Abstract
INTRODUCTION: We conducted a proof-of-concept study to evaluate the diagnostic performance of the serum creatinine/cystatin C ratio (CrCyR) in distinguishing pseudo-acute kidney injury (AKI) from true AKI. METHODS: This study included patients with confirmed AKI (excluding rhabdomyolysis) at the First Affiliated Hospital of Nanjing Medical University (May 2023-August 2024) and pseudo-AKI cases identified through a literature review (1994-2025). CrCyR values (unit: l/dl) measured before (CrCyR(pre)) and during AKI onset (CrCyR(post)) were collected. Diagnostic performance of CrCyR(post) was assessed using the area under the receiver-operating-characteristic curve (AUC). RESULTS: Of the 239 patients, 197 had true AKI and 42 had pseudo-AKI (mechanisms: reduced creatinine excretion [n = 18], assay interference [n = 14], urine leakage [n = 7], and increased creatinine production [n = 3]). Median CrCyR(post) was significantly higher in the pseudo-AKI group than in the true AKI group (1.89 [Inter Quartile Range {IQR}: 1.32-3.28] vs. 0.78 [0.64-0.94] l/dl; P < 0.001). CrCyR(post) showed a preliminary AUC of 0.97 (95% confidence interval [CI]: 0.95-1.00); an exploratory threshold of > 1.11 l/dl yielded 95% sensitivity and 91% specificity for diagnosing pseudo-AKI. After adjustment for age and sex, the covariate-adjusted AUC remained high at 0.98 (0.96-1.00). Diagnostic utility was consistently high across pseudo-AKI subtypes (AUCs: 1.00 for assay interference, urine leakage, and increased creatinine production; 0.94 for reduced creatinine excretion). A cross-center robustness assessment using patients with true AKI from the Salzburg Intensive Care database suggested consistent diagnostic utility (AUC: 0.94 [0.90-0.98]) in Europeans. CONCLUSION: CrCyR(post) preliminarily demonstrates promising diagnostic accuracy for distinguishing pseudo-AKI from true AKI. Further validation in prospective studies is warranted.