Article Figures & Data
Figures
- Figure 1.
Receiver-operating characteristics analyses for predicting AKI progression or AKI progression with death. (A) The area under the receiver operating curve (AUCs) of renal injury biomarkers (urinary angiotensinogen [uAGT], urinary neutrophil gelatinase-associated lipocalin [uNGAL], urinary IL-18 [uIL-18]) and clinical model, at the time of AKI diagnosis, for predicting AKI progression. (B) The AUCs of renal injury biomarkers (uAGT, uNGAL, uIL-18) and clinical model, at the time of AKI diagnosis, for predicting AKI progression with subsequent death. (C) The performance of combination of renal injury biomarkers for predicting AKI progression. The clinical risk model includes age, gender, hypertension, diabetes, preadmission eGFR, N-terminal pro-B-type natriuretic peptide (NT-proBNP), serum albumin, hemoglobin, diuretic dosage before AKI, use of spironolactone before AKI, use of RAS inhibitors before AKI, and change of serum creatinine from baseline at the time of AKI diagnosis.
Tables
Demographics AKI progression P Value Yes (n=50) No (n=163) Age, y 66.8±17.6 70.6±12.2 0.09 Male, n (%) 26 (52.0) 108 (66.3) 0.09 Hypertension, n (%) 24 (48.0) 105 (64.4) 0.05 Diabetes, n (%) 20 (40.0) 55 (33.7) 0.49 Prior CKDa, n (%) 22 (44.0) 60 (36.8) 0.41 Prior hospitalization for HF, n (%) 25 (50.0) 88 (54.0) 0.63 Primary diseases of heart failure Ischemic heart disease, n (%) 28 (56.0) 90 (55.2) 0.99 Hypertensive heart disease, n (%) 7 (14.0) 30 (18.4) 0.53 Rheumatic heart disease, n (%) 4 (8.0) 11 (6.7) 0.76 Cardiomyopathy, n (%) 7 (14.0) 21 (12.9) 0.81 Other, n (%) 4 (8.0) 11 (6.7) 0.76 Preadmission medication ACEI/ARB, n (%) 15 (30.0) 52 (32.0) 0.86 β-blockers, n (%) 9 (18.0) 40 (24.5) 0.44 Spironolactone, n (%) 10 (20.0) 44 (27.0) 0.36 Loop diuretics, n (%) 14 (28.0) 53 (32.5) 0.60 Preadmission (baseline) renal function Serum creatinine, mg/dl 1.45±0.7 1.30±0.5 0.11 eGFR, ml/min per 1.73m2 b 59.1±28.3 63.4±24.0 0.29 Parameters on admission LVEF (%) 42 (40–63) 41 (36–58) 0.22 NYHA (class IV), n (%) 20 (40.0) 89 (54.6) 0.08 NT-proBNP, pg/ml 9000 (3656–24139) 6647 (3185–9000) 0.02 Serum creatinine, mg/dl 1.6±0.8 1.5±0.8 0.41 Serum albumin, g/dl 2.9±0.6 3.2±0.5 0.001 Serum triglyceride, mmol/L 1.6±0.8 1.7±0.7 0.39 Serum cholesterol, mmol/L 3.8±0.9 3.8±0.6 0.99 Serum sodium, mmol/L 138.3±5.0 138.0±5.0 0.71 Serum potassium, mmol/L 4.2±0.8 4.1±0.6 0.34 Hemoglobin, g/dl 10.8±2.4 11.8±2.6 0.04 Continuous variables were expressed as mean±SD or median (25th percentile – 75th percentile, interquartile range). Categorical variables were expressed as a number (%). AKI progression is defined as worsening of AKI stage. HF, heart failure; ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin II type I receptor blockers; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; NT-proBNP, N-terminal pro-B-type natriuretic peptide.
↵a Defined as preadmission eGFR<60ml/min per 1.73m2. Preadmission eGFR was calculated by CKD-Epidemiology Collaboration equation according to at least three measurements of serum creatinine over a 6-month period before admission.
