|Year : 2019 | Volume
| Issue : 4 | Page : 1163-1168
Earlier start versus standard start dialysis in patients with acute kidney injury: systematic review and meta-analysis
Osama A El-Sharqawy1, Khaled M Gaballah1, Mohamed SM Elshahat2
1 Department of Anesthesia and Intensive Care, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Anesthesia and Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||03-Jun-2018|
|Date of Decision||25-Jul-2018|
|Date of Acceptance||29-Jul-2018|
|Date of Web Publication||31-Dec-2019|
Mohamed SM Elshahat
El Gomhyrea Street Mansoura City, Dakahlia 11711
Source of Support: None, Conflict of Interest: None
The aim of the present review is to synthesize evidence from the published literature about the effect of early versus late initiation of renal replacement therapy (RRT) on the outcomes of patients with acute kidney injury (AKI).
AKI is a serious clinical disorder with significant increase in risk of mortality and morbidity, especially among hospitalized patients.
A computer literature search of Medline via PubMed, Cochrane CENTRAL Register of Controlled Trials, SCOPUS, and Web of science was conducted.
Records were screened for eligible studies according to the predetermined inclusion and exclusion criteria.
Data were extracted and synthesized using standardized tables.
Dichotomous data were pooled as relative risk (RR) in a random-effect model using Mantel–Haenszel method. Continuous data were pooled as standardized mean difference (SMD) in generic-variance model. We used Review Manager 5.3 for Windows.
The present review included nine studies. Our pooled effect estimates did not favor early initiation of RRT versus late intuition in terms of all-causes mortality (RR = 0.88; 95% confidence interval (CI), 0.68, 1.14; P = 0.33), RRT dependence (RR = 0.81; 95% CI, 0.46, 1.42; P = 0.46), length of stay in ICU (SMD, −0.28; 95% CI, −0.58, 0.03; P = 0.08), and length of stay in hospital (SMD, −0.40; 95% CI, −0.83, 0.03; P = 0.07).
The present systematic review and meta-analysis shows that early initiation of RRT does not improve survival outcomes and hospital stay among patients with AKI, in comparison with late initiation of RRT.
Keywords: acute kidney injury, meta-analysis, mortality, renal dialysis, renal replacement therapy
|How to cite this article:|
El-Sharqawy OA, Gaballah KM, Elshahat MS. Earlier start versus standard start dialysis in patients with acute kidney injury: systematic review and meta-analysis. Menoufia Med J 2019;32:1163-8
|How to cite this URL:|
El-Sharqawy OA, Gaballah KM, Elshahat MS. Earlier start versus standard start dialysis in patients with acute kidney injury: systematic review and meta-analysis. Menoufia Med J [serial online] 2019 [cited 2020 Apr 2];32:1163-8. Available from: http://www.mmj.eg.net/text.asp?2019/32/4/1163/274226
| Introduction|| |
Acute kidney injury (AKI) is a serious clinical disorder with significant increase in risk of mortality and morbidity, especially among hospitalized patients . According to the recent guidelines by Kidney Disease Improving Global Outcome, AKI is defined as increase in serum creatinine by more than or equal to 0.3 mg/dl (≥26.5 μmol/l) within 48 h, or an increase in serum creatinine to more than or equal to 1.5 times baseline, which is known or presumed to have occurred within the preceding 7 days, or a urine volume less than 0.5 ml/kg/h for 6 h . The disorder can occur as a result of a variety of causes and was reported to affect 8–15% of hospitalized patients and up to 50% of critically ill patients ,. Moreover, previous reports have shown that AKI can lead to death in up to 60% of the affected patients, and it is associated with a more than fourfold increased likelihood of death . Therefore, early diagnosis and management of AKI is critical to avoid serious complications.
Renal replacement therapy (RRT) is the main primary supportive measure for patients with AKI, especially among patients with anuria, severe oliguria, hyperkalemia, or severe metabolic acidosis . However, the timing of initiation of RRT is still debatable within the current body of literature. Early initiation of RRT is proposed on the basis of providing better acid–base balance, early control of fluid/electrolytes balance before serious kidney injury, and early removal of uremic waste . On the contrary, early exposure to the RRT can lead to vascular access complications (as hemorrhage and thrombosis) and the complications of RRT (as intradialytic hypotension and hypersensitivity), especially among patients in whom spontaneous recovery of kidney function may occur . However, standard (late) initiation of RRT allows more time for hemodynamic stability before deciding to proceed with the replacement therapy .
Recently, a growing body of evidence has compared early versus late initiation of RRT, with conflicting results ,. Therefore, the aim of the present review is to synthesize evidence from the published literature about the effect of early versus late initiation of RRT on the outcomes of patients with AKI.
| Materials and Methods|| |
We followed Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines during the preparation of this review.
