A fine time for finerenone: another kidney drug that works

The For Kidneys Sake podcast series is brought to you by Imperial College Healthcare NHS Trust and North West London Integrated Care Board (NWL NHS)

Do we really need another kidney drug?

Many people still see finerenone as 'just another spironolactone ', but is that really the case? In this episode of For Kidney's Sake, Prof Jeremy Levy and Dr Andrew Frankel explore why finerenone is changing the management of diabetic kidney disease and where it fits alongside ACE inhibitors, ARBs and SGLT2 inhibitors.

The discussion covers the evidence behind finerenone, why patients remain at 'residual risk' despite current therapies, and how adding another treatment can further slow the progression of chronic kidney disease while reducing cardiovascular events. Jeremy and Andrew also share practical guidance on prescribing, monitoring potassium safely and overcoming the therapeutic inertia that can prevent patients from receiving effective treatments.

5 Key Takeaways

• Finerenone is not simply another spironolactone. Its selective mechanism and clinical trial evidence make it a distinct treatment for people with diabetic kidney disease.
• Many patients still have 'residual risk'. Even with ACE inhibitors, ARBs and SGLT2 inhibitors, ongoing albuminuria can signal continued kidney disease progression.
• Combination therapy matters. Adding finerenone to existing evidence-based treatments can further reduce the risk of kidney failure and cardiovascular events.
• Hyperkalaemia shouldn't be a barrier. With appropriate patient selection and routine monitoring, finerenone is straightforward to prescribe and generally well tolerated.
• Early optimisation is key. Identifying eligible patients during annual diabetes and CKD reviews gives clinicians the opportunity to protect kidney function before irreversible decline occurs.

Resource Links:
NICE GUIDELINES [NG203] chronic kidney disease: assessment and management Overview | Chronic kidney disease: assessment and management | Guidance | NICE

Northwest London CKD guidelines for primary care Chronic kidney disease (nwlondonicb.nhs.uk)

The purpose of this podcast is to inform and educate health care professionals working in the primary care and community setting. The content is evidence based and consistent with NICE guidelines and North West Guidelines available at the time of publication.

The content of this podcast does not constitute medical advice and it is not intended to function as a substitute for a healthcare practitioner’s judgement.

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Transcript

Jeremy

Hello, I'm Jeremy Levy, Consultant Nephrologist at Imperial NHS Trust.

Andrew 
And hello, I'm Andrew Frankel, consultant nephrologist and colleague of Jeremy's at Imperial College Healthcare NHS Trust. And welcome to another episode in our podcast series For Kidneys' Sake. So over the last few years we've talked about ACE inhibitors and more recently we've really pushed SGLT2 inhibitors as these drugs have the ability to transform the outlook for people with chronic kidney disease. Today we'd like to discuss another treatment that many GPs may have heard about but are almost certainly much less familiar with, which is Finerenone and the reason we've chosen this subject is because of the increasing evidence available indicating the benefit that Finerenone provides people with cardiac and kidney conditions over and above ACE and ARBS and SGLT2 inhibitor, particularly for people with diabetic kidney disease.

Jeremy
Andrew, it's true, many people are just going to think, well, this is just another mineralocorticoid receptor antagonist, aren't they? Is it really any different from those old drugs that we've had for, wait, 50 years or more? Spironolactone and the slightly more recent one, eplerenone. And you know, that's what I've fought for a long time, Andrew. Isn't this just an expensive spironolactone?

Andrew 
So that's a great place to start. So it of course Finerenone belongs to the same broad family, but it's different from spironolactone and a pellerinone in a number of ways. First of all, it is a non-steroidal mineralocorticoid receptor antagonist with much greater receptor selectivity for the aldosterone receptor, with virtually no effect on the other steroid receptors.

It has a number of pharmacokinetic differences from spironolactone and a eplerenone But the most important point is there is no real evidence for the benefit of spirolactone or a eplerenone in relation to kidney disease, but there most certainly is for Finerenone.

Jeremy 
Okay, so there's evidence trials that show it works. They're very different, as you say, Andrew, in terms of the chemistry. Does this mean that this new drug, Finerenone has fewer side effects? Because spironolactone, you you're trying to tell me no evidence, but also used to have really quite a wide range of side effects, breast tenderness and ganacomastia that we're all very familiar with.

Andrew 
Yes, and these drugs do have a number of hormonal effects. And I can be I can tell you I've been using finerenone now for a number of years and they have definitely fewer side effects and are very well tolerated. We will come back to talk about potassium and but the only only symptom that is reported really aside from that is that occasionally patients get a little nausea, but it's not something that I've seen in the real world.

