• Users Online: 700
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 2  |  Page : 176-181

The effect of renal replacement therapy timing on the outcome of acute kidney injury in critically ill patients


1 Department of Critical Care Medicine, Beni-Suef University, Beni-Suef, Egypt
2 Department of Critical Care Medicine, Beni-Suef University, Beni-Suef
3 Department of Critical Care Medicine, Cairo University, Cairo, Egypt

Date of Submission04-Apr-2018
Date of Acceptance29-Nov-2018
Date of Web Publication12-Jun-2019

Correspondence Address:
Hamdy M Saber
24 EL Fateh Manial El Roda Cairo

Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/roaic.roaic_28_18

Rights and Permissions
  Abstract 

Introduction The timing of renal replacement therapy (RRT) initiation in patients having acute kidney disease has been a controversial issue for many years. A recently published systematic review and meta-analysis on this topic failed to demonstrate measurable benefits of early RRT.
Patients and methods We compared RRT initiation timing in critically ill patients and defined early or late RRT in reference to the timing after which stage 3 Acute Kidney Injury Network criteria were met. Patients beginning RRT within 24 h after reaching stage 3 acute kidney injury (AKI) were considered early starters, whereas those beginning RRT past 24 h after reaching stage 3 AKI were considered late starters. Acute Kidney Injury Network criteria were evaluated by both urine output and serum creatinine. Patients with acute-on-chronic kidney disease were excluded. A propensity score methodology was used to control variables.
Results A total of 123 critically ill patients were subjected to RRT. Only 40 patients with pure stage 3 AKI were analyzed. Mortality was lower in the early RRT group than in the late RRT group (18.6 vs. 81.1%, P=0.000). Moreover, patients in the early RRT group had a lower duration of mechanical ventilation, RRT duration, vasopressor duration, and ICU discharge creatinine level.
Conclusion Using a time-based approach could be a better means of assessing the association between RRT initiation and outcomes in patients with AKI. In patients with stage 3 AKI, RRT initiation within 24 h should be considered.

Keywords: Acute Kidney Injury Network, mechanical ventilation, renal replacement therapy


How to cite this article:
Genina AM, Selait NS, Saber HM, Ahmed EM. The effect of renal replacement therapy timing on the outcome of acute kidney injury in critically ill patients. Res Opin Anesth Intensive Care 2019;6:176-81

How to cite this URL:
Genina AM, Selait NS, Saber HM, Ahmed EM. The effect of renal replacement therapy timing on the outcome of acute kidney injury in critically ill patients. Res Opin Anesth Intensive Care [serial online] 2019 [cited 2019 Oct 14];6:176-81. Available from: http://www.roaic.eg.net/text.asp?2019/6/2/176/260142


  Introduction Top


Renal replacement therapy (RRT) is found to be necessary in ∼6% of critically ill patients. Generally, RRT is provided as a supportive treatment to patients with acute kidney injury (AKI) to prevent additional disorders, such as hyperkalaemia, metabolic acidosis, or volume overload, and overt uremic complications, such as pericarditis and encephalopathy.

Although there is general agreement on the value of RRT in AKI, there is no consensus regarding the time of initiation; furthermore, there is no acceptable definition of initiation timing. The universal criteria of AKI have recently been used to facilitate research and progress in the field of acute renal failure.

Data mainly from observational studies have suggested that early RRT in critically ill patients with AKI may have a beneficial effect on survival [1],[2].

Although the RIFLE criteria were developed and validated for diagnosing and evaluating the severity of AKI and not as parameters for guiding RRT initiation, some observational studies [3],[4] have investigated whether initiating RRT in less severe renal injury (i.e. RIFLE classification − 0 or R) is associated with improved survival. Although one study analyzing AKI after major abdominal surgery demonstrated benefits of early RRT initiation [5], two other studies evaluating mainly patients with sepsis demonstrated similar outcomes with either early and late RRT [3],[4].

This study examined a different approach of using AKI severity classification. Our objective was to determine whether initiating RRT earlier or later than 24 h after stage 3 Acute Kidney Injury Network (AKIN) classification is associated with hospital mortality in critically ill patients.


