الفهرس 
INTRODUCTION AND AIM OF THE WORK
Diabetes MellitusOnly 14 pages are availabe for public view
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Abstract
Diabetic nephropathy (DN) is one of serious complications occurs in 30– 40%of diabetic patients and the most common single cause of end stage renal disease (ESRD).The exact pathogenesis of DN is complex and not completely understood.Hyperglycemia plays a central role in a cascade of damaging effects mediated by cytokines and growth factors that produces oxidative stress, abnormal glycosylation, lipid peroxidation, and the production of further inflammatory elements.Early detection of DN may enable development of specific drugs and early initiation of appropriate preventive therapy that can delay or prevent progression to later stages of disease. In clinical practice, DN is diagnosed by presence of proteinuria and/or changes in serum creatinine indicating decline in the glomerular filtration rate.Although these tests are appropriate in patients with advanced DN, high interindividual variability and, as a consequence, moderate specificity and sensitivity at early stages of disease are major limitations for early diagnosis with these standard tests.
In the present study, we evaluate the possible role of kim-1 in associated with alloxan-induced diabetic nephropathy in rats as a non-invasive, sensitive, and specific marker in this animal model of DN in compared to the traditional markers of acute kidney injury (serum creatinine, and urinary albumin). Also, studying the role of kidney injury molecule-1 (kim-1) in the pathogenesis of DN.
Materials and Experimental Design:
Forty albino rats were randomly divided into four experimental groups, where ten rats were taken in each group. Diabetes was induced in three of the groups and one was a healthy control. Induction of diabetes was performed by intraperitoneal (i.p)
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Summary and conclusion
injection of single dose of alloxan monohydrate (150 mg/kg body weight) dissolved in 0.9% NaCl saline solution immediate before use to 18 hours fasted rats. The normal control group was injected with equivalent amounts of 0.9% saline. During the first 24 h of diabetes induction, alloxan treated animals were allowed to drink 5% glucose solution to overcome drug induced hypoglycemia. Three days after alloxan administration, diabetes was confirmed by the presence of hyperglycemia and glucosuria. Rats with fasting blood glucose level ≥ 200 mg/dl were considered diabetic and induced in the present study. After the induction of diabetes, rats were randomly divided into three groups in addition to a normal control group, ten rats on each group as following: group 1: healthy non-diabetic rats.
Group2: diabetic rats were sacrificed after 14 days of induction of diabetes.
Group3: diabetic rats were sacrificed after 28 days of induction of diabetes.
Group4: diabetic rats were sacrificed after 42 days of induction of diabetes.
The study protocol was chosen according to previous study to represent a model of early stage diabetic nephropathy.
Methods
1 –Urinary Kim-1 was determined by ELISA.
2 – TGF-beta was determined by western blot analysis.
3 – Caspase-3 mRNA was determined by PCR.
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Summary and conclusion
4 – Urinary albumin, urinary creatinine, BUN, serum creatinine, and oxidative
stress markers were determined colorimetrically.
In conclusion, the present investigation shows:
1. The measurement of urinary kim-1 could be used as a non-invasive, specific, and early marker in this early DN animal model.
2. Traditional markers of AKI (albuminuria, serum creatinine&BUN), are not an ideal markers for early detection of DN due to its non-sensitivity and non-specificity.
3. Increasing urinary kim-1 in diabetic animals is positively correlated with increasing up-regulation of TGF-β protein expression in renal tissues, indicating
that, kim-1 may be playing a role in protective or in pathogenesis of DN.
4. Increasing urinary kim-1 in diabetic animals is positively correlated with increasing renal tissue expression of mRNA of caspase-3, indicating that; kim-1 may be playing a role in apoptosis.
5. Increasing urinary kim-1 in diabetic animals is positively correlated with increase renal tissue content of oxidants (MDA&NO), and decrease in renal tissue content of anti-oxidant (GSH), indicating that, kim-1is up-regulated as a response of renal injury.
6. The early diagnosis of DN protects the kidney functions of the patient from the rapid development of the disease by starting the therapy as early as possible.
7. Studying of those markers open the door for the rational development of the efficient and early therapy for DN. 115.