Journal of The Egyptian Society of Nephrology and Transplantation

ORIGINAL ARTICLE
Year
: 2017  |  Volume : 17  |  Issue : 4  |  Page : 119--124

Value of acute kidney injury staging for initiation of continuous renal replacement therapy in critically ill patients


Walid M Afifi1, Galal H Abdelnaby2, Ali M Elnabtiti3,  
1 Department of Internal Medicine, Nephrology Unit, Zagazig University, Zagazig, Egypt
2 Critical Care Department, Alexandria Faculty of Medicine, Alexandria, Egypt
3 Anaesthesia and Intensive Care Department, Zagazig University, Zagazig, Egypt

Correspondence Address:
Dr. Walid M Afifi
44519, Zagazig University, Faculty of Medicine, Sharkia
Egypt

Abstract

Background The optimal timing to start continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) in critically ill ICU patients has not been accurately estimated. The proposed risk, injury, failure, loss, end-stage kidney disease (RIFLE) criteria for diagnosis of AKI may provide a method for nephrologists to decide the ‘optimal timing’ for starting dialysis. Objective Our study aimed to analyze the correlation between RIFLE stages at the start of CRRT and 90-day survival rate and to detect the effect of the timing of CRRT on poor kidney outcome in 90-day survivors. Patients and methods A retrospective cohort analysis was performed on the data of 96 critically ill patients with AKI in ICU treated with CRRT during a 2-year period in international extended care hospital, Jeddah, Saudi Arabia, from January 2015 to January 2017. Information such as age, sex, RIFLE stage, sepsis, sepsis-related organ failure assessment score, number of organ failures before CRRT, CRRT time, survival, and kidney outcome conditions at 90 days after CRRT started was collected. According to their baseline severity of AKI at the start of CRRT, the patients were assigned to three groups according to the increasing severity of RIFLE stages, group I (risk of renal dysfunction, R), group II (injury to the kidney, I), and group III (failure of kidney function, F), using RIFLE criteria. The poor kidney outcome was classified as RIFLE-L (loss of kidney function, L) or RIFLE-E (end-stage kidney disease, E) using RIFLE criteria. The correlation between RIFLE stage and 90-day survival rate was analyzed among these three groups. Additionally, the association between RIFLE stage and the poor kidney outcome (RIFLE-L+RIFLF-E) in the 90-day survivors was analyzed. Results Of the overall 96 patients, 48 survived to 90 days after the start of CRRT. There were 14, 20, and 62 patients in group I, II, and III, respectively, with corresponding 90-day survival rate of 78.5% (11/14), 60% (12/20), and 40.3% (25/62) (P<0.01, compared among groups). The percentage of the poor kidney outcome of 90-day survivors in the three groups was 18.18% (2/11), 25% (3/12), and 56% (14/25), respectively (P<0.01). After adjustment for other baseline risk factors, the relative risk for the 90-day mortality significantly increased with baseline RIFLE stage. Conclusion The RIFLE classification may be used to predict 90-day survival after starting CRRT and the poor kidney outcome of 90-day survivors in the critically ill patients with AKI treated with CRRT. Early versus late initiation of dialysis before RIFLE-F stage may be the optimal timing.



How to cite this article:
Afifi WM, Abdelnaby GH, Elnabtiti AM. Value of acute kidney injury staging for initiation of continuous renal replacement therapy in critically ill patients.J Egypt Soc Nephrol Transplant 2017;17:119-124


How to cite this URL:
Afifi WM, Abdelnaby GH, Elnabtiti AM. Value of acute kidney injury staging for initiation of continuous renal replacement therapy in critically ill patients. J Egypt Soc Nephrol Transplant [serial online] 2017 [cited 2018 Feb 18 ];17:119-124
Available from: http://www.jesnt.eg.net/text.asp?2017/17/4/119/223408


Full Text



 Introduction



Clinical studies assessing the exact incidence of acute kidney injury (AKI) in the ICU proved sparse and were often complicated by differing criteria for the definition of AKI, especially before the adoption of the proposed risk, injury, failure, loss, end-stage kidney disease (RIFLE), and AKI network classifications.

