Abstract Background and Aims Chronic kidney disease (CKD) was one of the three reasons of mortality with the furthermost increase from 1990 to 2010 between the top 20 killers. Environmental toxins (Lead Pb and Cadmium Cd) are hidden factors incorporated in the increased prevalence of CKD. The aim of this study is to determine whether there is a relationship between CKD and alteration in blood Pb and Cd levels. Methods This is a case-control study which was held in Forensic department, Mansoura University, Egypt. The individuals were divided into 2 groups: Group I: 40 persons with normal kidney function used as a control group, group II: 40 patients suffering from CKD secondary to unknown cause who are attending to follow up at nephrology outpatient clinic, Mansoura insurance hospital. All participants were subjected to full history taking (Personal history about gender, age, residence and occupation (mechanics, plumbers, battery manufacturers, manufacturers and users of paint and electricians), The history of special habits like smoking, seafood, canned food consumption, using colored mugs and living in old houses, History about medical disorders associated with renal failure as diabetes and hypertension), laboratory investigations including serum creatinine, creatinine clearance, serum Pb and serum Cd. Results Eighty persons (49 males and 31 females) were included in the study with age range from 15 to 76 years. The majority was above 40 years and was coming from rural areas (62.5% in group I and 60% in group II) with no statistical significance (Figure 1). In group I (45.0%) was smokers and (55.0%) were non smokers while in group II (70.0%) were smokers and (30.0%) were non smokers. The difference was statistically significant (p =0.026). Among group I, (42.5%) out of them were using frequently colored food container ceramics while (65%) among group II were frequently use them and the difference was statistically significant (p =0.048). Other risk factors showed no significance (Figure 2). In group I Pb levels range from (9.51µg/100ml) to (42.67µg/100ml) while Cd levels range from (1.59µg/100ml) to (3.87µg/100ml); whereas in group II Pb levels range from (19.43µg/100ml) to (82.3µg/100ml) while Cd levels range from (2.04µg/100ml) to (6.12µg/100ml). There is statistically significant difference among both groups as regard blood Pb levels (p <0.001) with higher blood Pb levels in C.K.D patients (mean±SD=52.76±15.65) than healthy controls (mean±SD=18.06±5.61). Also, there is statistically significant difference among both groups as regard blood Cd levels (p <0.001) with higher blood Cd levels in C.K.D patients (mean±SD=4.27±0.87) than healthy controls (mean±SD=2.62±0.62) (Figure 3 & 4). There was negative correlation between blood Pb,Cd levels and patients` creatinine clearance ( for Pb;R:-0.755, p=0.001, for Cd;R:-0.712, p=0.001 ) (Figure 5, 6). There was positive correlation between blood Pb, Cd levels and serum creatinine (for Pb;R: +0.713, p =0.00, for Cd; R: +0.707, p =0.00) (Figure 7, 8). Conclusion Pb and Cd toxicity may lead to CKD and these environmental factors may explain the unknown etiology of many renal failure cases. With chronic exposure, blood level >25.8 µg/dl for Pb and >3.46 µg/dl for Cd carry the risk for renal failure incidence.