Javed Butler, MD, MPH, MBA

Javed Butler, MD, MBA
Credit: BAIM Institute

Albuminuria, measured as the urine albumin-to-creatinine ratio (UACR), is drawing renewed attention in cardiology as a marker that sits at the intersection of 

It rises before the glomerular filtration rate declines, making it an early signal of chronic kidney disease, and it also reflects systemic vascular endothelial dysfunction. Together, those properties position UACR as both an indirect cardiovascular risk factor, through chronic kidney disease, and a direct marker of vascular disease.

The clinical case for measuring UACR in patients with or at risk for 

 parallels how cardiology absorbed lipids and blood pressure into routine practice. The therapies prescribed for early chronic kidney disease, including MRAs, SGLT2 inhibitors, GLP-1 receptor agonists, and ACE inhibitors, lower UACR and reduce the risk of developing heart failure. That overlap is an argument for folding UACR into routine risk assessment now, even before guideline-directed targets are established.

A more difficult question for cardiology is whether therapy should be titrated to a UACR goal.  In the most recent 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome, the organizations endorse both eGFR and UACR testing for characterizing chronic kidney disease and guiding treatment decisions. The nephrology community has adopted a target of a 30% reduction in UACR, but those trials have not been conducted in cardiology. Because there is no physiologic floor for albuminuria, unlike cholesterol, an open question remains whether a 30% reduction is sufficient or whether clinicians should drive UACR as low as possible. Many patients retain persistent albuminuria despite standard combination therapy.

, Javed Butler, MD, MPH, MBA, president of the Baylor Scott & White Research Institute and a heart failure trialist, discussed whether albuminuria warrants a conceptual shift in heart failure risk assessment, when to act on an elevated UACR, and whether it could become a therapeutic monitoring target in future trials.

Q&A: Javed Butler, MD, MBA, on the Evolving Role of Albuminuria 

HCPLive: Does the emerging evidence justify a conceptual shift in how we approach heart failure and albuminuria measurement in these patients? And if so, do you agree this should be included in routine risk assessment in heart failure?

 The challenge that always comes up is risk factor versus risk marker. We have a lot of risk factors in cardiology, so how do we decide which tests to add? Historically, remember that at one point cardiologists had nothing to do with lipids. It was an endocrine disease until we found that lipids were associated with cardiovascular outcomes, and that lipid modulation was associated with improved outcomes, and now it is bread-and-butter cardiology. Hypertension used to be a nephrology disease, and now you obviously cannot go to a cardiologist's office and not get your blood pressure checked.

So if you look at the data with UACR, the reason it modulates cardiovascular risk is, one, that it is an earlier marker of chronic kidney disease, even before the GFR goes down; and two, that it is a marker of systemic vascular endothelial dysfunction. Hence it is a risk factor for cardiovascular disease indirectly, through CKD, and directly, as a marker of vascular disease. In my opinion, at least, the data are strong enough that when UACR goes up and you start giving the therapies you would give to patients with early CKD, all of those therapies reduce the risk of developing heart failure. For that reason alone, cardiology should do it now.

What if you already have heart failure and you are going to give heart failure therapies? Do you still need to do it? Now we are not talking about the risk going up, but about whether therapy should be targeted to UACR. You give somebody standard therapy and you measure the UACR, but it is still high. Should you then give even higher doses or add more medication? That part of the equation we have not solved just yet. But in terms of identifying high-risk patients and early targeting of comprehensive therapy, I think the data are pretty much there that UACR is a good marker, and I think the cardiology community will, hopefully, be embracing it.

HCPLive: When we talk about albuminuria, do you think the heart failure framework should begin treating it as early as possible? Or, in the absence of a guideline-directed approach, is this more of a fundamental limitation?

Let's break it down into a few component pieces. If you do not have heart failure, you are in general cardiology practice, and you are completely asymptomatic and otherwise doing well, you should check your hemoglobin A1C; if it is elevated, you need to be treated for diabetes. You should measure cholesterol; if it is elevated, you should be treated for dyslipidemia. I think you should develop the same mindset that you should check the UACR, and if it is elevated, you have CKD, and it needs to be treated with appropriate therapy to reduce cardiovascular risk. That is one bucket, about prevention.

The second bucket is the heart failure patient. Even if you adjust for other risk factors, if the UACR is substantially elevated, then close follow-up and aggressive management are important.

But the third part, which you are specifically asking about, is probably the most important question: whether, as with lipids, we should titrate therapy to a target. With lipids, we have the LDL, we start therapy, but we do not stop there; we titrate therapy to get the lipid to a certain level. Should we be titrating therapy to get UACR to a certain level? There is a lot of interest in it. In the nephrology community, they have set a target of a 30% reduction in UACR. We have not done those trials in cardiology just yet.

HCPLive: If albuminuria is both predictive and modifiable, do you foresee it becoming a core therapeutic monitoring target in future heart failure trials? And if so, why or why not?

