Q&A: The Pillared Approach and Reframing Goals of CKD Care, With Katherine Tuttle, MD

Chronic kidney disease affects an estimated 850 million people worldwide, yet awareness remains critically low among both patients and clinicians.

Survey data indicate that only approximately 20% of patients and healthcare professionals recognize CKD in an individual patient, and most diagnoses surface only after stage 4 disease prompts a referral to nephrology. This detection gap means that many patients never access the therapies now available to slow or stop nephron loss.¹

Over the past several years, a pillared approach to CKD management has taken hold across the field, drawing on strategies already proven in cardio-metabolic conditions such as heart failure. The framework encompasses renin-angiotensin-aldosterone system inhibition, SGLT-2 inhibitors, GLP-1 receptor agonists, and mineralocorticoid receptor antagonists, each targeting distinct but overlapping mechanisms including hemodynamic dysregulation, metabolic dysfunction, inflammation, and fibrosis.^1,2

Together, these therapies have redefined what preservation of kidney function can look like. The language of "watchful waiting" and inevitable progression is giving way to a clinical posture centered on kidney health preservation and, in some disease subtypes, remission.

Yet questions remain about sequencing, how to address the upstream etiology that the pillared approach does not directly treat, which patient populations carry the highest residual risk, and how emerging disease-modifying therapies for conditions such as IgA nephropathy should be integrated alongside established CKD regimens.^1,2

Katherine Tuttle, MD, professor of medicine and executive director for research at Providence Healthcare, spoke with HCPLive at the 10th Annual Heart in Diabetes meeting to share her perspective on optimizing CKD management through the pillared approach and beyond.

Q&A: The Pillared Approach and Reframing Goals of CKD Care, With Katherine Tuttle, MD

HCPLive: As we move beyond implementation and try to cascade that down toward optimized management, what's the next frontier in optimizing management of chronic kidney disease for the field?

Katherine Tuttle, MD: We now have delivered highly efficacious and safe therapies that save kidneys, hearts, and lives. The big lift now is increasing CKD awareness and detection to get to intervention, because we don't treat what we don't see or measure.

I think that is a huge effort that needs to happen globally — there may be different approaches depending on the region and how that may be accomplished — but the awareness is so low. We know from surveys of both patients and healthcare professionals that only about 20% of patients and healthcare professionals are aware of CKD in a person, and that's mostly in people with stage 4 disease by the time they're referred to nephrology.

So, I think our obligation now is really to get the message out.

HCPLive: With recent advances, have we shifted the goals of chronic kidney disease management to completely stoppingprogression of chronic kidney disease or are we still focused on slowing function loss?

Katherine Tuttle, MD: I have eliminated "CKD progression" from my lexicon. We now have such efficacious therapies that we should really be focusing on preservation of function and kidney health, and aspirationally, remission — especially for some forms of kidney disease.

For example, in the glomerular diseases, we have highly effective therapies that treat the inciting factors, like in IgA nephropathy, preventing production of abnormal IgA and the immune response to it, plus the CKD therapies that stop the vicious feedback cycle that historically led to CKD progression.

I say "led" because in the future it won't, because if we get it right and treat both the upstream inciting factor and the downstream progression factors, people should be able to maintain kidney function and kidney health for a lifetime. We need to completely reframe the conversation about what the goals of care are.

HCPLive: Where do you think the current approach to CKD management is falling short the most and what patient population still has the highest unmet need?

Katherine Tuttle, MD: One of the things we have neglected is cause — etiology — and it matters for the reasons I just described. We have highly effective therapies that deal with what we used to call progression, or nephron loss from final common pathways.

Those pathways are mostly metabolic, hemodynamic, fibrosis, and inflammation. Our pillared approach deals with progressive nephron loss: ACE inhibitors and ARBs are largely hemodynamic therapies; SGLT-2 inhibitors are largely hemodynamic with some metabolic benefits; and GLP-1 receptor agonists and finerenone are anti-inflammatory and anti-fibrotic.

That's all great — but if we haven't addressed the inciting factors, we can still drive progression through upstream mediators. That's why identifying cause is important. We know from biopsy studies, like the Kidney Precision Medicine Project, that even in people we have clinically diagnosed with diabetic kidney disease only, about half have good old-fashioned diabetic nephropathy. And these are protocol biopsies — not people who have some unusual form of kidney disease in the setting of diabetes where we're looking for something else.

About a quarter have diabetic nephropathy mixed with another disease, and these are largely glomerular diseases — IgA nephropathy was the most common. And then others have no diabetes-related kidney disease at all; they have something else entirely. So if we just treat them for diabetes, we've missed the boat. We need to pursue diagnosis, and in many cases that will include a kidney biopsy.

HCPLive: How would you encourage nephrologists to approach treatment sequencing as we move forward into an era that includes targeted therapies, such as with IgA nephropathy?

Katherine Tuttle, MD: With IgA nephropathy, there is a four-hit hypothesis: abnormal IgA production, antibody formation, formation of immune complexes, and complement activation. Understanding the biology was critical to targeting therapies.

Those therapies have been studied as individual treatments, so what we don't know yet is sequencing, timing, which one first, and combinations — that's a topic for future inquiry. But in the meantime, we should not have therapeutic inertia. Not all of these therapies are available everywhere, so use what you have. And this is where the practice and art of medicine comes in: look at the person in front of you and assess their totality of risks, because some of these drugs have side effects. Are they going to be able to tolerate this medicine? What might work best for them, considering their own priorities and preferences?

Here's the good news: we have choices.

It wasn't very many years ago that we were talking about fish oil and aspirin for IgA nephropathy — it seems so primitive now. Yes, there are new challenges, but they're a delight, because we have tools to work with. And it's not just IgA nephropathy. We're seeing amazing progress with lupus nephritis, membranous nephropathy, and focal segmental glomerulosclerosis — the most common forms of primary kidney disease outside of diabetes and hypertension.

We've got our common CKDs from diabetes and hypertension pretty well managed now with the four pillars, and there's more work to do. There's residual risk. But if we just got it right on awareness and detection and applied what we know now, we would see a significant improvement in survival, a reduction in major cardiovascular risks — which are the competing risks to kidney failure — and take so many people off the road to kidney failure.

People with diabetes who get CKD: 9 out of 10 will die on the road to kidney failure. They'll never make it to kidney failure. And of that surviving 10% who used to make it to kidney failure, that should be preventable too.

So, our goal should really be to prevent premature mortality and give treatments that save heart and kidney function. That's why our tagline now is "Save Kidneys, Hearts, and Lives." We have several highly effective therapies that can accomplish these goals, but we have to do the heavy lifting now — which is getting these treatments to the patients who can benefit.

Editor’s Note: This transcript was edited for grammar and clarity using artificial intelligence tools.

References:

1. Francis A, Harhay MN, Ong ACM, et al. Chronic kidney disease and the global public health agenda: an international consensus. Nat Rev Nephrol. 2024;20(7):473-485. doi:10.1038/s41581-024-00820-6

2. Chu CD, Chen MH, McCulloch CE, et al. Patient Awareness of CKD: A Systematic Review and Meta-analysis of Patient-Oriented Questions and Study Setting. Kidney Med. 2021;3(4):576-585.e1. Published 2021 Jun 1. doi:10.1016/j.xkme.2021.03.014