The Underestimated Threat of Kidney illness in the Australian Landscape

Dr Gavin Nimon: 0:28

Did you realise that Kidney Health Australia notes that 1. 8 million Australians probably suffer from renal disease and don't know they have it? And also that the Indigenous population has twice the incidence of renal disease than the general population. Renal disease is a really important condition which we all need to know about and today we're going to hear more about it from Professor Stephen McDonald. He's a consultant nephrologist at the Royal Adelaide Hospital and his role includes care of the inpatients with all stages of kidney disease including those with dialysis. and also those who have had kidney transplants. He works in clinics around South Australia including a variety of settings in metropolitan Adelaide and regional and remote locations. He's actively engaged in research around the epidemiology of kidney disease and he leads the Australia and New Zealand Dialysis and Transplant Registry which is based at the South Australian Health and Medical Research Institute in Adelaide.

Gavin Nimon: 1:17

G'day and welcome to Aussie Med Ed, the Australian medical education podcast, designed with a pragmatic approach to medical conditions by interviewing specialists in the medical field. I'm Gavin Nimon, an orthopaedic surgeon based in Adelaide, and I'm broadcasting from Kaurna I'd like to remind you that this podcast podcast players and is also available as a video version on YouTube. I'd also like to remind you that if you enjoy this podcast, please subscribe or leave a review or give us a thumbs up as I really appreciate the support and it helps the channel grow. I'd like to start the podcast by acknowledging the traditional owners of the land on which this podcast is produced, the Kaurna people, and pay my respects to the Elders both past, present and emerging.

Dr Gavin Nimon: 1:57

I'd like to remind you that all the information presented today is just one opinion and there are various ways of treating all medical conditions. Therefore, you should always seek the opinion from your health professionals in the area in which you live. Also, if you have any concerns about the information raised today, please speak to your general practitioner or seek advice from a health organisation such as Lifeline in Australia.

Gavin Nimon: 2:17

.It's my pleasure now to introduce Professor Stephen MacDonald, a consultant nephrologist from the Royal Adelaide Hospital. Welcome Stephen. Thank you very much for coming on Aussie Med Ed.

Prof Stephen McDonald: 2:25

Thank you, Gavin. Thanks for having

Gavin Nimon: 2:26

I'm really grateful for you , giving up your time, to be involved in this interview. So Stephen, can you tell me, first of all, how important is renal disease? How common is it? I believe there's a different incidence in the Indigenous population. Does it vary between other racial groups as well?

Prof Stephen McDonald: 2:40

Sure. Thanks. Great question, Gavin. And I'd like to start, of course, by acknowledging that I'm on the land of the Kaurna people and pay my respects to their elders past and present. So every year in Australia, about 3200, people actually start dialysis or have a Kidney transplant is their first form of kidney replacement therapy. So that's the very severe end of the spectrum that works out about 125, 130 people per million population per year, which puts us a little less than a lot of other comparable countries. So those rates are a little bit lower than most European countries. Of course, that's the most severe end of the spectrum. And there are many milder degrees of kidney disease, and the great majority of people, of course, don't have kidney disease of that severity. Surveys have shown that about 10 to 11 percent of the overall population in Australia actually have some form of kidney disease, and that's usually one of the very much milder forms of kidney disease that might be manifest simply as an abnormal blood test, or a bit of blood and protein in the urine, or some form of abnormality of the kidneys or the bladder. In terms of the people that affect, so there is a steep age gradient. So the kidney disease is much more common among older people than younger people. You mentioned Aboriginal and Torres Strait Islander people and sadly kidney disease is much more common among people of Aboriginal and Torres Strait Islander background than in the general population. It's a bit more complex though than just ethnicity. It's about being of Aboriginal and Torres Strait Islander background and alsoif you are living remotely and you have a number of the other health challenges that go with that. Those factors all interact so that the rates become much, much higher if you're living in a remote environment than in a metropolitan environment. But overall, the rates of kidney disease are three and a half, four times higher among Aboriginal and Torres Strait Islander people than the general population. Again, there are some age differences and that, like many other chronic diseases, it tends to affect Aboriginal and Torres Strait Islander people at a younger age. And that's, of course, really important when you think about the impact on families and societies.

Gavin Nimon: 4:49

right. Okay how do people actually present with it though?

Prof Stephen McDonald: 4:53

Yeah. So there's still a number of people, in fact, about one in five people who start dialysis actually present really in the last month or two before that. So they're so called late. presentations. And there are a number of factors that sometimes there's some form of catastrophic kidney disease that really is very rapidly progressive. But a lot of the time it really manifests the fact that the kidney disease can be, and often is just very slowly progressive. The signs and symptoms can be very mild, a little bit of fatigue or lethargy, or sometimes nothing at all until people go along to their doctor or they go along to the hospital and have a blood test done or whatever So there are that minority and that's a proportion that's been slowly declining over time, but it's still a really important factor. The great majority of people are picked up often through the routine general health care of people with chronic kidney disease. So about 40 percent of people who start dialysis actually have diabetes related kidney disease, and that's the most common form of kidney disease. And then on top of that, there's another 12 to 15 percent with vascular kidney disease. So more than half of people in that category, and they're a group of people that either are or should be having regular follow up and regular checks through their primary care networks. And those checks do include routinely screening for kidney disease on a six monthly basis, for example, if you have diabetes. So most people are picked up in that way. And then if the kidney disease progresses. They're referred on a lot of other people that picked up as part of other screens. For example people might've had a urine test, a dipstick to look for blood or protein in their urine as part of an employment medical or a superannuation medical or something like that. So there's a number of cases of kidney disease that are picked up like that. There's also a group of kidney diseases and about 30 percent of people with severe kidney disease have a form of glomerulonephritis and a number of those, are related to a systemic disease. So for example, lupus, it would be the most common one. And so there's that group of diseases as well.