The acute dialysis quality initiative group has suggested using AKI as the preferred nomenclature to replace acute renal failure with the consideration that the spectrum of AKI is broader with different degrees of severity [1],[2]. The staging of AKI made by acute dialysis quality initiative group [1] includes criteria for three categories of injury [risk of acute renal failure (R), injury to the kidney (I), and failure of kidney function (F) with increasing severity] and two classes of kidney outcome [loss of kidney function (L) and end-stage kidney disease (E)] (RIFLE, [Table 1]).{Table 1}

AKI is a well-recognized complication of critical illness with a large effect on morbidity and mortality [3]. Despite increases in our knowledge of the management of patients who are critically ill, mortality associated with AKI remains high [4],[5],[6], and the optimal timing of initiation of renal replacement therapy (RRT) in critically ill patients with AKI is still unknown [1],[7].

Therefore, we conducted this retrospective cohort study using originally gathered data of critically ill patients with AKI received CRRT in the ICUs during a 2-year period. The aims of this study were (i) to analyze the correlation between RIFLE classification at the start of CRRT and 90-day survival rate after CRRT start and (ii) to determine the influence of the timing of CRRT start guided by RIFLE classification on the 90-day survival rate and the kidney outcome.

 Patients and methods



Study population

All patients with AKI treated with CRRT between January 2015 and January 2017 in ICU of international extended care hospital, Jeddah, Saudi Arabia, were screened. AKI was diagnosed according to RIFLE criteria ([Table 1]). Patients were excluded if they were younger than 18 years or had preadmission RRT.

CRRT was ordered by the attending physicians (ICU and nephrology) based on the presence of AKI and hemodynamic instability or severity of illness. Different continuous renal replacement therapy (CRRT) modalities (continuous venovenous hemofiltration, continuous venovenous hemodialysis, and continuous venovenous hemodiafiltration) were in use during the study period with variable frequency and duration with average 24 h/session and one session every other day, provided that there is no adequate urine output, persistent congestion, or recurrent acidosis. Bicarbonate-buffered solution was used with a dialysis dose of 25–40 ml/kg/h. The filters in use were prismaflex M100, AN69 (Gambro, Lund, Sweden). Unfractionated heparin was used as an anticoagulant in the treatment modalities. The postfilter activated partial thromboplastin time was monitored every 8 h and maintained between 50 and 70, by regulating the dosage of heparin.

Data collection

All the data were collected at ICU entry during treatment and recorded, which included patients’ laboratory data, orders, CRRT order and flow sheets, nursing notes, and the ICU flow sheets. When reviewing a patient’s file, we looked at previous health status, organ function at the start of CRRT, and the relevant physiological and pharmacological data needed for the RIFLE classification. The indications for CRRT were documented and specific data regarding the CRRT including CRRT time in the ICU was recorded in detail. The data also contained the following information: sex, age, pre-existing diseases (diabetes mellitus and hypertension), main diagnosis including sepsis, baseline preadmission serum blood urea nitrogen, serum creatinine, urine output, sepsis related organ failure assessment, sepsis-related organ failure assessment (SOFA) score [8], and number of organ failures at the start of CRRT. Moreover, we gathered information on the causes of death for the patients who died within 90 days since CRRT started and the kidney outcome of 90-day survivors after CRRT started.

Organ function failure was defined when the SOFA score of an organ was equivalent to or greater than three points according to SOFA criteria ([Table 2]). The correlation of baseline RIFLE classification with the 90-day survival was analyzed using Cox regressions after adjustment for baseline age, sex, sepsis, SOFA score, and number of organ failures.{Table 2}

Patients were divided into three groups (RIFLE-R, RIFLE-I, and RIFLE-F) according to RIFLE staging at the start of CRRT.

