Reference Interval, Biological Variations and Distribution of Creatinine Level in Fasting Urine: A Cross-sectional Study

Abstract

Introduction: Serum creatinine, urine creatinine, and rate of urine formation are components of creatinine clearance and are under multiple influences. Of these, urine creatinine has the widest variability, especially in the tropical region. Reference intervals, biological variations, and distributions of urine creatinine in the reference individuals are related and important for clinical interpretations of kidney functions. Aim: To establish the reference intervals, biological variations, and distributions of creatinine in urine formed during morning fasting state from reference individuals in a tropical location. Materials and Methods: This observational cross-sectional study of the sample population was done from January 2017 to November 2021 for the establishment of reference interval. Reference individuals, defined by inclusion and exclusion criteria, were from the population at near sea levels plains, in Thrissur district, Kerala, avoiding the mountainous Western Ghats. Morning fasting, third sample of urine was collected to ensure that the urine collected was formed in the morning (n=156). A second set of 44 urine samples, collected from 10 reference individuals consecutively for 4 to 5 days, was used for estimating the analytical Coefficient of Variation (CVA), within-subject (CVI ), and between-subject (CVG) components of biological variation. Outliers in the creatinine data were identified and removed by the Box-Whisker plot to exclude the subclinical influences that affected the urine creatinine, followed by BoxCox transformation to bring the distribution to Gaussian and reference interval calculations of fasting urine creatinine. Results: As the total sample number was >120, non parametric percentile method was used to calculate the reference interval of 17.14 to 325.89 mg/dL. As the female sample number was between 40 and 120, double-sided, 95% reference interval, based on normal distribution was calculated as 12.41 to 328.71 mg/dL. As the male sample was <50, method of robust calculation was used to define the reference interval of 21.91 to 379.12 mg/dL. The reference interval and biological variation data showed gender differences in the distribution, CVI , and CVG due to lower concentration of fasting urine creatinine in females resulting from lower muscle mass. Conclusion: Reference intervals of creatinine in fasting urine formed in the morning were established. Gender differences were observed in the distribution of data, CVI , and CVG.