الفهرس 
Diabetes mellitusOnly 14 pages are availabe for public view
Abstract
Microalbuminuria has been accepted as the golden standard for diagnosing diabetic nephropathy; however, a large proportion of renal impairment occurs in non-albuminuric state. Early diagnosis of diabetic nephropathy may help in preventing irreversible renal damage. It will be more useful to find sensitive and specific noninvasive diagnostic tools, that precedes the histopathologic damage that has already occurred once albuminuria is noted.
Autophagy, a highly regulated lysosomal pathway involved in the recycling of cytosol and the removal of superfluous or damaged organelles, is essential for the survival, differentiation, development and homeostasis of cells . Dysregulated autophagy has been suggested to play pathogenic roles in a variety of disease processes including cancer, neurodegeneration, diabetes, aging and heart disease.
In diabetic nephropathy. the expression of several genes is dysregulated, contributing to the increased expression and accumulation of extracellular matrix proteins and increased pro-fibrotic signaling, ultimately resulting in renal fibrosis. Thus indicates the feasibility of the study of urinary genes for candidate biomarker discovery in diabetic and other renal diseases.
In this regards, we evaluate the clinical utility of urinary autophagy gene level of MAP1LC3B expression as a non invasive biomarker in diagnosis of diabeticnephropathy and to correlate its expression with different clinicopathological factors.
This study was done at Medical Biochemistry Department, Ain Shams Faculty of Medicine during the period from 2014– 2016 and included 65 patients and 15 normal volunteers.
The aim of the present study was to select biomarker relevant to diabetic nephropathy from the databases and to evaluate its usefulness as a urine molecular marker for early diabetic nephropathy detection. The bioinformatics analysis showed the involvement of MAP1LC3B in diabetic nephropathy. Urinary MAP1LC3B level was measured using quantitative real-time polymerase chain reaction (qPCR) in cellular pellets from voided urine samples.
Study groups were stratified according to the albumin / creatinine ratio into:
group 1 : (Control group) healthy volunteers aged from ( 45-63) years old (n= 15). The median age was (55 ) years old, mean age± SD (54.07±5.82 ).
group 2 : Nonalbuminuric diabetic patients aged from (40-71 ) years old (n=22 ). The median age was (55 ) years old, mean age± SD (55.27±9.36 ).group 3 : Microalbuminuric diabetic patients aged from (37-72 ) years old (n=24 ). The median age was (60.5 ) years old, mean age± SD (59.42±8.79 ).
group 4 : Macroalbuminuric diabetic patients aged from ( 45-78) years old (n=19 ). The median age was (58 ) years old, mean age± SD (58.58±7.94 ).
All patients in our study were subjected to complete detailed history , standardized physical examination and laboratory investigations including: measurements of the protein-to-creatinine ratio (P/C), HbA1C, Lipid profile and serum creatinine. Diabetic nephropathy staging was done based on eGFR. RNA extraction was done from urinary cellular pellets followed by quantitative real-time polymerase chain reaction (qPCR) for measuring urinary MAP1LC3B. The data were normalized using GAPDH as reference control. Then the results were calculated and statistically analyzed.
Applying 0.866 cut off value (calculated by ROC curve), the urinary MAP1LC3B RQ values showed that the overall sensitivity, specificity, PPV, NPV and accuracy of this method were (83.7% , 78.4% ,81.8 % ,80.5 % , 81.3%) respectively
A significant difference was observed in positivity rate of urinary MAP1LC3B level (RQ), in the macroalbuminuric group was 89.5% and microalbuminuric groups was 79.2% ascompared to non-albuminuric group 36.4% and healthy normal group 0% (p ≤ 0.001).
A highly significant correlation found between the four groups as regard fold change of urinary expression of MAP1LC3B indicating their synergistic effect (P<0.001).
These results suggested the usefulness of using MAP1LC3B biomarker for diagnosing early diabetic nephropathy and prediction of its progression and the need for more extensive research to implement these results.