Gender Differences of Creatinine Excretion in Mice

Previous experiments from our laboratory have shown that about 50% of urinary creatinine excretion is derived from tubular secretion. In the present study we determined gender differences in creatinine excretion and examined the effect of cimetidine on creatinine excretion. Under anesthesia C57 mice were infused with 0.5 % FITC‐inulin at 0.25 μl/min g BW; after 30 min the first of three blood samples (0, 30 and 60 min) was taken while urine was collected in 10 minute periods. FITC‐inulin fluorescence was determined by spectrometer and the creatinine concentration was measured by HPLC in both plasma and urine samples. The difference between the clearances of inulin (Cin) and creatinine (Ccr), the relative secretory component (RSC), was significantly higher in male mice (Cin: 222 ± 30 μl/min, Ccr: 456 ± 69 μl/min, RSC 50 ± 3 %; n = 7) than female mice (Cin: 329 ± 21 μl/min, Ccr: 525 ± 49 μl/min, RSC 35 ± 5 %; n = 8; p < 0.05). Cimetidine (iv bolus of 30 mg/kg BW and infusion at 10 mg/kg BW/h) reduced creatinine secretion in male mice (Cin: 259 ± 42 μl/min, Ccr: 361 ± 65 μl/min, RSC 27 ± 10 %; n = 4; p < 0.05 compared to control), and less so in female mice (Cin: 295 ± 13 μl/min, Ccr: 364 ± 50 μl/min, RSC 20 ± 7 %; n = 6). In both genders plasma creatinine increased when creatinine secretion was blocked. Thus, secretion of creatinine in male mice is twice that in female mice, suggesting a major difference in the expression of the responsible organic transporters.