<v SPEAKER_1>Welcome to this RCGP podcast on chronic kidney disease.

<v SPEAKER_1>I'm Dr.

<v SPEAKER_1>Emma Nash, GP and RCGP eLearning Fellow.

<v SPEAKER_1>Today, I'll be talking to Dr.

<v SPEAKER_1>Jim Moore, GP with a special interest in cardiovascular medicine and immediate past President of the Primary Care Cardiovascular Society.

<v SPEAKER_1>Thank you for joining us today, Jim.

<v SPEAKER_2>Pleasure.

<v SPEAKER_1>Let's start at the beginning.

<v SPEAKER_1>What do we mean by chronic kidney disease?

<v SPEAKER_2>So I think it's quite useful, Emma, to pick one definition and to discuss that.

<v SPEAKER_2>So let's go with the kidney disease, improving global outcomes definition for CKD.

<v SPEAKER_2>So it describes CKD chronic kidney disease as abnormalities of kidney structure or function, presence for greater than three months and with implications for health.

<v SPEAKER_2>And the KDIGO definition requires one of two criteria documented or inferred for over three months.

<v SPEAKER_2>And that's either an eGFR of less than 60 mls per minute or some marker of kidney damage.

<v SPEAKER_2>And commonly that would be albuminuria.

<v SPEAKER_2>And in fact, interestingly, some people would describe in a definition of kidney damage, they would say it's mainly albuminuria and or decreased kidney function.

<v SPEAKER_2>So important is the presence of albumin in urine as a prognostic finding.

<v SPEAKER_2>And of course, this is something that you would check after three months, both the albumin concentration in urine and the glomerular filtration rate.

<v SPEAKER_2>So most people would suggest that a confirmed albumin creatinine ratio, an ACR of three milligrams per millimole or more as clinically important proteinuria.

<v SPEAKER_2>And most of us will be familiar from a glomerular filtration rate that an eGFR of less than 60 is deemed to be CKD.

<v SPEAKER_2>Where you have an eGFR less than 60 and it's not been seen previously, there's no indication in the notes of that or in any letters then, the suggestion from NICE would be that we repeat that test within two weeks to exclude acute kidney injury and then downstream, three months and beyond, repeat the eGFR again and repeat the ACR to confirm the finding of CKD.

<v SPEAKER_2>I'm going to stress the point about albuminuria because it's one of the things we really don't do as frequently as we should within primary care, but it can be the earliest indication of kidney damage and maybe presence before, there's been a significant change in eGFR.

<v SPEAKER_2>So a very good example of this is what we see in the earliest stages of diabetic kidney disease where albuminuria is present but where the eGFR is normal, and this is related to a process called hyperfiltration.

<v SPEAKER_2>So in fact, when you monitor renal function, the early diabetic renal disease actually see an improvement in eGFR, which can give false reassurance that things are okay.

<v SPEAKER_2>Albuminuria, there's a number of different reasons for that.

<v SPEAKER_2>The filtration unit within, or filtration units because there are many, many, many within a kidney is damaged, and the basement membrane within that filtration unit becomes leaky and allows albumin or protein to leak into the urine.

<v SPEAKER_2>CKD is classified and you can see this in NICE guidance according to both eGFR and the presence or absence of albuminuria.

<v SPEAKER_2>You can have abnormalities in either of these individually, or in both.

<v SPEAKER_2>So if you wish to familiarise yourself around the detail with classification, it's on the NICE website.

<v SPEAKER_2>We recommend that it's best to test for albuminuria in the early morning, although we know that can be a challenge for people.

<v SPEAKER_2>So it's often said when looking for ACRs that any urine sample is better than no urine sample.

<v SPEAKER_2>But the reason we do the early morning testing for albuminuria is to exclude orthostatic proteinuria.

<v SPEAKER_2>And that's where overnight there's no leak of albumin into the urine, but there is the presence of albumin in the urine throughout the daytime.

<v SPEAKER_2>True, orthostatic proteinuria has a good prognosis.

<v SPEAKER_1>So we all know about the relationship between diabetes and cardiovascular risk.

<v SPEAKER_1>How does the risk from chronic kidney disease compare?

<v SPEAKER_1>And how should we manage it?

<v SPEAKER_2>It's worth stating that the kidney vasculature is a lens into the body's cardiovascular health.

<v SPEAKER_2>And we know that CKD should be considered as one of the most important risk factors for cardiovascular disease.

<v SPEAKER_2>If we refer back to a paper by Foley back in 2005 that looked at incident event rates for various common cardiovascular diseases and people with either diabetes alone, CKD alone, or people who had both those conditions.