Gavin Nimon: 6:58

So A lot of them are actually associated with other conditions such that the attending physician is keeping an eye out for kidney disease. there a role for doing screening of the population like we do for faecal occult blood? Should we all be having urine dipsticks regularly at an older age?

Prof Stephen McDonald: 7:13

So there have been a number of studies looking at whether that's effective and in particular whether that's cost effective and the answer is for people with defined risk factors, yes it is, and so it's incorporated into what is the routine standard of care for people with hypertension, for people with diabetes as part of the Standard health check for Aboriginal and Torres Strait Islander people that's incorporated in terms of the general population No, the current recommendation is not just to do a screening dipstick there is Discussion out there about dipsticks, which are very sensitive at finding blood and protein, but they also Take you down a path of false positives and it's quite common, in fact, about 10 percent of the population on any given day may have a trace of blood in the urine and, or a trace of protein. So there's then a process of follow up of that. I think the most important message though, is if there's any of those other associated risk factors, then that indicate screening and certainly if there's any other signs of kidney disease. So typically it'd be very early part of the workup if somebody presents with high blood pressure or an anemia, for example.

Gavin Nimon: 8:16

Excellent. I might start off with a classification and how you tend to classify kidney disease and then go onto the workup that a GP or a medical student needs to be aware

Prof Stephen McDonald: 8:25

of. Sure. Yeah so I think there's a a number of ways you can look at this and I think one of the really early concepts to differentiate is between Chronic Kidney Disease and Acute Kidney Disease or Acute Kidney Injury as it's called now. And, the names I guess tell you what they're on and the causes and the workup of those are quite different. Different and acute kidney injuries, a really big and important topic, especially for people working in hospitals. the definition of chronic kidney disease is that it needs to be there for three months. So that's the technical definition. But in, in fact, of course, acute kidney injury tends to evolve over hours and days for both of those. The first way I start thinking about those is a really old fashioned way, but one that stood the test of time that is divided into renal, and post renal. And that's a good way to approach both chronic and acute kidney injury and what that means in practice is, making sure that there's no obstruction and at a practical level that means some form of imaging although just occasionally we still get people who come along typically males and a urinary catheter solves the whole problem. But some form of imaging to make sure that there's no obstruction of the lower tracts and then thinking through whether there's a pre renal cause And that's a more common way of thinking with acute kidney injury, but that's basically about optimizing blood pressure and fluid So once you've dealt with that, you're then left with situation of saying, okay the problem's not before the kidney, it's not after the kidney, it's related to the kidney, and then from there, there's a process of taking a good history and understanding whether there's any of those other factors we spoke about earlier on that might point you towards the cause of the kidney disease, what the rate of change of the kidneys and then physical examination is not that helpful for most times in terms of kidney disease. And then there's the usual process of investigation. Now, the key investigations for kidney disease are of course, blood tests, looking at serum creatinine and the calculated. Estimated Glomerular Filtration Rate, which is calculated from that, and the one that tends to get overlooked is often the urine and looking for the presence of blood and protein in urine and from there , like any other area of medicine, is often a form of pattern recognition saying, okay, is this a situation that is typical, say, of diabetic kidney disease? So somebody might have diabetes, slowly progressive kidney disease, some moderate degree of proteinuria, Or do they have no previous history of diseases some blood and protein in the urine and more rapidly progressive kidney disease. And so from there you need to form an an opinion about do you have enough information on the history and the examination and those investigations to be comfortable with a presumed diagnosis, or do you need. More information and if there's concern about an underlying renal parenchymal or intrinsic kidney disease, then the question of a kidney biopsy often comes up and that's typically the case if you don't have a good other explanation for kidney disease Or you're worried that there's something that's progressive that will need treatment.

Gavin Nimon: 11:20

Okay. Excellent. So really then basically bloods urine test. Imaging and ultrasound, is there any role for anything like an MRI or CT at any stage?

Prof Stephen McDonald: 11:32

Occasionally a CT, if you're worried about a blood flow, if you're concerned that there might Stenosis or renal vein thrombus or you're concerned that there might be a Malignancy, then they will be the particular roles in which you would go to a CT scan And you're going to need contrast with that CT scan MRI in terms of the diagnosis doesn't have a lot to offer the story of renal artery stenosis is an interesting one and I think most of the people I get referred to with that we end up not doing anything because one of the important changes in renal medicine in the last really 20 years has been the demonstration that Angioplasty or stenting of renal artery stenosis really doesn't make any difference in the great majority of cases, and there's good trial evidence to suggest that so when I was at medical school , there was quite a teaching about doing a nuclear medicine scan, find and then treat renal artery stenosis. And we tend not to go down those paths now unless there's a really, unique situation, a single functional kidney or something like that.

