Kidney disease patients now have access to more effective medications than ever before, but doctors are unsure how to use them together safely and effectively. The National Kidney Foundation recently convened a major scientific workshop to tackle this challenge, bringing together specialists from nephrology, cardiology, endocrinology, and primary care to develop practical guidance on combination therapy for chronic kidney disease (CKD).

About 1 in 7 adults in the United States has CKD, and many of these patients also struggle with related conditions like diabetes, heart disease, obesity, or heart failure. Together, these interconnected conditions are known as cardiovascular-kidney-metabolic (CKM) syndrome. The good news is that modern medicine now offers multiple drug classes proven to slow kidney disease progression and protect heart health. The challenge is figuring out which medications should be started first, whether they should be given all at once or gradually, and how to coordinate care when patients see multiple specialists.

What Are the "Four Pillars" of Kidney Disease Treatment?

Recent clinical trials have demonstrated that four major medication classes can independently reduce kidney disease progression, cardiovascular events, and death risk. When combined strategically, these therapies may provide even greater benefits. A cross-trial analysis found that combining all four approaches reduced kidney disease progression by 58 percent compared with conventional care, compared with 37 percent, 23 percent, or 14 percent when adding just one medication class.

The four pillars include:

• RAS Blockade: Medications that block the renin-angiotensin-aldosterone system, a hormone pathway that affects kidney function and blood pressure
• SGLT2 Inhibitors: Drugs that help the kidneys remove excess glucose through urine, reducing strain on kidney tissue
• GLP-1 Receptor Agonists: Medications originally developed for diabetes that also protect kidney and heart health by reducing inflammation and improving metabolic function
• Nonsteroidal Mineralocorticoid Receptor Antagonists (nsMRAs): A newer class of drugs that target hormonal pathways contributing to kidney disease progression

Why Are Doctors Struggling to Use These Medications Together?

While each of these medications has proven benefits, translating this evidence into everyday practice remains challenging. Clinicians face difficult practical questions that current guidelines don't fully address. Should all four medications be started immediately, or should they be introduced gradually over time? The answer depends on each patient's kidney function, blood pressure, side effects, medication costs, and personal preferences.

The problem becomes even more complex when patients receive care from multiple specialists. Without coordinated communication, treatment recommendations may become fragmented or even conflicting, leading to therapeutic inertia, patient confusion, and missed opportunities for risk reduction.

"We have more tools than ever before to protect kidney and heart health, but now the challenge is figuring out how to use them together in a way that makes sense for each individual," said Dr. Sankar Navaneethan, workshop leader.

Dr. Sankar Navaneethan, Workshop Leader

How Can Healthcare Teams Improve Kidney Disease Care?

The National Kidney Foundation workshop identified several key strategies to improve how combination therapy is delivered in real-world settings:

• Interdisciplinary Collaboration: Nephrology, cardiology, endocrinology, primary care, and pharmacy specialists must communicate regularly and align treatment recommendations to avoid conflicting guidance
• Personalized Treatment Sequencing: Healthcare teams should develop individualized medication plans based on each patient's kidney function, cardiovascular risk, metabolic status, and personal preferences rather than applying a one-size-fits-all approach
• Quality Measurement and Accountability: Healthcare systems need standardized metrics to assess whether patients are receiving high-quality CKM care, identify gaps in treatment, and ensure timely screening and follow-up
• Workflow Integration: Successful implementation depends on workflow design, referral coordination, medication access, patient education, and shared decision-making between providers and patients
• Risk Stratification Tools: Existing calculators can estimate outcomes like progression to kidney failure, but they don't always accurately predict risk at the individual patient level; more precise and equitable tools are needed

Dr. Erin Michos, another workshop leader, emphasized the importance of teamwork. "No single field owns CKM care," she stated. "The only way we improve outcomes is by working together to develop guidance that reflects real-world complexity and centers the patient experience." She added that "the best intervention is prevention, and effective team-based care improves patient outcomes".

What Research Questions Still Need Answers?

Workshop participants identified several critical gaps in current knowledge that future research must address. These include determining which specific treatment combinations work best for different patient populations, establishing optimal timing for when therapies should be initiated, and developing practical strategies to make these complex medication regimens easier to use in everyday clinical practice. Researchers also need to understand how to promote long-term adherence to these therapies through pharmacist-led interventions, implementation of sick day rules, and remote monitoring programs.

The National Kidney Foundation is now synthesizing the workshop discussions, feedback, and recommendations into a comprehensive report that will inform future clinical guidance, educational programs, quality improvement efforts, and research priorities. As evidence supporting combination therapy continues to evolve, this guidance will help clinicians move from isolated disease management to integrated, patient-centered approaches that improve kidney health, cardiovascular outcomes, and overall quality of life.