Assessing the utility of fractional excretion of urea in distinguishing intrinsic and prerenal acute kidney injury in hospitalised patients: a systematic review and meta-analysis

Objective Acute kidney injury (AKI) is a significant challenge in hospital settings, and accurately differentiating between intrinsic and prerenal AKI is crucial for effective management. The fractional excretion of urea (FEUN) has been proposed as a potential biomarker for this purpose, offering an alternative to traditional markers such as fractional excretion of sodium. This study aimed to assess the diagnostic accuracy of FEUN for differentiating intrinsic from prerenal AKI in hospitalised patients. Designs We conducted a systematic review and bivariate random effects meta-analysis of diagnostic accuracy studies. The study followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Data sources PubMed, Embase and Cochrane databases were searched from inception to 1 November 2023. Eligibility criteria for selecting studies We included observational studies that focused on patient with AKI and reported FEUN data sufficient to reconstruct a complete 2 × 2 contingency table (true positives, true negatives, false positives and false negatives) for evaluating its diagnostic accuracy. Data extraction and synthesis Two reviewers extracted data, assessed risk of bias with Quality Assessment of Diagnostic Accuracy Studies-2 and graded certainty of evidence using the GRADE approach. Pooled sensitivity, specificity, positive and negative likelihood ratios, and the area under the summary receiver operating characteristic curve (SROC) were calculated; heterogeneity was measured with I². A prespecified subgroup restricted to patients receiving diuretics served as a sensitivity analysis. Results 12 studies involving 1240 patients were included, with an overall occurrence rate of intrinsic AKI of 38.8%. FEUN had a pooled sensitivity of 0.74 (95% CI 0.60 to 0.84) and specificity of 0.78 (95% CI 0.66 to 0.87), with positive predictive value and negative predictive value of 0.76 (95% CI 0.68 to 0.83) and 0.74 (95% CI 0.66 to 0.81), respectively. The SROC curve showed a pooled diagnostic accuracy of 0.83. Heterogeneity was substantial (I²>90%) for sensitivity and specificity. In a diuretic-only subgroup (six studies) specificity rose to 0.87 and heterogeneity declined (I²=56%). Overall certainty of evidence was low owing to inconsistency. Conclusions FEUN is a biomarker with moderate diagnostic accuracy for differentiating between intrinsic and prerenal AKI in hospitalised patients. Its application could enhance AKI management; however, the high heterogeneity observed in our study highlights the need for further research to evaluate its utility across diverse patient populations and clinical settings. PROSPERO registration number CRD42024496083.