Article Figures & Data
Figures
- 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).
Tables
- Table 1.
Studies that examined the performance of the fractional excretion of sodium in AKI
Study, Year Design, Settings Intrinsic AKI, n; Age, Mean, yr; Women, %; Creatinine, Mean, mg/dl Prerenal AKI, n; Age, Mean, yr; Women, %; Creatinine, Mean, mg/dl Inclusion Criteria Exclusion Criteria Reference Standard Fractional Excretion of Sodium Cutoff(s), % Intrinsic AKI: Oliguric, %; Receiving Diuretics, % Prerenal AKI: Oliguric, %; Receiving Diuretics, % Intrinsic AKI: CKD, %; Sepsis, % Prerenal AKI: CKD, %; Sepsis, % Espinel (6), 1976 P, N/R 9; N/R; N/R; 9.2±0.7 8; N/R; N/R; 8.3±1.1 Acute onset of oliguria (urinary output below 20 ml/hr) CKD, patients on diuretics, acute glomerular disease, or urinary tract obstruction Responsiveness to fluids. ATN cases were also confirmed by histologic
findings<1 and >3; 1 100; 0 100; 0 0; N/R 0; N/R Miller et al. (27), 1978 P, hospitalized 55; 58.1±3.5; 20; 3.9±0.26 30; 62±3; 34; 3±0.3 Acute elevation of serum creatinine from normal levels (<1.4 mg/dl) to >2.0 mg/dl CKD, patients on diuretics Responsiveness to fluids, urine microscopy findings 1 44; 0 N/R; 0 0; N/R 0; N/R Espinel and Gregory (7), 1980 P, hospitalized 65; N/R; N/R; 5.2±1.5 8; N/R; N/R; 5.4±0.8 Acute increase in creatinine level above 2 mg/dl CKD, patients on diuretics Response to fluids, urine microscopy, histopathology in some cases 1 56; 0 100; 0 0; N/R 0; N/R Zager et al. (28), 1980 P, hospitalized 22; N/R; N/R; N/R 5; N/R; N/R; N/R Patients with AKI, defining criteria are not reported N/R Response to fluids, urine microscopy 1 59; N/R 100; N/R 0; 0 0; 0 Chugh et al. (21), 1981 P, hospitalized 40; N/R; N/R; N/R 21; N/R; N/R; N/R Oliguric AKI, defining criteria are not reported CKD, acute GN, obstructive uropathy, diabetes mellitus, and cirrhosis Response to fluids and pathologic findings <1 and >3 100; 0 100; 0 0; N/R 0; N/R Brown et al. (29), 1983 P, hospitalized 10; N/R; N/R; N/R 7; N/R; N/R; N/R AKI defined by an acute rise in blood urea CKD, patients on diuretics Response to fluids, urine microscopy 1 80; 0 100; 0 0; N/R 0; N/R Anderson et al. (30), 1984 P, hospitalized 41; N/R; N/R; 4.4±0.5 21; N/R; N/R; 2.6±0.2 Acute rise in creatinine from <1.4 to >2.0 mg/dl N/R; patients with CKD were studied separately Responsiveness to fluids, urine microscopy findings 1 53; N/R 100; 0 0;a 0 0; 0 Tankhiwale and Ungratwar (26), 1987 P, hospitalized 22; N/R; N/R; N/R 20; N/R; N/R; N/R Patients with AKI, although the defining criteria are not reported Patients with CKD Responsiveness to fluid expansion; histopathologic findings 1 100; N/R 100; N/R 0; N/R 0; N/R Fushimi et al. (40), 1990 P, hospitalized 6; 52±16; 33; 5.2±1.3 8; 66.4±23; 50; 2.8±0.4 Acute elevation of serum creatinine to >1.5 mg/dl, with a decrease in creatinine clearance CKD, acute GN, and patients receiving diuretics Responsiveness to fluids, urine microscopy findings 1 N/R; 0 100; 0 0; 0 0; 0 Steinhäuslin et al. (18), 1994 P, ICU and ER 18; 39 (10th [21] to 90th [76] percentile); 64; 5.6 (10th [3.6] to 90th [9.5] percentile) 28; 65.5 (10th [18] to 90th [88] percentile); 65; 1.8 (10th [1.2] to 90th [3.5] percentile) A recent increase in plasma creatinine of >20% or plasma creatinine concentration above 200 μmol/L at the time of referral Presence of acute GN, acute interstitial nephritis, and obstructive uropathy Responsiveness to fluids, urine microscopy findings <1.3 and >3.5 N/R; 50 N/R; 39 0; 0 0; 0 Carvounis et al. (9), 2002 P, hospitalized (mostly ICU) 25; 47±3; 48; 5.9±0.5 