Gavin Nimon: 12:33

What about drugs that may be impacting on the cause of renal disease, such as ACE inhibitors also non steroidal anti inflammatories and things?

Prof Stephen McDonald: 12:40

Yes, there are a number and they do actually change over time. They do vary a little bit depending on whether you're in a community of practice or hospital practice. There's a really important piece of history here as well and we were all taught in medical school about the role of Bex and Vincent's powders in Australia and that was one of the things that really Put Australian Nephrology on the map and that was a combination of aspirin and phenacetin which is a relative of paracetamol and they were all banned in Australia in the late 1970s But they had a very toxic role in causing papillary necrosis and kidney damage and also transitional cell carcinomas. And that the tail of that epidemic really did take another 25 years to die out total, I think in terms of the drugs you mentioned the at recommended doses in people with normal kidney function, there's no particular downside to taking non steroidals. Clearly there are other issues in terms of GI side effects and so on. The angiotensin receptor blockers and ACE and SGLT2 inhibitors, all actually have an effect. Reducing renal blood flow, but that's actually not nephrotoxic as such. It is part of their mechanism, and in the longer term, both of those groups do slow the progression of kidney disease. But, and this is where the but is, and it's true for both of those groups, in some settings, and in particular if people have volume depleted. Then you do set up a situation where you've artificially reduced renal perfusion and you can potentiate kidney injury. And that, that also applies if you've got non steroidal anti inflammatory drugs on board. And so that's, so typically we would give advice and I would hope most people would be given advice, particularly when they have SGLT2 inhibitors about what to do on a sick day, if people have got bad diarrhea or for whatever reason, they're becoming dehydrated, those drugs need to be stopped as does metformin, by the way. In terms of the drugs that cause toxicities to the kidneys, the good old fashioned ones of gentamycin is still around and we still see a little bit of of acute kidney injury related to that together with, vancomycin. There are a few drugs that can cause idiosyncratic or allergic toxicity, typically as an interstitial nephritis, and while that's rare on an individual basis, if you've got drugs that are used very commonly, it does Pop up from time to time. And the two classes I'm thinking of here are the proton pump inhibitors, so pantoprazole and so on. And the cephalosporins. And in both of those groups we do occasionally see people that present with an interstitial nephritis so an acute deterioration as we do occasionally with allopurinol. That's not a reason not to use those drugs, but it is a reason just to be aware that if people start developing acute kidney injury in the context of those drugs, you do need to be a little bit suspicious about that There is an interesting other effect of the PPIs, the proton pump inhibitors, they do tend to drop people's magnesium levels a bit and there is some evidence suggesting that they do put people at higher risk of getting acute kidney injury if there's other factors around about the place and the area where that's best Demonstrated is with the immune checkpoint inhibitors as a new class of drugs that have been very effective for a number of malignancies And themselves actually have a number of renal toxicities, but the combination of that does seem to be a synergistic that would be the main drug toxicities We would see together with I guess the other age old one would be amphotericin, which we still see a little bit of, but

Gavin Nimon: 16:02

And of course the most common nephrotoxic drug would have to be sugar, with diabetes,

Prof Stephen McDonald: 16:06

absolutely. And that's, there's no doubt about that. Diabetes has, as I said earlier on, become the number one cause of kidney failure. That's true in Australia. It's true all over the world. The rates of kidney disease in Malaysia are now higher than they are in Australia. That's driven by diabetes. Taiwan has the highest national rate of kidney disease in the world. And that again is driven by diabetes and carbohydrates. One of the things that people have asked is it the fact, are we getting better or worse at treating diabetes or preventing kidney disease and The answer to that, in Australia at least, is that if you've already got diabetes, the risk of getting kidney disease hasn't increased over time. In fact, that's trickled down a bit, which is what you'd expect with the introduction of ACE inhibitors and Sgf2 inhibitors and so on. What's changing, though, is of course the number of people with diabetes and the duration of which they have diabetes for. And that's a really important predictor of kidney disease. It's a good thing that people are surviving longer and reflects the better treatment of All of the other comorbidities that go with having diabetes, but the reality is at the end of the day, there are more people in the population with diabetes, and so that does drive more people with kidney disease related to diabetes. The target hemoglobin A1c, if you've got diabetes, is the same whether you do or don't have kidney disease There's not a separate target. What does have separate targets is blood pressure. So if you have even mild levels of kidney disease or a bit of albuminuria, proteinuria or mildly abnormal kidney disease Then there is evidence to try and get blood pressure down to 130 on 80 as an average rather than the usual targets and that benefit is both in the slowing of the rate of progression of kidney disease as well as the risk of the usual vascular complications

Dr Gavin Nimon: 17:54

So Stephen, you know my passion for trying to divide things up into groups of three or four. Can interstitial renal disease be subclassified into three or four different subgroups? Is that a good way of thinking about it?