Inclusion and exclusion criteria for study selection
We included studies that fulfilled the following criteria: (a) randomized controlled trials (RCTs) that included patients with severe AKI who required mechanical ventilation, catecholamine infusion, or both; (b) studies that compared the early versus standard strategy of RRT; and (c) studies that reported all-cause mortality rates. Studies were excluded if they were in non-English language or were thesis or conference abstracts. In case of multiple reports, we analyzed data from the most complete data set.
We searched the following medical electronic databases such as PubMed, Cochrane CENTRAL Register of Controlled Trials, SCOPUS, and Web of science from the inception to February 2018 using the following keywords: 'Renal Replacement Therapy' [Mesh] AND 'Acute Kidney Injury' [Mesh]. Retrieved citations were downloaded, and duplicates of retrieved records were removed using EndNote, version 7 (Clarivate Analytics, Philadelphia, PA 19130 US).
Selection of studies
The authors screened the title and abstract of retrieved records for eligibility. We retrieved the full texts of potentially eligible abstracts, and they were screened for eligibility to be included in the present systematic review.
The authors extracted the raw data independently from each included study using a standardized online data extraction form. The extracted data included the following: (a) characteristics of the study design, (b) characteristics of the study population, (c) risk of bias domains, and (d) study outcomes.
Assessment of risk of bias in included studies
The quality of the retrieved RCTs was assessed according to Cochrane handbook of systematic reviews of interventions 5.1.0 (updated March 2011). Risk of bias assessment included the following domains: sequence generation (selection bias), allocation sequence concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective outcome reporting (reporting bias), and other potential sources of bias. The authors' judgment is categorized as 'low risk,' 'high risk,' or 'unclear risk' of bias. We used the quality assessment table provided in the same book (part 2, Chapter 8.5) .
Measures of treatment effect
The primary outcome measurements, in the studies comparing early versus late RRT, were all-cause mortality, RRT dependence, and ICU and hospital length of stay.
Dichotomous data were pooled as relative risk (RR) in a random-effect model using Mantel–Haenszel method. Continuous data were pooled as standardized mean difference (SMD) in generic-variance model. We used Review Manager 5.3 for Windows. In the case of missing SE of mean difference, it was calculated from 95% confidence interval (CI) according to Altman and Bland .
Assessment of heterogeneity
Heterogeneity was assessed by visual inspection of the forest plots and measured by I2 and χ2 tests. χ2 test was used to test the existence of significant heterogeneity, whereas I2 quantifies the variability in effect estimates owing to heterogeneity, if present. I2 test was interpreted according to the recommendations of Cochrane handbook of systematic reviews and meta-analysis (0–40%: might not be important; 30–60%: may represent moderate heterogeneity; 50–90%: may represent substantial heterogeneity; and 75–100%: considerable heterogeneity). In the case of a significant heterogeneity (χ2 P < 0.1), a random-effect model was used. Otherwise, a fixed-effect model was used.
According to Egger et al. , publication bias assessment is not reliable for less than 10 pooled studies. Therefore, in the present study, we could not assess the existence of publication bias by Egger's test for funnel plot asymmetry.
| Results|| |
We retrieved unique 2046 citations from the searched online databases. After title and abstract screening, 49 articles were retained for full-text screening. Finally, nine RCTs were included with a total of 1627 patients (early RRT group with 798 patients and late RRT group with 829 patients) (see PRISMA flow diagram; [Figure 1]).
|Figure 1: Shows the PRISMA flowchart. PRISMA, Preferred Reporting Items for Systematic Review and Meta-analysis.|
Click here to view
The quality of the included studies was from moderate to high quality according to the Cochrane risk of bias assessment tool. Only four RCTs reported adequate methods of randomization and allocation concealment ,,,. All studies were open label. Summary of quality assessment domains of included studies is shown in [Figure 2].
Regarding the characteristics of the included studies, they were open-label RCTs. The sample size of the included trials ranged from 28 to 619 patients. Surgical patients were included in four RCTs, whereas patients in either surgical or medical ICU were included in five trails. Continuous renal replacement therapy was used as the modality of choice in five trials, and two trials used intermittent hemodialysis (IHD). The remaining studies used a mixture of the two dialysis modalities. Summary of included studies and their main results are shown in [Table 1].
Regarding the results of meta-analysis, our pooled effect estimates did not favor early initiation of RRT versus late initiation in terms of all-causes mortality (RR, 0.88; 95% CI, 0.68, 1.14); P = 0.33; [Figure 3]), RRT dependence (RR, 0.81; 95% CI, 0.46, 1.42; P = 0.46), length of stay in ICU (SMD, −0.28; 95% CI, −0.58, 0.03; P = 0.08), and length of stay in hospital (SMD, −0.40; 95% CI, −0.83, 0.03; P = 0.07). The pooled effect estimates were heterogeneous (P < 0.1).
| Discussion|| |
Early initiation of RRT is thought to improve acid–base balance, fluid balance, and removal of uremic waste . However, its associated complications were reported to minimize those beneficial effects . In the present systematic review and meta-analysis, there was no statistically significant difference between early and late initiation of RRT in terms of patients' mortality and RRT dependence. Moreover, both timing strategies led to similar length of ICU and hospital stay.
