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 be treated with a comprehensive, multi-pronged strategy that includes lifestyle modifications as the foundation, SGLT2 inhibitors as first-line pharmacotherapy (regardless of diabetes status), RAS blockade for blood pressure control (especially with albuminuria), and statin therapy for cardiovascular protection. 1, 2

Foundation: Lifestyle Modifications

Every CKD patient requires aggressive lifestyle intervention before layering pharmacological therapies:

• Physical activity: Engage in moderate-intensity exercise for at least 150 minutes weekly to improve cardiovascular health and slow CKD progression 2
• Dietary approach: Adopt a plant-based "Mediterranean-style" diet to reduce cardiovascular risk and support kidney health 1, 2
• Weight management: Achieve optimal body mass index through structured weight loss programs 1, 2
• Smoking cessation: Complete cessation of all tobacco products is mandatory 1, 2
• Dietary sodium restriction: Reduce sodium intake, though population-level interventions may be needed for substantial reductions 1

First-Line Pharmacotherapy

SGLT2 Inhibitors (Cornerstone Therapy)

SGLT2 inhibitors should be initiated in all CKD patients when eGFR ≥20 ml/min per 1.73 m² and continued until dialysis or transplantation, regardless of diabetes status. 1, 2, 3

• This represents a paradigm shift—SGLT2 inhibitors are no longer just diabetes drugs but kidney-protective agents for all CKD patients 3
• Continue therapy as tolerated even as kidney function declines 1

Blood Pressure Control

Target systolic blood pressure <120 mmHg using RAS blockade as first-line therapy, particularly when albuminuria is present. 2, 4

• For patients with albuminuria and hypertension: Start with ACE inhibitor or ARB at maximum tolerated dose 1, 4
• For patients without albuminuria: Dihydropyridine calcium channel blockers or thiazide-type diuretics can be considered as alternatives 1
• Add-on therapy: Layer dihydropyridine calcium channel blockers and/or diuretics if needed to achieve blood pressure targets 1, 2
• Monitor blood pressure using 24-hour ambulatory devices for accurate assessment 2

Critical caveat: Accept up to 30% increase in serum creatinine after initiating RAS inhibitors—do not discontinue prematurely 2. Monitor eGFR and potassium closely, especially with dual RAAS blockade, which carries significant hyperkalemia and AKI risk 1

Cardiovascular Risk Reduction with Statins

For patients ≥50 years with eGFR <60 ml/min per 1.73 m²: Initiate statin or statin/ezetimibe combination 1

For patients ≥50 years with eGFR ≥60 ml/min per 1.73 m²: Initiate statin monotherapy 1

For patients 18-49 years: Consider statin therapy if any of the following are present: 1

• Known coronary disease (MI or revascularization)
• Diabetes mellitus
• Prior ischemic stroke
• Estimated 10-year cardiovascular risk >10%

Choose statin regimens that maximize absolute LDL cholesterol reduction to achieve largest treatment benefits 1

Additional Risk-Based Therapies

For Patients with Type 2 Diabetes

If SGLT2 inhibitors and metformin are insufficient to meet glycemic targets: Add GLP-1 receptor agonist 1, 2

• Metformin can be used when eGFR ≥30 ml/min per 1.73 m² 1

For patients with persistent albuminuria >30 mg/g despite first-line therapy: Add non-steroidal mineralocorticoid receptor antagonist (finerenone) to reduce residual risk of kidney disease progression and cardiovascular events 1, 2

Antiplatelet Therapy

For secondary prevention in patients with established ischemic cardiovascular disease: Prescribe low-dose aspirin 1, 2

• Consider P2Y12 inhibitors if aspirin intolerance exists 1
• For primary prevention, aspirin may be considered in patients with high atherosclerotic cardiovascular disease risk 1

Monitoring Strategy

Reassess all risk factors every 3-6 months, including: 1, 2

• Serum creatinine and eGFR
• Serum potassium (especially with RAS inhibitors or mineralocorticoid receptor antagonists)
• Albuminuria
• Blood pressure
• Lipid panel

Medication Safety

• Review all medications for appropriate dosing adjustments based on kidney function 2
• Avoid nephrotoxic agents, particularly NSAIDs, which can accelerate kidney function decline 2
• Monitor for drug interactions and adjust doses accordingly 2

Common Pitfalls to Avoid

• Do not delay SGLT2 inhibitor initiation—these agents have proven benefits in slowing CKD progression and should be started early 2, 3
• Do not stop RAS inhibitors for modest creatinine increases (up to 30% elevation is acceptable and expected) 2
• Do not ignore modifiable risk factors such as smoking, obesity, and sedentary lifestyle—these require active intervention 2
• Do not use dual RAAS blockade without extreme vigilance for hyperkalemia and AKI 1
• Do not use dihydropyridine calcium channel blockers as monotherapy in proteinuric CKD—always combine with RAS blocker 4