Prof Stephen McDonald: 18:05

I think so. You could divide it into glomerular disease, interstitial disease and tubular disease. That would be one way to do it. It's not a great fit because the other important group of kidney diseases are the inherited diseases. So there's having talked about diabetes and glomerular nephritis. The, one of the things that's changed a lot in kidney disease in the last five years or so has been the genetic element of that. So for traditionally polycystic kidney disease is in fact the most common inherited condition. And that's about 15 percent of all people that start dialysis. And there's about half that number. So six to 8 percent or so people with Alport syndrome, which is. Classically taught as an X linked disease with kidney diseases associated with hearing loss and some eye abnormalities and so on. What were now understanding with the availability of better genomic technology and the ability to massively sequence things is that firstly that the inheritance and the genetic. Basis of both of those is much more complex than we thought previously Rather than just having one or two diseases for polycystic kidney disease There's now a series of more minor disease sites has been identified There has been the development the understanding of what they just Gene codes for the polycystin protein and what that gene does and now the development of a specific Intervention for polycystic kidney disease something called Tovaptin. So for families now with polycystic kidney disease for people with Early stage disease that is progressing there is now a treatment that we can offer that will slow down the rate of progression , our understanding of All port syndrome and the the related conditions that affect glomerular basement membrane has changed dramatically. And we now know that's really part of a broader spectrum of inherited glomerular basement membrane disorders. And that many of those are not just x-linked in, inherited their inherited via variety of different ways. Now they're the sort of conditions, if you like, with a nice, simple, almost monogenic inheritance. One of the things over the years is there's always been this group of people, maybe 10 -15 percent overall, that have had kidney disease where we haven't been able to assign a clear cause. They've turned up, they've progressed and they've ended up going all the way through to starting dialysis without a good cause being defined. Biopsies might just show diffuse scarring and so on and that's an area where The genetic side of things is now uncovering a whole variety of candidate genes. We're not yet at a stage where we can link them to specific interventions, but it is clearly an area that's going to evolve over the next 10 15 years or so.

Gavin Nimon: 20:46

So obviously that's a significant cause areas

Prof Stephen McDonald: 20:49

yeah, and then it does get more complex because genes don't exist in isolation, and then there's this area of the interaction between genetics and the environmental influences. In some respects that's true even of diabetes, I mean there's a substantial inherited tendency to get diabetes, but that's not the thing, the genes haven't changed over the last 50 years, what's changed is the environment.

Gavin Nimon: 21:09

These treatments you're talking about for let's say polycystic kidney disease, how do these treatments work?

Prof Stephen McDonald: 21:14

Sure. The tolvaptan is something that, that specifically blocks the transporter pump that causes the development and the enlargement of the cysts in the kidney. And it is an aqua retic or a vasopressin agonist and causes people to have a, a diuresis effectively. The evidence base around that is fairly targeted so that if people are losing more than five mils per minute per year of EGFR then that's been shown to be a benefit. It's not a simple treatment in the sense that you're talking about tablets twice a day, but in particular, it pushes the your urine output up over. 3 litres and you're then drinking and then going to the toilet a fair bit. But for people who have progressive kidney disease, that's, that's a discussion we have and say, okay, look, that's the side effects of treatment. The beneficial effects of treatment are, it slows the progression by around about 30 to 40 percent and you can actually work that out. That equates to a number of years of deferral of dialysis. So that's that's clearly a decision that many people would go down the path

Gavin Nimon: 22:12

So is this something you'd start at a young age, even before you've got symptoms of or even signs of polycystic disease? Is there any genetic test to start it off and then start this treatment?

Prof Stephen McDonald: 22:22

Sure so typically people with polycystic kidney disease we would often end up screening family members and then if you followed them for a year or two, that's when you would have that discussion, even in the absence of any symptoms. Most, the great majority, well over 90 percent of cases of polycystic kidney disease are among people with known families and there are a couple of reasons, often people end up having some form of abdominal imaging for whatever reason, tends to happen more often in women than men because of period related abdominal pains and so on and so you would often Have a diagnosis made that way, but often people do want to just find out, particularly when they get into their early to mid twenties and start thinking about their own families. At the moment I mentioned that there's a number of different genes that drive and there's within those, there's a number of different mutations that drive. Polycystic Kidney Disease and so that unfortunately is not currently available a single genetic test that I can Order for somebody who comes to see me to say have I got polycystic kidney disease? The so that the screening is very much based on imaging, on ultrasound, and the reliability, or in particular the specificity of that, because that's the key thing we're looking at here, how confidently can you exclude that you've inherited polycystic kidney disease, and unfortunately, because there's always a few people that It's not really until you're around about 30 years of age that you can be confident that a clean ultrasound or an ultrasound with the absence of cysts would mean that you're not going to develop polycystic kidney disease later in life.

Gavin Nimon: 24:32

Okay.

Prof Stephen McDonald: 24:33

The other scenario where that often becomes important is when people are thinking about donating kidneys. So by definition, often family members are often thinking about donating kidneys to other family members or relatives who may already have polycystic kidney disease.

Gavin Nimon: 24:47

Okay. What about the other issue of the vesico-ureteric reflux causing kidney damage. That's obviously a post renal type condition, but that can lead to chronic kidney disease as well. Is that still common or is that less of an issue nowadays with better detection?

