It ain’t pretty, it’s Acute Kidney Injury. This case was probably brought on by leptospirosis. This is the face of a well known New Zealander. Do you recognise him? He’s kindly lent his name to my research on AKI. I will reveal that name in future posts as I tell his remarkable story.
I love living in NZ, it enables me to be the first in the world to wish everyone a happy World Kidney Day. May your kidneys never lack oxygen, be always filtering, and ever distant from the nephrologists biopsy needle!
Let me remind you:
If it weren’t for your kidneys where would you be
You’d be in the hospital or mortuary
If you didn’t have functioning kidneys
(with apologies to John Clarke)
Better, take a look at this video too (from www.worldkidneyday.org):
This year’s theme for World Kidney Day is “Kidneys for Life: Stop Kidney Attack.” If you’ve not caught up with my myriad of other posts, Kidney Attack (aka Acute Kidney Injury) is the rapid loss of kidney function and/or structural damage brought about by toxic damage to the kidneys or temporary loss of blood to the kidneys.
This week I published a blank post entitled “A list of effective treatments for Kidney Attack.” There is no known treatment – merely acute dialysis, a support for the kidneys, not a treatment. There is no treatment because detection is delayed and difficult and because not enough research has been done.
The good news is that I and many others around the world are engaged in finding new ways of detecting this disease. Before I list some of the good news I want you all to repeat after me “30,000 kidney attacks a year in New Zealand, 1300 deaths.” If you live out of New Zealand you may say “Two million die of Kidney Attack each year.” Now tell someone else … anyone … the next person you see (not your boss if you read this at work). Well done, thank you.
So, for some good news:
Hooray – we have for the first time means of measuring structural damage to the kidneys. For us, this is the X-ray moment. Imagine life before the X-ray – all that could be said is that you could no longer bowl a bouncer (throw a curve ball), play the piano, or dance a jig (whatever that is). In other words, all that could be said was function was lost. With the X-ray actual injury to the bone could be observed. Importantly, it could be observed before function was lost permanently. The measurement of various molecules we make in the urine are to us like the X-ray – they are measures of injury to the kidney (we call them biomarkers).
We are busy investigating how best to use these biomarkers and have been discovering:
- which are best after Cardiac surgery, Contrast procedures or in the ICU (all risk factors for Kidney Attack),
- what the optimal timing is for measurement of each biomarker,
- how to use the biomarkers in Randomised Controlled Trials aimed at testing new treatments,
- which biomarkers are best for detecting Kidney Attack when someone has additional co-morbidities like sepsis, and
- which biomarkers add the most value to what we already know and enable the best assessment of risk of poor outcomes.
In the meantime, some of my work has shown how we can better utilise the information we already have with urine output and the mainstay of nephrology, the plasma creatinine measure:
- the discovery that even when creatinine does not change after Cardiac Arrest there is likely to be Kidney Attack (it had been thought that it was only when creatinine was elevated there was a problem),
- a combined measurement of plasma & urine creatinine and urine flow rate (called creatinine clearance) over a short period of time in the ICU helps identify Kidney Attack patients otherwise missed,
- how best to estimate someone’s “normal renal function” so that a judgment can be made if it has recently changed, and
- how best to utilise creatinine in Randomised Controlled Trials to tell if an intervention is improving kidney function.
All these add up to progress. My own and my group’s work over the last 6 years has received funding from a number of funders (see logos attached) some of which originate with your tax dollar – hence my commitment to keep the tax payers informed. I am indebted to my boss, Professor Zoltan Endre, not only did her hire me (I think he mistook Physicist to mean Physician!), he has taught me heaps and consequently we have formed a strong collaboration. Our work has also depended on the good staff of Dunedin and Christchurch Hospital ICU’s, Christchurch Emergency Department, and the Canterbury Health Laboratories. Without the commitment to research these people make, progress would not have been made. Most important are the patients or their families who have consented for us to take extra samples or enroll them in a trial. The decision to participate is often made at a difficult time – families wrestling with issues of possible death or long term health issues of their loved ones. I salute them. I thank them. New hope, new medicines, new tests, and new procedures are built on the courage and generosity of the patients and families who participate in research.
This afternoon I have heard presentations from seven former students of the Christchurch Med School (University of Otago Christchurch), almost all now Professors. It has been fascinaying and moving.
1.00 – 1.25 Professor Vicky Cameron, Cardiovascular risk factors in Maori and non- Maori communities: Strategies for improved clinical management’
Fascinating comparision between an urban Maori, Rural Maori and urban non-Maori cohort. Despite good access to primary care and little access to fast food outlets urban Maori were exhibiting the highest risk factors.
1.25 – 1.45 Mr Tim Eglinton, ‘Starting at the bottom and working up: Perianal Crohn’s Disease in Canterbury’
Canterbury has one of the highestrates of Chrons disease in the world!
1.45 – 2.15 Dr Quentin Durward, ‘The Crash of United Flight 232 in Sioux City, Iowa, July 19 1989: Community and Medical Response to a Mass- Casualty Commercial Airliner Disaster’
Very moving account of dealin with an air disaster. Fortunately there was a great plan in place.
