Variability of Urinary Creatinine in Healthy Individuals

Overview

Journal Int J Environ Res Public Health

Publisher MDPI

Specialties Environmental Health
Public Health

Date 2021 Apr 3

PMID 33808539

Citations 14

Authors

Gerd Sallsten

Lars Barregard

Affiliations

Soon will be listed here.

Abstract

Many urinary biomarkers are adjusted for dilution using creatinine or specific gravity. The aim was to evaluate the variability of creatinine excretion, in 24 h and spot samples, and to describe an openly available variability biobank. Urine and blood samples were collected from 60 healthy non-smoking adults, 29 men and 31 women. All urine was collected at six time points during two 24 h periods. Blood samples were also collected twice and stored frozen. Analyses of creatinine in urine was performed in fresh urine using an enzymatic method. For creatinine in urine, the intra-class correlation (ICC) was calculated for 24 h urine and spot samples. Diurnal variability was examined, as well as association with urinary flow rate. The creatinine excretion rate was lowest in overnight samples and relatively constant in the other five samples. The creatinine excretion rate in each individual was positively correlated with urinary flow rate. The creatinine concentration was highest in the overnight sample and at 09:30. For 24 h samples the ICC was 0.64, for overnight samples it was 0.5, and for all spot samples, it was much lower. The ICC for urinary creatinine depends on the time of day of sampling. Frozen samples from this variability biobank are open for researchers examining normal variability of their favorite biomarker(s).

Citing Articles

Variable power functional dilution adjustment of spot urine.

Carmine T Sci Rep. 2025; 15(1):3688.

PMID: 39885184 PMC: 11782553. DOI: 10.1038/s41598-024-84442-9.

Creatine Supplementation Beyond Athletics: Benefits of Different Types of Creatine for Women, Vegans, and Clinical Populations-A Narrative Review.

Gutierrez-Hellin J, Del Coso J, Franco-Andres A, Gamonales J, Espada M, Gonzalez-Garcia J Nutrients. 2025; 17(1.

PMID: 39796530 PMC: 11723027. DOI: 10.3390/nu17010095.

Simple methods for estimating the maximum 24-hour urinary potassium excretion in kidney failure without replacement therapy patients.

Zhang D, Wang Y, Jiang S, Li W Ren Fail. 2025; 47(1):2445157.

PMID: 39780434 PMC: 11721948. DOI: 10.1080/0886022X.2024.2445157.

Physical Activity and Urinary Sodium Excretion Circadian Rhythm: A Population-Based Cross-Sectional Pilot Study.

Zandona M, Novotny J, Garo M, Sgro E, Del Giorno R, Gabutti L J Clin Med. 2024; 13(16).

PMID: 39200965 PMC: 11355672. DOI: 10.3390/jcm13164822.

Interpreting urinary iodine concentration: effects of urine dilution and collection timing.

Oblak A, Hribar M, Hristov H, Gregoric M, Blaznik U, Osredkar J Eur J Clin Nutr. 2024; 78(12):1105-1110.

PMID: 39117906 PMC: 11611732. DOI: 10.1038/s41430-024-01492-y.

References

Wang Y, Feng W, Zeng Q, Sun Y, Wang P, You L . Variability of Metal Levels in Spot, First Morning, and 24-Hour Urine Samples over a 3-Month Period in Healthy Adult Chinese Men. Environ Health Perspect. 2015; 124(4):468-76. PMC: 4829977. DOI: 10.1289/ehp.1409551. View

Araki S, Sata F, Murata K . Adjustment for urinary flow rate: an improved approach to biological monitoring. Int Arch Occup Environ Health. 1990; 62(6):471-7. DOI: 10.1007/BF00379066. View

Ikeda M, Ezaki T, Tsukahara T, Moriguchi J, Furuki K, Fukui Y . Bias induced by the use of creatinine-corrected values in evaluation of beta2-microgloblin levels. Toxicol Lett. 2003; 145(2):197-207. DOI: 10.1016/s0378-4274(03)00320-5. View

Spierto F, Hannon W, Gunter E, Smith S . Stability of urine creatinine. Clin Chim Acta. 1997; 264(2):227-32. DOI: 10.1016/s0009-8981(97)00080-6. View

