Tag Archives: Urine

Cheesecake files: A stadium full

As we’ve been enjoying the World Cup and the Commonwealth Games my latest cheesecake appeared in print online. The topic once more is Kidney Attack biomarkers – those pesky little proteins in the urine that appear when your kidney is injured.  This time I have been getting stuck into some math (sorry) to try and understand what it is that affects when these biomarkers appear in the urine after injury.  I call this a biomarker time-course.  A “Pee Profile” may be a better term but it would never get past the editor.  What I care about is whether the type of biomarker and/or extent of injury, affects the pee profiles.

There are three basic types of biomarkers.  First are those that are filtered from the blood by the two million odd filters in the kidney.  Often they are then reabsorbed back into the blood in the little tubules where the pee is produced – that is, they don’t appear in the urine.  Think of it like a stadium with many entrances.  People (biomarkers) come in and sit down (are reabsorbed).  If, though, a section of the stadium has been fenced off because of broken seating from the previous game (the injury), then some of those entering the stadium may end up exiting it again (the pee biomarkers).  The numbers being reabsorbed and exiting will also depend on whether all the entrances are open – if some are closed then this will have a flow on affect on the rate of people leaving the stadium.

The second are preformed biomarkers.  If we change the analogy slightly, imagine these as people already in the stadium (if the analogy was accurate they would have been born there!).  If some terrible injury happens (like the 4th, 5th, 6th and 7th goals of a now famous football match) some of those people would get up and exit quickly.  The overall rate of exit would reflect on the extent of the injury.

The third, are induced biomarkers.  These are ones that don’t already exist, but are produced in response to an “injury.”  Instead of being biomarkers, let us think of the spectators as produces of these biomarkers and let noise be the biomarker.  There is some background noise of course, but when an “injury” (goal, gold medal performance etc) occurs there is a sudden increase in noise which slowly dies down.  Depending on the team and the number of supporters this will be softer or loader and will carry on for shorter or longer periods (Goooooooooooaaaaaaaaaaaa……lllllllllllll).

The upshot of it all were many coloured graphs and a step towards understanding how we may better make use of the various types of novel biomarkers of kidney injury that have been recently discovered.

PlosOneFigs

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Pickering, J. W., & Endre, Z. H. (2014). Acute kidney injury urinary biomarker time-courses. PloS One. doi:10.1371/journal.pone.0101288

 

 

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A day to celebrate

If it weren’t for your kidneys where would you be?

You’d be in the hospital or infirmary,

If you didn’t have two functioning kidneys.

(with apologies to John Clarke aka Fred Dagg)

Happy World Kidney Day everyone.

This blog started off life as $100 Dialysis because I believe that if we can make a computer for $100 then surely we can do the same for dialysis!  Dialysis is a life saver, yet its cost kills as so many can not afford the treatment.

There’s some good news in the dialysis world.

Schematics of the zeolite nanonfibres and how they may look in practice

Schematics of the zeolite nanonfibres and how they may look in practice

Just last week the MANA – International Centre for Materials NanoArchitectionics announced  they have developed a method to remove waste from the blood using an easy-to-produce nanofibre mesh.  Importantly, they claim it is cheap to produce.  Details were published in Biomaterials Science (free access).  Despite the photograph, there have been no human studies yet, but I expect that won’t be too long in the future.

Dr Victor Gura and the Wearable Artificial Kidney (WAK)

Dr Victor Gura and the Wearable Artificial Kidney (WAK)

In the meantime, the FDA gave approval last month for human trials of a wearable dialysis device produced by Blood Purification Technologies Inc (the WAK).

New Zealand, and Dunedin and Christchurch in particular, lead the way in Home Dialysis.  One Dunedin tradesman has even taken Home Dialysis a step further and turned it into portable dialysis by dialysing in his work van during his lunch hour. Of course, those needing a holiday may go on the road in specially equipped camper vans (http://www.kidneys.co.nz/Kidney-Disease/Holiday-Dialysis/).

Cause for celebration in the New Zealand kidney community was the gong (Office of the New Zealand Order of Merit) given to Adrian Buttimore who for 40 years managed Christchurch’s dialysis service.

These are just a few pieces of good news as doctors and scientists work around the world to improve the lives of dialysis patients.

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Hot off the Press… I couldn’t resist adding this…. Pee, the answer to the world’s energy problems. http://www.bbc.com/future/story/20140312-is-pee-power-really-possible

 

Cheesecake files: Too little pee

This week’s post is really about the coloured stuff & why too little of it is dangerous.  Note, I say coloured stuff because it aint just yellow – check out this herald article if you don’t believe me (or just admire this beautiful photo).

 A rainbow of urine from a hospital lab. Credit:  laboratory scientist Heather West.

A rainbow of urine from a hospital lab.
Credit: laboratory scientist Heather West.

