Reappraising Urinary Amylase in Acute Pancreatitis: Methodological and Biological Heterogeneity Underlying Diagnostic Controversy

Acute pancreatitis (AP) is a common acute abdominal emergency for which serum lipase (LPS) is the preferred enzymatic biomarker. Urinary amylase (U-AMY) continues to attract clinical interest due to the noninvasive nature of urine sampling, its potential for repeatable testing, and its prolonged elevation relative to serum amylase (S-AMY) in some patients. However, the diagnostic performance of U-AMY varies substantially across studies—two systematic reviews published in December 2025 reached opposing conclusions. This review examines how methodological heterogeneity and biological variability may jointly contribute to the inconsistent diagnostic performance of U-AMY across studies. Rather than asking whether U-AMY can replace LPS—a question on which the literature remains divided—we critically examine the sources of heterogeneity that have precluded U-AMY from achieving guideline endorsement: non-standardized thresholds, variable sampling timing, diverse etiologic subgroups, and confounding renal physiology. We propose that U-AMY’s value should be understood through a stratified decision framework and that future research should prioritize assay harmonization, prospective evaluation of common versus subgroup-specific diagnostic thresholds, and integration into multi-marker diagnostic models.