A Longitudinal Renal Health Outcome for Clinical Trials in Acute Kidney Injury?

Thanks these are very natural questions Essentially AKI has several potential indices which are indirect reflections of true underlying kidney health - there is already an implicit equivalence in the KDIGO AKI definition by defining ‘equivalent AKI severity levels’ (1-3) based on either urine output or serum creatinine changes . This is arbitrary and imperfect but has the advantage of capturing different temporal aspects of kidney health. The truth is that there is no ‘best objective measure of AKI’ - at different timings and at different stages different indices will reflect underlying pathology best. Our intention is to adjudicate these differing metrics (which collectively are very difficult to handle) into a scale based on expert consensus and epidemiological evidence. This will be intrinsically imperfect but potentially a useful and implementable tool to interrogate clinical outcomes longitudinally. The approach suggested to urine output is essentially what we would implement but across several complementary domains and not one alone. We could of course merge these metrics into a semi-continuous ‘score’ based on some from of regression model, but I think that this would be more opaque in design and interpretation and not amenable to some of the methodology on state transition developed for longitudinal ordinal outcomes which is very attractive. It’s also important to remember that interventions such as dialysis are clinical decisions based on clinical information, thus a zero urine output (anuria) might be taken as equivalent to dialysis. Some clinicians would wait until other indications were met knowing that dialysis was inevitable while others would initiate dialysis immediately in anticipation of complications, so if we decided to assign the same level to both to these we might remove some clinical practice variation in the endpoint…