Viallet et al. Ann. Intensive Care (2016) 6:71 DOI 10.1186/s13613-016-0176-y
Open Access
RESEARCH
Daily urinary creatinine predicts the weaning of renal replacement therapy in ICU acute kidney injury patients Nicolas Viallet1, Vincent Brunot1, Nils Kuster2, Delphine Daubin1, Noémie Besnard1, Laura Platon1, Aurèle Buzançais1, Romaric Larcher1, Olivier Jonquet1 and Kada Klouche1,3*
Abstract Background: In acute kidney injury (AKI), useless continuation of renal replacement therapy (RRT) may delay renal recovery and impair patient’s outcome. In this study, we aimed to identify predictive parameters that may help to a successful RRT weaning for AKI patients. Methods: We studied 54 surviving AKI patients in which a weaning of RRT was attempted. On the day of weaning (D0) and the following 2 days (D1 and D2), SAPS II and SOFA scores, 24-h diuresis, 24-h urinary creatinine and urea (UCr and UUr), creatinine and urea generation rates (CrGR and UrGR) and clearances (CrCl and UrCl) were collected. Patients who remained free of RRT 15 days after its discontinuation were considered as successfully weaned. Results: Twenty-six RRT weaning attempts succeeded (S+) and 28 failed (S−). Age, previous renal function, SAPS II and SOFA scores were comparable between groups. At D0, 24-h diuresis was 2300 versus 1950 ml in S+ and S−, respectively, p = 0.05. At D0, D1 and D2, 24-h UUr and UCr levels, UrCl and CrCl, and UUr/UrGR and UCr/CrGR ratios were significantly higher in S+ group. By multivariate analysis, D1 24-h UCr was the most powerful parameter that was associated with RRT weaning success with an area under the ROC curve of 0.86 [0.75–0.97] and an odds ratio of 2.01 [1.27–3.18], p = 0.003. Conclusions: In ICU AKI, 24-h UCr appeared as an efficient and independent marker of a successful weaning of RRT. A 24-h UCr ≥5.2 mmol was associated with a successful weaning in 84 % of patients. Keywords: Acute kidney injury, Renal replacement therapy, Weaning, Urine output, Urinary creatinine Background Acute kidney injury (AKI) is a common condition in the intensive care unit (ICU). Approximately 5 % of ICU patients suffering from AKI require renal replacement therapy (RRT) [1]. Such patients have a hospital mortality rate of 45–70 % [1–6], and those surviving to hospital discharge continue to carry a high risk for long-term morbidity and mortality [7–10]. Several studies have shown that between 10 and 30 % of patients with AKI who required RRT will remain dialysis dependent at discharge *Correspondence: k‑klouche@chu‑montpellier.fr 1 Department of Intensive Care Medicine, Lapeyronie University Hospital, 371, Avenue du Doyen G. Giraud, 34295 Montpellier, France Full list of author information is available at the end of the article
[7–13]. Yet, renal function in AKI surviving patients requiring RRT ultimately recovers in the vast majority of case (more than 90 % of patients) [14]. However, performances of RRT may have untoward effects that contribute to the prolongation of renal failure or impede the ultimate recovery of renal function [15]. Indeed, RRT represents an independent and an added risk factor for mortality [16–18] as it exposes the patient to several complications like catheter-related infections or thrombosis, bleeding favored by anticoagulation, hemodynamic instability. The prolonged continuation of RRT could also be deleterious for renal recovery, particularly in cases of intradialytic hemodynamic instability, inducing renal ischemic lesions [19]. Renal biopsy in patients with prolonged AKI treated by hemodialysis showed regions
© 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Viallet et al. Ann. Intensive Care (2016) 6:71
of fresh tubular necrosis days-to-weeks after the initial insult [20]. RRT may also delay renal recovery possibly by purification of mediators and growth factors needful for the tubular repair [21]. Moreover, RRT may remove unpredictable amounts of antibiotics, amino acids and nutrients. Also, RRT represents a significant additional cost in the patient’s care. It is therefore a matter of concern to identify which factors present at the time of discontinuation may help physicians in predicting successful cessation of RRT [22]. To the best of our knowledge, a paucity of studies has been reported on RRT weaning during AKI [23–26]. Sepsis-related Organ Failure Assessment (SOFA) score [23, 26] and 2-h creatinine clearance [25] have been reported as a reliable predictive factors, but urine output remains the most consistent parameter significantly associated with the success of weaning [24]. This study was therefore undertaken to investigate and identify parameters, particularly 24-h urinary creatinine, present at the time of RRT weaning that would be associated with successful cessation of RRT during AKI.