77; 51±3; 51; 1.7±0.25 Rapidly increasing BUN and creatinine (BUN >30 mg/dl and creatinine >1.5 mg/dl) with or without oliguria or serum creatinine increase in excess of 0.5 mg/dl in the preceding 2 d Patients with acute interstitial nephritis, acute GN, and obstructive uropathy Responsiveness to fluids, urinalysis findings 1; 0.60; 0.80; 1.20; 1.50; 2; 3 N/R; 0 N/R; 35 0; 1 0; 32 du Cheyron et al. (39), 2003 P, ICU 19; N/R; N/R; 3.3±1.6 17; N/R; N/R; 2.1 ± 0.5 Sudden increase in serum creatinine level to ≥2 mg/dl or a value 50% greater than the basal concentration when CKD already existed Patients with hepatorenal syndrome, cirrhosis Responsiveness to fluids 1 N/R; N/R N/R; N/R 0; 0 0; 6 Pépin et al. (4), 2007 P, hospitalized 33; 66.3; 55; 3.8±1.6 66; 66.8; 47; 2.5±1.3 An increase in serum creatinine level of 30% or higher over the baseline with an abrupt onset (<1 wk) Contrast examination <48 h before the onset of AKI, rhabdomyolysis, obstructive uropathy, acute GN, drug nephrotoxicity, and kidney failure Responsiveness to fluids, urine microscopy findings 1 36; 64 24; 65 45; 42 36; 24 Diskin et al. (22), 2010 P, hospitalized 20; 67.5±12.7; 56; N/R 80; 66.8±12.3; 49; N/R AKI patients with oliguria; defined as urine output <600 ml/24 h and abrupt sustained rise in creatinine >1.9 mg/dl All patients with possible creatinine assay–interfering drugs/conditions Responsiveness to fluids <1 and >3 100; 55 100; 71 28; 0 0; 7 Darmon et al. (25), 2011 P, ICU 82; 66 (IQR, 56–74); 32; 2.5 (IQR, 1.6–4.1) 54; 71 (IQR, 49–76); 41; 1.4 (IQR, 1.1–1.9) AKI defined according to the AKIN or MDRD formula Patients on dialysis, obstructive uropathy Responsiveness to fluids 1; 0.58 N/R; 39 N/R; 33 28; 74 6; 61 Dewitte et al. (41), 2012 P, ICU 24; 69 (IQR, 54–73); 8; N/R 23; 64 (IQR, 43–75); 35; N/R AKI according to the consensus definition from the Acute Dialysis Quality Initiative group Patients with CKD, obstructive uropathy Responsiveness to fluids 1 75; 58 74; 61 0; 29 0; 39 Yassin et al. (23), 2013 P, ICU 14; 56.29±19.5; 42; 5.5±2.1 26; 60±15.15; 62; 2.2±0.6 Patients with AKI with circulatory shock; circulatory shock was diagnosed according to the empirical criteria, AKI according to the RIFLE criteria in oliguric patients CKD, obstructive uropathy, and patients on osmotic diuresis Response to fluids, urinalysis 1 100; 57 100; 46 0; N/R 0; N/R Patidar et al. (20), 2017 R, hospitalized 12; N/R; N/R; N/R 21; N/R; N/R; N/R Cirrhotic patients who were admitted for AKI, the defining criteria of AKI are not reported; HRS AKI was diagnosed on the basis of the International Club of Ascites definition Patients with ascites, patients not on diuretics, advanced kidney failure Clinical course decided by a nephrologist 1 N/R; 100 N/R; 100 0; 0 0; 0 Gowda et al. (D) (24), 2021 P, hospitalized 57; 48.47±10.8; 5; 3.2±1.78 143; 50.42±12.26; 6; 2.5±1.08 Cirrhotic patients who were screened for AKI as per revised International Club of Ascites definitions at admission CKD, history of KRT, diuretic use, exposure to potential nephrotoxic drugs, cardiovascular disease Responsiveness to fluids; ATN AKI was diagnosed if abnormal kidney finding is present on ultrasound, proteinuria >500 mg/d, microhematuria (>50 red blood cells per high-power field), or presence of active urinary sediments; HRS AKI was diagnosed on the basis of the International Club of Ascites definition 0.57 N/R; 0 N/R; 0 0; 0 0; 0 Gowda et al. (V) (24), 2021 P, hospitalized 17; 49.24±9.5; 0; 2.5±1.11 33; 51.24±12.7; 15; 2.5±1.08 Cirrhotic patients who were screened for AKI as per revised International