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.

H7N9 kills and attacks kidneys

27% of patients with H7N9 Influenza A died.  This is the finding of a report just released  in the New England Journal of Medicine is a study of 111 of the 132 confirmed cases of H7N9 Influenza A*.

Acute Kidney Injury or “Kidney Attack” was amongst the most common complications.

Of the 111 patients we evaluated, 85 (76.6%) were admitted to an intensive care unit (ICU); of these patients, 54 were directly admitted to the ICU, and 31 were admitted during hospitalization. Moderate-to-severe ARDS [Acute Respiratory Disease Syndrome] was the most common complication (in 79 patients), followed by shock (in 29 patients), acute kidney injury (in 18 patients), and rhabdomyolysis (in 11 patients).

In an analysis in the Appendix to the paper a comparison was made between the 30 patients who had died and 49 who had recovered (others were still in hospital).  100% of those who died had had ARDS compared with 40% of those who recovered.  One third of those who died had Acute Kidney Injury compared with 4% of those who recovered.  From a statistical perspective these numbers illustrate a real difference with a low probability (~ 1-2 out of 1000) of observing such a difference by chance.**

Note, all patients had been in close contact withe live chickens or pigeons within 2 weeks of hospitalisaton.

NEJM 23 May 2013

NEJM 23 May 2013

* Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection

Hai-Nv Gao, M.D., Hong-Zhou Lu, M.D., Ph.D., Bin Cao, M.D., Bin Du, M.D., Hong Shang, M.D., Jian-He Gan, M.D., Shui-Hua Lu, M.D., Yi-Da Yang, M.D., Qiang Fang, M.D., Yin-Zhong Shen, M.D., Xiu-Ming Xi, M.D., Qin Gu, M.D., Xian-Mei Zhou, M.D., Hong-Ping Qu, M.D., Zheng Yan, M.D., Fang-Ming Li, M.D., Wei Zhao, M.D., Zhan-Cheng Gao, M.D., Guang-Fa Wang, M.D., Ling-Xiang Ruan, M.D., Wei-Hong Wang, M.D., Jun Ye, M.D., Hui-Fang Cao, M.D., Xing-Wang Li, M.D., Wen-Hong Zhang, M.D., Xu-Chen Fang, M.D., Jian He, M.D., Wei-Feng Liang, M.D., Juan Xie, M.D., Mei Zeng, M.D., Xian-Zheng Wu, M.D., Jun Li, M.D., Qi Xia, M.D., Zhao-Chen Jin, M.D., Qi Chen, M.D., Chao Tang, M.D., Zhi-Yong Zhang, M.D., Bao-Min Hou, M.D., Zhi-Xian Feng, M.D., Ji-Fang Sheng, M.D., Nan-Shan Zhong, M.D., and Lan-Juan Li, M.D.New England Journal of Medicine Online May 22, 2013 DOI: 10.1056/NEJMoa1305584

** something called a multivariate analysis was attempted which trys to take into account correlations between diseases to see which diseases are the major factors.  However, with “only” 30 deaths such an analysis is very limited and I do not think of value in this situation.

The Face of Kidney Attack

The Face of Acute Kidney Injury.  (Published with permission).

The Face of Acute Kidney Injury. (Published with permission).

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.

Diabetes in NZ – new scary data

If this doesn’t scare you, you are an Ostrich.  Otago University researcher Dr Kirsten Coppell has released new data on the prevalence of diabetes in New Zealand.  See here for the press release.

Basic data:

  • 7% of New Zealanders over the age of 15 have diabetes
  • 18.6% have pre-diabetes which typically leads to Type II diabetes (therefore the prevalence is likely to go higher than 7%).
  • The pre-diabetes prevalence increases with age – it was 45% in 55-64 year age group.

For those interested in reading the research, it can be found in the NZ Medical Journal.  NZMJ 1 March 2013, Vol 126 No 1370; ISSN 1175 8716  URL: http://journal.nzma.org.nz/journal/126-1370/5555/  Dr Coppell kindly sent me a copy (*I’ve made a few more observations about the details of the study for those who are interested below).

In the meantime, this is rightly hitting the headlines.  We should be afraid, very afraid.  Our politicians must stop arguing over that which is petty (like selling less than half of a small fraction of our assets) and get focussed on what matters.  Next year is election year – we should demand a comprehensive diabetes policy from each political party.  Below is a letter I wrote to the Christchurch Press prior to the last election – not much has changed.  As for you – you can stop attacking the sugar – you don’t need it and it may kill you.  Beware of “fat free” food which substitutes sugar instead.  Get some advice – see your doctor.  Don’t become a statistic in the next survey.

As for the link with my work (Kidney Attack a.k.a. Acute Kidney Injury), the little diagram explains.Diabetes AKI

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*  The study was a representative sample of New Zealanders.  The study size was large (for an NZ study) – 4,721.

From the results

Overall the prevalence of diabetes was 7.0% (95% CI: 6.0, 8.0). Diabetes was more common among men (8.3%; 95% CI: 6.4, 10.1) compared with women (5.8%; 95% CI: 4.7, 7.0). The prevalence of diagnosed diabetes was 6.0% (95% CI: 4.5, 7.5) among men and 4.0% (95% CI: 3.1, 4.8) among women, and the prevalence of undiagnosed diabetes was 2.1% (95% CI: 1.2, 3.0) among men and 1.5% (95% CI: 1.0, 2.0) among women.

Scary for me is the percentage of undiagnosed diabetes.  This represents tens of thousands of New Zealanders!