Story time

A long time ago, when Greeks wore togas, and not because they couldn’t afford shirts, a chap named Galen* noted that if you didn’t pee you’re in big trouble.  It took 1800 more years before the nephrologists and critical care physicians got together to try and decide just how much pee was too little.  This was at some exotic location in 2003 where these medics sat around for a few days talking and drinking (I’m guessing at the latter, but I have good reason to believe…) until they came up with the first consensus definition for Kidney Attack (then called Acute Renal Failure, now called Acute Kidney Injury)1.  It was a brilliant start and has revolutionised our understanding of just how prevalent Kidney Attack is.  It was, though, a consensus rather than strictly evidence based (that is not to say people didn’t have some evidence for their opinions, but the evidence was not based on systematic scientific discovery).  Since then various research has built up the evidence for or against the definitions they came up with (including some of mine which pointed out a mathematical error2 and the failings of a recommendation of what to do when you don’t have information about the patient before they enter hospital3).  One way they came up with to define Kidney Attack was to define it as too little pee.  Too little pee was defined as a urine flow rate of less than half a millilitre per kiliogram of body weight per hour over six hours (< 0.5ml/kg/h over 6h).  Our groups latest contribution to the literature shows that this is too liberal a definition.

The story of our research is that as part of a PhD program Dr Azrina Md Ralib (an anaesthesist from Malaysia) conduct an audit of pee of all patients entering Christchurch’s ICU for a year.  She did an absolutely fantastic job because this meant collecting information on how much every patient peed for every hour during the first 48 hours as well as lots of demographic data etc etc etc. Probably 60-80,000 data points in all!  She then began to analyse the data.  We decided to compare the urine output data against  meaningful clinical outcomes – namely death or need for emergency dialysis.  We discovered that if patients had a flow rate of between 0.3 to 0.5 ml/kg/h for six hours it made no difference to the rates of death or dialysis compared to those with a flow rate greater than 0.5.  Less than 0.3, though, was associated with greater mortality (see figure).  For the clinician this means they can relax a little if the urine output is at 0.4 ml/kg/h.  Importantly, they may not give as much fluid to patients. Given that in recent times a phenomenon called “fluid overload” has been associated with poor outcomes, this is good news.

The full paper can be read for free here.

Proportion of mortality or dialysis in each group. Error bars represent 95% confidence intervals.From Ralib et al Crit Care 2012.

Proportion of mortality or dialysis in each group. Error bars represent 95% confidence intervals.From Ralib et al Crit Care 2013.

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*Galen 131-201 CE.  He came up with one of the best quotes ever: “All who drink of this remedy recover in a short time, except those whom it does not help, who all die.”

1.     Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky PM, Acute Dialysis Quality Initiative workgroup. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8(4):R204–12.

2.     Pickering JW, Endre ZH. GFR shot by RIFLE: errors in staging acute kidney injury. Lancet 2009;373(9672):1318–9.

3.     Pickering JW, Endre ZH. Back-calculating baseline creatinine with MDRD misclassifies acute kidney injury in the intensive care unit. Clin J Am Soc Nephro 2010;5(7):1165–73.

Cooking up a new kidney

The Boston Kidney Recipe

  1. Take an unwanted kidney.
  2. Disconnect from plumbing.
  3. Wash away cells (use plenty of detergent).
  4. Take resultant scaffold and reseed with a few cells obtained from someone needing the kidney.
  5. Place in bioreactor and “cook” for 3 to 5d (or until done)
  6. Place regenerated kidneys into the transplant recipient and connect to plumbing.
  7. Pee.

In Nature Medicine today Massachusetts General Hospital based researchers have announced the successful removal of an unwanted kidney from one rat, the removal of cells from that kidney, regeneration with stem cells from another rat, transplantation into that animal and the observation of  urine production*.  A  small step for a rat, a giant leap for anyone waiting for a transplant.  Why is this so important?  As the authors’ state:

“A bioengineered kidney derived from patient-derived cells and regenerated ‘on demand’ for transplantation could provide an alternative treatment for patients suffering from renal failure.”

While this study is “proof of context”, it is a beautiful proof and one which should bring hope to millions. There are many more people with End Stage Renal Disease than kidneys available for transplant.  Some donated kidneys currently considered not good for transplant may become viable in the future if the cells are stripped off and the patient’s own stem cells can be used to grow a new kidney over the scaffold of the old one.  By using the patient’s own cells the immune response may be reduced.  This will mean less dependence of immunosuppressant drugs and therefore fewer side effects, including  cancer, and less transplant rejection. This is the vision and one that can not come soon enough.  Have a look at the video and if you want to get into details, check out the paper* .

*Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Jeremy J Song, Jacques P Guyette, Sarah E Gilpin, Gabriel Gonzalez, Joseph P Vacanti & Harald C Ott1. Nature Medicine. Advance Publication Online. http://dx.doi.org/10.1038/nm.3154