[Expert Solution]: Please prepare a specific critique of the…

Please prepare a specific critique of the following medical study rationale (below) based on describing its strengths and weaknesses: The optimal time to commence maintenance dialysis in patients with chronic kidney disease is not clear. This uncertainty has been recognized by nephrologists internationally as potentially the most important dialysis-related question to be addressed in this decade. A number of groups have tried to resolve the issue of when to commence dialysis, using either cohort designs or case control studies (1–6). These investigations have, in general, supported the concept that starting dialysis with a relatively higher level of renal function affords a benefit with respect to morbidity, mortality, capacity for employment, and quality of life. However, these studies are subject to potential confounding factors, including referral-time and lead-time bias, patient age, comorbidity, and compliance. As a result, no firm conclusion can be reached about the optimal time to start dialysis. A recent cohort study concluded that, despite the clear need for a randomized study to address this issue, it would be unlikely to ever occur (7). Despite the lack of supporting evidence, guidelines have been issued by both national and international expert panels recommending the initiation of dialysis at a level of renal function much higher than is current usual practice. Adoption of these guidelines will have enormous implications in terms of finance and infrastructure of dialysis services internationally. The Dialysis Outcomes Quality Initiative (DOQI) of the National Kidney Foundation of the USA (8,9) has recommended that dialysis be commenced at a glomerular filtration rate (GFR) of approximately 10.5 mL/minute/1.73 m2, a level based on the minimum target level of total (residual renal and dialysis) clearance for peritoneal dialysis (PD). The Canadian Society of Nephrology (10) has recommended that dialysis be commenced at a GFR < 12 mL/minute, with a proviso that dialysis can be deferred if there is no evidence of uremia or malnutrition. Guidelines developed under the auspices of the Australian & New Zealand Society of Nephrology and Australian Kidney Foundation (11) recommended commencement of dialysis at a GFR of 10 mL/min/1.73 m2 in patients with evidence of uremia or malnutrition, or lower without uremia or malnutrition. Data from the USA (12) and Australia and New Zealand (13) show that, currently, dialysis is commenced well below these targets. Clearly, the adoption of recommendations to commence dialysis earlier than is current practice will have a huge impact on the costs of providing care to patients with end-stage renal disease (ESRD) and on health outcomes of individual patients. Thus, it is imperative that the effect on patient outcome and economic cost of commencing dialysis early be assessed prospectively in a randomized controlled trial. As a multicenter, Australia- and New Zealand-wide, prospective, randomized controlled trial, the Initiating Dialysis Early and Late (IDEAL) study is such a trial. Our trial will compare the outcome of patients followed from randomization at a common time point [GFR between 10 and 15 mL/min/1.73 m2, measured by the Cockcroft–Gault equation (14) with body surface area correction (15)] and assess the effect of commencement of dialysis at a GFR of 10 – 14 mL/min/1.73 m2 versus 5 – 7 mL/min/1.73 m2 over a 3-year follow-up period. This will provide information for patients, clinicians, and health economists on the cost-benefit implications of commencing dialysis “early” versus “late.”