What are the recommended first-line medications for a patient with chronic kidney disease (CKD)?

First-Line Medications for Chronic Kidney Disease

For patients with chronic kidney disease, ACE inhibitors or ARBs at maximum tolerated doses are the first-line antihypertensive medications, particularly when albuminuria is present, with SGLT2 inhibitors as essential first-line therapy for diabetic CKD patients with eGFR ≥20 mL/min/1.73 m². 1, 2

Primary Pharmacologic Approach

ACE Inhibitors or ARBs (First-Line for Hypertension/Albuminuria)

• Initiate ACE inhibitor OR ARB (never both) as first-line therapy for CKD patients with hypertension and albuminuria, titrating to maximum tolerated doses 1, 2
• For patients with severely increased albuminuria (A3) without diabetes, ACE inhibitors or ARBs receive a strong recommendation (Class 1B) 2
• For moderately increased albuminuria (A2) without diabetes, ACE inhibitors or ARBs are suggested (Class 2C) 2
• These agents reduce proteinuria, slow GFR decline, and provide cardiovascular protection through mechanisms beyond blood pressure reduction alone 1, 3

Critical monitoring requirements:

• Check serum creatinine and potassium within 2-4 weeks after initiation or dose increase 2
• Continue therapy unless creatinine rises >30% within 4 weeks of starting treatment 2
• An increase of 10-20% in creatinine is acceptable and does not require discontinuation 4

SGLT2 Inhibitors (First-Line for Diabetic CKD)

• For type 2 diabetes with CKD and eGFR ≥20 mL/min/1.73 m², SGLT2 inhibitors are recommended as first-line therapy alongside metformin or when metformin cannot be used 1, 2
• SGLT2 inhibitors reduce CKD progression risk by 39-40%, cardiovascular events, and hypoglycemia risk 1
• These agents work through direct renal effects: reducing tubular glucose reabsorption, intraglomerular pressure, albuminuria, and slowing GFR loss independent of glycemic control 1
• Continue SGLT2 inhibitors until dialysis or transplant 1

Metformin (First-Line for Diabetic CKD with Preserved Function)

• Metformin remains first-line glucose-lowering therapy for type 2 diabetes with CKD when eGFR ≥45 mL/min/1.73 m² 1
• Do not initiate metformin if eGFR <45 mL/min/1.73 m² 1
• Metformin is contraindicated when eGFR <30 mL/min/1.73 m² 1
• Reassess benefits and risks when eGFR falls below 45 mL/min/1.73 m² 1
• Temporarily discontinue before iodinated contrast procedures if eGFR 30-60 mL/min/1.73 m² 1

GLP-1 Receptor Agonists (First-Line for Diabetic CKD Requiring Additional Therapy)

• For diabetic CKD patients requiring additional glucose-lowering beyond metformin, add GLP-1 receptor agonists for cardiovascular risk reduction and possible CKD progression slowing 1, 2
• Liraglutide reduced new or worsening nephropathy risk by 22% in cardiovascular outcomes trials 1
• GLP-1 RAs have direct renal effects and reduce cardiovascular events and hypoglycemia risk 1

Blood Pressure Target and Additional Agents

Target Blood Pressure

• Aim for systolic blood pressure <120 mmHg for most CKD patients 1, 2
• This intensive target requires multiple antihypertensive medications in most patients 3

Second-Line Antihypertensive Additions

When blood pressure remains uncontrolled on optimized ACE inhibitor or ARB monotherapy:

• Add dihydropyridine calcium channel blockers (e.g., amlodipine) and/or diuretics 1, 2
• For Black patients with CKD, initial therapy should include thiazide-type diuretic or calcium channel blocker, either alone or combined with RAS blocker 2
• Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD but always combined with RAAS blocker 3
• Loop diuretics are preferred when volume overload is present or in moderate-to-severe kidney dysfunction 4

Statin Therapy

• Initiate moderate- or high-intensity statin-based therapy and continue until dialysis or transplant 1
• Add ezetimibe or PCSK9 inhibitors based on ASCVD risk and lipid levels 1

Critical Pitfalls to Avoid

Never combine ACE inhibitor with ARB - dual RAAS blockade substantially increases risks of hyperkalemia, acute kidney injury, and hypotension without cardiovascular or renal benefit 5

Avoid potassium supplements, potassium-sparing diuretics, and potassium-containing salt substitutes when using ACE inhibitors or ARBs 4, 6

Do not routinely discontinue RAAS antagonists when GFR falls below 30 mL/min/1.73 m² - they remain nephroprotective at this stage 4

Temporarily suspend ACE inhibitors/ARBs during high-risk periods: intercurrent illness, planned IV radiocontrast, bowel preparation for colonoscopy, and major surgery 4

Lifestyle Modifications (Essential Adjunct)

• Adopt plant-based diets with higher plant-based versus animal-based food consumption 2
• Maintain protein intake at 0.8 g/kg/day for CKD G3-G5; avoid high protein intake >1.3 g/kg/day 1, 2
• Restrict dietary sodium to <2,300 mg/day for blood pressure control 1
• Engage in moderate-intensity physical activity for ≥150 minutes per week 1, 2
• Achieve optimal BMI and avoid tobacco products 1

Monitoring Schedule

• Reassess risk factors every 3-6 months 1, 2
• Monitor for CKD complications: hyperkalemia, metabolic acidosis, anemia, mineral bone disorders 1, 2
• Laboratory evaluation frequency: every 6-12 months for stage 3 CKD, every 3-5 months for stage 4, every 1-3 months for stage 5 1