Cystatin C relates to metabolism in healthy, pubertal adolescents

Niels Ziegelasch, Mandy Vogel, Antje Körner, Eva Koch, Anne Jurkutat, Uta Ceglarek, Katalin Dittrich, Wieland Kiess, Niels Ziegelasch, Mandy Vogel, Antje Körner, Eva Koch, Anne Jurkutat, Uta Ceglarek, Katalin Dittrich, Wieland Kiess

Abstract

Introduction: The cystatin C (CysC) serum level is a marker of glomerular filtration rate and depends on age, gender, and pubertal stage. We hypothesize that CysC might overall reflect energy homeostasis and be regulated by components of the endocrine system and metabolites in pubertal adolescents.

Methods: Serum CysC levels and further possible effector parameters in 5355 fasting, morning venous blood samples from 2035 healthy participants of the LIFE Child cohort study (age 8 to 18 years) were analyzed. Recruitment started in 2011, with probands followed up once a year. Linear univariate and stepwise multivariate regression analyses were performed.

Results: Annual growth rate, serum levels of thyroid hormones, parathyroid hormone, insulin-like growth factor 1, hemoglobin A1c (HbA1c), uric acid, and alkaline phosphatase show relevant and significant associations with CysC serum concentrations (p <0.001). Furthermore, male probands' CysC correlated with the body mass index and testosterone among other sexual hormones. Multivariate analyses revealed that uric acid and HbA1c are associated variables of CysC independent from gender (p <0.001). In males, alkaline phosphatase (p <0.001) is additionally significantly associated with CysC. Thyroid hormones show significant correlations only in multivariate analyses in females (p <0.001).

Conclusions: The described associations strongly suggest an impact of children's metabolism on CysC serum levels. These alterations need to be considered in kidney diagnostics using CysC in adolescents. Additionally, further studies are needed on CysC in children.

Trial registration: ClinicalTrials.gov NCT02550236.

Keywords: Children; Cystatin C; Enzyme; Hormone; Metabolism; Puberty.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Heatmaps showing pairwise correlations between cystatin C and potentially influencing variables in males and females. Abbreviations: ALAT = alanine-aminotransferase, ALP = alkaline phosphatase, ASAT = aspartate-aminotransferase, BMI = body mass index, CI = confidence interval, GGT = gamma glutamyl transferase, FSH = follicle-stimulating hormone, FT3 = free thyroid hormone 3, FT4 = free thyroid hormone 4, HbA1c = hemoglobin A1c, IgG = immunoglobulin G, IGF1 = insulin-like growth factor, LH = luteinizing hormone, n = number of observations, obs = observations, SD = standard deviation, PTH = parathyroid hormone, TSH = thyroid-stimulating hormone. * marks variables with significant correlations in stepwise multivariate analyses (see also Table 4). # marks testosterone as the strongest potentially influencing, nonsignificant variable in multivariate analyses in male subjects. Anthropometric parameters and sexual hormones are listed in the columns; all other biochemical parameters are shown in the rows. Significance levels (p values) are illustrated in colors (0 [brick red], 10-4 [red], 0.001 [light red], 0.01 [orange], 0.05 [yellow], 1 [white]). All analyses were corrected for age and repeated measurements in follow-up examination

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