A single-compartment model is proposed to describe the pharmacokinetics of creatinine in man. Based on the information from the literature, it was estimated that the average biological half-life of creatinine in normal male adults between 20 to 39 years old is 3.85 hours. This half-life is prolonged in renal patients and becomes 77 hours when renal function decreases to 5 per cent of normal. Based on pharmacokinetic analysis, it was also shown that the time required to reach a new steady-state serum creatinine level after onset of renal failure is highly dependent upon the degree of renal insufficiency. For example, for the subjects analyzed in this paper, it was estimated that it will take 1.1, 2.5, 6.7, and 13.4 days to reach 95 per cent of the steady-state levels when the renal function drops to 50, 25, 10, and 5 per cent of the normal capacity. The model analysis also predicts that from a practical point of view the daily fluctuation in serum level in patients with better than 25 per cent of normal renal function is not very significant. On the other hand, the fluctuation in the early stage of severe renal failure is predicted to be very dramatic. The analysis also predicts that the serum level will decrease to a normal or near normal value within two days after improvement of renal function from moderately to severely impaired state. The data obtained from an anuric patient seems to support the validity of the pharmacokinetic approach used in this study. The implications of the above pharmacokinetic analyses for the monitoring of renal function and dosage regimen modifications in patients with renal insufficiency were discussed.

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The usage of glyphosate is increasing worldwide. Glyphosate and its major metabolite, aminomethylphosphonic acid (AMPA), are of potential toxicological concern in unknown chronic kidney disease (CKDu). As with Cd and other elements, glyphosate exposure has been reported as risk factor for CKDu in farmers. This study aimed to evaluate the in uence of co-exposure to glyphosate and heavy metals in chronic kidney disease. In this study, the urine samples from 55 patients with CKD and 100 participants without CKD were analyzed for glyphosate, As, Cd, and Pb concentrations, and eGFR. Negative associations between glyphosate, AMPA, As, and Cd concentrations in the urine and eGFR were found for study subjects (p < 0.05). With regard to the effect of co-exposure, the odds ratios (OR) for subjects with an eGFR of < 60 mL/min/1.73 m 2 was signi cant because of the high Cd concentration (> 1 µg/g creatinine; OR = 7.57, 95% CI = 1.91-29.95). With regard to the effect of co-exposure, the OR for subjects with an of eGFR < 45 mL/min/1.73 m 2 was signi cant at high glyphosate concentration (> 1 µg/g creatinine; OR = 1.57, 95% CI = 1.13-2.16) and As concentration (> 1 µg/g creatinine; OR = 1.01, 95% CI = 1.00-1.02). These results showed that glyphosate, AMPA, As, and Cd have an effect on CKD; notably, Cd, As, and glyphosate exposure can be important risk factors after stage 3a of CKD, and that there was a co-exposure effect of As and glyphosate in CKD after stage 3b.The potential health impacts of glyphosate should be considered, especial for patients with CKD and eGFR below 45 mL/min/1.73 m 2 .

The usage of glyphosate is increasing worldwide. Glyphosate and its major metabolite, aminomethylphosphonic acid (AMPA), are of potential toxicological concern in unknown chronic kidney disease (CKDu). As with Cd and other elements, glyphosate exposure has been reported as risk factor for CKDu in farmers. This study aimed to evaluate the influence of co-exposure to glyphosate and heavy metals in chronic kidney disease. In this study, the urine samples from 55 patients with CKD and 100 participants without CKD were analyzed for glyphosate, As, Cd, and Pb concentrations, and eGFR. Negative associations between glyphosate, AMPA, As, and Cd concentrations in the urine and eGFR were found for study subjects (p < 0.05). With regard to the effect of co-exposure, the odds ratios (OR) for subjects with an eGFR of < 60 mL/min/1.73 m2 was significant because of the high Cd concentration (> 1 µg/g creatinine; OR = 7.57, 95% CI = 1.91–29.95). With regard to the effect of co-exposure, the OR for subjects with an of eGFR < 45 mL/min/1.73 m2 was significant at high glyphosate concentration (> 1 µg/g creatinine; OR = 1.57, 95% CI = 1.13–2.16) and As concentration (> 1 µg/g creatinine; OR = 1.01, 95% CI = 1.00–1.02). These results showed that glyphosate, AMPA, As, and Cd have an effect on CKD; notably, Cd, As, and glyphosate exposure can be important risk factors after stage 3a of CKD, and that there was a co-exposure effect of As and glyphosate in CKD after stage 3b. The potential health impacts of glyphosate should be considered, especial for patients with CKD and eGFR below 45 mL/min/1.73 m2.