<v SPEAKER_2>And they were looking at cardiovascular disease outcomes such as those related to atherosclerosis, such as myocardial infarction or strokes related to cerebrovascular disease, the complications of PAD, peripheral arterial disease, heart failure.

<v SPEAKER_2>Or lastly, they also looked at cardiovascular death.

<v SPEAKER_2>The incidence of cardiovascular events in the CKD alone population were consistently and significantly greater than those in the diabetes alone population.

<v SPEAKER_2>And the combination of CKD and diabetes led to even worse outcomes, particularly with those with heart failure.

<v SPEAKER_2>We know that people with CKD are very much more likely to die from CVD when compared to dying from renal failure.

<v SPEAKER_2>I've seen a figure quoted of 20 times more likely to die of CVD.

<v SPEAKER_2>Though importantly, we know that if we can identify CKD early, it gives us an opportunity to assess and manage not only the kidney damage, but the associated risk factors and the comorbidities for CVD.

<v SPEAKER_2>When it comes to management, the key areas to address are hypertension.

<v SPEAKER_2>As we've just described, good blood pressure control is essential.

<v SPEAKER_2>We know with CKD and an ACR of under 70 milligrams per millimole, we'd aim for a blood pressure of 140 over 90 or below.

<v SPEAKER_2>But where we have CKD with a very significant albuminuria, that's 70 milligrams per millimoles or higher, we'd be aiming for a blood pressure of 130 over 80 or below.

<v SPEAKER_2>Not only is it important to address hypertension, but the other risk factors for CKD and CVD, such as those related to that pathophysiological process of atherosclerosis.

<v SPEAKER_2>It's no surprise that in the NICE guidance, given the risk of CVD, NICE recommend that we consider the use of statins in people with CKD, and more specifically, that we offer atorvastatin 20mg once daily for both primary prevention of CVD, but also in people who have established cardiovascular disease and CKD, the same dose.

<v SPEAKER_2>And that is quite an interesting recommendation, because many of you will be aware that in established cardiovascular disease, we would normally recommend 80 milligrams of atorvastatin once a day.

<v SPEAKER_2>Interestingly, the waters are somewhat muddied following the recent NICE publication related to CVD prevention.

<v SPEAKER_2>For a CVD risk assessment, that's in primary prevention, they recommend using the QRISC3 tool, which now includes CKD, that's stage 3, 4 or 5, as a risk factor.

<v SPEAKER_2>But certainly from my view and reflected in my practice, is that we do not rely on a QRISC assessment to guide us as to whether we should give statin therapy.

<v SPEAKER_2>My view is that anyone with CKD should be considered for statin lowering therapy.

<v SPEAKER_2>We can of course directly address CKD progression itself with a number of different therapeutic groups.

<v SPEAKER_2>So we've got RAS blockage inhibitors, angiotensin receptor blockers, we've got SGLT2 inhibitors, dapagliflozin and empagliflozin, and very recently the non-steroidal mineralocorticoid receptor antagonist finerenone.

<v SPEAKER_2>Lastly, and very importantly, let's not forget lifestyle, which can have a major influence over our CKD and CVD risk.

<v SPEAKER_2>Whether it be through exercise and diet influencing as an example, weight or obesity and its close link to blood pressure, lipid profile, insulin resistance, dysglycemia, these are all very important.

<v SPEAKER_2>So lifestyle can make a major contribution here to addressing those risks.

<v SPEAKER_2>And of course, let us not forget the importance of smoking and CVD risk.

<v SPEAKER_1>So there's plenty there that we're going to need to discuss with our patients.

<v SPEAKER_1>But the term chronic kidney disease can sound quite scary, especially when they see it coded in notes now they can access their records.

<v SPEAKER_1>How would you suggest we communicate it with patients?

<v SPEAKER_2>This is quite, I think, a challenging area, particularly with access to notes where patients may see this, though we have not had the opportunity to discuss this with them.

<v SPEAKER_2>I would suggest that in many cases, meeting the criteria for CKD is due in part just to a natural decline in kidney function related to age, something that's occurring going on in all of us.

<v SPEAKER_2>Only in a very small number of individuals would an end stage renal failure occur and where renal replacement therapy, that is dialysis or transplant, would be necessary.

<v SPEAKER_2>So when sharing this diagnosis, it's important to put it, I think, into that context.

<v SPEAKER_2>It's also important that when someone has CKD, again, we share with them that this gives us an opportunity to modify not only the risk that they have for chronic kidney disease, but also their cardiovascular disease risks.

<v SPEAKER_2>And I reassure people that with prompt and appropriate evidence-based therapies, we can significantly alter the long-term outcomes related to renal function and to the associated comorbidities.