Club of Ascites definitions at admission CKD, history of KRT, diuretic use, exposure to potential nephrotoxic drugs, cardiovascular disease Responsiveness to fluids; ATN AKI was diagnosed if abnormal kidney finding is present on ultrasound, proteinuria >500 mg/d, microhematuria (>50 red blood cells per high-power field), or presence of active urinary sediments; HRS AKI was diagnosed on the basis of the International Club of Ascites definition 0.57 N/R; 0 N/R; 0 0; 0 0; 0 P, prospective; N/R, not reported; ATN, acute tubular necrosis; ICU, intensive care unit; ER, emergency room; IQR, interquartile range; AKIN, Acute Kidney Injury Network; MDRD, Modification of Diet in Renal Disease; R, retrospective; HRS, hepatorenal syndrome; D, derivation cohort; V, validation cohort.
↵a This study included patients with CKD, but their data were not available.
Study Identification Could the Selection of Patients Have Introduced Bias? Are There Concerns that the Included Patients and Setting Do Not Match the Review Question? Could the Conduct or Interpretation of the Index Test Have Introduced Bias? Are There Concerns that the Index Test, Its Conduct, or Interpretation Differ from the Review Question? Could the Reference Standard, Its Conduct, or Its Interpretation Have Introduced Bias? Are There Concerns that the Target Condition as Defined by the Reference Standard Does Not Match the Question? Could the Patient Flow Have Introduced Bias? Espinel (6), 1976 Low risk Unclear concern Low risk Low concern Unclear risk Low concern Low risk Miller et al. (27), 1978 High risk Low concern Low risk Low concern Unclear risk Low concern Low risk Espinel and Gregory (7), 1980 Low risk Low concern Low risk Low concern Low risk Low concern Low risk Zager et al. (28), 1980 Low risk Low concern Low risk Low concern Unclear risk Low concern High risk Chugh et al. (21), 1981 Low risk Low concern Unclear risk High concern Unclear risk Low concern Unclear risk Brown et al. (29), 1983 Low risk Low concern Unclear risk Low concern Unclear risk Low concern Unclear risk Anderson et al. (30), 1984 Low risk Low concern Low risk Low concern Unclear risk Low concern Low risk Tankhiwale and Ungratwar (26), 1987 Low risk Low concern Unclear risk Low concern Unclear risk Low concern Unclear risk Fushimi et al. (40), 1990 Low risk Low concern Unclear risk Low concern Unclear risk Low concern Low risk Steinhäuslin et al. (18), 1994 High risk Low concern High risk High concern Unclear risk Low concern Low risk Carvounis et al. (9), 2002 Low risk Low concern Unclear risk Low concern High risk Low concern Unclear risk du Cheyron et al. (39), 2003 High risk Low concern Unclear risk Low concern High risk Low concern Low risk Pépin et al. (4), 2007 High risk Low concern Low risk Low concern Low risk Low concern Low risk Diskin et al. (22), 2010 Low risk Low concern Low risk Low concern Unclear risk Low concern Low risk Darmon et al. (25), 2011 Low risk Low concern Low risk Low concern Unclear risk Low concern Low risk Dewitte et al. (41), 2012 Low risk Low concern Low risk Low concern Unclear risk Low concern Low risk Yassin et al. (23), 2013 Low risk Low concern Unclear risk Unclear concern Unclear risk Low concern Unclear risk Patidar et al. (20), 2017 Low risk Low concern High risk Unclear concern Unclear risk Low concern Low risk Gowda et al. (D) (24), 2021 High risk High concern High risk High concern Unclear risk Low concern Low risk Gowda et al. (V) (24), 2021 High risk High concern Low risk High concern Unclear risk Low concern Low risk D, derivation cohort; V, validation cohort.