Variables AKI progression P Value Yes (n=50) No (n=163) Timing of AKI AKI on admission, n (%) 6 (12.0) 22 (13.5) 0.99 Within 4 d after admission, n (%) 46 (92.0) 135(82.8) 0.17 Use of loop-diureticsa Before AKI diagnosis, mg/d 46.5±22.1 40.5±20.6 0.08 On the day of AKI diagnosis, mg/d 49.0±23.5 42.1±22.8 0.06 Use of spironolactone Before AKI diagnosis, n (%) 20 (40.0) 78 (47.9) 0.41 On the day of AKI diagnosis, n (%) 20 (40.0) 78 (47.9) 0.41 Use of RAS inhibitors Before AKI diagnosis, n (%) 19 (38.0) 73 (44.8) 0.42 On the day of AKI diagnosis, n (%) 19 (38.0) 73 (44.8) 0.42 Biomarkers on the day of AKI diagnosis SCr, mg/dl 2.1±0.85 1.8±0.7 0.01 Change in SCr, mg/dlb 0.7±0.5 0.5±0.4 0.05 Change in SCrc, % 48.4±27.7 45.9±23.0 0.52 uAGT, μg/g Cr 224.5 (108.8–483.8) 44.8 (9.3–146.2) <0.001 pAGT, μg/L 27.8±5.7 26.5±5.5 0.15 uNGAL, μg/g Cr 311.3 (87.5–1883.8) 58.8 (29.8–197.3) <0.001 pNGAL, ng/ml 238.0 (152.9–335.4) 179.0 (115.2–258.2) 0.001 uIL-18, ng/g Cr 748.4 (68.7–1964.9) 52.0 (16.0–215.2) <0.001 uKIM-1, μg/g Cr 4.6 (2.5–8.0) 2.6 (1.6–4.9) 0.001 UACR, mg/g Cr 292.3 (138.2–964.9) 154.0 (49.8–382.0) 0.001 In-hospital outcomes Hospital-free daysd 0 (0–18) 18 (10–20) 0.001 ICU-free daysd 13 (0–21) 22 (15–24) <0.001 Acute dialysis, n (%) 13 (26.0) 0 (0) <0.001 In-hospital death, n (%) 18 (36.0) 25 (15.3) 0.002 Continuous variables were expressed as mean±SD or median (25th percentile – 75th percentile, interquartile range). Categorical variables were expressed as a number (%). SCr, serum creatinine; uAGT, urinary angiotensinogen; pAGT, plasma angiotensinogen; uNGAL, urinary neutrophil gelatinase-associated lipocalin; pNGAL plasma neutrophil gelatinase-associated lipocalin; uIL-18, urinary IL-18; uKIM-1, urinary kidney injury molecule-1; UACR, urinary albumin to creatinine ratio; ICU, Intensive-care unit.
↵a Average daily dose of intravenous furosemide (oral dosage × 0.5, as oral bioavailability is about 50%).
↵b Serum creatinine level on the day of AKI diagnosis minus baseline serum creatinine level.
↵c (SCr level on the day of AKI diagnosis − baseline SCr level)/ baseline SCr level × 100%.
↵d 28 minus the number of hospital or ICU days, with a score of zero assigned to patients who died.
- Table 3.
Biomarkers for predicting AKI progression: multivariate logistic regression analyses
Biomarker Cut Points N AKI Progression (%) Unadjusted OR (95% CI) P Value Adjusted ORa (95% CI) P Value SCr, mg/dl Low (T1) 0.8–1.4 70 14.3 1 (referent) 0.04 1 (referent) 0.21 Medium (T2) 1.5–2.0 72 23.6 1.9 (0.8 to 4.3) 2.3 (0.8 to 6.6) High (T3) >2.0 71 32.4 2.9 (1.2 to 6.6) 2.9 (0.8 to 10.5) uAGT, μg/g Cr Low (T1) 0.04–27.3 71 7.0 1 (referent) <0.001 1 (referent) <0.001 Medium (T2) 27.4–146.4 71 19.7 3.2 (1.1 to 9.5) 3.7 (1.1 to 12.1) High (T3) >146.4 71 43.7 10.2 (3.7 to 28.4) 10.8 (3.4 to 34.7) uNGAL, μg/g Cr Low (T1) 0.2–47.4 71 9.9 1 (referent) <0.001 1 (referent) 0.01 Medium (T2) 47.5–185.4 71 21.1 2.4 (0.9 to 6.4) 2.0 (0.7 to 5.7) High (T3) >185.4 71 39.4 5.9 (2.4 to 14.8) 4.7 (1.7 to 13.4) uIL-18, ng/g Cr Low (T1) 1.2–38.5 70 14.3 1 (referent) <0.001 1 (referent) 0.004 Medium (T2) 38.6–224.4 72 11.1 0.8 (0.3 to 2.0) 0.8 (0.3 to 2.3) High (T3) >224.4 71 45.1 4.9 (2.2 to 11.1) 3.6 (1.4 to 9.5) uKIM-1, μg/g Cr Low (T1) 0.01–2.2 71 15.5 1 (referent) 0.002 1 (referent) 0.11 Medium (T2) 2.3–4.6 71 16.9 1.1 (0.5 to 2.7) 0.9 (0.3 to 2.5) High (T3) >4.6 71 38.0 3.3 (1.5 to 7.5) 2.1 (0.8 to 5.3) UACR, mg/g Cr Low (T1) 1.0–104.7 71 12.7 1 (referent) 0.02 1 (referent) 0.19 Medium (T2) 104.8–308.5 71 23.9 2.2 (0.9 to 5.2) 1.7 (0.6 to 4.4) High (T3) >308.5 71 33.8 3.5 (1.5 to 8.2) 2.5 (0.9 to 6.9) pNGAL, ng/ml Low (T1) 8.8–151.3 71 14.1 1 (referent) 0.04 1 (referent) 0.63 Medium (T2) 151.4–238.0 74 24.3 2.0 (0.8 to 4.6) 1.5 (0.6 to 4.0) High (T3) >238.0 68 32.4 2.9 (1.3 to 6.8) 1.2 (0.4 to 3.2) AKI progression is defined as worsening of AKI stage (from stage 1 to either stage 2 or 3 or from stage 2 to 3). Biomarkers are measured at the time of stage 1 or 2 AKI diagnosis. SCr, serum creatinine; T, tertile; uAGT, urinary angiotensinogen; uNGAL, urinary neutrophil gelatinase-associated lipocalin; uIL-18, urinary IL-18; uKIM-1, urinary kidney injury molecule-1; UACR, urinary albumin to creatinine ratio; pNGAL plasma neutrophil gelatinase-associated lipocalin.