2.15 – 2.45 Professor Michael Ardagh, ‘After the dust settles – researching the health implications of seismic events’
Also very moving. Prof Ardagh is head of the Emergency Department here. He talked about the response to the earthquake. Again the importance of a plan can not be overesimated. Who knew that during those first few hours the blood bank was still processing requests while ankle deep in water, suffering power outages, in a basement of a very shakey multistory building, all at the same time as not knowing about their own families? More heroes unsung!
Chair: Professor Lisa Stamp
3.30 – 4.00 Professor Brian Darlow, ‘From small to
big – clinical research in newborn medicine’
4.00 – 4.30 Professor Rob Walker, ‘Nephrology: Ross Bailey – Drugs and the Kidney’
4.30 – 5.00 Professor Bridget Robinson, ‘Keeping Cancer Research Close to the Patient’
Quite a coup this morning for a group of 8 sufferers of a rare disease to get a plea for Pharmac to fund a new drug in to both the Herald and the Press. I’ve since discovered that Radio NZ and TV3 have picked up the story. There are also some slick videos on vimeo.com
These people are evidently very ill with a debilitating and very rare disease (less than a hand-full of cases per million). Paroxysmal Nocturnal Hemoglobinuria (PNH) does nasty things to one’s red blood cells. Blood clots which may result in death are a serious complication of the disease.
The campaign, backed by one haemotologist, is directly aimed at getting Pharmac to fund a drug. The drug is called eculizumab and is produced by the Pharmaceutical company Alexion under the name Solaris. Apparently the cost is $500,000 per year per patient every year for life. This is information in each of the very similar media articles. Apparently Pharmac thought the evidence limited last year, but sought the opinion of a specialist heamotology committee who are due to report back to Pharmac soon.
The Herald (only!) reports
“A support group for patients with PNH said Pharmac was taking too long to decide, has begun a lobbying campaign, whose costs are met in part by Alexion.”
Alexion are engaging in a very common practice to promote their own drug by engaging the media through support groups. That is not to say their drug is somehow “bad”, merely that they see it reasonable to use the media to raise sympathy in an attempt to put pressure on an independent committee which is supposed to be making decisions entirely based on the scientific evidence and a cost-benefit analysis. I don’t believe they will be swayed by this sort of campaign – and nor should they. It is not in the patients’ interests for them to be so. Having said that we have seen before in New Zealand how such a campaign can influence the Pharmac process and that was with Herceptin prior to the 2008 elections when the National party made policy promises*. I do hope there won’t be a politician who speaks out in support of this current campaign, but I don’t hold my breath.
Having bagged Alexion’s tactics I must also praise them. Not many drug companies seem to bother with rare diseases. The risks of not getting a return are greater than for common diseases. Good on them for developing this. With small numbers it is difficult for quality efficacy or safety trials to be done, therefore difficult for the evidence to be gathered.
Pharmac need to assess the evidence. I had a look on PubMed for trials of PNH with eculizumab. There is precious little. The FDA summarised the evidence in a freely available publication: http://theoncologist.alphamedpress.org/content/13/9/993.long in which they discuss one and one only randomised controlled trial of just 87 patients (with a positive result) along with some other “open label” studies. I could find no trials that provide evidence of extension of life (not unusual). What is often the case is that a surrogate marker (eg measurement of some substance in the blood) which is thought to relate to the risk of death is measured instead and a change in risk of death is then inferred from this. Not the best kind of evidence, but often all there is. The studies all seem to say something positive.
The difficulty Pharmac has to deal with is that nearly all the trials are sponsored by Alexion and the principal authors receive consultancy fees etc from Alexion. This does not automatically mean the trials are biased, but it does mean that Pharmac should proceed very cautiously given the history of Pharmaceutical companies (and I am not pointing at Alexion here) tendency to publish only the positive results.
A very tricky decision for Pharmac- I don’t envy the decision makers. A very difficult disease to live with for the patients – I wish them all the best.
* Disclaimer – I was a candidate for another Party in that election. When I told a soon to be National MP in a debate that decisions on drugs should not be made by Politicians he turned around and accused me of wanting to kill women! For the record, I don’t, and I did lose my rag. Ho hum.
Kidney’s are being attacked every day. Yours could be next. So common and deadly are kidney attacks that the theme for this year’s World Kidney Day is “Kidneys for Life: Stop Kidney Attack!”
Kidney Attack, or as Physicians and scientists call it “Acute Kidney Injury,” is a syndrome which affects several thousand people a year here in New Zealand. It is notoriously difficult to detect and can be deadly. For more than 5 years now I have been researching how better to detect, and ultimately to treat, Kidney Attack. Over the past 12 months I have posted several times about this – here are links to just a few of the previous posts:
There will be more as we lead up to World Kidney Day 2013.
Some of you may know Lewis Carroll’s classic nonsense poem “The hunting of the Snark”. Eight men set off with a blank map to find the mythical Snark.