Tables in the paper show how the prevalence increases with age and body mass index and that there are marked differences according to ethnicity.  One third of Pacific people over the age of 45 had diabetes, yet about 40% of this was undiagnosed diabetes!

By the way – 95% CI with two numbers following means a that the 95% confidence interval for the prevalence is between the two numbers.  What this means is that there is a 95% chance that confidence interval contains the true prevalence (which can only be known if everyone is measured).  Eg There is a 95% chance that the 6% to 8% confidence interval contains the true prevalence of diabetes (note – 7% should be thought of as an estimate).

1300

Today’s number brought to you by Funeral Directors of New Zealand.

 

1300

 

Kidney Attack (aka Acute Kidney Injury) is responsible for at least 1300 deaths a year in New Zealand.  It used to be said that people died with Acute Kidney Injury rather than of Acute Kidney Injury.  The paradigm has shifted in the last few years.  Now it is recognised that an acute attack on the kidneys is a killer all by itself.  Of course, the attack is still most often precipitated by another event – heart attack, serious infection, cardiac surgery etc etc etc.

How did I come up with 1300?

A comprehensive study of nearly 20,000 hospital admissions showed that there was a 4.1 times increase in risk of death in hospital for those with Kidney Attack compared to those without.  The Ministry of Health in New Zealand do not report hospital mortality data, but a very helpful MOH information analyst, Chris Lewis (thanks Chris), dug out some numbers for me.  There were 7582 patients out of 548,965 discharges from public hospitals in 2011/12 who were “Discharged Dead”, Died in the emergency department, or Discharged for organ donation.  This does not necessarily capture all deaths (eg Private Hospitals are not included).  However, it gives me enough to go on using the proportion who died overall, the increased odds of death with Kidney Attack (4.1), the estimated number of Kidney Attack patients (30,000), and a little bit of math. The result is at least 1300 Kidney Attack deaths.

 

30,000

Today’s number brought to you by <You could have your name here, contact the blog writer to arrange sponsorship>

30,000 – the number of Kidney Attacks in New Zealand each year.

30000

Where does this number come from?

Research in other parts of the world has Kidney Attack, or Acute Kidney Injury, at ~5% of all hospital admissions.  Estimates range from 2% to >9%.  5% is the generally accepted incidence.  New Zealand has more than 1.1 million hospital admissions a year, with 410,000 of them day cases.  5% of the 690,000 longer stays is 34,500.  30,000 is, therefore, a conservative estimate.  The NZ health stats don’t report these numbers because they are not collected.  They are not collected because nearly always the cause for hospital admission is something else – heart attack, infection etc.  These “something elses” all can cause Kidney Attack.   Kidney Attack raises the chances of dying in hospital 4 fold.

I’d like to find the NZ incidence of Kidney Attack instead of relying on estimates based on overseas numbers.  In particular, I’d like to see if there are any differences related to ethnicity.  I’m searching for funding to do this.

Deadly ignorance

How many deaths does it take?  We hear that question asked time and again following a tragic event.  We also hear it with calls for changes to our public health priorities.  Well, I am now asking it with respect to Acute Kidney Injury.

  • Acute Kidney Injury (AKI) is one of the most common hospital events (4-5% of patients get it).
  • The most severe forms of AKI result in emergency dialysis.
  • Research out of the US has shown that there has been a doubling of dialysis for AKI over the past decade (1).
  • Now there are 533 cases of dialysis requiring AKI per million people each year in the US.*
  • 24% of those needing dialysis died in hospital
  • About 10 times the number who need dialysis actually get AKI.
  • Even mild AKI raises the risk of in-hospital death and long term kidney problems.
  • More people each year now have dialysis for AKI than those who start dialysis as a result of a chronic kidney disease.

Comparative New Zealand statistics

I would like to do them but have had problems getting funding.  I especially want to look to see if there are any ethnic biases in the numbers.

If we take the US numbers and apply them to our population of 4.4 Million then there would be:

  • 2350 cases of dialysis-requiring AKI of whom 564 would die.
  • Over 20,000 people each year would have AKI.  Many more than 564 would die.

My gut reaction based on the use of dialysis in the Christchurch hospital intensive care unit is that 2350 is probably too high, maybe two to four times too high.  This may reflect differences in dialysis protocols and admittance to ICU.  It is less likely to reflect a lower incidence of AKI.  My best guestimates are:

  • 4000 to 8000 cases of AKI each year with 400 to 800+ deaths.

These numbers are greater than the road toll – another acute event.

They are comparable with Breast Cancer**.

I would like them not to be guestimates.

Maybe the funding will come next year.

The good news

My research and others over the past few years has:

  • identified new biological markers of injury to the kidney
  • assessed many of these and determined that they are of clinical value
  • come up with better ways of defining the disease
  • determined that some pre-existing tools can be applied in slightly different ways to give early warning of changes in kidney function
  • come up with some promising interventions which may reduce the risk of developing AKI

Here endeth the 2012 report.

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1.  Hsu RK, McCulloch CE, Dudley RA, Lo LJ, Hsu C-Y. Temporal Changes in Incidence of Dialysis-Requiring AKI. J Am Soc Nephrol 2012; Online ahead of print.

* the data was expressed in “million-person-years” but as the data was for one year then it is OK to express it as per million people.

**The difference between AKI and many other diseases is that while AKI causes death it is almost always secondary to another event – heart attack, severe infection, cardiac surgery etc, so it is rarely recorded as THE cause of death.