Renal Replacement Therapy in Acute Kidney Injury Patients.

1.Background And Introduction

Acute Kidney Injury (AKI) presents a substantial challenge within intensive care units (ICUs), where it frequently complicates the management of critically ill patients (S.D. Barbar et al., October 11, 2018) Its prevalence underscores its significance, with approximately half of ICU admissions experiencing AKI. This condition not only increases mortality rates but also escalates treatment costs, placing a considerable burden on healthcare systems. Despite improvements in the critical care, AKI remains a serious concern due to its association with adverse outcomes and substantial healthcare expenditure (Deepa and Muralidhar, 2012). In this context, understanding the diagnostic criteria, optimal management strategies, and implications of AKI in the ICU setting is most important. This introduction provides an overview of the composite nature of AKI within ICUs, highlighting the need for comprehensive approaches to its diagnosis, management, and prevention.(S.D. Barbar et al., October 11, 2018)

?2.Indications Of RRT

In my clinical unit, the utilization of continuous renal replacement therapy (CRRT), for managing acute kidney injury (AKI) is guided by established protocols and guidelines, such as those outlined by the Kidney Disease: Improving Global Outcomes (KDIGO) (KDIGO AUGUST 07 2012) . CRRT is indicated in patients presenting with severe fluid overload refractory to diuretic therapy, or those experiencing hemodynamic instability and are unable to tolerate rapid fluid removal. By facilitating continuous fluid removal, CRRT serves to improve pulmonary edema, diminish peripheral edema, and optimize hemodynamic status. Moreover, CRRT initiation is warranted in cases of severe electrolyte imbalances, including hyperkalaemia, hyponatremia, hyperphosphatemia, and severe metabolic acidosis, that remain unresponsive to conventional medical management. Through the continuous removal of electrolytes, CRRT endeavours to restore normal electrolyte balance and avert potential complications such as arrhythmias and metabolic derangements.(Srijan Tandukar MD a, March 2019)

CRRT is recommended for patients presenting with severe uremic symptoms, such as encephalopathy, pericarditis, and neuropathy, resulting from the accumulation of uremic toxins in the bloodstream. By providing continuous clearance of urea and other waste products, CRRT contributes to mitigate uremic symptoms and overall clinical improvement. Additionally, CRRT may be initiated in cases of drug overdose or toxicity, particularly when conventional interventions such as haemodialysis or antidote therapy are ineffective or contraindicated. By facilitating continuous removal of toxins, CRRT aids in preventing toxicity and support patients to recovery. Following the established guidelines and protocols ensures the timely initiation of CRRT to efficiently tackle these critical conditions and optimize patient outcomes in AKI management.(Srijan Tandukar MD a, March 2019)

?3.Critical Appraisals

3.1 Rationales For Choosing Studies And Guideline For Critique.

I have selected two research papers and one global guideline provided by KDIGO for critical evaluation. Both research papers are concentrating on the timing of renal replacement therapy (RRT) in acute kidney injury (AKI) patients. The primary result evaluated in both studies is the overall mortality rate. Besides that, these two studies are considered as the latest investigations into the influence of RRT timing on mortality rates. According to the KDIGO guideline, it is globally accepted set of recommendations for AKI management.

4.Critical Appraisal Of Studies And Guideline

4.1 First Study

The study is a multicentre, randomized controlled trial (RCT) aimed to assess the effect of the timing of renal-replacement therapy (RRT) on the survival rates of individuals with early-stage septic shock and severe acute kidney injury (AKI) (S.D. Barbar et al., October 11, 2018).It was appropriate for evaluating the impact of early versus delayed initiation of RRT in this patient population. Patients who were diagnosed with failure-stage AKI (early approach) or after 48 hours whose renal recovery had not occurred (delayed approach) were randomly assigned to undergo RRT. The primary result was death at 90 days. Due to ineffective outcome the trial was discontinued early after preliminary assessment , with 488 patients randomized. The baseline characteristics had no specific difference. The mortality rate at 90 days was similar between the early-approach groups (58%) and the delayed-strategy (54%) groups, where 38% of patients in the delayed-approach group were not receiving RRT. Criteria for emergency RRT were met in 17% of the delayed-strategy group. The study finalised that there was no specific difference in overall mortality at 90 days between the two strategies (early versus late).(S.D. Barbar et al., October 11, 2018)

4.1.1 Critical Appraisal of the first study

The study regarding the effect of the timing of renal-replacement therapy (RRT) initiation on mortality in patients with early-stage septic shock and severe acute kidney injury (AKI) was clearly stated. It is a multicentre, RCT trial. The recruitment strategy had specific criteria for early-stage septic shock and severe AKI, aligning with the research aims. However, there was limited details about the recruitment process.

