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Decrease in urinary creatinine in acute kidney injury influences diagnostic value of urinary biomarker-to-creatinine
Yutaka Tonomura1, Takeki Uehara, Emi Yamamoto
1Drug Safety Evaluation, Drug Developmental Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan. yutaka.tonomura@shionogi.co.jp
Toxicology
|October 19, 2011
Summary
Urinary creatinine correction (Ucr-correction) may overestimate acute kidney injury (AKI) but offers higher diagnostic power for biomarkers like NAG and LDH compared to urine flow rate correction (UFR-correction). This study clarifies their relationship in non-steady states.
Area of Science:
- Nephrology
- Biomarker Discovery
- Renal Dysfunction
Background:
- Urinary biomarkers are crucial for assessing renal dysfunction, including acute kidney injury (AKI).
- Urine flow rate (UFR) variation influences biomarker evaluation, necessitating correction methods like UFR-correction or urinary creatinine correction (Ucr-correction).
- Previous studies on Ucr-correction vs. UFR-correction were limited to steady-state conditions and specific biomarkers.
Purpose of the Study:
- To comprehensively evaluate the relationship between Ucr-correction and UFR-correction for ten urinary biomarkers in non-steady state conditions like AKI.
- To compare the diagnostic power of Ucr-correction versus UFR-correction for AKI detection.
Main Methods:
- Linear regression analysis was used to compare Ucr-correction and UFR-correction for ten urinary biomarkers (NAG, LDH, total protein, albumin, KIM-1, NGAL, clusterin, β2M, cystatin-c, GST-α) in AKI.
- Receiver operating characteristic (ROC) curve analysis assessed the diagnostic power of each correction method.
- Investigated changes in Ucr excretion, creatinine clearance, and OCTN2 mRNA expression in AKI.
Main Results:
- All ten biomarkers showed larger amplitude increases with Ucr-correction than UFR-correction in AKI.
- ROC analysis indicated that Ucr-correction provided higher diagnostic power than UFR-correction for NAG and LDH.
- AKI was associated with decreased Ucr excretion, reduced creatinine clearance, and lower OCTN2 mRNA expression.
Conclusions:
- Ucr-correction can overestimate AKI severity but may offer superior diagnostic utility for certain urinary biomarkers compared to UFR-correction.
- Observed changes in creatinine transport may mechanistically explain Ucr-correction phenomena.
- Consideration of these factors is essential when applying Ucr-correction for AKI assessment.
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