  Patients and methods Top


This was a retrospective analysis of a prospective sample of 40 critically ill adult patients (>18 years of age) undergoing RRT. The study was conducted in the ICU of the National Institute of Urology and Nephrology, Kasr Al Ainy Hospital, the Egypt Air International Hospital, and the Palestine International Hospital in Cairo.

All patients needing RRT fulfilling stage 3 AKIN criteria [serum creatinine (sCr) criteria: increase in sCr>300% (three-fold) from baseline or urine output (UO) criteria: 0.3 ml/kg/h for 24 h, or anuria for 12 h] from August 2014 to September 2015 were initially included. We excluded patients undergoing maintenance RRT, those with renal transplantation, those with RRT initiated before ICU admission, those who needed RRT before stage 3 AKIN classification, and those with an ICU length of stay (LOS) less than 24 h. Patients who did not have a sCr level less than or equal to 1.5 mg/dl during their hospital stay were considered as having previous chronic kidney disease (CKD) and were excluded.

All data, including the UO at each six intervals, were prospectively collected during the ICU stay after a standardized database record was implemented. Data preceding ICU admission were obtained from medical records and patient history. We did not have access to UO data before ICU admission.

Study design

All patients were subjected to detailed medical history with stress on risk factors of renal impairment and exclusion criteria, detailed physical examination, and clinical and laboratory parameter tests. The severity scores included the Glasgow Coma Scale and Acute Physiology and Chronic Health Evaluation II scores. RRT was prescribed and initiated by nephrologists who did not work with the present researcher. When patients were receiving vasopressor drugs, sustained low-efficiency RRT or continuous venovenous hemodialysis was performed; otherwise, conventional intermittent hemodialysis was performed. For sustained low-efficiency RRT, the blood and dialysate flow rates were 200 and 300 ml/min, respectively, and the duration was 6 h. Conventional intermittent hemodialysis was performed for 4 h with a dialysate flow of 600 ml/min and a blood flow of 300 ml/min. For continuous venovenous hemodialysis, the blood and dialysate flow rates were 150–300 and 1500 ml/min, respectively; as hemodynamics changed during the ICU stay, patients changed between RRT modalities.

Outcomes

The endpoint of this study was in-hospital mortality. The survival period was calculated from RRT initiation to mortality in nonsurvivors or to hospital discharge in survivors. Secondary endpoints included ICU LOS, mechanical ventilation duration, RRT duration, vasopressor duration, and ICU discharge creatinine level.

Statistical analysis

SPSS, version 18 (IBM, Chicago, USA) was employed to analyze the data. Frequencies and percentages (for categorical data) and means and SD (for paired data) were calculated. An unpaired independent samples t-test was applied to compare continuous variables. Categorical data were tested using the χ2-test. A propensity score methodology was used to control for bias owing to the selection of patients placed on early RRT using the inverse probability of treatment weighting method. First, the propensity score model included the demographic, clinical and laboratory data at ICU admission and at RRT initiation that could have influenced the decision of placement on early RRT. This model estimated the probability of each study subject being placed on early RRT.

Then, the contribution of each subject was weighted by 1/propensity score for the early RRT group, and by 1/(1−propensity score) for the late RRT group.

The results are expressed as absolute and relative average treatment effects. Statistical significance was set at P value less than 0.05.


  Results Top


This study included 40 patients. We compared RRT initiation in these critically ill patients and defined early (19 patients) and late (21 patients) RRT in reference to the time of RRT initiation after stage 3 AKIN classification: patients beginning RRT within and after 24 h after stage 3 AKI classification were considered early and late starters, respectively. This study was conducted from August 2014 to September 2015 in the ICU of the National Institute of Urology and Nephrology, the Egypt Air International Hospital, the Palestine International Hospital, and the Kasr Al Ainy Hospital.

Patient characteristics

Among the 40 included patients, 23 (57.5%) were males and 17 (42.5%) were females. The age of our patients ranged between 21 and 81 years. Overall, 42.5% of the patients were between 60 and 70 years of age, whereas 25% of them were older than 70 years. Diabetes mellitus was present in 24 patients (60% of the total sample), including 12 (73.7%) early starters and 12 (57.1%) late starters. We found that hypertension was present in 26 patients (65% of the total sample), including 14 (73.7%) early starters and 12 (57.1%) late starters. Cardiomyopathy was present in eight patients (20% of the total sample), including four (21.1%) early starters and four (19%) late starters. End-stage liver disease was present in 10 patients (25% of the total sample), including four (21.1%) early starters and six (28.6%) late starters.