The sample size calculation was based on a presumed difference in mortality rates between the early and delayed initiation groups. However, the decision to stop the trial early for futility might have influenced the adequacy of the sample size.

Whereas patients from multiple centres, enhanced the generalizability of the findings. Informed consent procedures were outlined, ensuring ethical recruitment practices.

Both the early and delayed strategies for RRT initiation were clearly described, allowing for replication and comparability across settings.

The primary outcome of death at 90 days was clearly defined. Secondary outcomes provided additional insights into patient outcomes and the effect of treatment, enhancing the depth of the study.

The risk of bias was not clearly evaluated within the study report, which could affect the interpretation of results and confidence in the findings.

The statistical analysis utilised complete case analysis and accounted for potential confounding variables, demonstrating appropriateness. While terminating the trial prematurely due to futility may have affected result reliability. Although the study adjusted for baseline prognostic factors, the potential influence of unmeasured confounders remain unsure.

The study received ethical approval and followed informed consent procedures, binding with current ethical standards for clinical research. (S.D. Barbar et al., October 11, 2018)

There was no significant difference in overall mortality at 90 days between patients assigned to early versus delayed initiation of RRT. The results were reported with appropriate measures of precision, including confidence intervals, enhancing the reliability of the findings.

The study suggests that there may be no mortality benefit with early initiation of RRT in patients with early-stage septic shock and severe AKI. Clinicians should consider individual patient factors and preferences when making treatment decisions in this population.

The study findings prompt reflection on the optimal timing of RRT initiation in patients with septic shock and severe AKI. While they may not significantly change current practice, they highlight the need for individualized treatment approaches and further research in this area.

4.2 Second study

Timing of Renal-Replacement Therapy Initiation in critically ill patients with Acute Kidney Injury. Acute kidney injury (AKI) frequently complicates the management of critically ill patients, often in need of renal-replacement therapy (The STARRT-AKI Investigators, July 15, 2020). However, the optimal timing for initiating RRT remains uncertain, particularly in the absence of major metabolic disturbances. To compare the efficacy of an accelerated RRT initiation strategy (within 12 hours) versus a standard strategy (deferred initiation) in critically ill patients with severe AKI. The STARRT-AKI trial, a multicentre, randomized controlled trial (RCT), enrolled 3019 critically ill patients with severe AKI. Patients were randomized to receive either accelerated or standard initiation of RRT. The primary endpoint was all-cause mortality at 90 days. Analysis of 2927 patients revealed that the accelerated-strategy group (43.9%) and the standard-strategy group (43.7%) had no specific difference in 90-day mortality. Rates of dependence on RRT at 90 days were similar between the two groups. Adverse events were more frequent in the accelerated-strategy group. Contrary to expectations, an accelerated strategy for initiating RRT did not demonstrate a mortality benefit at 90 days compared to a standard strategy in critically ill patients with severe AKI. These findings challenge the current uncertainty surrounding the optimal timing of RRT initiation in this patient population and emphasize the need for individualized patient management. Further investigation is warranted to explore alternative strategies for optimizing outcomes in critically ill patients with AKI.(The STARRT-AKI Investigators, July 15, 2020)

4.2.1 critical appraisal of the second study

The study question regarding the timing of renal-replacement therapy initiation in critically ill patients with acute kidney injury is clearly focused. The study employed a multinational, randomized controlled trial design, which is appropriate for assessing the efficacy of different strategies for initiating renal-replacement therapy. The recruitment strategy involved enrolling critically ill patients with severe acute kidney injury from a wide spectrum of ICUs in several countries, enhancing the generalizability of the findings. The sample size was substantial, with 3019 patients randomized, which provided sufficient power to detect clinically important differences in mortality between the two treatment strategies. Baseline characteristics were well balanced between the two groups, indicating successful randomization and minimizing potential confounding factors. The study was open label, which may not introduce bias in outcome assessment and management decisions. The follow-up period of 90 days is appropriate for assessing mortality and other relevant outcomes in critically ill patients with acute kidney injury.(The STARRT-AKI Investigators, July 15, 2020)

The modified intention-to-treat analysis included 2927 patients (97.0%) out of 3019 randomized, indicating minimal loss to follow-up. Outcomes such as mortality, dependence on renal-replacement therapy, adverse events, and quality of life were measured using standardized and validated methods, enhancing the validity and reliability of the findings.