Prof Stephen McDonald: 25:02

look, I think it's incidence is neither high or lower than it has been for some time. I think there've been a number of trials and the pediatricians over the years have tried various approaches to treatment of urinary tract infections and treatment of surgery. And More broadly though, that category is now tends to be called ca, KUT, congenital abnormalities of the kidney and the urinary tract. and that's an area where the early detection and the early treatment more broadly, not just specifically of vesico-ureteric, has made a difference., the other comment to make about that is that's an area where. The impact of genetics is really very substantial, as has now been demonstrated. There are strong genetic drivers for a number of those conditions. As an adult nephrologist, I guess I don't actually see or really get involved in the diagnosis of that. We do see people who have chronic kidney disease as they shift from the pediatric to the adult environment. But happily, from my perspective, that's something that my colleagues at the Children's Hospital tend to take care of.

Gavin Nimon: 26:00

And what sort of level of functional deterioration can you have in a kidney before you actually start getting abnormalities in the numbers? Does it deteriorate right at the end or is it a slow deterioration?

Prof Stephen McDonald: 26:10

So typically, so if typically we would talk about the estimated glomerular filtration rate, which is calculated using some standard formulas from somebody's serum creatinine, so if a normal EGFR 80 to 110 or so, people would often talk about EGFR as percent of normal kidney function, which is the shorthand. And Technically stage 3 kidney disease, which is the first one that's defined just on the basis of Blood tests is less than 60 really from 60 down to about 30 or so Which is stage 3. People wouldn't I wouldn't expect them to feel a lot if any in the way of symptoms and secondly, it's not going to have much of an effect on the other electrolytes, for example, nor would you expect, it would be unusual to see an anemia or other specific renal complications as you start getting down into stage 4 chronic kidney disease, so an EGFR of less than 30 That's very much where you start to see a lot of the other metabolic complications of kidney disease. So you start to see phosphates rise initially because your kidneys are not excreting phosphates. That leads to some hyperparathyroidism. Of renal anemia starts to come into play, and that's quite a complex area because there's a relative lack of erythropoietin reduction, but there are also changes in how we absorb iron in the setting of chronic kidney disease. And then there are some changes to vitamin D at. Activation and the development of a metabolic acidosis. So they're broadly speaking. That's the metabolic changes that you see with an EGFR from 30, 25 down to 20 and there's also the range in which you would often expect people to develop some form of symptoms. Many people would not but, those symptoms would typically be and Nonspecific lethargy and fatigue and so on. As people's kidney disease progresses and it gets down to that more severe phase, now we're talking EGFR is around about 15 or so, then that's where people would start to see more severe manifestation of those symptoms and depending on the type of kidney disease there of course can be other symptoms, classically fluid retention may well be an issue and so on. does raise the question about what happens next and where do you start and when do you start thinking about dialysis, kidney transplantation and all those sorts of options. And so typically that point around EGFRs of 15 to 20 would be where you would be, if somebody's having kidney disease that's slowly progressing or rapidly progressing, you would be having conversations around what are the treatment options in your situation? Is is dialysis something that's going to be appropriate and if so, what type of dialysis is kidney transplantation an option, bearing in mind that for people that have a, an available living donor then so called preemptive transplantation or transplant more or less at the time at which you would otherwise start dialysis is the ideal form of kidney replacement therapy. For And there are some people, quite a few people, particularly elderly people in whom dialysis really doesn't offer any particular benefits and in that group we'd be going down a path, a conservative path of supportive care but not necessarily providing dialysis.

Gavin Nimon: 29:23

You've touched upon the various treatment options then, so if we go through them you've obviously got dialysis the first option, or there's other medications you can use to help pre dialysis or is it purely just dialysis? And what about the old peritoneal dialysis? I presume that's not done anymore,

