What medication helps modify cardiovascular and renal risk in a patient with diabetes and Chronic Kidney Disease (CKD) with poorly controlled blood pressures?

From the Guidelines

For patients with diabetes and chronic kidney disease (CKD) who have poorly controlled blood pressure, ACE inhibitors or ARBs are recommended as first-line therapy to modify cardiovascular and renal risk. These medications should be started at standard doses, such as lisinopril 10-40mg daily or losartan 50-100mg daily, to provide additional blood pressure control and kidney protection 1. They work by reducing hyperfiltration and decreasing albuminuria, which helps preserve kidney function over time.

• Key benefits of ACE inhibitors or ARBs include:
  • Reduction in the risk of progression to end-stage renal disease (ESRD)
  • Decrease in cardiovascular events
  • Slowing of CKD progression
• A blood pressure level <130/80 mmHg is recommended to reduce CVD mortality and slow CKD progression among all people with diabetes 1.
• In addition to ACE inhibitors or ARBs, SGLT2 inhibitors (such as empagliflozin, dapagliflozin, or canagliflozin) may be considered for their cardiovascular and renal benefits, particularly in patients with high risk of CKD progression or established cardiovascular disease 1.
• However, the most recent and highest quality study 1 prioritizes ACE inhibitors or ARBs as the preferred first-line agents for blood pressure treatment among people with diabetes, hypertension, and CKD.

From the FDA Drug Label

The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial (CREDENCE) was a multinational, randomized, double-blind, placebo-controlled trial comparing canagliflozin with placebo in adult patients with type 2 diabetes mellitus, an eGFR ≥ 30 to < 90 mL/min/1. 73 m 2and albuminuria (urine albumin/creatinine > 300 to ≤ 5,000 mg/g) who were receiving standard of care including a maximum-tolerated, labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)

Canagliflozin 100 mg significantly reduced the risk of the primary composite endpoint based on a time-to-event analysis [HR: 0.70; 95% CI: 0.59,0.82; p<0. 0001]

The primary composite endpoint in the CREDENCE trial was the time to first occurrence of ESKD (defined as an eGFR < 15 mL/min/1. 73 m 2, initiation of chronic dialysis or renal transplant), doubling of serum creatinine, and renal or CV death.

The medication that helps to modify cardiovascular and renal risk in a patient with diabetes and Chronic Kidney Disease (CKD) with poorly controlled blood pressures is canagliflozin.

• Key benefits of canagliflozin include:
  • Reduced risk of cardiovascular death
  • Reduced risk of hospitalization for heart failure
  • Reduced risk of end-stage kidney disease (ESKD)
  • Reduced risk of doubling of serum creatinine 2

From the Research

Medications for Modifying Cardiovascular and Renal Risk

To modify cardiovascular and renal risk in patients with diabetes and Chronic Kidney Disease (CKD) who have poorly controlled blood pressures, several medication classes have been studied. The key medications include:

• Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors: These have shown potential in preventing kidney and cardiovascular outcomes in people with CKD and diabetes 3. SGLT2 inhibitors decrease the risk of all-cause death, cardiovascular death, and kidney failure, and probably decrease major cardiovascular events while incurring less hypoglycaemia compared to placebo in people with CKD and diabetes.
• Angiotensin II receptor blockers (ARBs): ARBs are effective in both preventing renal damage and reducing progression toward end-stage renal failure in type 2 diabetic patients 4. They also reduce hospitalizations for heart failure and are considered first-choice drugs in secondary and tertiary prevention of diabetic nephropathy.
• Angiotensin-converting enzyme inhibitors (ACE-I): ACE inhibitors effectively reduce systemic vascular resistance and have renoprotective effects in patients with diabetic and non-diabetic renal disease 5. However, their use must be carefully managed, especially in patients with heart failure, diabetes mellitus, and/or chronic renal failure, due to the risk of acute renal failure.

Specific Medications and Their Effects

Some specific medications within these classes have been studied for their effects on patients with diabetes and CKD:

• Empagliflozin: This SGLT2 inhibitor has been shown to control blood glucose levels and slow the progression of renal injury in both hypertensive type 1 and type 2 diabetic rats, especially when given in combination with lisinopril to lower blood pressure 6.
• Canagliflozin: The CREDENCE trial demonstrated that canagliflozin significantly reduced the risk of the primary composite outcome of doubling of serum creatinine, end-stage kidney disease, or renal or cardiovascular death compared with placebo in patients with T2DM and CKD 7.

Considerations for Treatment

When selecting a medication to modify cardiovascular and renal risk in patients with diabetes and CKD, it is essential to consider the individual patient's profile, including the presence of hypertension, the stage of CKD, and the presence of other cardiovascular risk factors. The choice of medication should be based on the evidence of its effectiveness in reducing the risk of kidney failure, cardiovascular events, and mortality, as well as its safety profile.