Clinical and laboratory variables

Shock was present in 37 patients (92.5% of the total sample), including 16 (84.2%) early starters and 21 (100%) late starters. Moreover, 32 patients (80% of the total sample) were mechanically ventilated before RRT, including 15 (78.9%) early starters and 17 (81%) late starters ([Table 1]).
Table 1 Clinical and laboratory variables in the early and late renal replacement therapy groups

Click here to view


Effect of timing on outcome

Effect of renal replacement therapy timing on mechanical ventilation duration

Regarding the results of evaluating the effect of RRT timing on mechanical ventilation duration in the early and late RRT groups, we compared the mean mechanical ventilation duration in the early RRT group (M=4.14, SD=2.30) and the late RRT group (M=6.54, SD=4.24) and found that a significant difference was found in the mechanical ventilation duration between the two groups [t(77)=−3.020, P=0.003].

These results indicate that there is a significant reduction in the need for mechanical ventilation, of two days on average, among critically ill patients with AKI receiving RRT in the first 24 h after diagnosis with stage 3 AKI ([Table 2]).
Table 2 Duration of mechanical ventilation among the early and late renal replacement therapy groups

Click here to view


Effect of renal replacement therapy timing on ICU length of stay

Regarding the results of evaluating the effect of RRT timing on the ICU LOS in the early and late RRT groups, we compared the mean ICU LOS in the early RRT group (M=9.75, SD=3.73) and the late RRT group (M=8.88, SD=4.27) ([Table 3]). There was no significant difference in the ICU LOS between the two groups [t(77)=0.960, P=0.340]. These results indicate that there is no effect of RRT timing on the ICU LOS. [Table 4] shows the results of evaluating the effect of timing of RRT on ICU LOS in early versus late RRT group, before and after controlling for confounders.
Table 3 Length of ICU stay among the early and late renal replacement therapy groups

Click here to view
Table 4 Time on renal replacement therapy among the early and late renal replacement therapy groups

Click here to view


Effect of renal replacement therapy timing on renal replacement therapy duration

Regarding the results of evaluating the effect of RRT timing on the RRT duration, which is the duration the patient needed RRT, in the early and late RRT groups, we compared the mean RRT duration in the early RRT group (M=4.20, SD=2.51) and the late RRT group (M=5.59, SD=3.45). There was a significant difference in RRT duration between the two groups [t(77)=−2.004, P=0.049].

These results indicate that there is a significant reduction in RRT duration, of two days on average, among critically ill AKI patients receiving RRT in the first 24 h after diagnosis with stage 3 AKI.

[Table 4] shows the results of evaluating the effect of timing of RRT on the duration of RRT − which is the duration during which patient needed RRT − in early and late RRT group, before and after controlling for confounders.

Effect of renal replacement therapy timing on vasopressor duration

Regarding the results of evaluating the effect of RRT timing on vasopressor duration in the early and late RRT groups, we compared the mean vasopressor duration in the early RRT group (M=2.61, SD=2.51) and the late RRT group (M=6.91, SD=2.80). There was a significant difference in the vasopressor duration between the two groups [t(77)=−7.102, P=0.000].

These results indicate that there is a significant reduction in the duration of vasopressor use, of three days on average, among critically ill patients with AKI receiving RRT in the first 24 h after diagnosis with stage 3 AKI ([Table 5]).
Table 5 Duration of vasopressors use among the early and late renal replacement therapy groups

Click here to view


Effect of renal replacement therapy timing on ICU discharge creatinine level

Regarding the results of evaluating the effect of RRT timing on the creatinine level at discharge in the survivors of the early and late RRT groups, we compared the mean discharge creatinine in the early RRT group (M=1.88, SD=0.55) and the late RRT group (M=2.80, SD=1.22). There was a significant difference in the discharge creatinine level between the two groups [t(35)=−3.059, P=0.004].

