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Farewell to Dialysis? (interview with Prof. Darren Kelly)

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  • Farewell to Dialysis? (interview with Prof. Darren Kelly)

    Farewell to Dialysis?

    VOICEOVER
    Welcome To Melbourne University Up Close, a fortnightly podcast of research, personalities, and cultural offerings of the University of Melbourne, Australia. Up Close is available on the web at upclose.unimeld.edu.au. That’s upclose.u-n-i-m-e-l-b.edu.au.

    SHANE HUNTINGTON
    Hello and welcome to Up Close, coming to you from Melbourne University, Australia. I’m Dr Shane Huntington. In Australia and New Zealand there are about 6,000 people on dialysis as a result of renal or kidney disease. Being hooked up to a dialysis machine for four or five hours a day three times a week with this routine going on indefinitely is extremely stressful for the patients and their families. While all these patients hope to receive a kidney transplant, the reality is only a small portion of the dialysis patients we have will ever become recipients. One common cause of renal disease is called fibrosis.

    Our guest today is Professor Darren Kelly from the Department of Medicine in the Bio21 Institute here at the University of Melbourne, Australia. Darren will discuss the nature and causes of fibrosis, particularly as it occurs in the kidney, and will give us an insight into the groundbreaking research he’s been leading in the development of anti fibrosis drugs. The success that Professor Kelly has had thus far, for the first time, offers a ray of hope for many dialysis patients around the world.
    Welcome to Up Close, Darren.

    DARREN KELLY
    Thanks a lot, Shane.

    SHANE HUNTINGTON
    I’d firstly like to ask what fibrosis actually is.

    DARREN KELLY
    Well you actually have fibrosis following trauma or injury. So a little bit like when you have a surgical wound and the fibrosis that causes wound healing to repair back together. When it occurs in organs like the kidney and the heart as a response to injury from something like diabetes this aberrant fibrosis then stops the organ from functioning normally.

    SHANE HUNTINGTON
    Is fibrosis one of those things that affects different parts of the body in different ways?

    DARREN KELLY
    It seems to be a pretty similar response in most of the organs actually, so hence the reason our concept is to develop anti fibrotics that may work in other organs. We’re focusing at the moment on the kidney but there certainly is potential for other treatments in other organs.

    SHANE HUNTINGTON
    Let’s talk about the kidney. As an expert in this area, what do they actually do for us, and how do they go about that?

    DARREN KELLY
    The kidneys are obviously the filtering units that clean up our blood and play a really vital role in maintaining our health and wellbeing. So if you affect the kidneys in any way, say for from diabetes or chronic illnesses, then you obviously build up waste products in the kidney and require dialysis to basically clean up the blood.

    SHANE HUNTINGTON
    In the kidneys when we have this fibrosis scenario the structure of the kidney I can imagine is being modified in some way. Can you tell us a bit more about what’s actually happening there?

    DARREN KELLY
    As I was saying, a little bit like wound healing on the skin following a surgical incision, that’s what happens to the kidney as well. It undergoes this fibrotic process where you get scarring which, if you think about it, then stops the kidney from functioning because you’re obliterating cells that normally have a specific role.

    SHANE HUNTINGTON
    When we talk about scarring, we’ve all got scars somewhere on our body and they look a little bit different but it’s not dead tissue, is it? It’s doing something?

    DARREN KELLY
    It’s basically a structural thing, fibrosis or scarring. It’s really holding the skin or the organ together. If an organ undergoes trauma it often fibroses to try to protect the organ or maintain its integrity, but it’s when this aberrant scarring occurs that it excessively causes the deletion of cells or the loss of cell function.

    SHANE HUNTINGTON
    In the case of renal fibrosis - we’re talking about the kidneys here - what sort of symptoms can a person expect to be experiencing when this starts to occur?

    DARREN KELLY
    To be honest most of the symptoms would not be noticed very early on if fibrosis did occur. It’s when it really gets into the later stages where you do require dialysis that obviously you’d have noticeable changes.

    SHANE HUNTINGTON
    What sort of changes?

    DARREN KELLY
    Things like oedema and just general feeling of unwellness and nausea. Feeling quite sick, actually.

    SHANE HUNTINGTON
    Presumably if the toxins continue to build up you’ll actually die from that?

    DARREN KELLY
    Correct.

    SHANE HUNTINGTON
    At the moment, the treatment being primarily dialysis, can we be on that permanently? Can that just continue on, or is a process that over time fails?

    DARREN KELLY
    Dialysis is usually instigated when kidney function is at the very end, so it’s sort of a last resort to keep someone alive long enough so they can get a kidney transplant. So at that particular stage the disease is quite advanced.

    SHANE HUNTINGTON
    I’m guessing we have an almost oversupply of kidney function, and I ask that question because I know people can donate a kidney. What percentage of our total kidney function can we get away with?

    DARREN KELLY
    That’s an interesting point. We do have an excess of kidney function, and hence you really need to lose more than 80 per cent of your kidney function before you require dialysis so it’s a significant amount of kidney loss.

    SHANE HUNTINGTON
    In many cases our bodies are designed in certain ways and it makes sense. Does it make sense for us to have such a redundancy of kidney functions?

    DARREN KELLY
    I wouldn’t say it’s a redundancy of kidney function because with age you progressively lose nephrons, or kidney function and viability, so it’s sort of a backup supply that, depending on how long you live or how rapidly your kidney function declines, is a necessary backup of kidney function.

    SHANE HUNTINGTON
    In Australia we have a relatively good - relatively good - medical system compared to many countries in the world. How common is renal fibrosis here?