In the RIFLE system, RIFLE-L and RIFLE-E are two categories of kidney outcome for patients with AKI ([Table 1]).

In this study, RIFLE-L and RIFLE-E were defined as poor kidney outcome. The proportion of the poor kidney outcome (RIFLE-L+RIFLE-E) in 90-day survivors was determined among the three RIFLE-categorized groups.

Statistical analysis

Continuous variables were presented as mean±SD, and categorical variables were presented as number and percent. A χ2-test was used to analyze categorical variables, whereas analysis of variance and F-test were used to analyze continuous variables. The 90-day cumulative survival was calculated according to the Kaplan–Meier method. The log-rank test was used to compare the 90-day survival rate among the three RIFLE-categorized groups ([Figure 1]). The correlation of baseline RIFLE classification with the 90-day survival was analyzed using Cox regressions after adjustment for baseline age, sex, sepsis, SOFA score, and number of organ failures ([Table 3]). In addition, the incidence of poor kidney outcome of 90-day survivors among RIFLE-categorized groups was compared using χ2 test with linear trend test. Adjusted odds ratio of the poor kidney outcome was calculated by logistic regression with adjustment for baseline age, sex, sepsis, SOFA score, and number of organ failure ([Table 4]). All analyses were performed using the SPSS 19 package (SPSS for Windows, version 19; SPSS Inc., Chicago, Illinois, USA). P values less than 0.05 were considered statistically significant.{Figure 1}{Table 3}{Table 4}

 Results



The present study included 96 critically ill patients with AKI, treated with CRRT, which started at different RIFLE stages. Overall, 33% were women and 67% men. The average age of all patients was 57.0±13.4 years. In all, 95% of all patients who had SOFA score of at least 6.75% required mechanical ventilation and 50% required inotropic support.

[Table 3] presents the clinical features of the overall study population according to RIFLE classification. At the start of CRRT, 14, 20, and 62 patients met the criteria for RIFLE-R, RIFLE-I, and RIFLE-F, respectively. All those 34 patients at RIFLE-R or RIFLE-I stage were complicated with sepsis, hemodynamic instability, or multiple organ dysfunction syndrome.

CRRT was ordered for them to eliminate inflammatory mediators and cytokines in the body so as to protect the vital organ function. The other 62 patients at RIFLE-F stage at the start of CRRT had conventional indications of dialysis, such as high blood urea nitrogen, high serum creatinine, or pulmonary edema. By 90 days after the start of CRRT, all-cause mortality was 50.0% (48 of 96 patients). The causes of death within 90 days were multiple organ dysfunctions, cardiovascular events, stroke, and unidentified causes.

The 90-day survival rates for RIFLE-R, RIFLE-I, and RIFLE-F groups were 78.5% (11/14), 60% (12/20), and 40.3% (25/62), respectively. When the Kaplan–Meier plot was stratified according to RIFLE classification ([Figure 1]), the differences among the survival curve of the three groups were significant (P<0.01). Further multivariate analysis was performed after the adjustment of other baseline risk factors including sex, age, sepsis, SOFA score, and the number of organ failures. This analysis revealed that the relative risk (RR) for the 90-day mortality significantly increased with the increment of baseline RIFLE stage (Ptrend<0.01, [Table 3]).

Eighteen of the 48 90-day survivors had poor kidney outcome (RIFLE-L or RIFLE-E). In the 90-day survivors, the percentages of the poor kidney outcome was higher in group III, when compared with groups I and II; it means that poor kidney outcome significantly increased with the increment of the severity of RIFLE stage (Ptrend<0.01, [Table 5]).{Table 5}

 Discussion



Indication and timing for RRT varies in different countries and institutions. Conventionally, RRT was not administered until patients met dialytic criteria of serum blood urea nitrogen of at least 80 mg/dl (34.1 mmol/l) or creatinine of at least 6 mg/dl (530.4 µmol/l) or other indications especially if the patient is not critically ill.