<v SPEAKER_1>And so we all know that general practice is very skilled in managing all manner of chronic diseases, and the majority of chronic kidney disease is managed in general practice.

<v SPEAKER_1>But at what point should we be considering involving our specialist colleagues?

<v SPEAKER_2>So in my view, the majority of background CKD management can be effectively delivered in primary care.

<v SPEAKER_2>But I would refer people to the NICE CKD guidelines, which actually lists at what point or identifies the points of where we may seek the views of our specialist colleagues.

<v SPEAKER_2>So a sustained decrease in their eGFR of equal to or greater than 25 percent, and a change in eGFR category, which you can see the different categorisation, the classification within the NICE guidance.

<v SPEAKER_2>So a change in GFR category within a 12 month period, or a sustained decrease in eGFR of greater or equal to 15 mls per minute, again, is another reason to consider referral.

<v SPEAKER_2>If the ACR, the albuminuria, is equal to or in excess of 70 mg per mls, unless this is known to be related to diabetes and already appropriately treated, then that should give consideration to referral.

<v SPEAKER_2>An ACR of 30 mg per mls and the presence of haematuria should indicate seeking further advice.

<v SPEAKER_2>There is such a thing as the kidney failure risk equation, which provides us with an estimation of what downstream the likely need of renal replacement therapy is.

<v SPEAKER_2>So there is a 5-year risk calculated by what is called the 4-factor kidney failure risk equation.

<v SPEAKER_2>And if your 5-year risk of needing renal replacement therapy is in excess of 5%, then again, this would indicate consideration to referral.

<v SPEAKER_2>Where we have someone with CKD in hypertension, poorly controlled despite the use of 4 antihypertensives at therapeutic doses, then we should consider seeking advice.

<v SPEAKER_2>Though we know in the majority of hypertensives who are not managed to target, it's more likely that compliance is a problem.

<v SPEAKER_2>Where we suspect or have known rare genetic causes of CKD, either in the individual or a family history of kidney disease, a good example of that would be polycystic kidney disease, but there are other inherited kidney problems such as Alport syndrome or cystinosis.

<v SPEAKER_2>Again, where there's a clear family history there, then that would give consideration to seeking advice.

<v SPEAKER_2>People often talk about renal artery stenosis.

<v SPEAKER_2>The commonest reason for renal artery stenosis is indeed atherosclerosis.

<v SPEAKER_2>And therefore, if you see individuals who've got established vascular disease, particularly if they have a PAD, peripheral arterial disease or a more generalized vasculopathy, that raises the possibility of having suspected renal artery stenosis.

<v SPEAKER_2>Congenital renal artery stenosis is rare, and it's due to fibromuscular abnormality in blood vessels.

<v SPEAKER_2>Unless there's bilateral renal artery stenosis, then unilateral findings of renal artery stenosis, most likely related to atherosclerosis, will be managed by medication.

<v SPEAKER_1>So it's helpful to have a clear idea of when we might need to refer, and the NICE guidance is a good reference for this.

<v SPEAKER_1>Obviously, most patients remain in general practice though, so can you tell us about the most recent developments in the management of CKD that are relevant to us in primary care?

<v SPEAKER_2>There are a number of new therapies that are available for people with CKD, and many will be aware around the introduction in the last few years to the use of SGLT2 inhibitors.

<v SPEAKER_2>But it may be just useful to go back and just review the national recommendations around the use of RAS blockers, so ACEIs or ARBs in people with CKD.

<v SPEAKER_2>So what NICE suggests is that an individual with CKD but without diabetes, that if that individual has an ACR of 70 mg per mmol or more, that not only, as I mentioned previously, do we refer for a specialist, kidney specialist assessment, but we also offer an ARB or an ACE inhibitor at the same time.

<v SPEAKER_2>Where we have people with CKD and their ACR is above 30 but below 70, the recommendations are that we simply monitor these individuals, that's watching their albuminuria or watching their eGFR, and consider discussing with a nephrologist if the eGFR declines or the ACR increases.

<v SPEAKER_2>So moving on to the new, newer group of drugs now recommended around SGLT2 inhibitors.

<v SPEAKER_2>We know that this group of drugs will delay CKD progression, but in addition, they've been shown to reduce risks of AKI, acute kidney injury, cardiovascular disease, death and hospitalisation for heart failure.

<v SPEAKER_2>And of course, that evidence is both for people with type 2 diabetes and people who do not have diabetes.

<v SPEAKER_2>They're drugs that act in a variety of different ways within the kidney.

<v SPEAKER_2>They alter the way the glomerulus is perfused.

<v SPEAKER_2>And as a consequence, and this is quite important, when you introduce drugs like SGLT2 inhibitors, you may see a reduction initially in the glomerular filtration.