These results indicate that there is a significant reduction in discharge creatinine, of 1 mg/dl on average, among critically ill AKI patients receiving RRT in the first 24 h after diagnosis with stage 3 AKI ([Table 6]).
Table 6 Creatinine on discharge among the early and late renal replacement therapy groups

Click here to view


Effect of renal replacement therapy timing on in-hospital mortality

The overall in-hospital mortality rate was 47.5% (19/40).

Regarding the results of evaluating the effect of RRT timing on in-hospital mortality in the early and late RRT groups, we compared the proportion of in-hospital mortality in the early RRT group (18.6%) and the late RRT group (84.1%). There was a significant difference in in-hospital mortality between the two groups (P=0.000).

These results indicate that 65.5% less in-hospital mortality occurred in the early RRT group than in the late RRT group ([Table 7]).
Table 7 In-hospital mortality among the early and late renal replacement therapy groups

Click here to view



  Discussion Top


The timing of RRT initiation has been a controversial issue for many years in both patients having CKD and those having acute kidney disease. A recently published systematic review and meta-analysis on this topic concluded that earlier RRT initiation in critically ill patients with AKI may have a beneficial effect on survival [1].

In our study, we compared RRT initiation among critically ill patients and defined early or late RRT in reference to the timing after the stage 3 AKIN criteria were met: patients beginning RRT within 24 h after reaching stage 3 AKI were considered early starters. The AKIN criteria were evaluated by both UO and sCr.

The reference sCr was the lowest level achieved during the hospital stay before RRT initiation. We included patients with a known baseline sCr level for the hospital stay to exclude those who may have had renal impairment before admission not recorded on their history.

After controlling for the confounders, we found a significant reduction in the following: mortality (P=0.000), mechanical ventilation duration (P=0.003), duration of the patient needing RRT (P=0.049), creatinine level on discharge (P=0.004), and duration of shock (vasopressor-dependent time), among the early starters (P=0.000).

However, the study did not reveal a significant reduction in the ICU LOS among the early group versus the late group (P=0.340). This result may be owing to the study population being insufficiently large; in addition, sepsis and other comorbidities were present in a large number of patients, which may have affected the results.

Our data agree with the findings of Leite et al. [6], who performed the only study to evaluate the timing of RRT using the AKIN criteria. A total of 358 critically ill patients were subjected to RRT. Only 150 patients with pure stage 3 AKI were analyzed. Mortality was lower in the early RRT group (51.5 vs. 77.9%, P=0.001). After achieving balance between the groups using a propensity score, there was a significant relative decrease of 30.5% (95% confidence interval: 14.4–45.2%, P=0.002) in mortality in the early RRT group. Moreover, patients in the early RRT group had shorter mechanical ventilation and RRT durations and showed a trend toward a shorter ICU LOS.

Our results showed that there was not a significant reduction in the ICU LOS in the early group (P=0.340).

Here, we found two new outcomes not reported by Leite et al. [6]: reduction in creatinine level on ICU discharge (P=0.004), and reduction in duration of shock (vasopressor-dependent time), among the early starters (P=0.000).

Four studies [3],[4],[5],[6] have evaluated early RRT using the AKIN/RIFLE approach.

In the study by Leite et al. [6], time to RRT was measured starting when patients reached stage 3 AKIN, and a reduction in mortality, RRT duration, ICU LOS, and mechanical ventilation duration was found. We selected this time instead of the time of diagnosis with earlier stages of AKI because it seemed to be a more practical approach. Not all patients with AKI will need RRT or will even progress to stage 3 AKI; it is more likely that patients reaching stage 3 AKIN will need RRT. In addition, previous studies have not examined the effect of RRT timing on the duration of vasopressor use or the creatinine level at discharge.

Shiao et al. [5] demonstrated better survival among patients undergoing abdominal surgery who were submitted to early RRT, as defined by the RIFLE criteria.

In our data, fewer patients starting RRT were classified as stage 3 AKI by sCr without considering the UO; these patients were instead classified as having earlier AKI stages. We attempted to eliminate these pitfalls by separately analyzing only patients in whom CKD could be excluded (patients with baseline sCr>1.5 mg/dl). Moreover, only patients reaching stage 3 AKI were included; thus, a population with the same degree of AKI severity was selected. Finally, we applied both the sCr and UO criteria. In the study performed by Maccariello et al. [3], 52% of patients initiated RRT at RIFLE stages − R or I. In both studies by the National Taiwan University Surgical ICU Associated Renal Failure study group [4],[5], approximately half of the patients initiated RRT at RIFLE stages − 0 or R. It is probable that these patients would have had more severe AKI stages if the UO criterion had been applied.

