Original Paper Nephron Clin Pract 2014;126:8–13 DOI: 10.1159/000357678
Received: June 27, 2013 Accepted: November 29, 2013 Published online: January 11, 2014
Transient versus Persistent Acute Kidney Injury and the Diagnostic Performance of Fractional Excretion of Urea in Critically Ill Patients K.A. Wlodzimirow a A. Abu-Hanna a A.A.N.M. Royakkers d P.E. Spronk e L.S. Hofstra f M.A. Kuiper g M.J. Schultz b, c C.S.C. Bouman b a
Department of Medical Informatics, b Department of Intensive Care and c Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam, Amsterdam, d Department of Anesthesiology, Zaans Medical Center, Zaandam, e Department of Intensive Care, Lukas Hospital, Gelre Hospitals, Apeldoorn, f Department of Intensive Care, Scheper Hospital, Emmen, and g Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, The Netherlands
Abstract Aims: To evaluate the performance of fractional excretion of urea (FeU) for differentiating transient (T) from persistent (P) acute kidney injury (AKI) and to assess performance of FeU in predicting AKI in patients admitted to the ICU. Methods: We performed secondary analysis of a multicenter prospective observational cohort study on the predictive performance of biological markers for AKI in critically ill patients. AKI was diagnosed according to RIFLE staging. Results: Of 150 patients, 51 and 41 patients were classified as having TAKI and P-AKI, respectively. The diagnostic performance for FeU to discriminate T-AKI from P-AKI on the day of AKI was poor (AUC-ROC = 0.61; 95% CI: 0.49–0.73). The diagnostic performance of FeU to predict AKI 1 and 2 days prior to AKI was poor as well (AUC-ROC = 0.61; 95% CI: 0.47–0.74, and 0.58; 95% CI: 0.43–0.73, respectively). Conclusions: FeU does not seem to be helpful in differentiating T- from P-AKI in critically ill patients and it is a poor predictor of AKI.
Introduction
Acute kidney injury (AKI) remains associated with high morbidity and mortality [1, 2]. The incidence among critically ill patients reaches 35%, with an in-hospital mortality rate above 50% when AKI develops as a part of multiple organ dysfunction [3]. Early recognition of AKI and identification of those at high risk for worsening may ultimately improve outcomes [4, 5]. The RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease) and AKIN (Acute Kidney Injury Network criteria) methods for AKI in critically ill patients, based on changes in serum creatinine (SCr) and urine output (UO) were a step forward in AKI diagnosing. Both methods, however, have limited predictive power [6, 7]. Discriminating transient (T-) from persistent (P-) AKI could have advantages [8, 9], e.g. in optimization of treatment such as limiting fluids or starting of renal replacement therapy (RRT) [10]. Fractional excretion of urea (FeU) is suggested to have discriminative power with respect to T-AKI and P-AKI [11], and unlike the fractional excretion of sodium it is not affected by concomitant diuretic use. Little is known,
© 2014 S. Karger AG, Basel © 2014 S. Karger AG, Basel 1660–2110/14/1261–0008$39.50/0 E-Mail [email protected] www.karger.com/nec
Kama Wlodzimirow Academic Medical Center, University of Amsterdam Department of Medical Informatics, Suite J1B-127 PO box 22700, NL–1100 DE Amsterdam (The Netherlands) E-Mail k.a.wlodzimirow @ amc.uva.nl
Downloaded by: University of Pittsburgh 132.174.255.116 - 3/13/2015 3:50:27 AM
Key Words Acute kidney injury · Transient · Persistent · Fractional excretion of urea · Intensive care
however, about its utility in critically ill patients [12, 13]. We hypothesized that (1) FeU differentiates T- from PAKI on the first day of AKI, and (2) FeU can predict AKI in the days preceding AKI according to RIFLE. Methods The study was conducted as part of a multicenter prospective observational cohort study on cystatin C as a predictor for AKI. Detailed methods have been described previously [14]. Briefly, the study included adult patients who were expected to need mechanical ventilation for at least 48 h and/or have an ICU stay of at least 72 h. Exclusion criteria were chronic RRT, preadmission treatment with corticosteroids (>5 mg prednisone, or equivalent, per day), treatment with plasmapheresis during ICU admission and participation in another clinical trial. Patients’ data were documented
