Diagnostic Performance of Fractional Excretion of Sodium for the Differential Diagnosis of Acute Kidney Injury: A Systematic Review and Meta-Analysis

Abstract

Background and objectives: AKI is classified as prerenal, intrinsic, and postrenal. Prerenal AKI and intrinsic AKI represent the most common causes for AKI in hospitalized patients. This study aimed to examine the accuracy of the fractional excretion of sodium for distinguishing intrinsic from prerenal AKI.

Design, setting, participants, & measurements: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, the Cochrane Library, and Scopus for all available studies that met the criteria until December 31, 2021. We included studies that evaluated fractional excretion of sodium in differentiating AKI etiologies in adults, whereas studies that did not have sufficient data to extract a 2×2 table were excluded. We assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool and extracted the diagnostic accuracy data for all included studies. We conducted a meta-analysis using the bivariate random effects model. We performed subgroup analysis to investigate sources of heterogeneity and the effect of the relevant confounders on fractional excretion of sodium accuracy.

Results: We included 19 studies with 1287 patients. In a subset of 15 studies (872 patients) that used a threshold of 1%, the pooled sensitivity and specificity for differentiating intrinsic from prerenal AKI were 90% (95% confidence interval, 81% to 95%) and 82% (95% confidence interval, 70% to 90%), respectively. In a subgroup of six studies (511 patients) that included CKD or patients on diuretics, the pooled sensitivity and specificity were 83% (95% confidence interval, 64% to 93%) and 66% (95% confidence interval, 51% to 78%), respectively. In five studies with 238 patients on diuretics, the pooled sensitivity and specificity were 80% (95% confidence interval, 69% to 87%) and 54% (95% confidence interval, 31% to 75%), respectively. In eight studies with 264 oliguric patients with no history of CKD or diuretic therapy, the pooled sensitivity and specificity were 95% (95% confidence interval, 82% to 99%) and 91% (95% confidence interval, 83% to 95%), respectively.

Conclusions: Fractional excretion of sodium has a limited role for AKI differentiation in patients with a history of CKD or those on diuretic therapy. It is most valuable when oliguria is present.

Keywords: AKI; DTA; FENa; meta-analysis; sodium; systematic review.

Graphical abstract

Figure 1.

Flow chart of literature search and selection.

Figure 2.

Forest plots for the included studies at the reported threshold of the fractional excretion of sodium (FENa) for intrinsic AKI versus prerenal AKI. (A) The forest plot for the 15 studies uses a 1% cutoff, including a quantitative meta-analysis of the sensitivity and specificity. The size of the square is proportional to the size of the population. The diamonds represent the pooled estimates. (B) The forest plot for studies that did not use a 1% threshold: FENa <1% and >3%, FENa <1% and >4%, FENa=1%, and FENa 0.57%. Output was from Review Manager (computer program). 95% CI, 95% confidence interval; D, derivation cohort; df, degrees of freedom; FN, false negative; FP, false positive; NPV, negative predictive value; PPV, positive predictive value; TN, true negative; TP, true positive; V, validation cohort.

Figure 3.

Summary receiver operating characteristic plot for the 15 studies used for FENa at the 1% threshold. The summary operating point (filled circle) for the 15 studies included in the meta-analysis is shown with the 95% confidence interval (dotted curve) and the 95% prediction region (dashed curve). The different legends represent the characteristics of each study population. The sizes of the ellipsoids, diamonds, squares, triangles, and crosses are proportional to the sample sizes for each study. Output was from Review Manager (computer program).