Here is my best prediction. The nephrology community right now is a little bit divided over whether everybody should get all the therapies, or whether, if somebody responds very favorably to UACR reduction with, say, two medicines, you really need the third or the fourth. In the cardiology community, we have a slightly different orientation right now, in that pretty much everybody believes in combination therapy. The combination therapy we give to patients includes MRA, SGLT2 inhibitor, aldosterone synthase inhibitor (possibly coming down the pike), GLP-1 receptor agonist (possibly coming down the pike), and ACE inhibitors, and all of these therapies reduce UACR. So if you go with the target of a 30% reduction, I think with standard therapy you will probably find that most patients get there anyway, and that this becomes a moot point.

The question that comes up is that, unlike cholesterol, where a certain degree of cholesterol is needed for us to live, UACR is different. For cholesterol, the right number is not zero; it is quite low, but not zero. For UACR, there is no right number. You should not be leaking protein at all. So should we be satisfied with a 30% reduction in UACR, or should we really try to drive it as far down as possible? That science has not been done. I can bet you that even on standard therapy, there are a lot of patients who have a substantial reduction but still have persistent albuminuria, and what to do about that is maybe something we should work on for the next 10 years.

This transcript has been edited for grammar and clarity using artificial intelligence tools. 


Butler J, Jamil A, Cherney DZI, Jafar TH, Testani JM, Khan MS. Albuminuria and heart failure. 

. Published online June 12, 2026. doi:10.1093/eurheartj/ehag426 

Writing Committee Members, Ndumele CE, Rodriguez F, et al. 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. 

. Published online June 9, 2026. doi:10.1161/CIR.0000000000001453

Articles

Urine albumin-to-creatinine ratio (UACR) is re-emerging as an actionable cardio–renal biomarker that rises before eGFR decline and reflects systemic endothelial dysfunction. These features link albuminuria to heart failure risk both indirectly via early CKD and directly as vascular disease biology. Broad cardiometabolic therapies—MRAs, SGLT2 inhibitors, ACE inhibitors, and emerging GLP-1 RAs/aldosterone synthase inhibitors—reduce UACR and lower incident HF risk, supporting routine incorporation into risk assessment. Whether to titrate therapy to UACR targets remains unresolved.

Butler explains why the urine albumin-to-creatinine ratio belongs in routine heart failure risk assessment and where the open questions remain.

The Value of Albuminuria in Heart Failure Risk Assessment, with Javed Butler, MD, MBA

Javed Butler, MD, MBA, discusses how aldosterone synthase inhibition could shift treatment across heart failure, CKD, and resistant hypertension.

Javed Butler, MD, MBA, on Aldosterone & Aldosterone Synthase Inhibitors in Cardiology

Aldosterone is drawing renewed scientific attention as a treatment target across 

. A new generation of aldosterone synthase inhibitors aims to lower aldosterone production directly, rather than blocking its receptor.

, Javed Butler, MD, MBA, president of the Baylor Scott & White Research Institute, examined where this approach fits in cardiorenal care. He weighed the evidence behind aldosterone synthase inhibition and its potential role in guideline-directed medical therapy for heart failure.

Recapping a session he led at the meeting, Butler emphasized how earlier aldosterone modulation data came largely from heart failure with reduced ejection fraction, along with post-myocardial infarction trials in reduced ejection fraction and heart failure. Noting evidence in chronic kidney disease and in prevention lagged, and findings in heart failure with preserved ejection fraction were contested.

Butler highlighted the unresolved question remains whether the aldosterone hypothesis itself is flawed or whether current receptor-targeted therapies leave meaningful residual benefit unharnessed. Lowering aldosterone levels directly through synthase inhibition offers a way to test the second possibility.

When asked on choosing between mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, Butler highlighted this debate remains unsettled until further trial data becomes available. He called attention to earlier MRA trials enrolling few patients on SGLT2 inhibitors or GLP-1 receptor agonists, whereas the synthase inhibitor trials use active comparators in which every participant receives an SGLT2 inhibitor.

ClinicalTrials.Gov. A Phase IIb Study of AZD5462 in Patients With Chronic Heart Failure (LUMINARA). Clinicaltrials.gov. Published February 18, 2026. Accessed June 21, 2026. https://clinicaltrials.gov/study/NCT06299826 

Videos

The Role of Aldosterone & Aldosterone Synthase Inhibitors in Cardiology, with Javed Butler, MD, MBA

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Ultimately, addressing systemic barriers is essential for translating clinical advances into real-world benefit. The panel agreed that equity in care delivery must remain a central goal as HFpEF management continues to evolve.

The discussion concludes with strategies to overcome access barriers and ensure equitable implementation of novel HFpEF therapies.

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They emphasized simplifying care through patient education, digital reminders, and coordinated follow-up. Addressing cost and access issues is equally important to ensuring long-term persistence with therapy.

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