What is the initial treatment approach for patients with Chronic Kidney Disease (CKD)?

Initial Treatment Approach for Chronic Kidney Disease

All patients with CKD should receive a comprehensive, multi-pronged treatment strategy centered on lifestyle modifications, blood pressure control with RAS inhibition, SGLT2 inhibitors, and statin therapy to reduce risks of kidney disease progression and cardiovascular disease. 1

Foundation: Lifestyle Modifications (Required for ALL Patients)

Every CKD patient must implement these core lifestyle changes as the foundation upon which all pharmacotherapy is built: 1

• Physical activity: 150 minutes per week of moderate-intensity exercise 2, 3
• Diet: Plant-based "Mediterranean-style" diet to reduce cardiovascular risk 1, 2
• Weight management: Achieve optimal body mass index 1, 2
• Smoking cessation: Complete abstinence from all tobacco products 1, 2
• Sodium restriction: Reduce dietary sodium intake 1
• Alcohol limitation: Restrict alcohol consumption 3

Consider referral to specialized providers (renal dietitians, physical therapists, smoking cessation programs) when patients struggle with adherence. 2

First-Line Pharmacotherapy

1. Blood Pressure Control

Target: Systolic BP <120 mmHg for most patients, though <140/90 mmHg is acceptable in elderly (>60 years). 1, 2

Initial agent: RAS inhibitor (ACE inhibitor or ARB) at maximum tolerated dose, particularly when albuminuria is present. 1, 4 This is non-negotiable for patients with hypertension and albuminuria. 1

Additional agents if needed: 1

• Dihydropyridine calcium channel blockers (CCBs)
• Thiazide-type diuretics
• All three classes are often required to achieve BP targets 1

Critical monitoring: After initiating RAS inhibitors, up to 30% increase in serum creatinine is acceptable and should NOT prompt discontinuation. 2 Monitor potassium and creatinine regularly. 1

2. SGLT2 Inhibitors (Regardless of Diabetes Status)

Initiate when eGFR ≥20 mL/min/1.73 m² and continue until dialysis or transplantation. 1, 2 These provide kidney and heart protection independent of glucose-lowering effects. 1

For patients with type 2 diabetes, combine with metformin (if eGFR ≥30 mL/min/1.73 m²). 1

3. Statin Therapy

For patients ≥50 years: Statin or statin/ezetimibe combination regardless of CKD stage. 1

For patients 18-49 years: Statin therapy if ANY of the following: 1

• Known coronary disease
• Diabetes mellitus
• Prior ischemic stroke
• 10-year cardiovascular risk >10%

Choose statin regimens to maximize absolute LDL cholesterol reduction. 1

Additional Risk-Based Therapies

For Patients with Type 2 Diabetes:

GLP-1 receptor agonists: Add if SGLT2 inhibitors and metformin are insufficient to meet glycemic targets or if unable to use these agents. 1

Non-steroidal mineralocorticoid receptor antagonist (finerenone): Add for patients with persistent albuminuria >30 mg/g (>3 mg/mmol) and normal potassium, indicating high residual risk. 1

Antiplatelet Therapy:

Low-dose aspirin: Recommended for secondary prevention in patients with established ischemic cardiovascular disease. 1 May be considered for primary prevention in high-risk patients. 1

Alternative P2Y12 inhibitors if aspirin intolerance. 1

Regular Monitoring Schedule

Reassess all risk factors every 3-6 months: 1

• Serum creatinine and eGFR
• Serum potassium
• Albuminuria (urine albumin-to-creatinine ratio)
• Blood pressure (preferably with 24-hour ambulatory monitoring) 2
• Lipid panel
• Glycemic control (if diabetic)

Critical Pitfalls to Avoid

Do NOT discontinue RAS inhibitors for creatinine increases up to 30% unless hyperkalemia develops. 2 This initial rise is expected and acceptable.

Avoid dual RAAS blockade (ACE inhibitor + ARB) due to increased risk of hyperkalemia and acute kidney injury. 1

Eliminate nephrotoxic medications, particularly NSAIDs, which accelerate kidney function decline. 2

Do NOT delay SGLT2 inhibitor initiation - these have proven benefits in slowing CKD progression and should be started early. 2, 5

Adjust all medication doses appropriately for kidney function to prevent toxicity. 2

Treatment Algorithm Summary

1. Immediate: Lifestyle counseling + RAS inhibitor (if hypertensive or albuminuric) + SGLT2 inhibitor + Statin (age-appropriate)
2. Add as needed: CCB and/or diuretic for BP control
3. For diabetes: Metformin + GLP-1 RA if needed for glycemic control
4. For persistent albuminuria in diabetes: Non-steroidal MRA (finerenone)
5. For established CVD: Low-dose aspirin
6. Monitor: Every 3-6 months with dose adjustments as needed

This approach prioritizes preventing cardiovascular events and slowing kidney disease progression, which are the primary drivers of morbidity and mortality in CKD. 1, 5