Prof Stephen McDonald: 29:38

No still very much so I guess nephrologists, like everybody we're pretty clever and we can do multiple things. So as you taking care of somebody with deteriorating kidney disease. There's at least three get back to your rule of threes. There's at least three lines of thinking and talking to, to patients that you're doing. One is making sure that you've got all of the various measures in place to slow the progression of kidney disease. So blood pressure control. Blood sugar control for people with diabetes and so on. The second is making sure that you have particularly in those more severe stages of kidney disease, detected and have treated the complications of kidney disease and a lot of those can be easily treated. So I mentioned the anemia that might involve some erythropoietin injections and so on and that's really important in terms of keeping people well and so on. Now, having said that, the third line of discussion is really one of them saying, okay, in an ideal world, you are well, your rate of progression is still slow, but if it's still progressing, then there's going to come a time at which you're. You will reach a stage of so called you do nothing, you're going to get sick of kidney failure and potentially even go on and die of kidney failure. So that's the situation in which dialysis and kidney transplantation become options. Dialysis doesn't make people walk differently. It doesn't make people smarter or faster. It just simply replaces the kidney function to stop you dying of kidney failure. There is very, one of the things that Australia contributed to nephrology is to. Provide the definitive trial that says, okay, there's no gain on starting dialysis before really the development of symptoms. There were some suggestions that starting at an EGFR of, 12 to 15 might prevent or might lead to reduced mortality and better outcomes. That's not the case. So typically dialysis would be started around an EGFR of 7 to 8 or so. Having said that you mentioned Peritoneal dialysis there are two main forms of dialysis hemodialysis and peritoneal dialysis from a nephrological perspective. They both do the job They both do it equally as well and so that the decision of one versus the other is really one of horses for courses for an individual patient Across Australia, depending on where you are, somewhere between a quarter and a third of people are doing peritoneal dialysis. There are some basic medical requirements, so for dialysis obviously involves having a catheter placed in your stomach and then running fluid in and out. Typically that's done overnight via an automated cycler. There are some situations, so for example if people have had a lot of abdominal surgery and a lot of adhesions where it's not technically going to be possible But for people going down that path, it is a really good treatment that allows you to Keep your flexibility of travel, of timing, it clearly does involve the placement of a peritoneal dialysis catheter, so that's a piece of surgery that we do in a month or two or three before starting dialysis. Similarly for people going down the path of hemodialysis. is best done using an arteriovenous fistula, which again is a small piece of surgery where we would connect up the artery to the vein, typically wrist or up in the cubital fossa in the elbow. That fish takes usually a good eight weeks or so for the blood flow to increase and for the vein to mature to a stage where we could then use that with needles to access for hemodialysis. So they're the technical preparations for dialysis. There's also a lot of talking about what dialysis means and particularly hemodialysis often does put some constraints around people's lives, around the timing of what they can do. The other element to treatment associated with dialysis, but also in those latter stages of chronic kidney diseases around diet, and making sure that people in fact maintain nutrition. People can often become a bit of anorexic and funnily enough their protein Intake can drop right off. It used to be taught the protein restriction was a good thing and that's not in fact the case. People have tried If you like therapeutic protein restriction and demonstrated that it makes no difference to the rate of progression of kidney disease but people do tend to Themselves restrict the amount of protein, but there are some very important areas of dietary advice particularly around phosphate and potassium And making sure that people don't run into problems with high potassium so the dialysis side of things. And along with that, we would also in, people look like they're going to be eligible for transplantation, we'd be talking to them about kidney transplantation from an early stage, particularly if there's a possibility of a living donor because that's something that you'd want to get onto sooner rather than later. Now having said all that, I made a comment earlier on that dialysis is not necessarily for everybody. And there's no question that firstly, dialysis puts a substantial imposition on people's quality of life. And particularly for older people or people with comorbidities. There are a number of complications. And so broadly speaking for people over about 80 especially if they've got comorbidities and even in the late seventies there's good evidence showing that if you if your baseline state of health, isn't very good that you don't end up, for example, spending more days independent at Home. You might live a few months longer, but that extra time is comprised of time going back and forth to hospitals. The other really powerful data comes from a number of areas, but particularly the UK and the US, showing that overall people's level of independence drops. And so if you are independent at home, then That's maybe a price that you and everybody prepared to take. But if you're already on the verge of a nursing home level of functional dependence, then that's going to change. And if you're already in a nursing home, then that's the new level of dependence is going to change. And so against that context the conservative care pathway that I outlined earlier on is actually also really important. And as part of that preparation, we would be. Having very honest conversations with patients long before they get to dialysis because the thing to avoid is having Pressured conversations at four o'clock on a Friday afternoon with everybody saying gosh, we've got to do something. We've got to do something Whereas it's a chronic disease and you're much better off having those conversations with the people while they're and also I guess for me the other really important piece of information to share with people in the part of those conversations, particularly older people in the family is getting around the perception that comes to us all from television that you've got kidney disease, whack, you can pop on the dialysis and that'll solve the whole problem. As I outlined, it's really important to understand what it does mean for people to go on dialysis. And also the data that suggests in Australia, like in Canada, if you look at the proportion of any given age, you start with kidney failure, you start dialysis first. Now there's a very steep change after about age of 75. So that if you look at people up to about 75, the great majority of people do start down a dialysis pathway. But once you get over 75, that really drops off. And so after the age of 80, the great majority of people don't start dialysis with kidney failure, and that's good medical practice. Okay, and the reason for that is there's really no advantage to people's quality or quantity of life for doing that and that's a really important discussion to have with people.

Gavin Nimon: 36:38

listener, the dialysis involves, what, three days a week coming in to sit at a machine for eight hours a day?

Prof Stephen McDonald: 36:44

Yeah, so it does typically would be three times a week. And a typical dialysis treatment is about four and a half to five hours. Duration of treatment, but there's a bit of time before and after that. So it does take up basically most of the day for people that are able to do home hemodialysis is a really good option in terms of helping fit that in around life because it does tend to dominate. The other factor that is very prevalent, particularly among the older people, is post dialysis fatigue, which is, as the name implies, fatigue that seems to happen to people for a number of dialysis. So most people would actually go home and have a nap for an hour or two after dialysis. So it really does tend to wipe out your whole day.

Gavin Nimon: 37:24

But a renal transplant too is not a walk in the park either, I believe. It's even, if you get a successful donor, I believe there's a few other medications you're going to need to remain on afterwards as well,

Prof Stephen McDonald: 37:33

yeah, absolutely. Sure, so firstly there's no question that for people that are eligible, that having a kidney transplant is a much better option than dialysis, there's better, people live longer and there's much better quality of life, but it's not going back to normal existence unless you happen to have an identical twin. And that's incredibly rare because in any other circumstances, there are going to be some genetic immunological differences that, and so that with that goes immunosuppressive or anti rejection therapy and that that is a a series of tablets, usually three different drugs taken multiple different times of day, which come with their own side effects. Kidney transplants are really successful now. Yeah. But they don't last indefinitely a typical deceased donor kidney transplant you would expect would have a graft survival, well over 10, getting out towards 15 years, and for a living donor, you would be looking, you would be hoping for getting them for 20 years, so That's great and that's wonderful. But if you are a 35 or a 40 or a 45-year-old, that's also not gonna be the rest of your life. So that we would so that we would treat kidney transplant as a transplantation, as a long-term treatment, but it's not a cure as such. The immunosuppressive drugs do come with a bunch of side effects. They bugger up blood pressure, they bugger up lipids, they put you at increased risk of cancers, particularly of skin cancers, and they put you at increased risk of infections. So with that is a whole variety of other them are preventive strategies. For example, people are on long term antibiotics to reduce the risk of pneumocystis infection or sometimes of CMV infection. There's a regarding malignancies, especially skin malignancy. And so there's a bunch of other things that come with that. So it's a long way from a trouble free existence.

