Keeping a promise 1

By John Pickering 03/05/2012

I believe in open access and the right of the public to know what I am doing.  Putting my money where my mouth is, is another story.  When I started this blog in January I promised myself to write something every time an article of mine appeared in print. That’s happened three times already this year and I’ve yet to fulfill that promise…so this is the first of several posts (promise).

Ideally all my research would be freely available online as soon as it has been through the peer review process.  Unfortunately, that costs a lot of money which few research budgets can meet (in the journals I publish it typically costs an extra US$3000 above and beyond normal page charges of around $70 per page and $500 per colour figure).  Nevertheless, this year I have managed to make two articles “Open Access” and another is on the way.   The one I have chosen today is my first book chapter in the field of Acute Kidney Injury.  I received an invite to contribute to a book  and responded positively for a change – for a reasonable cost (US$1000) it was an opportunity to produce a longer treatise on an important area of my work and to make it freely available to anyone and everyone.

 Pickering JW, Endre ZH. The Metamorphosis of Acute Renal Failure to Acute Kidney Injury [Internet]. In: Sahay M, editor. Basic Nephrology and Acute Kidney Injury. Rijeka: InTech; 2012. p. 125–49.

Freely downloadable from:

The story begins with a lament as to the repeated failure of clinical trials to discover any effective therapy for Acute Kidney Injury (AKI).  We then discuss the history of how the thinking has changed from Acute Renal Failure – the idea that the kidney filtration function is suddenly reduced – to Acute Kidney Injury – the idea that the kidney tissue is injured which often results in a reduction in function.  For the mathematically minded there is a section on how to determine the function of the kidney on the basis of the concentrations of a marker (plasma creatinine) in the blood.  Those who prefer words to symbols, though, can skip this.  We discuss the current definitions of Acute Kidney Injury (still based on function!  – That is soon to change…watch this space), then I introduce three things important to clinical trials.

  1. Although AKI is associated with higher mortality rates it is financially ruinous to run a trial with mortality as an outcome because of the very high numbers of patients needed.  For that reason, a surrogate for kidney function is used.  Often this has been a definition of Acute Kidney Injury that is categorical – ie the plasma creatinine concentration increases by more than 50% you have AKI, if it doesn’t, you don’t.  A trial will then compare the proportions of patients in the placebo and treatment groups with AKI.  A couple of years ago I published an article in which I demonstrated that such a categorical trial outcome was not the best idea – better was to use a continuous measure of the change of creatinine that takes into account the duration as well as the extent of that change (I called this the RAVC). I explain this in the chapter.
  2. When we use plasma creatinine to judge kidney function, we need to know what the concentration was prior to someone ending up in intensive care (ie we are interested in the change from a baseline).  About half of patients have a suitable measurement on record.  What do we do about the other half?  I present a way of dealing with the problem from a clinical trial perspective.  Previously I had shown that the first recommendations given to solve this problem were no better than using a random number generator.  There are some more clinically relevant (and less mathematical!) ways of determining baseline creatinine.
  3. Finally I deal, a little (for this is an ongoing saga) with how to use the new injury biomarkers (often little enzymes measured in the urine – see “I am a pee scientist”).  Ideally, we would initiate therapy (or placebo) on the basis of measured injury even before we were able to detect a change in function.  My colleague (Prof Zoltan Endre) was the first to attempt a randomized control trial based on just such a measurement.  I was brought in to manage the numbers and since then have managed to show that it isn’t quite as easy as we hoped…hence the ongoing saga

I hope that wasn’t too boring.  I think the chapter is pretty accessible to most, and what’s more anyone can download it.  If you do do that, let me me know just if it was understandable at all.

Addendum: One of the nice things about Open Access is that people from all over the world get access to your article – according to  one person from the Dominican Republic, 2 from Macedonia, 8 from Poland, and 9 from New Zealand have downloaded this book chapter…cool.

Tagged: Acute Kidney Injury, health, Research