What is the first-line treatment for Chronic Kidney Disease (CKD)?

First-Line Treatment for Chronic Kidney Disease (CKD)

Renin-angiotensin system inhibitors (ACE inhibitors or ARBs) are the first-line treatment for most patients with chronic kidney disease, especially those with albuminuria, as they slow CKD progression and provide cardiovascular protection. 1, 2

Comprehensive Treatment Approach

The management of CKD requires a holistic approach targeting multiple risk factors:

Blood Pressure Control

• ACE inhibitors or ARBs should be first-line therapy for hypertension when albuminuria is present, administered at maximum tolerated doses 1, 2
• Target blood pressure should be <120 mm Hg systolic for most patients with CKD 1
• Dihydropyridine calcium channel blockers and/or diuretics can be added if needed to achieve BP targets 1
• For Black patients with CKD, initial therapy should include a thiazide-type diuretic or calcium channel blocker, either alone or in combination with a RAS blocker 1, 2

Albuminuria Management

• ACE inhibitors or ARBs are strongly recommended (Class 1B) for patients with severely increased albuminuria (A3) without diabetes 1, 2
• ACE inhibitors or ARBs are suggested (Class 2C) for patients with moderately increased albuminuria (A2) without diabetes 1, 2
• ACE inhibitors or ARBs are strongly recommended (Class 1B) for patients with moderately to severely increased albuminuria (A2 and A3) with diabetes 1, 2

Medication Monitoring

• Monitor serum creatinine and potassium within 2-4 weeks after initiation or dose increase of ACE inhibitors or ARBs 1, 3
• Continue therapy unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase 1, 3
• Avoid any combination of ACE inhibitor, ARB, and direct renin inhibitor as this increases adverse effects without additional benefit 1, 2

Additional First-Line Therapies Based on CKD Etiology

For Diabetic CKD

• SGLT2 inhibitors are recommended for patients with eGFR ≥20 mL/min/1.73 m² and type 2 diabetes, as they slow CKD progression and reduce heart failure risk 1
• GLP-1 receptor agonists are suggested for cardiovascular risk reduction 1

For Non-Diabetic CKD

• Optimize blood pressure control with RAS inhibitors as the cornerstone of therapy 1, 2
• Consider adding mineralocorticoid receptor antagonists in resistant hypertension 1

Lifestyle Modifications

• Advise patients to adopt healthy and diverse diets with higher consumption of plant-based foods compared to animal-based foods 1
• Suggest maintaining a protein intake of 0.8 g/kg body weight/day in adults with CKD G3-G5 1
• Avoid high protein intake (>1.3 g/kg/day) in adults with CKD at risk of progression 1
• Encourage moderate-intensity physical activity for at least 150 minutes per week, or to a level compatible with cardiovascular and physical tolerance 1
• Advise patients to stop using tobacco products 1

Monitoring and Follow-up

• Regular risk factor reassessment every 3-6 months 1
• Monitor for complications of CKD such as hyperkalemia, metabolic acidosis, hyperphosphatemia, vitamin D deficiency, secondary hyperparathyroidism, and anemia 1, 4
• Adjust medication dosages as needed based on kidney function 1, 4

Common Pitfalls and Caveats

• A temporary reduction in GFR may occur shortly after initiation of RAS inhibitors; this is generally hemodynamic and not indicative of kidney injury unless persistent 3
• Inadequate dosing of diuretics can result in fluid retention, while excessive doses may lead to volume contraction, increasing the risk of hypotension and renal insufficiency 2
• Avoid nephrotoxic medications such as NSAIDs in patients with CKD 4
• Do not restrict protein in patients who are metabolically unstable, cachexic, sarcopenic, or undernourished 1

By implementing this comprehensive approach to CKD management with RAS inhibitors as the cornerstone of therapy, clinicians can effectively slow disease progression and reduce the risk of cardiovascular complications in patients with chronic kidney disease.