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Interference-Free Measurement of Urinary Angiotensin-Converting Enzyme (ACE) Activity: Diagnostic and Therapeutic
Attila Ádám Szabó1,2, Enikő Edit Enyedi1,2, Tamás Bence Pintér1,2
1Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
A new, rapid assay allows accurate measurement of urinary angiotensin-converting enzyme (uACE) activity. This method overcomes previous limitations and enables uACE to serve as a practical biomarker for cardiovascular and kidney diseases.
Area of Science:
- Biochemistry
- Clinical Chemistry
- Biomarker Discovery
Background:
- Urinary angiotensin-converting enzyme (uACE) activity is a potential biomarker for kidney and cardiovascular diseases.
- Clinical use is hindered by endogenous inhibitors and complex assays.
- This study aimed to develop a simpler, reproducible uACE assay and identify inhibitors.
Purpose of the Study:
- To establish a fast and reproducible method for measuring uACE activity.
- To identify endogenous urinary inhibitors of uACE.
- To define practical preanalytical conditions for routine laboratory use.
Main Methods:
- Optimized a fluorescence-based kinetic assay for urine samples.
- Isolated and characterized endogenous inhibitors using membrane filtration.
- Evaluated sample dilution as a method to overcome inhibition.
- Assessed uACE activity stability under various storage conditions.
Main Results:
- Urea, uric acid, and urobilinogen were identified as major reversible inhibitors.
- A 128-fold dilution effectively eliminated inhibitory effects.
- uACE activity was stable at 25 °C for 24 hours but lost upon freezing.
- Normalized uACE activity (uACE/creatinine) was significantly lower in patients on ACE inhibitors.
Conclusions:
- Accurate uACE activity measurement is feasible with a rapid dilution-based protocol.
- Normalized uACE activity is a practical biomarker for detecting ACE inhibition and monitoring therapy.
- This biomarker may offer insights into renal pathophysiology, including tubular injury.
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