AKI is a well-recognized complication of critical illness with a large effect on morbidity and mortality [3]. Despite increases in our knowledge of the management of patients who are critically ill, mortality associated with AKI remains high [4],[5],[6], and the optimal timing of initiation of RRT in critically ill patients with AKI is still unknown [1],[7].

In our study, critically ill patients with AKI were treated with CRRT in different RIFLE stages, most of the 62 cases in the RIFLE-F group met routine indications for dialysis, but most of the cases of RIFLE-R or RIFLE-I did not have routine indications for dialysis. Our primary purpose to give CRRT to patients who did not have traditional dialytic indications was to eliminate inflammatory mediators and cytokines in the patient’s body to reduce the inflammatory organic insult, which in turn was to decrease the mortality.

As the RIFLE criteria are fairly straightforward and practical to give a clear AKI classification with different severity, we hypothesized that RIFLE classification could help us to identify the optimal timing of RRT for critically ill patients with AKI.

To test this hypothesis, we first analyzed the correlation between RIFLE stage at the start of CRRT and 90-day survival rate after CRRT start, and then investigated the influence of timing of the start of CRRT on the kidney outcome of 90-day survivals.

Most of the studies on RIFLE criteria confirmed the correlation between RIFLE classification and prognosis [9],[10],[11],[12]. Ostermann et al. [13] performed a multicenter, retrospective study including 41,972 patients admitted to 22 ICUs. Of the 15 019 (35.8%) patients who met the RIFLE criteria, 7207 (17.2%), 4613 (11%), and 3199 (7.6%) were assigned to the risk, injury, and failure groups, respectively, with corresponding hospital mortality of 20.9, 45.6, and 56.8, whereas the hospital mortality of patients without AKI was 8.4%.

Uchino et al. [14] have also reported similar results. They suggest that RIFLE criteria are suitable for the definition and classification of AKI in ICUs. The classification reflecting the severity of AKI can facilitate clinical research by allowing the comparison of data of different studies carried out by various institutions.

Only two published studies discussed the clinical significance of RIFLE classification for the special population of AKI patients in need for RRT [15],[16]. RIFLE stage was an exclusive independent risk factor correlating with mortality [15]. In the other study, however, older age, number of organ dysfunctions, the presence of comorbidities, and reduced functional capacity were the main prognostic factors, but the RIFLE stage did not discriminate the prognosis [16]. However, there is no uniform standard to decide the optimal timing of starting RRT for patients with AKI in clinic [17]. Our present study shows RIFLE stage at the start of CRRT correlates with 90-day mortality.

The significant correlations of the RIFLE stage with the 90-day survival rate and the poor kidney outcome in the survivors suggest starting CRRT before RIFLE-F stage may be optimal for critically ill patients with AKI.

These also support the rationale that early CRRT can eliminate a significant amount of inflammatory mediators and cytokines, which in turn restrains the cascade of inflammatory reaction and ultimately plays a protective role on kidney and other vital organs [18],[19],[20].

Our results are concurrent with the ELAIN Randomized Clinical Trial [20], which concluded that among critically ill patients with AKI, early RRT compared with delayed initiation of RRT reduced mortality over the first 90 days; however, it divided the patients to early and delayed depending on Kidney Disease Improving Global Outcomes (KDIGO) staging (within 8 h of diagnosis of KDIGO stage 2; n=112) (within 12 h of stage 3; n=119).

Our results are not aligned with that of AKIKI trial [21], which found no significant difference regarding mortality between an early and a delayed strategy for the initiation of RRT. In this trial, they assigned patients with severe acute kidney injury (KDIGO classification, stage 3) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of RRT. With the early strategy, RRT was started immediately after randomization. With the delayed strategy, RRT was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg/dl, or oliguria for more than 72 h after randomization. The primary outcome was overall survival at day 60. In this trial, they had already started dialysis in late stage of AKI, so the value of early initiation of CRRT can not be counted.