Patients and methods This retrospective study was conducted, from January 2008 to December 2012, in two medical ICUs of the Montpellier University Hospital, France. It was approved by our local institutional review board (Ethic Committee of Montpellier; Comité de protection des personnes: CPP Sud Mediterranée 4) which waived informed consent from the patients or their relatives. Study population
Patients admitted to the ICU for AKI requiring RRT that survived and in which an attempt of weaning was realized were enrolled in the study. Exclusion criteria included pregnancy, age 8.5 ml/ kg/24 h was also found to predict IHDF weaning [32]. In our study, at the day of attempt, 24-h urine output failed to predict the success of weaning (2300 vs 1900 ml/24 h, p = 0.052) but a high proportion of our patients, more
Viallet et al. Ann. Intensive Care (2016) 6:71
Page 6 of 9
Table 3 Serum urea, serum creatinine, 24-h urine output, diuretics, urea and creatinine clearance, 24-h urinary urea and creatinine, urea and creatinine generation rate, urinary urea/urea generation rate and urinary creatinine/creatinine generation rate ratios at the day (D0) of attempt of weaning and the following two days (D1, D2) D0
D1
S+
S−
p
D2
S+
S−
p
17 [14–21]
S+
S−
p
S urea (mmol/l)
10 [7.6–13]
7.3 [6.2–12]
0.56
16 [12–24]
0.26
22 [15–37]
24 [20–27]
0.54
S creat (µmol/l)
105 [73–170]
83 [64–117]
0.36
177 [136–294] 158 [115–197]
0.15
227 [137–309]
218 [155–314]
0.65
24-h urinary output (l)
2.3 [1.5–3.5]
1.9 [1.0–2.5]
0.05
2.4 [1.8–3.7]
2.6 [1.7–3.3]
0.46
2.7 [2.1–3.4]
2.5 [1.7–3.3]
0.32
Use of furo [n (%)]
19 (73)
24 (86)
0.42
15 (59)
25 (89)
Dose of furo (mg/24 h)
470 [215–1000] 1000 [483–1000] 0.06
500 [125–970] 1000 [500–1000]
0.01
500 [250–1000] 1000 [500–1000]
Diuretic RI (ml/mg)
6 [2.9–15.4]
2.1 [1.1–6.4]
0.02
4.6 [3.6–26.4]
3.2 [1.9–4.3]
0.06
5.8 [2.5–8.2]
UrCl (ml/min)
15 [8–20]
6 [4–12]
0.008 12.5 [8–20]
7 [5–9]
0.001 13 [9–18]
15 [8–21]
0.009 9 (35)
CrCl (ml/min)
31 [15–41]
18 [7–26]
0.009 31 [18–40]
UUr (mmol/24 h)
187 [72–339]
85.9 [44–157]
0.031 357 [195–569] 147 [95–224]
UCr (mmol/24 h)
4.9 [2.5–6.4]
2.55 [0.7–3.9]
0.002 6.65 [5–8.8]
3.5 [1.6–4.4]
21 (75)
0.005 0.01
3.4 [2.6–5.8]
0.09
6 [4–8]
Open Access
RESEARCH
Daily urinary creatinine predicts the weaning of renal replacement therapy in ICU acute kidney injury patients Nicolas Viallet1, Vincent Brunot1, Nils Kuster2, Delphine Daubin1, Noémie Besnard1, Laura Platon1, Aurèle Buzançais1, Romaric Larcher1, Olivier Jonquet1 and Kada Klouche1,3*
Abstract Background: In acute kidney injury (AKI), useless continuation of renal replacement therapy (RRT) may delay renal recovery and impair patient’s outcome. In this study, we aimed to identify predictive parameters that may help to a successful RRT weaning for AKI patients. Methods: We studied 54 surviving AKI patients in which a weaning of RRT was attempted. On the day of weaning (D0) and the following 2 days (D1 and D2), SAPS II and SOFA scores, 24-h diuresis, 24-h urinary creatinine and urea (UCr and UUr), creatinine and urea generation rates (CrGR and UrGR) and clearances (CrCl and UrCl) were collected. Patients who remained free of RRT 15 days after its discontinuation were considered as successfully weaned. Results: Twenty-six RRT weaning attempts succeeded (S+) and 28 failed (S−). Age, previous renal function, SAPS II and SOFA scores were comparable between groups. At D0, 24-h diuresis was 2300 versus 1950 ml in S+ and S−, respectively, p = 0.05. At D0, D1 and D2, 24-h UUr and UCr levels, UrCl and CrCl, and UUr/UrGR and UCr/CrGR ratios were significantly higher in S+ group. By multivariate analysis, D1 24-h UCr was the most powerful parameter that was associated with RRT weaning success with an area under the ROC curve of 0.86 [0.75–0.97] and an odds ratio of 2.01 [1.27–3.18], p = 0.003. Conclusions: In ICU AKI, 24-h UCr appeared as an efficient and independent marker of a successful weaning of RRT. A 24-h UCr ≥5.2 mmol was associated with a successful weaning in 84 % of patients. Keywords: Acute kidney injury, Renal replacement therapy, Weaning, Urine output, Urinary creatinine Background Acute kidney injury (AKI) is a common condition in the intensive care unit (ICU). Approximately 5 % of ICU patients suffering from AKI require renal replacement therapy (RRT) [1]. Such patients have a hospital mortality rate of 45–70 % [1–6], and those surviving to hospital discharge continue to carry a high risk for long-term morbidity and mortality [7–10]. Several studies have shown that between 10 and 30 % of patients with AKI who required RRT will remain dialysis dependent at discharge *Correspondence: k‑klouche@chu‑montpellier.fr 1 Department of Intensive Care Medicine, Lapeyronie University Hospital, 371, Avenue du Doyen G. Giraud, 34295 Montpellier, France Full list of author information is available at the end of the article