Jeremy 
very very helpful. So it's not just a new version of spironolactone, this really is a different clinical proposition and it's not just replacing it, it's actually filling a gap in people with diabetic kidney disease who are at high risk of progression. So that's diabetic kidney disease even if your blood pressure is controlled to remain proteinuric. But Andrew, I'm going to challenge you a bit more, we've got ACE and ARBS and we've got SGLT2, so we're now giving people both these drugs that we know are effective at slowing progression of chronic kidney disease and reducing mortality. Do we really need this as a third agent on top of those two? And of course, patients will still be taking other drugs for their diabetes and lestatine and possibly aspirin. So on top of ACEs and SGLT2s, is that where Finerenone really is sitting?

Andrew 
I I actually think that's a really important challenge 'cause whenever I talk about these drugs and talk about C K D, this is something that I regularly get asked about in primary care and of course people talk about polypharmacy as a an issue. But I think this is a really important addition and we really need to understand that as we develop new drugs we are going to be increasingly in this position.

So take it from the perspective of both the individual patient and also from a population health perspective. What we really need to emphasise is that despite good blood pressure control and treatment with reninangitensin inhibitors and SGLT2 inhibitors, many patients will continue to lose kidney function year after year. We refer to this as residual risk. The clinical aim has to be to try and ensure.

That patients do not reach end stage kidney failure in their lifetime or to delay this as much as possible. And the way I explain this to patients is I imagine a train heading towards dialysis. Every effective treatment slows that train down. The ACE inhibitors slow it down. The SGLT2 inhibitors slow it further. And Finerenone slows it again.

And the hope is that by combining therapies in people with CKD, dialysis is pushed further and further into the future and for many patients beyond their natural lifespan, so that they never require kidney replacement therapy. And in addition, all these medicines that I've just described, the three of them, will also reduce cardiovascular morbidity and mortality.

Jeremy 
I like your analogy, Andrew, it's not one that I've used, but I may nick it from you because I think you're right. We've got to persuade people that and our colleagues in primary care about the value of adding more therapies. And a bit like you reflect, I was a bit skeptical and we were going to do this chat. Also looked at the evidence that you've always been telling me about for the last year. And I can see there are a really large number now of really high quality studies confirming that.

Finerenone added onto ACEs, ARBs, SGLT2 inhibitors really does slow your train down, reduce the progression of kidney disease and reduce major cardiovascular events- that's strokes and heart attacks and admissions with heart failure. Which is why, course, NICE very rapidly have now recommended finerenone to be added in people with diabetic kidney disease with what you labeled residual risk, particularly meaning...ongoing albuminuria, raised albumin creatinine ratios. And that's where the current sort of prescribing and licensing is sitting. Isn't that right? It's patients with type 2 diabetes, diabetic kidney disease, chronic kidney disease with residual proteinuria and where we should be using the drug. But do think we should be using it more than we are? So tell me when should GPs and colleague nephrologists actually be using finerenone

Andrew 
So the key for primary care is the annual diabetes review and annual diabetes CKD review. Essentially all patients with type 2 diabetes and CKD who are already on inhibitors of the renin anti-tensin system and an SGLT2 inhibitor or who are intolerant to either of these drugs should be considered for Finerenone if they have ongoing albuminuria.

And that's an ACR of more than three. I do need to highlight that in the UK Finerenone is only licensed between a GFR of 20 to 60. So we're not really able to start it in people with GFRs of 60 to 90, which is a real pity because I get so many questions about this through our virtual service and advice and guidance. My suspicion is that the drug would be just as effective at this point, but at present I think we have to keep to what NICE and the license recommends.

I would reiterate though that as you described there's a significant amount of new data being published, and this situation is likely to evolve rapidly over the year. I want to highlight one important study that I think is relevant to initiation called the confidence study. And this demonstrated that it's not just safe, it's actually advantageous in a person with diabetes and albuminuria to consider starting the Finerenone alongside rather than sequentially with SGLT2 inhibitors. It was safe and well tolerated. And that raises the possibility that instead of waiting months and introducing the therapies in sequence, we may begin to be able to use them earlier together, allowing patients to benefit sooner. I think you're going to see guidelines evolve as more of this evidence emerges.

Jeremy 
Really helpful but then we need to persuade both patients and colleagues that we're about the whether there are risks and the possible side effects or downsides of this. So go on tell me and colleagues, so why is venerian and different from others? What are the potential risks? And we raised it at the beginning. Hyperkalemia has been raised as an issue. This is an antagonist of the mineralcorticoid system. So yeah, in theory, hypokalemia is an issue. We're starting it with ACEs and ARBs. Go on, clear this up for me, Andrew.

Andrew 
Well i i there's no difference in hyperkalemia to some extent from the other MRAs and primary care has been using spironolactone for many, many years. it's actually an easier drug to prescribe. As you s I've said and we've described it has less side effects. Hyperkalemia certainly occurs particularly with people with more advanced CKD and that in my experience is the key. And you do need to do monitoring.

