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

JohnProwle:

the scientific question is very much a pragmatic one - how do we understand if a randomised intervention effectively modifies kidney injury/kidney health in early phase studies

This is, in my view, the very opposite of a scientific question: it is a question rather about how to industrialise the AKI research enterprise. The core principle seems to be to deliver a generic outcome definition that liberates researchers from the burden of formulating sharply defined scientific theories specific to the particular intervention being ‘studied’.

JohnProwle:

however GFR itself is still just a physiological variable indicative of organ function - not directly paralleling structural injury or prognosis

This is indeed precisely the problem addressed by state-space modeling: there is some latent physiologic state X_t which — we theorise — evolves over time according to some ‘equations of motion’, and this state gets reflected in noisy observations Y_t (or measurements) which we may ‘filter’ to recover estimates of the underlying state variables. A basic application of these ideas can be found in this conference poster on tacrolimus dosing [1].

1. Norris DC, Gohh RY, Akhlaghi F, Morrissey PE. Kalman filtering for tacrolimus dose titration in the early hospital course after kidney transplant. F1000Research. 2017;6. doi:10.7490/f1000research.1113595.1