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

First-Line Treatment for Chronic Kidney Disease

For most patients with CKD, first-line treatment consists of SGLT2 inhibitors combined with comprehensive lifestyle modifications, blood pressure control targeting <120 mmHg systolic, and statin therapy, with RAS inhibitors (ACE inhibitors or ARBs) added at maximum tolerated doses specifically when hypertension and/or albuminuria are present. 1

Core First-Line Pharmacologic Therapies

SGLT2 Inhibitors as Universal First-Line Therapy

• SGLT2 inhibitors should be initiated in all patients with CKD and eGFR ≥20 mL/min/1.73 m² and continued until dialysis or transplantation 1
• For patients with type 2 diabetes and CKD with eGFR ≥30 mL/min/1.73 m², SGLT2 inhibitors are strongly recommended (Class 1A) as they substantially reduce risks for CKD progression and cardiovascular disease 1
• These agents provide kidney and heart protection independent of their glucose-lowering effects 1

Blood Pressure Management

• Target systolic blood pressure <120 mmHg for most patients with CKD 1, 2
• RAS inhibitors (ACE inhibitors or ARBs) at maximum tolerated doses are first-line therapy when hypertension is present, particularly if albuminuria exists 1, 2
• When albuminuria is absent, dihydropyridine calcium channel blockers or diuretics can be considered as alternatives 1
• Monitor serum creatinine and potassium within 2-4 weeks after initiating or increasing RAS inhibitor doses 2, 3
• Continue therapy unless serum creatinine rises by more than 30% within 4 weeks of initiation 2, 3

Lipid Management

• Moderate- or high-intensity statin therapy should be initiated in all patients with CKD and continued until dialysis or transplant 1
• Statin-based therapy is recommended for adults aged ≥50 years with eGFR <60 mL/min/1.73 m² 3

Essential Lifestyle Modifications

Dietary Interventions

• Advise patients to adopt diets with higher consumption of plant-based foods compared to animal-based foods 1, 2, 3
• Maintain protein intake at approximately 0.8 g/kg body weight/day 1, 2, 3
• Avoid high protein intake (>1.3 g/kg/day) as it accelerates kidney function decline 1, 2, 3
• Limit sodium intake to <2 g/day (or <5 g sodium chloride) 1

Physical Activity

• Recommend moderate-intensity physical activity for a cumulative duration of at least 150 minutes per week 1, 2
• Physical activity should be compatible with cardiovascular health, tolerance, and level of frailty 1

Tobacco and Weight Management

• Strongly encourage cessation of all tobacco products 1
• Achieve and maintain optimal body mass index through weight management 1

Additional First-Line Therapies for Specific Populations

For Patients with Type 2 Diabetes and CKD

• Metformin should be used as first-line therapy when eGFR ≥30 mL/min/1.73 m² 1
• SGLT2 inhibitors are strongly recommended (Class 1A) and should be combined with metformin 1
• GLP-1 receptor agonists are recommended as third-line therapy if glycemic targets are not achieved with metformin and SGLT2 inhibitors, or if those medications cannot be used 1

For Patients with Albuminuria

• ACE inhibitors or ARBs are strongly recommended (Class 1B) for patients with severely increased albuminuria (A3) without diabetes 2
• ACE inhibitors or ARBs are suggested (Class 2C) for patients with moderately increased albuminuria (A2) without diabetes 2
• Nonsteroidal mineralocorticoid receptor antagonists (finerenone) should be added if albuminuria persists ≥30 mg/g (≥3 mg/mmol) despite first-line therapy in patients with type 2 diabetes 1

Monitoring and Follow-Up

• Regular risk factor reassessment every 3-6 months 1, 2
• Monitor for complications including hyperkalemia, metabolic acidosis, hyperphosphatemia, vitamin D deficiency, secondary hyperparathyroidism, and anemia 2, 3

Critical Pitfalls to Avoid

• Never combine ACE inhibitors with ARBs as this increases risk of hyperkalemia and acute kidney injury without providing additional benefits 3
• Avoid NSAIDs as they worsen kidney function and interfere with antihypertensive medication effectiveness 3
• Do not restrict protein intake in patients who are cachexic, sarcopenic, or undernourished 1
• An expected creatinine increase of 10-30% after initiating RAS inhibitors is acceptable and does not require discontinuation 4