Background: Creatinine clearance (Ccr) overestimates glomerular filtration rate (GFR) due to the tubular secretion of creatinine. It is known that fractional excretion of creatinine (FE-Cr) increases with decreasing GFR. Association of serum albumin level with the tubular secretion of creatinine was also reported previously. Alteration of FE-Cr may affect the performance of GFR estimating equations based on serum creatinine. Therefore, we analyzed the factors influencing FE-Cr and compared the performance of GFR equations in subjects stratified by serum albumin levels.
Methods: Seven hundred and fifty-seven Japanese subjects were included. GFR was measured by inulin renal clearance. GFR and Ccr were measured simultaneously. FE-Cr was calculated as the ratio of Ccr to GFR. Multivariate analysis was performed to evaluate the factors influencing FE-Cr. Age, gender, GFR, body mass index (BMI), body weight, height and serum albumin level were analyzed as the parameters. Estimated GFR was calculated by Japanese GFR equations based on serum creatinine (Eq-cr), serum cystatin C (Eq-cys) and 5 variables including serum albumin (Eq-5var).
Results: FE-Cr in subjects with serum albumin <3.0, 3.0-3.9 and ≥4.0 g/dl were 1.63 ± 0.48, 1.53 ± 0.55, and 1.40 ± 0.36, respectively. FE-Cr in subjects with serum albumin <3.0 or 3.0-3.9 g/dl were significantly higher than the value in subjects with serum albumin ≥4.0 g/dl. Multivariate analysis showed that GFR (p < 0.0001) and serum albumin level (p = 0.004) were independent parameters affecting FE-Cr. Biases of Eq-cr, Eq-cys and Eq-5var in subjects with serum albumin <3.0 g/dl were -9.5 ± 17.5, -0.7 ± 17.1 and -0.6 ± 14.8 ml/min/1.73 m(2), respectively. Eq-cr significantly overestimated GFR compared with Eq-cys or Eq-5var. Biases in subjects with serum albumin ≥4.0 g/dl were 6.4 ± 18.8, 2.0 ± 18.1 and 3.0 ± 18.3 ml/min/1.73 m(2), respectively. Eq-cr significantly underestimated GFR compared with Eq-cys or Eq-5var.
Conclusion: GFR and serum albumin level were independent parameters affecting FE-Cr. Alteration of FE-Cr according to the serum albumin levels may be one of the reasons of the bias of GFR equation based on serum creatinine.