Experts' Perspectives: Top Story in Nephrology for 2023

Depending on who you ask, the field of nephrology is either on the cusp of or already fully engrossed in a renaissance period of sorts marked by historic advances in care and management practices, with the potential to alter the lives and prognosis of millions of patients now and in the future.

These claims are evidenced by the sheer level of interest in the field, not only from nephrologists but clinicians across multiple other specialties. At this year’s American Society of Nephrology Kidney Week, more than 12,000 attendees descended upon Philadelphia, Pennsylvania to gain perspective on the latest advances in the management of glomerular disease. At Kidney Week 2023, the late-breaking session brought forth multiple new trials with clinical implications, including PROTECT, DUPLEX, ALCHEMIST, ZENITH-CKD, and more.

Kidney Week not only serves as a platform for the latest news and updates in nephrology, but also represents the final flagship meeting in nephrology each year. To celebrate the advancements that have defined the past year in nephrology, the editorial team of HCPLive Nephrology asked interview guests from our Kidney Week 2023 coverage what they will remember as the most important news or theme to emerge from the past year.

Below we have highlighted answers from these guests, including Richard Lafayette, MD, founder and director of the Stanford Glomerular Disease Center, Rajiv Agarwal, MD, professor of medicine at the Indiana University School of Medicine, Michelle Rheault, MD, a pediatric nephrologist and professor of pediatrics at the University of Minnesota, Patrick Rossignol, MD, PhD, head of medical specialties service at Princess Grace Hospital and medical director at Monaco Private Haemodialysis Centre,Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester, Richard Johnson, MD, professor in the Division of Renal Diseases and Hypertension at the University of Colorado, Brendon Neuen, MBBS, MSc, nephrologist and senior research fellow at Royal North Shore Hospital and The George Institute for Global Health, Amit Garg, MD, PhD, professor at Schulich School of Medicine and Dentistry at Western University, Rajnish Mehrotra, MD, MS, head of the division of nephrology at the University of Washington, and Oliver Gross, MD, of the department of nephrology and rheumatology at the University of Göttingen Medical Center.

^{Top Row (L to R): Richard Lafayette, MD; Rajiv Agarwal, MD, MS; Michelle Rheault, MD; Patrick Rossignol, MD, PhD; Jonathan Barratt, MD}

<sup>Bottom Row (L to R): Richard Johnson, MD; Brendeon Neuen, MBBS; Amit Garg, MD; Rajnish Mehrotra, MD; Oliver Gross, MD

Credit: Stanford Health Care; X.com; University of Minnesota; Boehringer Ingelheim; IgA Nephropathy Foundation; University of Colorado; X.com; Kidney Foundation of Canada; University of Washington; Gottingen Medical Center</sup>

Lafayette: I think in terms of IgA nephropathy, the major theme will be that this is really the year where multiple drugs were shown to be efficacious in IGA nephropathy and that we really transformed the disease from one where it was really supported and intermittently treated with somewhat risky immunosuppression to one where patients could have targeted therapy that offer much better long-term outcomes.

Agarwal: I think a major advance in my mind is that we are making a concerted campaign to raise awareness of detection of kidney disease early and addressing it early. 10 years ago, we did the same thing for going from creatinine to eGFR and, when people started looking at that, we really made a difference. It took about 10 years to get there.

We're just getting started with recognition of albuminuria as a marker of kidney damage. I think it'll take 10 years to get there and, when we get there, we will find that these were really groundbreaking discoveries. It is one thing to find these discoveries, but it is another to implement it in broad populations. The implementation in broad populations would be through the message to the primary care physician that "We don't just measure the albuminuria and forget about it". That was true 5 years ago, when we didn't really have many treatments. Now, we know that if you have it, you can modify cardiovascular risk in this population. I think this would really change the behavior and the thinking of primary care physicians that Nephrology is not all doom and gloom, but that, if I measure the albuminuria, I can modify the cardiovascular and kidney risk. I think that's really the major message that I'm getting.

Rheault: I think that the big theme that I'm that I'm seeing is just new therapies for glomerular disease. For years and years all we really had steroids and that was about it. Now, we're really developing all of these specific targeted therapies for glomerular disease that are able to reduce protein in the urine and slow progression of the disease. So, I think that it's a huge benefit for patients.