Gavin Nimon: 39:23

And the surgery as it goes, it's fairly straightforward though. It's usually just an overnight stay in hospital or a couple of nights or is it a week or so?

Prof Stephen McDonald: 39:30

For a kidney transplant yeah. So it's as a physician, of course, I think it's really straightforward. It's a, it is major surgery. It is something that's done through a, a groin incision that, that's, that, that long. And when I talk to surgical colleagues and they say don't forget, you've actually got to anastomose an artery, a vein, and you've also got to get a a ureter plumbed into the bladder and you've got to get that all so sitting so that there's no kinks in the in the Arteries or veins or vessels that will obstruct It typically would take about four, four hours or so for having a kidney transplant from woe to go People would stay in hospital Around about four to five days usually after that so it's substantial surgery that's largely I think driven by the size of the incision and the placement of the incision There have been overseas early reports of robotic transplantation to try and address some of those issues. That's may will be the way of the future. The major surgical change in the last 25 years though has been on the donor side for living Kidney donors, whereas previously they had quite a large incision of an open nephrectomy. What has been done really now established practice for the last 20 years is laparoscopic donation. So people are now in and sometimes out of hospital, the afternoon after or. If you have your operation on Wednesday, home on Friday morning, that's dramatically shortened the recovery period of donors, which in itself has been a really good thing in terms of encouraging or facilitating more people to come through as donors. It's not totally laparoscopic, you've still got to get the whole kidney out, so there is a small incision in the hypochondrium, but it's an enormous advance and also the placement of that incision is well away from the muscles that you use when you're standing and walking. It does make a big difference. So it is major surgery.

Gavin Nimon: 41:21

And do they need anticoagulation afterwards as well to help keep things open

Prof Stephen McDonald: 41:24

Yeah. In the long term, no, in the short term we do both for kidney reasons and also for prophylaxis of DVTs for people who are on Heparin. of weeks after surgery. It is one of those operations that is associated with a particular high rate of pulmonary embolism. Unless there is a reason otherwise, we would be having people on initially Heparin and then low molecular weight Heparin injections for a period of time. The other factor in terms of the longer term care people is a lot of this group of patients also have vascular disease, so they'll be on aspirin for vascular indications anyway.

Gavin Nimon: 41:57

A couple of thoughts have come through as we've been talking is I see a lot young people eating a lot of protein. Would that be a effect for the kidneys long term?

Prof Stephen McDonald: 42:04

Look, in a healthy person, it all depends on how much because if you're having very high amounts of protein than that, and you do have underlying kidney disease, that will accelerate the decline. And one of the things that if people present with early stage chronic kidney disease, one of the things I do actually specifically ask people is, Are you taking protein supplements? Do you go to the gym? Do you go to the gym shop? And so there's that, that is going to be a factor if you have very high levels of protein. But like all of those things, it's a question of how, how much and how often. And protein shake occasionally is not going to do anybody any harm, of course not but very high levels of hyperfiltration and accelerate obsolescence of glomeruli.

Gavin Nimon: 42:46

And what about the other conditions where you get the older person who's got both cardiac disease, congestive cardiac failure and renal disease, which are quite a common scenario together. And you can't give enough fluid for the kidneys, but you can't give too much fluid for the heart. Obviously it's a very delicate balancing act. It's probably something you see a bit of, is it?

Prof Stephen McDonald: 43:05

It is something we see a lot of, and the jargon is Cardio Renal Syndrome, and the Europeans have actually tried to classify that into five different types but that balancing act at its core a clinical one, and The understanding the pathophysiology is some help but at the end of the day, I think you really have to be guided by symptoms. People need to be able to breathe and move around. There's no point having their kidney function a little bit better if you can't lie flat in bed and breathe at night. So it's quite common for us or for the cardiologists to, if you like, accept a degree of elevated serum creatinine or reduced EGFR due to the need to keep heart failure in particular, symptoms under control. It's one of those things that often is jointly managed, but interestingly, I'm sure the cardiologists look after or monitor a bunch of people's kidney function, and there's a bunch of people I look after who do have a cardiologist who I might need to touch base with from time to time, but juggle their symptoms and their diuretic dose. Having said that, it is one of those things that I think it's doesn't matter who does it. It's just a question of what actually is important is that somebody does it who knows the patient well and can make sure that you are monitoring them, both their kidney function and their heart function closely. And also that the patient. Knows how to look after themselves and in particular there are a couple of scenarios which tend to upset things. One is where people, for whatever reason, have a rapid deterioration in kidney function. And typically, classically, there might be the food poisoning or the diarrhea side of things. Or their cardiac function changes. Talking to people about routinely weighing themselves and keeping their fluid intake relatively constant is important.

