What is the initial treatment approach for a patient with Chronic Kidney Disease (CKD) and diabetes who has uncontrolled Hypertension (high blood pressure)?

Initial Treatment Approach for CKD and Diabetes with Uncontrolled Hypertension

Start a renin-angiotensin system inhibitor (ACE inhibitor or ARB) immediately at the highest tolerated dose, combined with an SGLT2 inhibitor, and target a systolic blood pressure of 120-129 mmHg. 1

First-Line Pharmacologic Therapy

RAS Inhibitor (Mandatory Foundation)

• Initiate an ACE inhibitor or ARB as the cornerstone of therapy for all CKD patients with diabetes and hypertension, particularly when albuminuria is present (moderately-to-severely increased, A2 or A3). 1
• Titrate to the maximum approved dose that is tolerated—the proven renoprotective and cardiovascular benefits were achieved in trials using these doses, not lower doses. 1
• If ACE inhibitor causes intolerable cough, switch to an ARB; both classes provide equivalent renoprotection. 1

SGLT2 Inhibitor (Add Immediately)

• Start an SGLT2 inhibitor for all patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² regardless of albuminuria level—this provides kidney protection, cardiovascular benefit, and modest blood pressure lowering. 1
• Continue SGLT2 inhibitor even if eGFR falls below 20 mL/min/1.73 m² once initiated, unless not tolerated or kidney replacement therapy begins. 1
• Temporarily withhold during prolonged fasting, surgery, or critical illness due to ketosis risk. 1

Blood Pressure Target

• Target systolic BP of 120-129 mmHg using standardized office measurement if tolerated—this provides superior cardiovascular and renal protection compared to less intensive targets. 1
• The 2024 KDIGO guidelines represent the most current evidence, superseding older JNC-8 recommendations of <140/90 mmHg. 1
• For patients with diabetes and CKD with eGFR >30 mL/min/1.73 m², this intensive target is strongly supported. 1

Monitoring After RAS Inhibitor Initiation

• Check blood pressure, serum creatinine, and serum potassium within 2-4 weeks of starting or increasing the dose of ACE inhibitor or ARB. 1
• Continue the RAS inhibitor unless creatinine rises >30% within 4 weeks—increases up to 30% reflect expected hemodynamic changes and are not harmful. 1
• A creatinine rise ≤30% indicates appropriate intraglomerular pressure reduction and predicts long-term kidney protection. 1

Add-On Therapy When BP Goal Not Achieved

Second-Line Agent

• Add either a long-acting dihydropyridine calcium channel blocker (amlodipine, nifedipine) OR a thiazide-like diuretic if BP remains ≥130/80 mmHg despite RAS inhibitor. 1, 2
• For patients with eGFR <30 mL/min/1.73 m² or serum creatinine >2.0 mg/dL, use a loop diuretic instead of thiazide, as thiazides become ineffective at this level of kidney function. 3, 4

Third-Line Agent

• Add the other class not yet used (CCB if diuretic was added second, or diuretic if CCB was added second). 2
• Most CKD patients with diabetes require three or more antihypertensive medications to achieve BP <130/80 mmHg. 1, 5

Fourth-Line Consideration

• For resistant hypertension despite maximal doses of RAS inhibitor, diuretic, and CCB, consider adding a nonsteroidal mineralocorticoid receptor antagonist (finerenone) if eGFR >25 mL/min/1.73 m², serum potassium is normal, and albuminuria persists (>30 mg/g) despite maximum tolerated RAS inhibitor dose. 1
• Nonsteroidal MRAs are most appropriate for patients at high risk of CKD progression with persistent albuminuria despite standard therapy. 1

Managing Hyperkalemia

• Do not immediately stop or reduce the RAS inhibitor dose for hyperkalemia—first implement potassium-lowering measures such as dietary potassium restriction, diuretic adjustment, sodium bicarbonate, or GI cation exchangers. 1
• Stopping RAS inhibition eliminates critical renoprotection and should be a last resort. 1
• Only reduce dose or discontinue RAS inhibitor if hyperkalemia remains uncontrolled despite medical management. 1

Critical Contraindications

• Never combine ACE inhibitor + ARB + direct renin inhibitor—this triple combination increases adverse events (hyperkalemia, acute kidney injury, hypotension) without additional benefit. 1
• Never use dual RAS blockade (ACE inhibitor + ARB together)—this combination is explicitly contraindicated. 1
• ACE inhibitors and ARBs are absolutely contraindicated in pregnancy. 1

Lifestyle Modifications (Concurrent with Medications)

• Restrict dietary sodium to <2.3 g/day (100 mmol/day or <5 g sodium chloride) to enhance medication effectiveness and reduce fluid retention. 1
• Recommend 150 minutes per week of moderate-intensity physical activity if cardiovascular and physical tolerance permits. 1
• Advise smoking cessation to reduce cardiovascular and kidney disease progression risk. 1
• Encourage a plant-based diet with reduced ultra-processed foods while maintaining protein intake of 0.8 g/kg/day. 1

Common Pitfalls to Avoid

• Do not stop RAS inhibitor for creatinine increases ≤30%—this modest rise is expected, hemodynamic, and not harmful. 1
• Do not use thiazide diuretics when eGFR <30 mL/min/1.73 m²—switch to loop diuretics as thiazides lose efficacy. 3, 4
• Do not apply the intensive BP target (<120 mmHg) to non-standardized BP measurements—this target requires standardized office measurement with proper technique. 1
• Do not underdose RAS inhibitors—maximum approved doses are required for full renoprotective benefit. 1
• Do not delay SGLT2 inhibitor initiation—start immediately alongside RAS inhibitor for additive kidney and cardiovascular protection. 1