    DARREN KELLY
    Renal fibrosis is the leading cause of kidney failure and it’s very common.

    SHANE HUNTINGTON
    What are some of the causes of renal fibrosis?
    DARREN KELLY
    The main cause is diabetes. High glucose contributes to loss of kidney function. High blood pressure is another factor that’s involved in kidney failure. There’s a lot of unknown causes as well, that are associated with chronic renal disease. It could be virally instigated or chemically induced.

    SHANE HUNTINGTON
    The reason for this interview, we have to be truthful, is because of the incredible work you’ve been doing in anti fibrotic agents. Tell me a bit about what’s happening there. Why did you choose renal fibrosis as the area you wanted to focus on?

    DARREN KELLY
    We’ve been working in the area of renal fibrosis for a number of years, our research group with Professor Richard Gilbert and also Professor Henry Krum from Monash University. We’ve been focusing on fibrosis in particular in the kidney and also on the heart. It’s an area that we’ve worked on for 15 or more years now. We’ve been looking at testing the pharmaceutical industry’s compounds against fibrosis, and the way this current project got underway was one of those sorts of serendipitous moments where I was talking to someone at Bio21 Institute in Melbourne. We started talking about a series of anti fibrotic compounds that we’d been using in some of our animal models, and how we could potentially develop them or improve their actual anti fibrotic activity, and the project just snowballed from there.

    SHANE HUNTINGTON
    The drug that you guys are working on must somehow halt the fibrosis mechanism. Tell us about what’s happening in the process itself with fibrosis? Is it just terminating, is it just being reduced, how effective is the drug?

    DARREN KELLY
    Our drug is looking inhibiting fibrosis. One of the questions is whether it can actually reverse fibrosis - we haven’t looked at that. We’ve shown in our animal models that it can inhibit fibrosis and the way that it inhibits the fibrosis is probably associated by blocking certain cellular mechanisms that are triggered off by these injurious responses like high glucose from diabetes, and high blood pressure. So inhibiting those downstream pathways and more centrally looking at inhibiting some of the specific growth factor pathways, like transforming growth factor beta, which is thought to be one of the central growth factors involved in the development of fibrosis.

    SHANE HUNTINGTON
    The drug you’ve chosen is one many I assume. Were there a number of candidates you tried before you got to this one?

    DARREN KELLY
    There actually are no anti fibrotics available on the market at the moment, and the drug that we’ve developed is an analogue of a compound that we’ve been working on for some years now called Tranilast. Tranilast is widely available in Japan, and Professor Richard Gilbert and I had been looking at this drug a number of years ago in some of our animal models looking at kidney and heart failure, and showing that it had this profound anti fibrotic effect. And interestingly, the reason it wasn’t picked up and taken into clinical development is that it’s off patent and doesn’t really have a potential market as such. So the compound we’ve developed is based on basically that core structure, and we’ve developed it further so we think we can get better anti fibrotic activity and less toxicity in the long term.

    (read the rest here!)
    Type II Diabetes & Stage 3 CKD

  • #2
    Re: Farewell to Dialysis? (interview with Prof. Darren Kelly)

    Maybe I missed it. But at what stage will this drug be effective? Is this a drug that will be given to someone in Stage 1 or Stage 5?

    I truly hope this becomes what Dr. Kelly hopes it will be.
    Stage 3 (GFR 35) & Diabetes.

    Comment


    • #3
      Re: Farewell to Dialysis? (interview with Prof. Darren Kelly)

      What I mean is will it work when someone is in stage 5 or do you have to start it in stage 2 for it to be effective.
      Stage 3 (GFR 35) & Diabetes.

      Comment


      • #4
        Re: Farewell to Dialysis? (interview with Prof. Darren Kelly)

        There are a good many people also hoping that this drug will work. I would personally like to see if it can reverse damage already done.

        in center hemo dialysis since May 2009
        Sudden ESRD - non diabetic (but have 2 at home)
        turned down for list "lack of support" WHAT!!! starting over at different transplant center)

        Comment


        • #5
          Re: Farewell to Dialysis? (interview with Prof. Darren Kelly)

          I have been very excited about this drug BUT im concerned because in a previous post about this drug it said that it was initially going to be used to treat patients with ckd due to diabetes and that doesnt make sense to me because I do not have diabetes the only thing that I have is fibrosis due to birth defect{reflux] /renal nephropathy so this drug would benefit me so why just patients with diabeties? also its unclear but I dont see how it can reverse scarring the only thing that I know that can reverse scarring by making new healthy cells thus eliminating scarring curing many ckd patients is embryonic stemcell ..from what I understand of this drug is that it stops the progression of scarring in its tracks so you could maintain the function you have left without ever progressing but its confusing as to does that mean we could live normal lives again and eat like normal or do we still have to follow the renal diet?I dont see what would be the point of the med. if it didnt improve our lives? I hope and pray it is a miracle for all of us until stem cell cure is here in the USA
          ckd,stage3,due to birth defect/refulx,controlled b/p

          Comment


          • #6
            Re: Farewell to Dialysis? (interview with Prof. Darren Kelly)

            when was this interview taken?
            ckd,stage3,due to birth defect/refulx,controlled b/p

            Comment


            • #7
              Re: Farewell to Dialysis? (interview with Prof. Darren Kelly)

              DARREN KELLY
              Our drug is looking inhibiting fibrosis. One of the questions is whether it can actually reverse
              fibrosis - we haven’t looked at that.

              So I take that comment meaning a preemptive measure.
              Stage 3 (GFR 35) & Diabetes.

              Comment

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