New ASN Project Focuses on Saving Kidneys, Hearts, and Lives With Early Intervention, New Therapies, and Multidisciplinary Care

CKM syndrome

Workshop Cochair Katherine Tuttle, MD, FASN, said that mechanistic research has led to the recognition of cardiovascular-kidney-metabolic (CKM) syndrome. She explained that dysfunctional adiposity contributes to well-known risk factors for both heart and kidney diseases, such as hypertension, diabetes, and atherosclerosis, and creates a state of chronic inflammation that can exacerbate both heart and kidney diseases. “The kidney is very important in terms of accelerating multiple paths of cardiovascular disease,” she said. “Cardiovascular disease also increases the risk of losing kidney function and having adverse kidney failure outcomes should you survive…. They are interconnected, have shared origins, and shared risk factors.”

The American Heart Association's (AHA's) Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory, published in October 2023, highlighted the situation's urgency (1). The advisory coined the term “CKM syndrome” and issued a rallying cry to break down specialty silos and foster interdisciplinary collaboration to boost prevention, diagnosis, and care for CKM syndrome. As many as 90% of US adults have CKM syndrome across stages 1 to 4. Notably, more than half of them are at stage 2 or higher, inclusive of chronic kidney disease from both metabolic and nonmetabolic causes (2).

“Complicating the burden of these interconnected conditions is fragmented patient care,” said Janani Rangaswami, MD, cochair of the Scientific Advisory Group that wrote the AHA Cardiovascular-Kidney-Metabolic Health advisory. Individuals with lower levels of education, lower incomes, food insecurity, and public insurance are at greatest risk. “We know very well that not only are minoritized and underserved communities at higher risk for CKM interconnected conditions, but they are also less likely to be interfaced with appropriate guideline-directed therapies that can be life, heart, and kidney saving,” said Rangaswami, who is also chief of nephrology at the Washington, DC, VA Medical Center and professor of medicine at The George Washington University.

Time as nephrons

Those delays and barriers to diagnosis and care can be costly for patients who progressively lose kidney function and face multiorgan complications including kidney failure. “Cardiologists think of time as myocytes,” said workshop Cochair Adeera Levin, MD, FASN. “We don't think of time as nephrons. We wait [until the estimated glomerular filtration rate changes after a 50% loss of kidney function] to do something.”

The workshop aimed to change that approach and develop a roadmap for kidney-preserving care through early identification, preventive care, and utilization of a growing arsenal of medications that prevent kidney and cardiovascular complications, as well as death. “The good news is, we now have treatments that work across CKM syndrome mechanisms,” Tuttle said.

Clinicians have long used renin-angiotensin system inhibitors in the form of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to lower kidney and cardiovascular risks. New classes of medications have emerged that when used with these renin-angiotensin system inhibitors, can preserve kidney and heart health:

• Sodium-glucose cotransporter-2 inhibitor trials have demonstrated that this class of drugs reduces relative risks of major kidney outcomes by nearly 40% with concurrent benefits on reducing risks of heart failure events by 23% and cardiovascular death by 14% (3).

• A nonsteroidal mineralocorticoid receptor antagonist, finerenone, also meaningfully reduced relative risks of major kidney and heart failure events by 15% to 23% (4).

• A glucagon-like peptide-1 receptor agonist, semaglutide, reduced relative risks of major kidney outcomes by 24%, along with reductions in major adverse cardiovascular events by 18% and all-cause death by 20% (5).

“The new therapies give us an opportunity to break out of the small, comfortable, often dialysis-dominated nephrology bubble,” said ASN President Prabir Roy-Chaudhury, MD, PhD, FASN. “It gives us the opportunity to play in a much larger playing field—a playing field that prioritizes education and awareness, and early screening, diagnosis, and treatment; that focuses on cardiovascular health in people with CKD; and which aims to bring precision medicine into the kidney world, so that we can get the right kidney care to the right patients at the right time.”

There is also growing evidence that combining these drugs may further improve patient outcomes and increase the potential for care personalization, Tuttle explained. However, challenges remain in translating these therapies into practice. “We now have the opportunity to save kidneys, hearts, and lives,” Tuttle said. “Unfortunately, the majority of people with chronic kidney disease are unaware they even have the disease. How do we find and treat people who do not know they’re about to go off a cliff?”

Nephrology 2.0

ASN's Saving Kidneys, Hearts, and Lives initiative is working to reboot the role of nephrologists in delivering holistic care for people with CKM syndrome, identify and address systems-level barriers, and promote the implementation of new therapies. The initiative is working in concert with AHA's CKM initiative.

AHA's Cardiovascular-Kidney-Metabolic Health advisory laid out a multidisciplinary framework to overcome the challenges of identifying people with CKM and delivering more effective care at a population level. AHA is also developing 150 CKM Centers of Excellence in 15 regions across the United States to test some of the advisory's proposed care models. Many models emphasize bolstering the ability to proactively address CKM syndrome early in the primary care setting and facilitating more collaboration across specialties, including endocrinology, cardiology, and nephrology. “We truly have to move from siloed care to holistic care, and importantly, health achieved on the kidney side translates into health achieved on the cardiovascular side and the other way around,” Rangaswami said. “It is truly a partnership, and it truly is multidisciplinary.”

Among some of the key challenges to implementing more holistic care models identified at the ASN Saving Kidneys, Hearts, and Lives workshop were the limited nephrology workforce, the high cost of kidney- and life-saving medications, limitations in existing payment models, and the need to improve nutrition, physical activity levels, and the food system in the United States.

“The elephant in the room is payment,” Levin said. “There are ways that we have been reimbursed for nephrology around the world that perhaps have made us a bit more complacent than we should be. What we want to do in this workshop is figure out nephrology as we want it to be academically, clinically, [and] from a policy perspective.”

Roy-Chaudhury also highlighted the need to ensure that the rollout of new therapies does not exacerbate underlying disparities in access and outcomes. “The challenge is that we have to ensure that these new therapies reduce disparities in care as opposed to increasing them,” Roy-Chaudhury said. “In order to do this, we have to deliver the benefits of integrated cardio-kidney-metabolic care to people from regions with a [resource]-poor socioeconomic status, in inner city zones, rural areas, and border areas. If done right, the maximum impact of these therapies could be felt in vulnerable populations in parts of the world where there is limited access to specialized heart and kidney care.”

Participants also identified many opportunities to overcome barriers to CKM care. They emphasized the role of nephrologists in helping to educate primary care clinicians and other specialists on kidney-saving care and the effectiveness of new therapies and working with them in a consulting role. Participants outlined the potential to use electronic health records to help drive early identification and improved care across specialties. Attendees also envisioned creating a preventive nephrology specialty, CKM-focused fellowships across specialties, and inpatient and outpatient CKM health clinics or services. Levin proposed embedding nephrologists in each of AHA's CKM Centers of Excellence. Many also saw the new models of care as a good way to help recruit talented young people to the field.

“By demonstrating the value and excitement that nephrology and nephrologists now bring to health care systems as a whole, the new therapies could also help to attract young physicians into nephrology and change our specialty for the better,” Roy-Chaudhury said.

The workshop leaders are compiling and refining the workshop's recommendations into a report that will be published later this year. “There's a huge gap, and nephrologists are prepared to fill it,” Tuttle said. “We have the right skills to do it.”