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

f2harrell: > here Many thanks for your positive comments I think the crux of the issue is to design a combined scale purely by consensus and then test it, or - as you suggest - derive a weighted combination of the components by some form of modelling. The problem here is that the various components are not directly in parallel ie dialysis is a yes/no near the top with creatinine sitting below this. I completely appreciate the issues with creatinine changes - however to some extent one does need to bring the clinical community along and at least consider the pros and cons of the existing definitions within the scheme. In my defence I would say 1. We do propose an absolute estimate of kidney function (imperfect through it is outside of steady state) in addition to a ‘rate of rise’ and score based on the worst level. Creatinine does need transformation here as it is reciprocally related to kidney function and is dependent on underlying muscle mass so just a creatinine scale would not work. This also allows other methods of GFR estimation to also be used. There is a big problem with decreased creatinine. generation in critical illness - to some extent up-grading the scale based on ICU location is an attempt to offset this and incorporate global illness severity. 2. For AKI creatinine changes are fold changes x1.5, x2 or x3 (not subtractive) within a seven day period and indicate the slope of rise, and thus the eventual plateau in creatinine reflecting the actual underlying kidney function outside of steady state. We would also discount any state based on creatinine change when the latest creatinine measurement was >72h ago. 3. the 0.3mg/dl rise (which is subtractive) has to occur within a 48h window and thus represents a swift uptick of creatinine - this has a lot of sensitivity at the lower end of the ordinal scale for worsening kidney health - if this does not continue to rise then the ordinal scale will revert to the lower level after 2 days Actually - from scoping real world datas - the estimated absolute kidney function is likely to be the driver of the ordinal state during most of the ICU stay and the AKI thresholds potentially just getting there a little quicker offsetting the delay in creatine accumulation rise with and abrupt change in GFR thus the rationale for a combination. The draft formulation is a bit complex and is designed as a starting point for a design process not a finalised version - so I didn’t want to over emphasise it. However here’s the working formulation that I applied to the examples. I have some extensive discussion/justification for these choices for our publication. many thanks again John