[7–13]. Yet, renal function in AKI surviving patients requiring RRT ultimately recovers in the vast majority of case (more than 90 % of patients) [14]. However, performances of RRT may have untoward effects that contribute to the prolongation of renal failure or impede the ultimate recovery of renal function [15]. Indeed, RRT represents an independent and an added risk factor for mortality [16–18] as it exposes the patient to several complications like catheter-related infections or thrombosis, bleeding favored by anticoagulation, hemodynamic instability. The prolonged continuation of RRT could also be deleterious for renal recovery, particularly in cases of intradialytic hemodynamic instability, inducing renal ischemic lesions [19]. Renal biopsy in patients with prolonged AKI treated by hemodialysis showed regions
© 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Viallet et al. Ann. Intensive Care (2016) 6:71
of fresh tubular necrosis days-to-weeks after the initial insult [20]. RRT may also delay renal recovery possibly by purification of mediators and growth factors needful for the tubular repair [21]. Moreover, RRT may remove unpredictable amounts of antibiotics, amino acids and nutrients. Also, RRT represents a significant additional cost in the patient’s care. It is therefore a matter of concern to identify which factors present at the time of discontinuation may help physicians in predicting successful cessation of RRT [22]. To the best of our knowledge, a paucity of studies has been reported on RRT weaning during AKI [23–26]. Sepsis-related Organ Failure Assessment (SOFA) score [23, 26] and 2-h creatinine clearance [25] have been reported as a reliable predictive factors, but urine output remains the most consistent parameter significantly associated with the success of weaning [24]. This study was therefore undertaken to investigate and identify parameters, particularly 24-h urinary creatinine, present at the time of RRT weaning that would be associated with successful cessation of RRT during AKI.
Patients and methods This retrospective study was conducted, from January 2008 to December 2012, in two medical ICUs of the Montpellier University Hospital, France. It was approved by our local institutional review board (Ethic Committee of Montpellier; Comité de protection des personnes: CPP Sud Mediterranée 4) which waived informed consent from the patients or their relatives. Study population
Patients admitted to the ICU for AKI requiring RRT that survived and in which an attempt of weaning was realized were enrolled in the study. Exclusion criteria included pregnancy, age 8.5 ml/ kg/24 h was also found to predict IHDF weaning [32]. In our study, at the day of attempt, 24-h urine output failed to predict the success of weaning (2300 vs 1900 ml/24 h, p = 0.052) but a high proportion of our patients, more
Viallet et al. Ann. Intensive Care (2016) 6:71
Page 6 of 9
Table 3 Serum urea, serum creatinine, 24-h urine output, diuretics, urea and creatinine clearance, 24-h urinary urea and creatinine, urea and creatinine generation rate, urinary urea/urea generation rate and urinary creatinine/creatinine generation rate ratios at the day (D0) of attempt of weaning and the following two days (D1, D2) D0
D1
S+
S−
p
D2
S+
S−
p
17 [14–21]
S+
S−
p
S urea (mmol/l)
10 [7.6–13]
7.3 [6.2–12]
0.56
16 [12–24]
0.26
22 [15–37]
24 [20–27]
0.54
S creat (µmol/l)
105 [73–170]
83 [64–117]
0.36
177 [136–294] 158 [115–197]
0.15
227 [137–309]
218 [155–314]
0.65
24-h urinary output (l)
2.3 [1.5–3.5]
1.9 [1.0–2.5]
0.05
2.4 [1.8–3.7]
2.6 [1.7–3.3]
0.46
2.7 [2.1–3.4]
2.5 [1.7–3.3]
0.32
Use of furo [n (%)]
19 (73)
24 (86)
0.42
15 (59)
25 (89)
Dose of furo (mg/24 h)
470 [215–1000] 1000 [483–1000] 0.06
500 [125–970] 1000 [500–1000]
0.01
500 [250–1000] 1000 [500–1000]
Diuretic RI (ml/mg)
6 [2.9–15.4]
2.1 [1.1–6.4]
0.02
4.6 [3.6–26.4]
3.2 [1.9–4.3]
0.06
5.8 [2.5–8.2]
UrCl (ml/min)
15 [8–20]
6 [4–12]
0.008 12.5 [8–20]
7 [5–9]
0.001 13 [9–18]
15 [8–21]
0.009 9 (35)
CrCl (ml/min)
31 [15–41]
18 [7–26]
0.009 31 [18–40]
UUr (mmol/24 h)
187 [72–339]
85.9 [44–157]
0.031 357 [195–569] 147 [95–224]
UCr (mmol/24 h)
4.9 [2.5–6.4]
2.55 [0.7–3.9]
0.002 6.65 [5–8.8]
3.5 [1.6–4.4]
21 (75)
0.005 0.01
3.4 [2.6–5.8]
0.09
6 [4–8]