<v SPEAKER_2>We're not entirely sure how SGLT2 inhibitors work, but we know they alter glucose and sodium reabsorption through the tubules and they affect tubuloglomerular feedback.

<v SPEAKER_2>Studies have also shown that SGLT2 inhibitors may reduce their blood pressure.

<v SPEAKER_2>So if we look at the recommendations for SGLT2 inhibitors, there are global recommendations and there are individual recommendations for these drugs.

<v SPEAKER_2>If we look at the individual recommendations within the NICE technology appraisals, therefore with Dapagliflozin, it's seen as an add-on to optimized, particular emphasis around optimized standard of care, including the highest tolerated licensed dose of ACE inhibitors or ARBs and less contraindicated.

<v SPEAKER_2>And they will be or should be used where the EGFR is above 25 mls per minute at the start of treatment and have either type 2 diabetes or a urinary ACR above 2.6.

<v SPEAKER_2>For empagliflozin, similar-ish recommendations.

<v SPEAKER_2>Again, it's an add-on to optimized standard of care with RAS blockade but people should have an eGFR between 20 to less than 45 or 45 up to 90.

<v SPEAKER_2>And either an ACR of 22.6 and above or type 2 diabetes.

<v SPEAKER_2>Empagliflozin also has some evidence for benefit in CKD and diabetes, but has not been technology appraised.

<v SPEAKER_2>If you look at the global NICE recommendation around SGLT2 inhibitors, then it's suggested in CKD and diabetes, on max RAS blockade, then offer an SGLT2 inhibitor if the urinary ACR is 30 or above, and consider using an SGLT2 inhibitor if the urinary ACR is 330.

<v SPEAKER_2>It's also important to appreciate in diabetes that if the eGFR is 45 or less, then the resulting glycosuria, which is the central mechanism for glucose lowering when using an SGLT2 inhibitor, that's significantly reduced and therefore will not contribute to managing the hyperglycemia.

<v SPEAKER_2>It won't help with the diabetes management.

<v SPEAKER_2>Lastly, a very new drug which has come to market and has NICE technology appraisal is a non-steroidal MRA, a highly selective mineralocorticoid receptor antagonist called finerenone, which may be considered in addition to RAS blockade SGLT2 inhibition in CKD and in type 2 diabetes.

<v SPEAKER_1>So GPs are becoming more familiar with these medications initially because of diabetes.

<v SPEAKER_1>But can you give us a quick recap on things that we need to be aware of or counsel patients about with these drugs?

<v SPEAKER_2>So SGLT2 inhibitors, firstly, part one of the areas I work in is within heart failure and these are amongst the easiest group of drugs to use in heart failure.

<v SPEAKER_2>And I suspect also within CKD, particularly in the non-diabetes population.

<v SPEAKER_2>So where you do have someone with type 2 diabetes and you're introducing an SGLT2 inhibitor, you obviously have to be cognisant of what their current diabetes management looks like in terms of HbA1c.

<v SPEAKER_2>And you may, if you introduce an SGLT2 inhibitor with someone CKD and an eGFR above 45, you may have to consider whether you have to alter the other glucose-lowering medication.

<v SPEAKER_2>And that's particularly relevant to those who are either taking insulin or those who are on sulfonylureas.

<v SPEAKER_2>If you have someone with diabetes, CKD, and they have a history of diabetic ketoacidosis, then we would not prescribe or consider SGLT2 inhibitors.

<v SPEAKER_2>I've described the importance of knowing what eGFR is in terms of the likelihood of influencing the glucose metabolism.

<v SPEAKER_2>Genital candidiasis, basically thrush, will be more common in people who have diabetes because you'll see, and an SGLT2 inhibitor, because you see an increased excretion of glucose.

<v SPEAKER_2>So as a consequence, they're more likely to get thrush.

<v SPEAKER_2>Though in a non-diabetes population, it's something that you would not commonly see.

<v SPEAKER_2>And lastly, we wouldn't use these drugs in people with type 1 diabetes.

<v SPEAKER_2>When it comes to finerenone, the main considerations will be around hyperkalemia and the need to monitor their renal function, which is again clearly outlined in guidance.

<v SPEAKER_1>Fantastic.

<v SPEAKER_1>Thank you.

<v SPEAKER_1>I think that's all we've got time for today.

<v SPEAKER_1>So I'd like to say a really big thank you to Jim for joining us to discuss chronic kidney disease.

<v SPEAKER_1>Thank you for listening.

<v SPEAKER_1>And if you enjoyed this RCGP podcast, then please have a look at the eLearning website to find others on a variety of subjects.

<v SPEAKER_1>Goodbye.