Emerging Treatments and Preventative Care for CKD

Transcript

Dhiren Patel, PharmD: That’s a great segue into some of these newer and emerging treatment options. Historically, we’ve seen the efficacy and where RAS inhibition has made [its] way into kind of standard of care, but now it seems like we have more tests to even be able to detect some of this early stage, but then now we also have more options to treat it once you’ve diagnosed it. So maybe can you talk a little bit about how your practice has changed, as you’re looking at diabetic kidney disease and what options you’re utilizing for that?

Robert Busch, MD: So up until several years ago, your patient was on a RAS blocker, and you try to maximize the RAS blocker, control their blood pressure with other blood pressure drugs, and control their diabetes and avoid NSAIDs [nonsteroidal anti-inflammatory drugs], COX-2s [cyclooxygenase-2s], and dye studies and keep them well hydrated. Now we have drugs beyond RAS blockers that can benefit the kidneys. RAS blockers dilate the efferent arteriole, so [it] lowers the pressure within the glomerulus. SGLT2s [sodium-glucose cotransporter 2 proteins] by urinating out sugar, salt, and water—the kidney is constricting the afferent arteriole, so less blood in, more blood out, less pressure in the kidney. And SGLT2s with canagliflozin and dapagliflozin, and now, as of last week, empagliflozin, all have shown to benefit the kidneys and prevent end-stage renal disease. The nonsteroidal mineralocorticoid inhibitor finerenone [was investigated in] a study called the [FIDELIO-DKD] trial [NCT02540993], showing if you added finerenone to a RAS blocker with or without an SGLT2, you benefited the kidneys and lowered end-stage renal disease. And there are studies being done with the GLPs [glucagon-like peptides] that hopefully will show GLPs have the same benefit in a different fashion. So we may have 4 pillars of therapy. Currently, we have 3—RAS, SGLT2, finerenone—but GLP1 in the future, and who knows what else we’ll have to protect the kidneys.

Dhiren Patel, PharmD: So it seems like now, all of a sudden, we haven’t had anything for 20 years, and now, all of a sudden, we have a lot of options. Why do we still see some underutilization of these newer classes? When I say newer, they’re not necessarily newer, right? SGLT2s now have been around for quite some time, finerenone [as well]. But what do you think have been the drivers of some of this underutilization?

Robert Busch, MD: So some people think if you give a RAS blocker, even if it’s a low dose, the patient’s protected, I’m done. But it’s been shown the higher the dose of the RAS blocker, the more likelihood to avoid not only kidney disease but also heart disease. So you try to maximize the RAS. But that’s not enough, right? The RAS blockade with the RENAL trial [NCT00221013] showed you lowered end-stage kidney disease 16%, which means 84% still went on to kidney disease. So just like we do in cardiology and other fields, we look at residual risk. What is the residual risk, despite being on therapy, to progressing your kidney disease? So when the SGLT2s developed in the package insert, based on their studies, whether it’s CREDENCE [NCT02065791], or DAPA-CKD [NCT03036150], or EMPA-KIDNEY NCT03594110], showing that these drugs benefit kidney disease on top of the RAS blocker, now SGLT2s should be used. When they’ve done surveys, interestingly, people who have worse kidney disease are less likely to get an SGLT2. That’s the paradox of using these drugs, because they think, “Oh, the drug won’t work.” They were trained that if the GFR [glomerular filtration rate] is too low, you don’t get glycemic benefit, but you will get the renal benefit. So people tend not to use them when the kidney disease is there, because they don’t think they work as a glycemic beneficial drug, but it still will benefit the kidneys. And same as GLP1s. GLP1s could be used, no matter what the renal function is—the newer GLP1s, such as semaglutide and tirzepatide—but they tend not to be used as much when there’s kidney disease. Maybe there’s a fear of whatever [adverse] effects will happen, even though they can be used with kidney disease.

Transcript was AI-generated and edited for clarity.