Subgroup No. Subgroup No. of Studies No. of Participants Intrinsic AKI, N (%) Pooled Sensitivity [95% Confidence Interval]; I2 Pooled Specificity [95% Confidence Interval]; I2 Diagnostic Odds Ratio [95% Confidence Interval]; I2 Positive Likelihood Ratio [95% Confidence Interval]; I2 Negative Likelihood Ratio [95% Confidence Interval]; I2 Positive Predictive Value [95% Confidence Interval]; I2 Negative Predictive Value [95% Confidence Interval]; I2 1 Patients not on diuretics 12 502 270 (54) 92% [85% to 96%]; 57% 88% [83% to 92%]; 20% 88 [34 to 226]; 24% 7.83 [5.10 to 12.01]; 0% 0.09 [0.05 to 0.17]; 47% 91% [83% to 95%]; 62% 92% [82% to 96%]; 65% 2 Patients on diuretics 5 238 88 (37) 80% [69% to 87%]; 0% 54% [31% to 75%]; 86% 5 [1 to 16]; 59% 1.71 [0.97 to 3.02]; 77% 0.38 [0.18 to 0.80]; 27% 54% [31% to 75%]; 89% 82% [61% to 93%]; 76% 3 Without patients with CKD 13 632 294 (47) 92% [87% to 96%]; 50% 85% [73% to 93%]; 84% 69 [25 to 191]; 36% 6.22 [3.21 to 12.02]; 88% 0.09 [0.05 to 0.16]; 38% 89% [73% to 96%]; 92% 92% [84% to 96%]; 69% 4 Patients without CKD and not on diuretics 11 464 225 (49) 93% [86% to 96%]; 54% 89% [84% to 93%]; 14% 107 [41 to 279]; 0% 8.60 [5.53 to 13.38]; 0% 0.08 [0.04 to 0.16]; 46% 92% [85% to 96%]; 58% 92% [82% to 97%]; 68% 5 Oliguric patients 9 355 154 (43) 93% [82% to 97%]; 62% 88% [71% to 96%]; 87% 97 [20 to 471]; 46% 7.84 [2.91 to 21.10]; 90% 0.08 [0.03 to 0.22]; 62% 90% [70% to 97%]; 92% 93% [82% to 98%]; 60% 6 Oliguric patients without CKD and not on diuretics 8 264 130 (49) 95% [82% to 99%]; 62% 91% [83% to 95%]; 20% 197 [38 to 1017]; 0% 10.07 [5.58 to 18.15]; 0% 0.05 [0.01 to 0.22]; 65% 92% [81% to 97%]; 51% 96% [81% to 99%]; 57% 7 Studies including patients with CKD or on diuretics 6 511 194 (38) 83% [64% to 93%]; 88% 66% [51% to 78%]; 84% 10 [3 to 34.0]; 78% 2.42 [1.52 to 3.87]; 82% 0.26 [0.10 to 0.63]; 85% 56% [43% to 69%]; 82% 88% [66% to 97%]; 94% 8 Studies published before 2000 7 325 205 (63) 93% [84% to 97%]; 63% 92% [85% to 95%]; 1% 148 [43 to 508]; 0% 10.93 [5.89 to 20.30]; 0% 0.07 [0.03 to 0.18]; 55% 95% [91% to 97%]; 36% 90% [75% to 96%]; 55% 9 Studies published after 2000 8 547 213 (39) 83% [67% to 92%]; 86% 67% [53% to 78%]; 82% 10 [3 to 30]; 76% 2.52 [1.64 to 3.86]; 80% 0.25 [0.12 to 0.55]; 84% 60% [46% to 72%]; 82% 87% [68% to 96%]; 93%
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Diagnostic Performance of Fractional Excretion of Sodium for the Differential Diagnosis of Acute Kidney Injury
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