↵a Adjusted for age, gender, hypertension, diabetes, preadmission eGFR, NT-proBNP, serum albumin, hemoglobin, diuretic dosage before AKI, use of spironolactone before AKI, use of RAS inhibitors before AKI, and change of serum creatinine from baseline at the time of AKI diagnosis. Site is adjusted as a random effect.
- Table 4.
NRI and IDI of including biomarkers in the clinical model to predict AKI progression or progression with death
Outcome Category-Free NRI (95% CI) P Value NRI in Progressors (95% CI) P Value NRI in Nonprogressors (95% CI) P Value IDI (95% CI) P Value Predicting AKI progression Clinical risk factorsa referent referent Clinical risk factors plus uAGT 0.76 (0.46–1.06) <0.001 0.48 (0.22–0.74) <0.001 0.28 (0.13–0.43) <0.001 0.14 (0.10–0.18) <0.001 Clinical risk factors plus uNGAL 0.64 (0.32–0.96) <0.001 0.28 (0.01–0.56) 0.04 0.36 (0.21–0.51) <0.001 0.11 (0.07–0.15) <0.001 Clinical risk factors plus uIL-18 0.60 (0.30–0.90) <0.001 0.36 (0.10–0.62) 0.01 0.24 (0.08–0.40) 0.002 0.09 (0.05–0.13) <0.001 Clinical risk factors plus pNGAL 0.23 (−0.09–0.55) 0.15 −0.08 (-0.36–0.20) 0.57 0.31 (0.17–0.45) <0.001 0.04 (0.00–0.08) 0.01 Clinical risk factors plus uKIM-1 0.17 (−0.15–0.49) 0.29 0.24 (-0.04–0.52) 0.08 −0.07 (−0.23–0.09) 0.39 0.01 (0.00–0.03) 0.30 Clinical risk factors plus UACR 0.03 (−0.29–0.35) 0.87 0.24 (−0.04–0.52) 0.09 −0.21 (−0.37 to −0.05) 0.006 0.01 (0.00–0.03) 0.36 Predicting AKI progression with death Clinical risk factorsa referent referent Clinical risk factors plus uAGT 0.93 (0.50–1.36) <0.001 0.44 (-0.01–0.90) 0.06 0.49 (0.37–0.61) <0.001 0.19 (0.09–0.29) <0.001 Clinical risk factors plus uNGAL 0.86 (0.43–1.30) <0.001 0.44 (-0.01–0.90) 0.06 0.42 (0.30–0.54) <0.001 0.07 (0.01–0.13) 0.04 Clinical risk factors plus uIL-18 0.88 (0.45–1.31) <0.001 0.44 (-0.01–0.90) 0.06 0.44 (0.32–0.56) <0.001 0.08 (0.00–0.16) 0.03 AKI progression is defined as worsening of AKI stage (from stage 1 to either stage 2 or 3 or from stage 2 to 3). NRI, net reclassification improvement; IDI, integrated discrimination improvement.
↵a The clinical risk factors for AKI progression are comprised of age, gender, hypertension, diabetes, preadmission eGFR, NT-proBNP, serum albumin, hemoglobin, diuretic dosage before AKI, use of spironolactone before AKI, use of RAS inhibitors before AKI, and change of serum creatinine from baseline at the time of AKI diagnosis.
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