Tag Archives: End stage renal failure

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

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

378524_2646852331216_1123939800_n

________________________

*  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).

An implantable artificial kidney

$100 Dialysis is my vision.  University of California San Francisco researchers are doing some exciting research that may well be a step on the way.  They are developing an implantable artificial kidney .  They have a facebook page http://www.facebook.com/ArtificialKidney for those wishing to follow progress.  $13M is needed to bring it clinical trials – I think they should try Kickstarter.  With 400,000 on dialysis in the US alone there will be plenty of contributors (If you are feeling generous now you can contribute by going to their website).  Alternatively, $13M is a drop in the bucket of the $29Bn that Medicaid (6% of its budget)* spends on dialysis every year!

A few interesting facts about UCSF’s artificial kidney:

  • No pumps and no power supply.  It relies on the body’s blood pressure to perform filtration.
  • The key to cleaning the blood is a good filter – they have developed nano technology to produce a silicon based filter with pores small enough and a structure that does not induce blood clotting.  See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607036/
  • Beyond simply filtering the nasties, the kidney’s role is to regulate salt and water reabsorption and blood pressure.  This is being achieved by using bioengineered grown tissue – that is real cells from inside the kidney. They call this the bioreactor.
  • They are currently in the “pre-clinical” stage where they are miniaturising the machine and preparing it for implantation into humans.

* If you want to know why this is so high and the practices in the US then see http://www.propublica.org/series/dialysis.  You may be shocked (a must read for every for anyone in the US making choices about dialysis).

The Hunting of the SNARF

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).

The Hunting of the SNARF

The Hunting of the SNARF: A Hype Cycle of the hunt for the perfect biomarker of Acute Kidney Injury

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.

Have you got diabetes?

I am sitting in a meeting of the Australian and New Zealand society of nephrologists.  I want to do them out of a job.  Will you help?

Diabetes is the number one risk factor for Chronic Kidney Disease (CKD).  High blood pressure is number two.

About 10% of the population has CKD.  They are much more likely to die than the rest of us.  Some of them will go on to need dialysis or a transplant.

Scared?  You should be.

What can you do?  Eat well, shut your computer and go for a 30 minute walk.  Do the same tomorrow.  Take a friend with you, especially if they are overweight and at risk of diabetes themselves.  If you are wise, you are already out the door and not reading this, if not…please act soon.

The critical 1st 6 months post dialysis

Know someone about to start dialysis?  I am sitting in a conference hall and have just heard a fascinating talk by Prof Chris MacIntyre about the danger to other organs for those undertaking dialysis.  The stress dialysis puts on the vasculature is the culprit.  Myocardial stunning can occur in nearly 2 out of 3 paients each dialysis session .  The effect in creases many fold with every extra litre of fluid removed.  The death rates are much higher amongst those who exhibit the stunning than those who don’t.

It is not all bad news.  Cold dialysis and more frequent dialysis seem to help.  Randomised Control Trials are underway to test these interventions.  A portable continuous $100 Dialysis machine may not just be cheaper, but may have less side effects!

In the meantime, support from friends and family are all the more important in those few months.

Hopeful signs

I began blogging with $100 Dialysis – the vision.  The technical challenge is to develop cheap and perhaps novel  means to filter the blood of nitrogenous waste products.  Below is an example of three approaches, one is a more user-friendly way to use existing technology, another utilizes nanotech, and the third although not aimed at dialysis is an example of new thinking.

Peritoneal dialysis is a form of dialysis whereby the abdomen lining (called the peritoneum) within the body is used to filter the blood.  Simply, the dialysis fluid is pumped into the cavity formed by this natural filter.  Once it has absorbed some of the waste from the blood filtered through the peritoneum it is pumped back out again.  Not everyone is eligible for periotoneal dialysis, but for those who are the concept of a portable dialysis is very welcome.  Progress is definitely being made, have a look here.

Also developing wearable dialysis, but this time using an external device to remove the waste is the Dutch company Nanodialysis.   Rather than simply filter the unwanted particles through small pores they get them to adhere to a surface, a process called adsorption.  From there they get them to decompose to nitrogen, hydrogen, and carbon dioxide.  The company claims that not only will this be cheaper (yeah) and more convenient it will also increase life expectancy 10 to 15 years over standard hemodialysis! This is quite an incredible claim and as they are yet to complete animal trials is premature.  Nevertheless, it is definitely a space worth watching.

Some clever people in MIT and the National University of Singapore have demonstrated that they can remove bacteria from blood making use of a concept from normal biological process called margination in which leukocytes (white blood cells) adhere to blood vessel walls (see here).   Whilst the nitrogenous waste products are much smaller, using fluid flow technology similar to what MIT and NUS have demonstrated may be another way forward.