الفهرس 
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Abstract
Chronic Kidney disease (CKD) is an increasing global health problem. Its incidence and prevalence differ across countries, and certain population groups. Environmental causes of kidney disease including heavy metals as arsenic, cadmium and others are likely to play role in conjunction with proved risk factors. Considering the fact that; heavy metals have been linked to risk factors such as hypertension and diabetes; measures to decrease environmental exposure would contribute in decreasing CKD as health problem.
Our aim was to study the occurrence of global DNA methylation (% methylated DNA 5 methylctosine) an epigenetic phenomenon and environmental exposure to Arsenic and Cadmium in early stages of chronic Kidney disease (CKD).
Subjects studied included 30 patients at early stages of CKD with exclusion of diabetics, history glomerulonephritis, and acute liver disease, 30 workers potentially exposed to arsenic randomly selected from workers of the pesticide industry and 30 healthy individuals as control with normal estimated glomerular filtration rate (eGFR).
History taking, clinical examination, laboratory investigations including : (routine laboratory investigations: - CBC, complete urine analysis, renal function and estimation of GFR using Cockcroft-Gault equation. A colorimetric assay (MethylFlash Methylated DNA 5-mC Quantification Kit, Epigenetic group Inc., NY, USA) was used to determine the global DNA methylation levels, urinary arsenic (uiAs) and cadmium (uCd) were measured by atomic absorption spectrophotometer. Butyrylcholinesterase measured by colorimetric assay. Diffusion weighted imaging (DWI) was done as a functional imaging method to 36/90 subjects who accepted to do the study; 22 CKD patients, 4 workers and 9 control as a method of estimation of renal function.
The study showed that eGFR negatively correlated to uAs and uCd levels.
Urinary arsenic level had a highly significant positive correlation with albumin creatinine ratio, while uCd had a borderline positive correlation.
Methylated DNA % had a positive significant correlation with uCd. It was noticed that the CKD patients having (mean value of the control + 2SD) had significantly higher DNA methylation % than those who had less than 23 µg/L and the control group (p=0.016) after excluding an extremely odd value of methylated DNA% (0.3%).
There was a positive significant correlation between serum creatinine level in the studied groups and methylated DNA%.
There was a significant negative correlation between BChE. level and eGFR, and significant positive correlation with serum creatinine. There was no significant correlation between BChE. level and uAs, uCd and, DNA methylation percentage.
The correlation between the apparent diffusion coefficient ADC and eGFR was positive and highly significant.
ADC had a significant negative correlation with arsenic level and cadmium. There was a significant negative correlation with age ,but no correlation with gender, urea or albumin creatinine.
ROC curve for average ADC of both kidneys revealed an ADC cutoff value ≤ 1.93 ×10-3 mm2/s statistically predicted in CKD patients to distinguish from pesticide workers and control; with 100% sensitivity and 100% specificity.
Multivariate analysis for average ADC value of both kidneys (n=36) revealed that the most independent factor affecting it; was eGFR with p value<0.001.