upon ICU admittance. Blood and urine sampling were performed on the day of admission, next day and alternating days until RRT was started or ICU discharge. The UO was measured hourly. Patients were scored daily for the presence of AKI based on the RIFLE criteria [6]. Baseline SCr was defined as the lower of the premorbid and ICU admission values. When premorbid SCr (within 1 year prior to hospital admission) was unknown, it was estimated using the Modification of Diet in Renal Disease (MDRD) equation assuming a GFR of 75 ml/min/1.73 m2. The first day of AKI was defined as the day of the first RIFLE event and was termed ‘day 0’. The 2 days prior to this day were termed ‘day –2’ and ‘day –1’, respectively. Patients were classified as having P-AKI when AKI was sustained for more than 3 days according to RIFLE or when the patient died with AKI within 3 days [11, 15]. The RIFLE class cannot be determined once continuous venovenous hemofiltration (CVVH) is started; therefore, we classified patients who received CVVH within 3 days after day 0 as P-AKI. Patients were classified as having T-AKI
Table 1. Baseline characteristics
Age, years Men BMI APACHE II SAPS II Admission type Surgical Medical Comorbidity Hypertension Diabetes mellitus Chronic renal failure1 Admission diagnosis Cardiovascular failure Cerebrovascular event Hemorrhagic shock Multiple trauma Peripheral vascular surgery Cardiopulmonary surgery Respiratory failure Septic shock Renal function at admission UO, ml/24 h SCr, μmol/l Serum urea, mmol/l ICU stay, days Outcome RRT ICU mortality Hospital mortality
No AKI (n = 58)
P-AKI (n = 41)
T-AKI (n = 51)
59 ± 16 37 (64) 25 ± 4 18 ± 9 37 ± 13
74 ± 9 26 (63) 27 ± 7 26 ± 13 53 ± 17
70 ± 14 34 (65) 26 ± 5 19 ± 8 40 ± 12
23 (40) 35 (60)
20 (49) 21 (51)
21 (41) 30 (59)
15 (26) 6 (10) 2 (3)
21 (51) 8 (20) 7 (17)
17 (33) 6 (12) 0
2 (3) 2 (3) 7 (12) 4 (7) 1 (2) 1 (2) 23 (39) 18 (31)
4 (10) 0 5 (12.5) 1 (2.5) 3 (7.5) 1 (2.5) 6 (15) 21 (51)
4 (8) 0 3 (6) 2 (4) 3 (6) 1 (2) 19 (36) 19 (37)
p
Received: June 27, 2013 Accepted: November 29, 2013 Published online: January 11, 2014
Transient versus Persistent Acute Kidney Injury and the Diagnostic Performance of Fractional Excretion of Urea in Critically Ill Patients K.A. Wlodzimirow a A. Abu-Hanna a A.A.N.M. Royakkers d P.E. Spronk e L.S. Hofstra f M.A. Kuiper g M.J. Schultz b, c C.S.C. Bouman b a
Department of Medical Informatics, b Department of Intensive Care and c Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam, Amsterdam, d Department of Anesthesiology, Zaans Medical Center, Zaandam, e Department of Intensive Care, Lukas Hospital, Gelre Hospitals, Apeldoorn, f Department of Intensive Care, Scheper Hospital, Emmen, and g Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, The Netherlands
Abstract Aims: To evaluate the performance of fractional excretion of urea (FeU) for differentiating transient (T) from persistent (P) acute kidney injury (AKI) and to assess performance of FeU in predicting AKI in patients admitted to the ICU. Methods: We performed secondary analysis of a multicenter prospective observational cohort study on the predictive performance of biological markers for AKI in critically ill patients. AKI was diagnosed according to RIFLE staging. Results: Of 150 patients, 51 and 41 patients were classified as having TAKI and P-AKI, respectively. The diagnostic performance for FeU to discriminate T-AKI from P-AKI on the day of AKI was poor (AUC-ROC = 0.61; 95% CI: 0.49–0.73). The diagnostic performance of FeU to predict AKI 1 and 2 days prior to AKI was poor as well (AUC-ROC = 0.61; 95% CI: 0.47–0.74, and 0.58; 95% CI: 0.43–0.73, respectively). Conclusions: FeU does not seem to be helpful in differentiating T- from P-AKI in critically ill patients and it is a poor predictor of AKI.