Karvellas et al. [1] investigated the effect of early versus late RRT initiation on clinical outcomes in critically ill patients with AKI by conducting a systematic review and meta-analysis. PubMed, Embase, Scopus, Web of Science and Cochrane Central Registry of Controlled Clinical Trials were searched, among other sources. The study identified 15 unique studies (two randomized, four prospective cohort, and nine retrospective cohort) of 1494 citations. Compared with late therapy, early therapy was associated with a significant improvement in 28-day mortality. Five studies (out of seven) reported greater renal recovery, seven (out of eight) studies showed decreased RRT duration, and five (out of six) studies showed decreased ICU LOS in the early compared with the late RRT group [1].

Although showing promising results in terms of performing early RRT in critically ill patients, this study only evaluated stage 3 AKIN; as such, the influence of RRT on earlier AKI stages was not evaluated. This limitation is counterbalanced by considering UO. When using the UO criterion, many patients classified as AKIN 3 would otherwise be classified as AKIN 1 or 2 using only sCr alone. Including the UO criterion could explain why a minority of patients needed RRT before reaching stage 3 AKI. A second limitation is that excluding patients who could not achieve a sCr level lower than 1.5 mg/dl might mean that patients with community-acquired AKI have been considered as having CKD. In these patients, it would not be possible to precisely determine when stage 3 AKI was reached, making it difficult to classify them into the early or late RRT group. We attempted to balance all variables that could influence the decision to initiate RRT earlier by using the propensity score and inverse probability of treatment weighting methods to balance variables.

Finally, the relatively small number of patients is counterbalanced by the homogeneity of this population, which included only patients with pure AKI. Using a time-based approach from the point of reaching stage 3 AKI to the point of RRT initiation, as determined by applying both UO and sCr, this study demonstrated a reduced mortality rate, mechanical ventilation duration, RRT duration, and vasopressor duration among critically ill patients with AKI receiving RRT within the first 24 h after diagnosis with stage 3 AKI. We suggest that in critically ill patients with stage 3 AKI, RRT must be considered in less than 24 h.


  Conclusion Top


We suggest that in patients with stage 3 AKI, RRT must be considered in less than 24 h, as performing RRT within the first 24 h of diagnosis with stage 3 AKIN results in reduced in-hospital mortality, mechanical ventilation duration, RRT duration, vasopressor duration, and ICU discharge creatinine level.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Karvellas CJ, Farhat MR, Sajjad I, Mogensen SS, Leung AA, Wald R, Bagshaw SM. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care 2011; 15:R72.  Back to cited text no. 1
    
2.
Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL. Timing of renal replacement th erapy initiation in acute renal failure: a meta-analysis. Am J Kidney Dis 2008; 52:272–284.  Back to cited text no. 2
    
3.
Maccariello E, Soares M, Valente C, Nogueira L, Valença RVR, Machado JES, Rocha E. RIFLE classification in patients with acute kidney injury in need of renal replacement therapy. Intensive Care Med 2007; 33:597–605.  Back to cited text no. 3
    
4.
Chou YH, Huang TM, Wu VC, Wang CY, Shiao CC, Lai CF et al., NSARF Study Group. Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury. Crit Care 2011; 15:R134.  Back to cited text no. 4
    
5.
Shiao CC, Wu VC, Li WY, Lin YF, Hu FC, Young GH et al., National Taiwan University Surgical Intensive Care Unit-Associated Renal Failure Study Group. Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery. Crit Care 2009; 13:R171.  Back to cited text no. 5
    
6.
Leite TT, Macedo E, Pereira SM et al. Timing of renal replacement therapy initiation by AKIN classification system: a retrospective analysis of a prospective cohort of consecutive critically ill adult patients undergoing RRT (General Hospital of Fortaleza and Haroldo Juaçaba Hospital) in Fortaleza, Brazil. Crit Care 2013; 17:R62.  Back to cited text no. 6
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed241    
    Printed33    
    Emailed0    
    PDF Downloaded40    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]