.5;7.7±1.8 and 91.4±19.8) and in A2 were ( 2.2±1.5; 7.6±1.9 and 104.5±20.9) and in A3 were (5.2±3.9; 8.7±1.2 and 120.6±18.2).  The differences between the mean of NLR, PA1-1 and, TIMP in A2 and that of A3 were significant (p <0.007, p =0.03 and, p < 0.011; respectively).  TIMP-1 was the most efficient marker with AUC of 0.72 for discriminant diabetics with A1 from A2; 0.88 for A1 vs A3 and 0.82 for A2 vs A3. A novel index was developed for differentiated between stages of DN based on three blood markers (TIMP-1, PAI-1 and NLR) named TPN.  The mean ± SD  of TPN index  in healthy was  (1.1±0.4)  and in A1 was  (1.2 ±0.3) and in A2 was (1.3 ±0.2) and in A3 were (1.8±0.3) with high significant difference between A2 and A3.The AUC of TPN index was 0.61, 0.88, and 0.88  for discriminant diabetics with A1  from A2 ,A1 vs A3, and A2 vs A3. Conclusions: A novel index named TPN based on three blood markers (TIMP-1, PAI-1 and NLR) may be potentially useful for early detection and to discriminate macro-albuminuria from micro-albuminuria stages.

Tissue inhibitor metalloproteinase1 Plasminogen activator inhibitor 1 and neutrophil lymphocyte ratio as potential early biomarkers for diabetic nephropathy-converted

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