Introduction
Acute kidney injury (AKI) remains associated with high morbidity and mortality [1, 2]. The incidence among critically ill patients reaches 35%, with an in-hospital mortality rate above 50% when AKI develops as a part of multiple organ dysfunction [3]. Early recognition of AKI and identification of those at high risk for worsening may ultimately improve outcomes [4, 5]. The RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease) and AKIN (Acute Kidney Injury Network criteria) methods for AKI in critically ill patients, based on changes in serum creatinine (SCr) and urine output (UO) were a step forward in AKI diagnosing. Both methods, however, have limited predictive power [6, 7]. Discriminating transient (T-) from persistent (P-) AKI could have advantages [8, 9], e.g. in optimization of treatment such as limiting fluids or starting of renal replacement therapy (RRT) [10]. Fractional excretion of urea (FeU) is suggested to have discriminative power with respect to T-AKI and P-AKI [11], and unlike the fractional excretion of sodium it is not affected by concomitant diuretic use. Little is known,
© 2014 S. Karger AG, Basel © 2014 S. Karger AG, Basel 1660–2110/14/1261–0008$39.50/0 E-Mail [email protected] www.karger.com/nec
Kama Wlodzimirow Academic Medical Center, University of Amsterdam Department of Medical Informatics, Suite J1B-127 PO box 22700, NL–1100 DE Amsterdam (The Netherlands) E-Mail k.a.wlodzimirow @ amc.uva.nl
Downloaded by: University of Pittsburgh 132.174.255.116 - 3/13/2015 3:50:27 AM
Key Words Acute kidney injury · Transient · Persistent · Fractional excretion of urea · Intensive care
however, about its utility in critically ill patients [12, 13]. We hypothesized that (1) FeU differentiates T- from PAKI on the first day of AKI, and (2) FeU can predict AKI in the days preceding AKI according to RIFLE. Methods The study was conducted as part of a multicenter prospective observational cohort study on cystatin C as a predictor for AKI. Detailed methods have been described previously [14]. Briefly, the study included adult patients who were expected to need mechanical ventilation for at least 48 h and/or have an ICU stay of at least 72 h. Exclusion criteria were chronic RRT, preadmission treatment with corticosteroids (>5 mg prednisone, or equivalent, per day), treatment with plasmapheresis during ICU admission and participation in another clinical trial. Patients’ data were documented
upon ICU admittance. Blood and urine sampling were performed on the day of admission, next day and alternating days until RRT was started or ICU discharge. The UO was measured hourly. Patients were scored daily for the presence of AKI based on the RIFLE criteria [6]. Baseline SCr was defined as the lower of the premorbid and ICU admission values. When premorbid SCr (within 1 year prior to hospital admission) was unknown, it was estimated using the Modification of Diet in Renal Disease (MDRD) equation assuming a GFR of 75 ml/min/1.73 m2. The first day of AKI was defined as the day of the first RIFLE event and was termed ‘day 0’. The 2 days prior to this day were termed ‘day –2’ and ‘day –1’, respectively. Patients were classified as having P-AKI when AKI was sustained for more than 3 days according to RIFLE or when the patient died with AKI within 3 days [11, 15]. The RIFLE class cannot be determined once continuous venovenous hemofiltration (CVVH) is started; therefore, we classified patients who received CVVH within 3 days after day 0 as P-AKI. Patients were classified as having T-AKI
Table 1. Baseline characteristics
Age, years Men BMI APACHE II SAPS II Admission type Surgical Medical Comorbidity Hypertension Diabetes mellitus Chronic renal failure1 Admission diagnosis Cardiovascular failure Cerebrovascular event Hemorrhagic shock Multiple trauma Peripheral vascular surgery Cardiopulmonary surgery Respiratory failure Septic shock Renal function at admission UO, ml/24 h SCr, μmol/l Serum urea, mmol/l ICU stay, days Outcome RRT ICU mortality Hospital mortality
No AKI (n = 58)
P-AKI (n = 41)
T-AKI (n = 51)
59 ± 16 37 (64) 25 ± 4 18 ± 9 37 ± 13
74 ± 9 26 (63) 27 ± 7 26 ± 13 53 ± 17
70 ± 14 34 (65) 26 ± 5 19 ± 8 40 ± 12
23 (40) 35 (60)
20 (49) 21 (51)
21 (41) 30 (59)
15 (26) 6 (10) 2 (3)
21 (51) 8 (20) 7 (17)
17 (33) 6 (12) 0
2 (3) 2 (3) 7 (12) 4 (7) 1 (2) 1 (2) 23 (39) 18 (31)
4 (10) 0 5 (12.5) 1 (2.5) 3 (7.5) 1 (2.5) 6 (15) 21 (51)
4 (8) 0 3 (6) 2 (4) 3 (6) 1 (2) 19 (36) 19 (37)
p