And the Banker, inspired with a courage so new It was matter for general remark, Rushed madly ahead and was lost to their view In his zeal to discover the Snark
Snarks were dangerous creatures, however
“For, although common Snarks do no manner of harm, Yet, I feel it my duty to say, Some are Boojums—”
I dwell in a world where inspired by the new many have rushed on ahead to discover the SNARF (SigNals of Acute Renal Failure). The hunting of the SNARF has followed contours familiarly trodden and graphically illustrated by a Hype cycle(1).
It was kickstarted by new technologies called proteomics and genomics which gave the hope that soon would be discovered a rapid, accurate, and, most importantly, early biomarker of Acute Renal Failure (later renamed Acute Kidney Injury, AKI). This was the beginning of the hype that was driven in no small part by some fantastic early results. A paper published in the Lancet in 2005 was an important driver in the hype that followed(2). As with many early studies this involved children and cardiac surgery. Importantly the biomarker involved almost perfectly distinguished between those who had the disease and those who didn’t (ie not false negatives or false positives). As the field progressed and more and more studies were investigated across a more diverse range of patient groups and potential AKI causes the ability to discriminate between those with and without the disease became much more modest. It became apparent that one biomarker to rule them all was not going to be the solution – rather a panel of biomarkers whereby the clinician would choose which biomarkers, if any, to use according to the timing and suspected etiology of the renal injury, the baseline renal function and specific illness of the patient. We do not yet have such a panel, nor have we conducted sufficient investigations to find if an AKI biomarker(s) adds value to what the clinician can already deduce. That is partly my job and these are the greater challenges that must drive us up the slope of enlightenment to reach the plateau of productivity where finally we may capture the SNARF.
(1) Jackie Fenn, “When to Leap on the Hype Cycle,” Gartner Group, January 1, 1995
(2) Mishra J, Dent CL, Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005;365(9466):1231–8.
Vitamin D has had big raps lately. We know that low levels of it correlate with higher levels of some diseases, but does taking a supplement help? An article in the Herald this morning by Martin Johnson nicely outlines a study being undertaken by Professor Robert Scragg of the University of Auckland. His is the quote in the title.
Why is there need for an expensive trial when lots of observation studies show low levels of Vit D mean you are more likely to get Cardiovascular (and other) diseases, high levels mean you are less likely? Isn’t it obvious that by taking supplements that health outcomes will improve? Sadly, no it isn’t. Correlation does not mean causation (or “Post hoc ergo propter hoc” for you latinistas out there – I learnt this from a re-run of West Wing this week). What this means is that there is more than one reason for the correlation ie:
- Illnesses are because Vit D is an essential component in the biochemical pathway’s that provide a defense against these illnesses (causation), or
- Low Vit D is a consequence of something else that has gone wrong that also causes the diseases (ie Vit D is a “flag” or “marker” for something else).
If 1 is true, then raising Vit D levels may help. If 2 is true, then raising levels probably won’t help. For the moment assume 1 is true, then the next question is “does supplementation help?” Again, most would think “Of course.” However, it is possible that by bypassing the mechanism by which the body makes its own Vit D (ie beginning with exposure to the sun) the body’s response to the increased Vit D is different. These, and others, are reasons why a Randomised Controled Trial (RCT) in which some participants get Vit D and some get Placebo (in this case sunflower lecithin) is conducted. There is some information about the trial in the Herald article, more can be found on the Aust NZ Clinical Trials Registry here. Briefly, participants (50 to 84 years of age) will receive 1 capsule a month for 4 years. The incidence rate of fatal and non-fatal cardiovascular disease is the primary outcome. Secondary outcomes include the incidence of respiratory disease and fractures. They need to recruit 5100 people (so get involved!).
Why so many people? This is because they want to avoid making two mistakes. They want to know with high certainty that if they see a difference in the rates of cardiovascular disease between the Vit D and Placebo group, the that it is not a difference that occurred randomly (ie seeing a difference when there really is no difference). It is most common to accept a 5% chance of seeing a difference by chance (tossing 4 heads in a row is about a 6% chance). The second mistake is if the trial were to show no difference between the groups, but for this to be a false conclusion (ie not seeing a difference when there really is a difference). It is common to accept about a 10% chance of this happening. Notice, I have talked about “difference” not Vit D being “better” than placebo. This is very important, because it is possible that Vit D is worse and scientists must take into account that possibility. That is why scientists also start with what we call the “null hypothesis” – the presumption, in this case, that there is “no difference” in the rates of cardiovascular disease between those taking Vit D and those taking placebo.
I liked the quote of Prof Scragg in the Herald:
“GPs are very supportive of it and I know they are prescribing it extensively to patients. Hospital specialists are sceptical. Me, I’m in the middle. My heart says I want it to work. My head says I have to keep an open mind.”
I too often find myself in the “middle” – hoping with my heart that something works for the good of all, but working with my head so that we don’t end up peddling false hope or worse.