Appropriate statistical analyses, including chi-square tests, relative risks, logistic regression, Kaplan-Meier analysis, and adjusted analyses, were employed to assess outcomes and compare treatment strategies.

Overall, the study demonstrates rigorous methodology and provides valuable insights into the timing of renal-replacement therapy initiation in critically ill patients with acute kidney injury. However, the lack of blinding and potential subjective judgment in confirming eligibility may introduce bias, warranting cautious interpretation of the findings.(The STARRT-AKI Investigators, July 15, 2020)

5.Critical Appraise KDIGO Guidelines

The guideline clearly outlines its objectives, focusing on the definition, prevention, treatment, and management of acute kidney injury (KDIGO AUGUST 07 2012). It provides a comprehensive overview of the topic. Involvement of stakeholders such as nephrologists, intensivists, general physicians, and surgeons is evident in the development process. However, details about the extent and nature of involvement are not explicitly stated. The guideline is based on an extensive review of the literature, which indicates a rigorous development process. However, the grading of recommendations and level of evidence could be more transparently presented. The guideline is well-structured and presented in a clear format. Key recommendations are highlighted, making it easy for clinicians to navigate and understand. The guideline appears to be free from undue influence, with no conflicts of interest disclosed. However, transparency regarding the funding source and independence of the guideline development group could be improved. Overall, while the guideline provides valuable insights into the management of AKI, there are areas for improvement, particularly in enhancing stakeholder involvement, transparency of grading, and providing implementation support. Further clarification on the development process and independence would enhance confidence in the guideline's recommendations.(Srijan Tandukar MD a, March 2019)

6.Applicability 0f The Studies And Guideline, And Their Influences

The studies and guideline on acute kidney injury (AKI) have several influences on clinical practice and research:

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In Clinical Practice:

Clinicians can use the findings from the studies to inform their decisions regarding the initiation of renal-replacement therapy (RRT) in critically ill patients with AKI. They can weigh the benefits and risks of early versus delayed initiation of RRT based on the evidence provided.

The studies emphasize the importance of individualized patient management, considering factors such as severity of illness, underlying conditions, and treatment preferences. Clinicians can tailor treatment strategies to each patient's unique clinical circumstances. The AKI guideline serves as a reference tool for clinicians, providing evidence-based recommendations for the definition, prevention, treatment, and management of AKI. Adhering to these guidelines can help standardize care and improve patient outcomes.(Park et al., 2016)

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In Research:

The studies highlight areas of uncertainty and controversy in the management of AKI, such as the optimal timing for initiating RRT. These gaps in knowledge provide opportunities for further research to address unanswered questions and improve clinical practice. Research findings can inform quality improvement initiatives aimed at optimizing the care of patients with AKI. Clinicians and healthcare organizations can use evidence-based practices to enhance patient outcomes and reduce the burden of AKI-related morbidity and mortality. Researchers can use the methodologies and findings from the studies to design future trials investigating the management of AKI. They can build upon existing evidence and address limitations identified in previous studies to generate higher-quality evidence and improve the care of patients with AKI.(Deepa and Muralidhar, 2012)

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Education and Training:

Clinicians, including nephrologists, intensivists, general physicians, and surgeons, can use the studies and guideline as educational resources to enhance their understanding of AKI management. Continuous education and training are essential for staying updated on the latest evidence and best practices in the field. Healthcare institutions and organizations can incorporate the AKI guideline into their educational curricula and clinical practice guidelines. By circulating evidence-based recommendations, they can promote standardized care and improve patient outcomes across different healthcare settings.(Park et al., 2016)

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In summary, the studies and guidelines on AKI have significant influences on clinical practice, research, education, and training. By integrating evidence-based practices and recommendations into patient care, healthcare professionals can improve the management and outcomes of patients with AKI.

7.Modification Of RRT In Acute Respiratory Distress Syndrome

Renal replacement therapy (RRT) plays a crucial role in the management of patients with acute respiratory distress syndrome (ARDS) who develop acute kidney injury (AKI), yet the optimal timing of RRT initiation remains a subject of debate. To address this question, a retrospective study was conducted over a 2-year period, reviewing clinical data of ARDS patients admitted to a health system. The study aimed to assess the timing of RRT initiation and its impact on patient survival.(Dill et al., 2018)

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The study identified 75 ARDS patients, among whom 95% required RRT during their hospital stay. This high incidence of RRT utilization underscores the significant renal complications often observed in ARDS patients and the essential role of RRT in managing these cases. Notably, the study found a mortality rate of 56% among patients who required RRT, highlighting the severity of the condition and the need for effective treatment strategies.