Gavin Nimon: 44:54

Where do you think all this development is going? What's the way of the future? Is AI got a role to play? Is there any other new developments in in some of the biologic agents and things for the future?

Prof Stephen McDonald: 45:06

so we've talked about, ACE inhibitors and ARBs and SGLT2 inhibitors and there's finerenones just become available and there is a pipeline that we'd expect to see in the next 10 to 20 years of therapeutic agents that broadly speaking fall into the anti fibrotic category, but we'd There's a common pathway, regardless of whether you have diabetes or inflammatory kidney disease or of that gradual deterioration. And so one of my expectations is that we'll see more agents to slow that progression of kidney disease. Dialysis as a technology has been in evolution rather than revolution for a long time now. The Holy Grail, if you like, has been some form of wearable artificial kidney. And there are two models of that. One is having using The techniques of peritoneal dialysis and having a regeneration module using a sorbent to have a circulate a fixed volume of dialysate, but actually regenerate that. And the other approach is to use essentially hemodialysis machine, but again, a sorbent based technology. Both of those are evolving slowly, but the Achilles heel is having on, particularly for the vascular one, is having permanent vascular access somehow or other, be that a plastic tube or some other access and the infection issues associated with that. In terms of kidney transplantation, There are two areas to watch going forward in the years to come. Stem cells have been, actually been slowly getting there and they're not there ready yet. And sometimes people are a bit cynical saying they've been around forever. If you go and look at the the reports from lab scientists, they can now retrieve stem cells from somebody from your buccal mucosa, they can then prime them and get them to a stage where in a dish they can now form little organelles. So arrange themselves almost like a little glomerulus and a little tubule. So the technology that's now needs to be developed is really an engineering one about how do you get those cells into arrange themselves around a 3d scaffold and start to grow a kidney. So look, that's something that I don't think I'll see in my professional lifetime but it's clearly something that's going to be, a decade or two away, not a century or two away. And that will obviously revolutionize transplantation. If you need a kidney transplant, then we'll go away, go off and grow a kidney and away you go. And that would be, and that would also get around the issues of immunosuppression. Because if you're using something that's your own genetic makeup, and that's the, if you like, the holy grail, the the critical limitation now, the moment of course to transplantation is a lack of donor organs. And the issue of xenotransplantation or trans donor, using animals, in particular pigs as donors, has been around a long time and has been an area that's been stop started, stop start, and in the last year or so there have actually been a couple of instances where a group in the U. S. have actually got to a stage where they've now moved in. Done Xenotransplantation and got a functioning kidney now for up to a week or so and it's an interesting and really mind bending ethical area so this is a group in Alabama and they've demonstrated that they can get function for a number of days and so on. So that's early days, yet, but from an area that's now clearly come out of the lab. Decades of work into a lab about how to genetically modify a pig so that it's not rejected out of hand So there's clearly a substantial development trajectory there But that may end up being if you like the bridge to the long term stem cell technology And of course, there's an enormous amount of overlap in terms of the technologies in those two areas and the genetic modifications

Gavin Nimon: 48:46

it's truly amazing.'cause obviously stem cells can work. That's my whole job is an orthopedics. Bones do reform itself, it's the only structure in the body that can. And so that's a stem cell type of model. So it can work somewhere in the body, so it has to be elsewhere. So yeah, it'll be interesting to see.

Prof Stephen McDonald: 49:03

Oh yes, yeah, unfortunately kidneys can recover a lot after acute kidney injury. Tubules, kidneys can have zero function for days, a week and then they can start again and tubules can regrow but once you've got kidneys that have been damaged for longer than that, they don't recover.

Gavin Nimon: 49:17

Look, it's been brilliant hearing all about this hearing how it's all developed the actual process along the way. Fantastic hearing from you, Steven. Is there any thoughts to the gps or the medical students listening about what they should be focusing on as young doctors coming through the system?

. Prof Stephen McDonald: 49:33

Really, kidney disease Can be very complex, but it's not. It's actually very simple and in terms of the key messages One is being aware of that. Secondly, is it's a really easy thing to test for Blood test and the urine test and that urine dipstick or sending a urine off to the lab for an albumin creatinine ratio those are really easy things and really important things and a lot of those early detection will be people with some persistent albuminuria and some hypertension or something so that's the key thing together with an awareness that, rare things do happen and just if you have a doubt, pick up the phone and talk to one of us. We would always much rather spend five or 10 minutes sorting these out over the phone than drag somebody in and waste your time and waste my time in an hour of the patient's time sorting through something.

Gavin Nimon: 50:15

Look, really appreciate your time. Much appreciated, and wishing you all the best and thank you very much for giving up your valuable time to talk about this really important topic. Thank you.

Prof Stephen McDonald: 50:24

Thanks. Thanks, Gavin.

Gavin Nimon: 50:24

Thank you very much for listening to our podcast today. I'd like to remind you that the information provided is just general advice and may vary depending on the region in which you are practicing or being treated. If you have any concerns or questions about what we've discussed, you should seek advice from your general practitioner. I'd like to thank you very much for listening to our podcast and please subscribe to the podcast for the next episode. Until then, please stay safe.