Blog Post
January 12th, 2025
CKD and Cardiovascular Risk: The Importance of Integrated Clinical Trials
Chronic kidney disease (CKD) and cardiovascular disease (CVD) are closely linked, yet clinical trials often treat them as separate conditions. Research shows that CKD patients are more likely to die from cardiovascular events than progress to end-stage renal disease (ESRD). Despite this, many cardiology trials exclude CKD patients, while nephrology trials fail to adequately assess cardiovascular outcomes.
To develop more effective, patient-centered therapies, clinical trials must integrate both renal and cardiovascular endpoints. This article explores why CKD and cardiovascular risk must be studied together, the gaps in current research, and how integrated clinical trials can lead to better patient outcomes and regulatory success.
1. The CKD-CVD Connection: Why It Matters
🚧 Cardiology Trials Exclude CKD Patients – Many large cardiovascular outcome trials (CVOTs) exclude patients with reduced kidney function due to concerns over drug clearance and nephrotoxicity.
🚧 Nephrology Trials Focus on Renal Outcomes – Many CKD studies prioritize eGFR decline and proteinuria over CVD risk reduction, missing a key opportunity for dual-benefit therapies.
🚧 Regulatory Barriers to Approval – The FDA and EMA often require separate approvals for nephrology and cardiology indications, delaying drug availability for patients who need treatments addressing both risks.
💡 Key Insight: Clinical trials must be designed to evaluate both kidney and heart health simultaneously to create more effective, multi-targeted therapies.
2. Gaps in Current Clinical Research
CKD is a major risk factor for cardiovascular disease due to shared pathophysiological mechanisms such as:
🔹 Endothelial Dysfunction & Atherosclerosis – Impaired kidney function leads to chronic inflammation, oxidative stress, and arterial calcification, increasing the risk of heart attacks and strokes.
🔹 Hypertension & Left Ventricular Hypertrophy (LVH) – Poor kidney function raises blood pressure, causing cardiac remodeling and heart failure.
🔹 Fluid Overload & Electrolyte Imbalances – CKD disrupts sodium, potassium, and calcium homeostasis, increasing the risk of arrhythmias and sudden cardiac death.
💡 Key Insight: Cardiovascular events are the leading cause of death in CKD patients, yet most trials focus solely on slowing kidney decline rather than preventing CVD deaths.
3. The Case for Integrated CKD-CVD Trials
💊 1. SGLT2 Inhibitors: A Breakthrough in Dual-Outcome Research
- Dapagliflozin (DAPA-CKD, DAPA-HF) & Empagliflozin (EMPA-KIDNEY, EMPEROR-Preserved) have demonstrated both renal and cardiovascular protection, reducing heart failure hospitalizations and slowing CKD progression.
- These trials changed treatment guidelines and led to expanded drug indications for both nephrology and cardiology patients.
💊 2. Finerenone: A New Era in Cardiovascular-Kidney Protection
- The FIGARO-DKD and FIDELIO-DKD trials demonstrated that non-steroidal mineralocorticoid receptor antagonists (MRAs) can reduce renal decline and major cardiovascular events in CKD patients with diabetes.
- These findings highlight the need for dual-focused trial endpoints rather than separate studies for each condition.
💊 3. The Need for More CKD Patients in Heart Failure Trials
- Many heart failure trials do not include CKD patients with reduced eGFR (<30 mL/min/1.73 m²), even though this population has the highest CVD risk.
- Future trials must proactively include CKD patients to ensure better therapeutic strategies.
💡 Key Insight: Sponsors should prioritize integrated CKD-CVD trials to develop multi-indication therapies that address both cardiovascular and renal risks.
4. How Integrated Trials Benefit Sponsors & CROs
🔹 Broader Drug Labeling & Market Expansion – Demonstrating both kidney and cardiovascular benefits can lead to broader regulatory approvals and increased market potential.
🔹 More Representative Real-World Data – CKD patients are frequently excluded from CVOTs, leading to less applicable real-world evidence. Integrated trials ensure better clinical translation.
🔹 Improved Trial Efficiency & Cost Savings – Conducting one well-designed integrated trial is more efficient than running separate CKD and CVD studies, reducing redundancy and costs.
Final Thoughts
CKD and cardiovascular disease are inseparable, yet clinical research often treats them as distinct conditions. Sponsors and CROs must prioritize integrated CKD-CVD trials to develop more effective, dual-indication therapies that reduce cardiovascular mortality and slow kidney disease progression.
✅ Better patient outcomes – Addressing both CKD and CVD risks leads to lower mortality and hospitalization rates.
✅ Regulatory advantages – Integrated endpoints may accelerate drug approvals and broaden indications.
✅ Stronger real-world impact – Trials that reflect real-world CKD-CVD patient populations create more applicable treatment guidelines.