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One of the key findings of the study was the lack of a significant survival benefit associated with the timing of RRT initiation. The study compared outcomes between patients who received early initiation of RRT (within 48 hours post-intubation) and those who received late initiation (more than 48 hours post-intubation). Contrary to expectations, there was no statistically significant difference in survival between these two groups. This finding challenges the notion that early initiation of RRT improves outcomes in ARDS patients and suggests that other factors may influence patient survival.(Park et al., 2016)

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The study also examined the main indications for RRT initiation in ARDS patients. Fluid overload emerged as the most common indication, with 75% of patients requiring RRT due to this complication. Metabolic acidosis and hyperkalaemia were also significant contributing factors, indicating a huge range of renal complications observed in ARDS patients. These findings had shown the complexity of managing AKI in ARDS and the need for unique treatment approaches based on individual patient characteristics.(Dill et al., 2018)

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Logically, the study employed Kaplan-Meier analysis and Cox proportional hazards regression to examine survival outcomes and potential confounders. While the statistical analysis appeared reliable, certain limitations must be acknowledged. The retrospective nature of the study and the relatively small sample size may have influenced the results. Whereas, the study focused on a single health system, which may limit the generalizability of the findings to other settings.(Dill et al., 2018)

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In conclusion, the study provides valuable insights into the management of ARDS patients requiring RRT. Despite the lack of a significant survival benefit associated with the timing of RRT initiation, the high incidence of renal complications in this population underscores the importance of timely intervention. Future research, including prospective studies, is needed to further clarify the optimal timing of RRT initiation and its impact on patient outcomes in ARDS. Additionally, efforts to specific treatment approaches based on individual patient characteristics and underlying comorbidities may help improve outcomes and reduce complications in this challenging patient population.

8.Conclusion

In conclusion, the multifaceted nature of acute kidney injury (AKI) in intensive care units (ICUs) poses significant challenges to patient management, mortality rates, and healthcare costs. The studies discussed shed light on the timing of renal replacement therapy (RRT) initiation, a critical aspect of AKI management. While one study found no significant difference in mortality rates between early and delayed RRT initiation in patients with septic shock and AKI, another trial revealed that an accelerated RRT initiation strategy did not confer a mortality benefit compared to a standard approach in critically ill patients with severe AKI.(Srijan Tandukar MD a, March 2019)

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Moreover, the guideline reviewed offers valuable insights into AKI management, emphasizing the need for comprehensive approaches and individualized patient care. Additionally, the retrospective study focusing on ARDS patients underscores the complexities of RRT initiation timing and its impact on survival, suggesting a need for specific approaches based on patient-specific factors. These findings highlight the ongoing uncertainty surrounding optimal RRT initiation timing and the importance of personalized, evidence-based approaches in AKI and ARDS management.(Dill et al., 2018) Further research is warranted to clarify these aspects and improve patient outcomes in critical care settings.(The STARRT-AKI Investigators, July 15, 2020)

9. Reflection

In reflecting on my one-year experience in the ICU and my recent completion of the course, I acknowledge a significant evolution in my understanding and approach to managing patients with multi-organ failure (MOF). Initially, my practical experience was valuable but lacked a comprehensive understanding of underlying mechanisms and evidence-based practices. Through the course, I delved deeper into MOF management, enhancing my knowledge through weekly sessions, bedside teaching, discussions with peers, and self-study. While the course provided valuable insights, I encountered challenges in locating specific studies and adhering to word limits in assignments. However, these challenges offered opportunities for growth, particularly in critically evaluating guidelines and refining content planning. The feedback received on formative assignments was instrumental in identifying weaknesses and improving critical appraisal skills. Additionally, the poster assignment honed my ability to summarize information effectively and create well-designed visuals. Looking back, I recognize the importance of bridging theory with practice through more clinical observational and simulation sessions. Overall, this course has significantly enriched my understanding of MOF management and equipped me with valuable skills for future practice.

?10. References

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Barbar, S.D., Clere-Jehl, R., Bourredjem, A., Hernu, R., Montini, F., Bruyère, R., Lebert, C., Bohé, J., Badie, J., Eraldi, J.P. and Rigaud, J.P., 2018. Timing of renal-replacement therapy in patients with acute kidney injury and sepsis.?New England Journal of Medicine,?379(15), pp.1431-1442.

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Deepa, C. and Muralidhar, K., 2012. Renal replacement therapy in ICU.?Journal of Anaesthesiology Clinical Pharmacology,?28(3), pp.386-396.

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