Smolders R, Koch H, Moos R, Cocker J, Jones K, Warren N . Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 1: metals. Toxicol Lett. 2014; 231(2):249-60. DOI: 10.1016/j.toxlet.2014.08.014. View

Barr D, Wilder L, Caudill S, Gonzalez A, Needham L, Pirkle J . Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. Environ Health Perspect. 2005; 113(2):192-200. PMC: 1277864. DOI: 10.1289/ehp.7337. View

Boeniger M, Lowry L, Rosenberg J . Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review. Am Ind Hyg Assoc J. 1993; 54(10):615-27. DOI: 10.1080/15298669391355134. View

Levey A, Stevens L, Schmid C, Zhang Y, Castro 3rd A, Feldman H . A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150(9):604-12. PMC: 2763564. DOI: 10.7326/0003-4819-150-9-200905050-00006. View

Pleil J, Ariel Geer Wallace M, Stiegel M, Funk W . Human biomarker interpretation: the importance of intra-class correlation coefficients (ICC) and their calculations based on mixed models, ANOVA, and variance estimates. J Toxicol Environ Health B Crit Rev. 2018; 21(3):161-180. PMC: 6704467. DOI: 10.1080/10937404.2018.1490128. View

10.

Symanski E, Greeson N . Assessment of variability in biomonitoring data using a large database of biological measures of exposure. AIHA J (Fairfax, Va). 2002; 63(4):390-401. DOI: 10.1080/15428110208984727. View

11.

Mayersohn M, Conrad K, Achari R . The influence of a cooked meat meal on creatinine plasma concentration and creatinine clearance. Br J Clin Pharmacol. 1983; 15(2):227-30. PMC: 1427867. DOI: 10.1111/j.1365-2125.1983.tb01490.x. View

12.

Akerstrom M, Barregard L, Lundh T, Sallsten G . Variability of urinary cadmium excretion in spot urine samples, first morning voids, and 24 h urine in a healthy non-smoking population: implications for study design. J Expo Sci Environ Epidemiol. 2013; 24(2):171-9. DOI: 10.1038/jes.2013.58. View

13.

Lin Y, Kupper L, Rappaport S . Air samples versus biomarkers for epidemiology. Occup Environ Med. 2005; 62(11):750-60. PMC: 1740917. DOI: 10.1136/oem.2004.013102. View

14.

Aylward L, Hays S, Zidek A . Variation in urinary spot sample, 24 h samples, and longer-term average urinary concentrations of short-lived environmental chemicals: implications for exposure assessment and reverse dosimetry. J Expo Sci Environ Epidemiol. 2016; 27(6):582-590. PMC: 5658679. DOI: 10.1038/jes.2016.54. View

15.

Cocker J, Mason H, Warren N, Cotton R . Creatinine adjustment of biological monitoring results. Occup Med (Lond). 2011; 61(5):349-53. DOI: 10.1093/occmed/kqr084. View

16.

Ogna V, Ogna A, Vuistiner P, Pruijm M, Ponte B, Ackermann D . New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population. BMC Med. 2015; 13:40. PMC: 4354997. DOI: 10.1186/s12916-015-0275-x. View

17.

Aono H, Araki S . Circadian rhythms in the urinary excretion of heavy metals and organic substances in metal workers in relation to renal excretory mechanism: profile analysis. Int Arch Occup Environ Health. 1988; 60(1):1-6. DOI: 10.1007/BF00409371. View

18.

Suwazono Y, Akesson A, Alfven T, Jarup L, Vahter M . Creatinine versus specific gravity-adjusted urinary cadmium concentrations. Biomarkers. 2005; 10(2-3):117-26. DOI: 10.1080/13547500500159001. View

19.

Koopman M, Koomen G, Krediet R, De Moor E, Hoek F, Arisz L . Circadian rhythm of glomerular filtration rate in normal individuals. Clin Sci (Lond). 1989; 77(1):105-11. DOI: 10.1042/cs0770105. View

20.

Yeh H, Lin Y, Kuo C, Weidemann D, Weaver V, Fadrowski J . Urine osmolality in the US population: implications for environmental biomonitoring. Environ Res. 2014; 136:482-90. PMC: 5794013. DOI: 10.1016/j.envres.2014.09.009. View