Accurate evaluation of kidney function is vital in the pediatric intensive care unit (PICU), where even small changes in cystatin C and creatinine concentrations can affect clinical decision-making. Diurnal patterns in renal biomarkers have been reported in adults, but their relevance in critically ill children remains unclear. Understanding whether sampling time contributes to biological variability is essential for reliable interpretation of kidney function tests. This retrospective study included 8619 cystatin C and 9314 creatinine results collected in a tertiary PICU between April 2014 and September 2025. The hourly distribution of sampling and hourly biomarker percentiles (0.10, 0.25, and 0.50) were evaluated across the 24-h cycle. Diurnal variation was quantified using coefficients of variation (CVs). Sampling was strongly clustered in the early morning, with 38.6% of cystatin C and 37.4% of creatinine samples drawn at 5:00–5:59 AM. The 0.10–0.50 percentiles of cystatin C showed minimal diurnal variation (CV 4.5–6.3%). Creatinine exhibited slightly greater variability, with CVs of 7.4–11.6% across the same percentiles. Median creatinine was significantly higher in the afternoon/evening than in the early morning, while cystatin C showed no clinically relevant hourly fluctuations. Conclusion: In critically ill children, cystatin C demonstrates limited diurnal variation, while creatinine shows modest but measurable fluctuations across the 24-h period. These findings suggest that cystatin C is relatively robust to sampling time in the PICU, whereas creatinine may vary enough to influence interpretation in borderline cases. Incorporating knowledge of sampling time may improve the accuracy of kidney function assessment and AKI classification in pediatric critical care.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> What is Known: • Creatinine and cystatin C can show biological and circadian variability in adults and older children, with creatinine generally exhibiting greater within-day fluctuation than cystatin C. </entry> </row> <row> <entry nameend="c2" namest="c1"> What is New: • In critically ill children, cystatin C shows minimal diurnal variation, whereas creatinine displays modest but measurable time-of-day–related increases, indicating that sampling time may influence creatinine interpretation but not cystatin C in the PICU setting. </entry> </row> </tbody> </tgroup> </Table>

Creatinine, but not cystatin C, varies diurnally in critically ill children: a retrospective analysis from a tertiary pediatric intensive care unit

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2026年4月24日

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Robert Frithiof,
Mats B. Eriksson,
Jonathan Cedernaes,
Ali Reza Modiri,
David Smekal,
Anders Larsson

摘要

Accurate evaluation of kidney function is vital in the pediatric intensive care unit (PICU), where even small changes in cystatin C and creatinine concentrations can affect clinical decision-making. Diurnal patterns in renal biomarkers have been reported in adults, but their relevance in critically ill children remains unclear. Understanding whether sampling time contributes to biological variability is essential for reliable interpretation of kidney function tests. This retrospective study included 8619 cystatin C and 9314 creatinine results collected in a tertiary PICU between April 2014 and September 2025. The hourly distribution of sampling and hourly biomarker percentiles (0.10, 0.25, and 0.50) were evaluated across the 24-h cycle. Diurnal variation was quantified using coefficients of variation (CVs). Sampling was strongly clustered in the early morning, with 38.6% of cystatin C and 37.4% of creatinine samples drawn at 5:00–5:59 AM. The 0.10–0.50 percentiles of cystatin C showed minimal diurnal variation (CV 4.5–6.3%). Creatinine exhibited slightly greater variability, with CVs of 7.4–11.6% across the same percentiles. Median creatinine was significantly higher in the afternoon/evening than in the early morning, while cystatin C showed no clinically relevant hourly fluctuations.

Conclusion: In critically ill children, cystatin C demonstrates limited diurnal variation, while creatinine shows modest but measurable fluctuations across the 24-h period. These findings suggest that cystatin C is relatively robust to sampling time in the PICU, whereas creatinine may vary enough to influence interpretation in borderline cases. Incorporating knowledge of sampling time may improve the accuracy of kidney function assessment and AKI classification in pediatric critical care.

What is Known:

• Creatinine and cystatin C can show biological and circadian variability in adults and older children, with creatinine generally exhibiting greater within-day fluctuation than cystatin C.

What is New:

• In critically ill children, cystatin C shows minimal diurnal variation, whereas creatinine displays modest but measurable time-of-day–related increases, indicating that sampling time may influence creatinine interpretation but not cystatin C in the PICU setting.