In concordance with these findings, Lai and colleagues included 1627 critically ill patients with AKI and reported no significant survival benefits in patients who underwent earlier versus later RRT. The pooled mortality rates were 38.7% (309 of 798) and 42.5% (352 of 829) in the groups of patients who underwent earlier and later RRT (P = 0.33) . Similarly, Gaudry S and colleagues conducted a RCT on 620 critically ill patients with AKI and reported no significant difference regarding mortality between an early and a delayed strategy for the initiation of RRT . Another report did not support the earlier initiation of dialysis therapy in community-acquired AKI . Combes et al.  demonstrated the early RRT did not lower 30-day mortality and did not affect other important patient-centered outcomes, compared with a conservative strategy with delayed RRT initiation for patients with persistent, severe AKI.
In contrary to this findings, Zarbock and colleagues conducted a single-center RCT on 231 critically ill patients with AKI. They found that early initiation of RRT significantly reduced 90-day mortality (39.3%) compared with delayed initiation of RRT (65 of 119 patients, 54.7%; P = 0.03). Moreover, duration of RRT and length of hospital stay were significantly shorter in the early group than in the delayed group . Similarly, Sugahara and Suzuki  reported that early start of dialysis therapy may help improve the survival of patients with acute renal failure following cardiac surgery.
The exact reason of the significant heterogeneity in the results of the published literature, and in our analysis, is unclear. However, these discrepancies can be attributed to the difference in study population, RRT technique, and sample size among the included trials. In the present systematic review, surgical patients were included in four RCTs, whereas patients in either surgical or medical ICU were included in five trails. Continuous renal replacement therapy was used as the modality of choice in five trials, and two trials used intermittent hemodialysis. The remaining studies utilized a mixture of the two dialysis modalities.
The present review has number of strength points. We followed the guidelines provided within PRISMA guidelines and Cochrane collaboration handbook. Moreover, our search strategy was comprehensive, and our inclusion criteria ensured the inclusion of a wide variety of patients. However, we acknowledge that the present study has some limitations. The number of patients and included studies in our pooled analysis were relatively small. Moreover, a statistically significant heterogeneity was found in our pooled analysis.
| Conclusion|| |
In conclusion, the present systematic review and meta-analysis shows that early initiation of RRT does not improve survival outcomes and hospital stay among patients with AKI, in comparison with late initiation of RRT.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Abelha F, Botelho M, Fernandes V, Barros H. Determinants of postoperative acute kidney injury. Crit Care 2009; 13
Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, et al
. Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int 2012; 2
Fang Y, Ding X, Zhong Y, Zou J, Teng J, Tang Y, et al
. Acute kidney injury in a chinese hospitalized population. Blood Purif 2010; 30
Riley S, Diro E, Batchelor P, Abebe A, Amsalu A, Tadesse Y, et al
. Renal impairment among acute hospital admissions in a rural Ethiopian hospital. Nephrology 2013; 18
Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet 2012; 380
Rondon-Berrios H, Palevsky PM. Treatment of acute kidney injury: an update on the management of renal replacement therapy. Curr Opin Nephrol Hypertens 2007; 16
Wald R, Bagshaw SM. The timing of renal replacement therapy initiation in acute kidney injury: is earlier truly better? Crit Care Med 2014; 42
Wald R, Adhikari NKJ, Smith OM, Weir MA, Pope K, Cohen A, et al
. Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury. Kidney Int 2015; 88
Shingarev R, Wille K, Tolwani A. Management of complications in renal replacement therapy. Semin Dial 2011; 24
Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, et al
. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med 2016; 375
Sugahara S, Suzuki H. Early start on continuous hemodialysis therapy improves survival rate in patients with acute renal failure following coronary bypass surgery. Hemodial Int 2004; 8
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al
, (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from: www.training.cochrane.org/handbook. [Last accessed on 2018 Jan 10].
Altman DG, Bland JM. Standard deviations and standard errors. BMJ 2005; 331
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315
Combes A, Bréchot N, Amour J, Cozic N, Lebreton G, Guidon C, et al
. Early high-volume hemofiltration versus standard care for post-cardiac surgery shock the HEROICS study. Am J Respir Crit Care Med 2015; 192
Jamale TE, Hase NK, Kulkarni M, Pradeep KJ, Keskar V, Jawale S, et al
. Earlier-start versus usual-start dialysis in patients with community-acquired acute kidney injury: a randomized controlled trial. Am J Kidney Dis 2013; 62
Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C, Pavenstädt H, et al
. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury. JAMA 2016; 315
Lai T-S, Shiao C-C, Wang J-J, Huang C-T, Wu P-C, Chueh E, et al
. Earlier versus later initiation of renal replacement therapy among critically ill patients with acute kidney injury: a systematic review and meta-analysis of randomized controlled trials. Ann Intensive Care 2017; 7
[Figure 1], [Figure 2], [Figure 3]