Most episodes though are mild, most episodes are predictable and manageable, and very few patients in the trials discontinue treatment. I think that's less than 1%. And with sensible potassium monitoring and mitigation, it's a safe drug. So if one indeed looks at the studies, patients who started finerenone with GFRs of 45 or greater.

There wasn't actually any increased instance of hyperkalemia between the finerenone treated group compared to the placebo group. But you have to remember a key point is we should only be starting Finerenone in people whose baseline potassium levels are five or lower.

Jeremy 
that's really really helpful Andrew. So I'm going to repeat what you just said. I think it just it just shows how easy it is to you. So if your GFR is over 45 which with diabetics and CKD is a very common issue and your potassium is lower than five actually this risk of hyperkalemia is essentially near non-existence. It's incredibly rare in that setting. Really really helpful. So just how should people start initiate finerenone and what should they in practice do?

Andrew
So at that diabetes CKD annual review, you've made the decision that this patient needs further optimisation. You start the Finerenone 10 milligrams as a starting dose. You check the potassium and creatinine in the same manner for all of the inhibitors of the renangotensin system around two to four weeks after starting. And thereafter the monitoring should only be at the same time interval of the underlying comorbidity.

So it shouldn't really increase the monitoring burden. Again I'm going to reiterate that we only should be starting pheneronome when the baseline potassium is five or lower, and that's the way to avoid problems.

Jeremy 
really helpful. Do you keep people on 10 milligrams or do you then double them up to 20?

Andrew 
Good question. I tend to use the twenty, particularly in the people with more preserved kidney function. I think once the GFR is below thirty, I find that the twenty often does result in potassium rising above five or five point five. but you should increase the Finerenone dose to twenty if their potassium remains below five and they still have albaminuria.

Jeremy 
Really, really helpful. So we really shouldn't be allowing sort of a possible fear of a problem to deny patients a treatment that really is effective at reducing proteinuria further and reducing progression. That's right isn't it?

Andrew 
Yeah, we shouldn't we we really need to g get the message across. We need to try and defeat therapeutic inertia so that patients don't miss out on therapies that could substantially and you know the data is this is substantial improvement, reduce their chance of future kidney and cardiovascular events. there's a real i d issue that we have across the country with the rules and regulations around starting finerenone and I think over the last few years I know in many places it's been a secondary care started drug. However I think that you're gonna see that change in the near future. It's likely to be a primary care drug, perhaps with secondary care advice. And as I've said, it's really not a difficult drug to use.

Jeremy 
really helpful. And then the last thing, how do we know if it's actually having an impact? Is this just going to be over the next two years watching GFRs stabilise? We had had a decline, but that's quite a long time. Is there anything else that we can look out for to

Andrew 
Yeah.

Jeremy 
try and give us or patients confidence that this extra drug really is having benefit?

Andrew 
Well, I want to just tell you in many of the patients I'm looking after now with diabetic kidney disease, we see this wonderful optimisation effect. You've got them on the RAS, the SGL2, you start the Finerenone, there is a little bit of a drop in GFR, and then you just see the GFR trend flatlining. And that's lovely to visually show the patients. Of course that happens over time. What I've found is that the marker

For your likely success is the albuminuria, you are likely to see a drop in albuminuria. But I really wouldn't stop the drug even if you haven't seen that change. So Jeremy, a new drug, well not so new, but one that's going to be used increasingly in primary care. What are the three takeaways you're going to give primary care?

Jeremy 
Yeah, it's my turn to do this because I've learnt more than you have on this episode. It's been really helpful. So you have persuaded me, I think, that finerenone is not just spironolactone in an expensive form. It is selective. It's got fewer side effects. There's much more evidence about it. We should be using it. So I am absolutely persuaded about finerenone. Diabetic kidney disease management is multi-layered and adding these extra treatments will slow down our train to end-stage kidney disease with high quality evidence that adding finerenone definitely slows progression and reduces risks of end-stage renal failure and cardiovascular disease. So I am persuaded about that as well. And that with appropriate monitoring, really this is a straightforward drug to use, that hyperkalemia is really a very low risk problem, low problem in the right settings and starting it in patients appropriately and should not stop us using it and this is straightforward to use. So yeah, all there my three takeaways that I think I'm persuaded that we really should be adding this on much more frequently than we are.

Andrew 
Beautifully put as always. Thanks very much, Jeremy. And we need to watch this space. I'm sure we're going to be coming back to Feneronone as I think it's going to have a wider place in the management of CKD in due course. So thank you very much for listening to us here on For Kidney's Sake.

Jeremy 
Thank you everybody. I hope this has been helpful and useful and all our previous episodes are available and if you were worried about hyperkalemia when it really occurs, not with finererone listen to our episode on hyperkalemia. Bye for now.