In conclusion, the RIFLE stage may be used to predict 90-day survival rate and the poor kidney outcome in the critically ill patients with AKI treated with CRRT.

Starting CRRT before RIFLE-F stage may be the optimal timing. Prospective, multicenter, randomized controlled trials are crucial to confirm the predictive value of RIFLE staging.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1KDIGO AKI Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012; 2:1–138.
2Bellomo Re, Ronco C, Kellum JA, Mehta RL, Palesky P, Acute Dialysis Quality Initiative Workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology ne eds the Second International Consensus Conference Of The Acute Dialysis Quality Initiative (ADQI) Group. Cit Care 2004; 8:R204–R212.
3Hoste EA, Bagshaw SM, Bellomo R et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 2015; 41:1411–1423.
4Bellomo R, Cass A, Cole L et al. RENAL Replacement Therapy Study Investigators. Intensity of continuous renal replacement therapy in critically ill patients. N Engl J Med 2009; 361:1627–1638
5Palevsky PM, Zhang JH, O’Connor TZ et al. VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 359:7–20.
6Jun M, Heerspink HJ, Ninomiya T et al. Intensities of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2010; 5:956–963.
7Ronco C, Ricci Z, De Backer D et al. Renal replacement therapy in acute kidney injury: controversy and consensus. Crit Care 2015; 19:146.
8Vencent JL, Moreno R, Takala J, Willatts S, De Mendonca A. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22:707–710.
9Maccarilello E, Soares M, Valente C, Nogueira L, Valenca R, Machado JES et al. RIFLE classification in patients with acute kidney injury in need of renal replacement therapy. Intensive Care Med 2007; 33:597–605.
10Overberger P, Pesacreta M, Palevsky PM. Management of renal replacement therapy in acute kidney injury: a survey of practitioner prescribing practices. Clin J Am Soc Nephrol 2007; 2:623–630.
11Wald R, Adhikari NK, Smith OM et al. Canadian Critical Care Trials Group. Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury. Kidney Int 2015; 88:897–904.
12Ostermann M, Chang RW. Acute kidney injury in the intensive care unit according to RIFLE. Crit Care Med 2007; 35:1837–1843.
13Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med 2006; 34:1913–1917.
14Piccinni P, Dan M, Barbacini S, Carraro R, Lieta E, Marafon S et al. Early isovolaemic haemofiltration in oliguric patients with septic shock. Intensive Care Med 2006; 32:80–86.
15Elahi MM, Lim MY, Joseph RN, Dhannapuneni RR, Spvt TJ. Early hemofiltration improves survival in post-cardiotomy patients with acute renal failure. J Card Surg 2004; 19:17–20.
16Hoste EJA, Clermont G, Kersten A, Verkataraman R, Angus DC, Bacquer DD et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 2006; 10:R73.
17Lin CY, Chen YC, Tsai FC, Tian YC, Jeng CC, Fang JT et al. RIFLE classification is predictive of short-term prognosis in critically ill patients with acute renal failure supported by extracorporeal membrane oxygenation. Nephrol Dial Transplant 2006; 21:2867–2873.
18Jeng CC, Tsai MH, Tian YC, Lin CY, Yang C, Liu NJ et al. RIFLE classification can predict short-term prognosis in critically ill cirrhotic patients. Intensive Care Med 2007; 33:1232–1238.
19Bagshaw SM, Uchino S, Bellomo R et al. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury. J Crit Care 2009; 24:129–140.
20Zarbock A, Kellum JA, Schmidt C, Van Aken H et al. ELAIN randomized clinical trial, effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury. JAMA 2016; 315:2190–2199.
21Gaudry S, Hajage D, Schortgen F et al. the AKIKI Study Group. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med 2016; 375:122–133.