Rossignol: So, for 2023, I think it is our new players. In other words, aldosterone synthase inhibitors, which can act as potential new key players both in resistant hypertension and in chronic kidney disease. This will be interesting to follow up in the next few years because these were initially phase two trials, but with promising results on resistant hypertension on the one hand and in CKD on the other, as presented [at Kidney Week 2023] during the late-breaking sessions (in reference to ZENITH-CKD). We know the limitations of steroidal mineral corticoid receptor antagonists; we know we have an asset in finerenone as a nonsteroidal critical receptor antagonist was also not straight or mineral corticoid receptor have been assessed in phase three trials. Now there is a new class, potentially with a new mode of action complementary to previous one. It will be really interesting to follow up these new trials, because this may provide our patients potentially an alternative, first pillar of therapeutics.

Barratt: Well, I'm completely biased on this, but I think what's going to stand out is we have a had a rare kidney disease, the commonest cause of glomerular disease in the world, that, for at least the last 50 years, has had no treatments. Now, we are seeing drugs coming through from phase 3 trials with exciting data. We're getting approvals, we're getting new drugs with eGFR data now, and what we're going to see at this meeting is more phase 3 data and we're going to see exciting phase 2 data of novel therapies. The drugs are coming thick and fast for this disease. It is a completely transformative age for rare kidney disease at the moment and for glomerular disease—where we've had very little to really shout about over the last 2 or 3 decades. So, I think when we look back, we'll realize there was a complete change in how we approach glomerular disease and the treatment options we're going to have available.

Johnson: I think that in the last few years, there's been really a number of new treatments for kidney disease that are really making an impact. We've really been in a stall for the last 10 to 15 years, where there's not been many new therapies that have had so much impact, but, recently, there are a lot of drugs coming to market that are really affecting the health and improving the health of the patient with kidney disease.

Neuen: We've seen at the meeting a lot of excitement and therapeutic developments in IGA nephropathy, a lot of new developments in drug classes like the endothelial receptor antagonists, which have now been studied in the PROTECT trial in IGA nephropathy and in the DUPLEX trial in FSGS as well as in proteinuric CKD, more generally, in the ZENITH-CKD trial.

I think [ZENITH-CKD] is a really interesting development, because that class of medical medication is one, we'verecognized as having risk of fluid retention, but, with SGLT2 inhibitors on board, perhaps they can mitigate that risk of fluid retention. That's exactly what we saw with low doses of zibotentan in the ZENITH-CKD trial. That offers a really attractive combination therapy that might reduce CKD progression further and is being studied in a big phase three trial that is planned. So that's a really interesting development. I think we're just seeing the start of what is going to be a really interesting couple of years, looking at how we use endothelin receptor antagonists more effectively and more safely.

The other thing to comment on is the huge amount of therapeutic development in IGA nephropathy targeting immunological mechanisms of action and targeting the immune system through things like targeting B cell-producing lymphocytes and even targeting the complement pathway. There are so many new therapeutic agents being evaluated in the IGA nephropathy space and it will be really interesting to see how that plays out. I think we're just at the cusp of what is going to be a very interesting time.

Garg: Well, one of the really amazing stories in nephrology is the drugs we have now prevent kidney failure. So, that's been a real boom of activity, with several agents now showing promise to do so. In my own clinical practice, I'm using these drugs and I think they really have shown that, through rigorous clinical trials and promising interventions, we can move the needle and prevent kidney failure. We have new tools in our toolbox to do so for the patients we serve. So, I'd say in the last decade, what stands out to me the most is really that set of discoveries.

Mehrotra: That's a significant question, and there are multiple ways to approach it. In our field, there have been notable developments in recent years, particularly concerning the availability of new treatments for diabetic kidney disease. Additionally, there are emerging treatments for rare diseases like IGA nephropathy, membranous nephropathy, and others that are currently under evaluation. A prominent theme in nephrology revolves around these emerging therapeutics. The next crucial step is making these treatments accessible to the patients who require them.

Another noteworthy development, particularly in the United States, is the implementation of substantial policy changes in healthcare delivery. These changes extend beyond dialysis care and encompass transplant care, with a focus on increasing access to home dialysis and transplant services. These nationwide policy changes are set to bring about transformative improvements in patient care.

Lastly, we are still in the process of emerging from the COVID-19 pandemic. This goes beyond concerns related to infection risks and the associated responses. The pandemic has fundamentally reshaped the healthcare landscape. Telehealth, for example, was once considered a niche service primarily accessible in rural areas due to government regulations. However, the pandemic has propelled telehealth into the mainstream, and it is expected to remain a widely available option. The entire healthcare delivery landscape has been profoundly influenced by the COVID-19 pandemic, and we have yet to fully understand its lasting effects.

Gross: I think the rise in precision medicine in nephrology is the most interesting topic. Right now, we apply nonspecific medication patients with any kind of CKD but within a few years, we will be able to apply this precision medicine approach that we have in other medicine areas.