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Title: The role of systematic reviews in improving patient outcomes in acute renal failure and end-stage renal disease
Author: Rabindranath, Kannaiyan Samuel
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2008
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Background: Dialysis is an intervention that involves the use of fairly advanced technology and is fairly expensive. Patients and health care funders are increasingly demanding evidence for the effectiveness for such high technology high cost interventions. While dialysis therapy has improved immediate prognosis in patients with kidney failure, the long-term survival of patients on chronic renal replacement therapy (dialysis or renal transplantation) is much lower than that of the general population and the mortality rates remain high for patients with acute renal failure needing dialysis. There are considerable variations between different countries and even between the dialysis centres within the same country with regards to the selection of the primary type of dialysis (haemodialysis or peritoneal dialysis) and in the different methods or equipment used to perform the various components of these various modalities. It is possible that variations in clinical practice are associated with variations in clinical outcomes such as mortality and morbidity. It is then important to identify the best practices from the various variations in current use and implementing these best practices may reduce morbidity and mortality of these patients. Methods: Systematic reviews, identifying and including only randomised trials, focusing on key clinical policy decision points in the dialysis process were undertaken. The review of literature was done in a systematic way according to a detailed scientific methodology. For all of the systematic reviews, a detailed protocol was written and agreed to by the authors of the review. The protocol detailed the clinical question, the types of studies, participants, interventions and outcomes to be included, search strategy and the statistical methods to be employed. Relevant randomised studies were then identified by systematically searching the electronic medical databases and reference lists of published studies; data relevant to predetermined outcome measures were extracted and where appropriate summary statistics were derived from meta-analysis. Recommendations and implications for clinical practice and future research studies were made following each review. The areas of dialysis policy reviewed were (1) Comparison of high-flux versus low-flux haemodialysis (HD) membranes for patients with end-stage renal disease (ESRD), (2) Comparison of extracorporeal renal replacement therapy technologies for patients with ESRD, (3) Comparison of intermittent (IRRT) and continuous renal replacement therapy (CRRT) for acute renal failure (ARF) in adults, (4) Comparison of antimicrobial interventions for the prevention of HD catheter related infections, (5) Comparison of continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) for patients with ESRD, and (6) Comparison of treatment measures for depression in dialysis patients. Conclusions: As the currently available evidence has not demonstrated superiority with high-flux membranes with respect to important clinical outcomes such as mortality, quality of life and hospitalisation, it is not possible to recommend the use of these membranes in preference to low-flux membranes. It has not been possible at present to demonstrate with the current evidence available that convective modalities (HF, HDF or AFB) have significant advantages over HD with regard to clinically important outcomes of mortality, dialysis-related hypotension and hospitalisation. It is not therefore possible to recommend the use of one modality in preference to the other. In ARF patients who are haemodynamically stable, the RRT modality does not appear to influence important patient outcomes, and therefore the preference for CRRT over IRRT in such patients does not appear justified in the light of available evidence. CRRT was shown to achieve better haemodynamic parameters such as MAP. APD appears to be more beneficial than CAPD, in terms of reducing peritonitis rates and with respect to certain social issues that impact on patients' quality of life. Further, adequately powered trials are required to confirm the benefits for APD found in this review and detect differences with respect to other clinically important outcomes that may have been missed by the trials included in this review due to their small size and short follow-up periods. APD may however be considered advantageous in select group of patients such as in the younger PD population and those in employment or education due to its psychosocial advantages. Firm conclusions on the efficacy of treatment measures for depression in chronic dialysis patients cannot be made as we identified only one small RCT that was of short duration. Current screening tools for depression are recognised to have poor specificity in the medically ill due to overlap of somatic symptoms of the medical illness. The development of a valid diagnostic tool would be helpful. The systematic reviews in general highlighted the paucity of large-scale randomised trials in nephrology even on topics of great practical relevance such as depression in dialysis. In many of the areas assessed adequate conclusions could not be reached as there was a lack of large-scale well designed randomised controlled trials raising the possibility that important clinical differences between the interventions assessed may have been missed due to Type 2 statistical error. We identified numerous RCTs which were small in size looking at surrogate end-points such as molecular markers of inflammation, especially in the areas of membrane flux and extracorporeal RRT technologies. Unfortunately benefits with surrogate end-points do not necessarily translate to better clinical outcomes. The urgent need of the hour is to conduct well-designed large scale RCTs in major areas of clinical importance such as the use of extracorporeal renal replacement therapy technologies looking at hard clinical end-points such as mortality, hospitalisation and quality of life.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Acute renal failure ; Outcome assessment (Medical care) ; Systematic reviews (Medical research)