What is the recommended management of hypertension in a patient with diabetes, chronic kidney disease (CKD), and impaired renal function?

Management of Hypertension in Diabetes with CKD

In patients with diabetes and CKD, initiate an ACE inhibitor or ARB immediately and titrate to the maximum tolerated dose, add a loop diuretic (not thiazide) when eGFR <30 mL/min, and target a blood pressure <130/80 mmHg using multiple agents as needed. 1

First-Line Pharmacologic Approach

Start with an ACE inhibitor or ARB as the cornerstone of therapy, particularly when albuminuria is present (albumin-creatinine ratio >30 mg/g). 1 This recommendation applies to all patients with diabetes, CKD, and hypertension, regardless of CKD stage (stages 1-4). 1

• Titrate to the highest approved dose that is tolerated, as the proven renoprotective and cardiovascular benefits in clinical trials were achieved using maximal doses. 1, 2
• If ACE inhibitor causes intolerable cough, switch to an ARB—both classes provide equivalent renoprotection in type 2 diabetes. 1, 2
• Never combine ACE inhibitor + ARB together, as this dual RAS blockade increases adverse events without additional benefit. 1, 3

Specific Dosing Examples

• Lisinopril: Start 10 mg daily, titrate to 20-40 mg daily 1
• Losartan: Start 25-50 mg daily, titrate to 25-100 mg daily 1
• Ramipril: Start 1.25 mg daily if eGFR <40 mL/min, titrate to 1.25-20 mg daily 1

Blood Pressure Target

Target blood pressure should be <130/80 mmHg using standardized office measurements. 1 More recent evidence suggests targeting systolic BP 120-129 mmHg when tolerated provides superior cardiovascular and renal protection. 2, 4

• For patients with persistent high-level macroalbuminuria (ACR ≥500 mg/g), consider an even lower systolic target below 130 mmHg. 1
• Avoid lowering systolic BP below 110 mmHg, as this may cause harm. 1

Adding Diuretic Therapy

Multiple antihypertensive agents are usually required to reach target blood pressure—clinical trials show an average of 2.4-2.7 agents needed. 1

• Use loop diuretics (not thiazides) when eGFR <30 mL/min or serum creatinine >2.0 mg/dL, as thiazides become ineffective at this level of kidney function. 3
• Add diuretics preferentially as the second agent after ACE inhibitor/ARB. 1

Third-Line and Additional Agents

If blood pressure remains uncontrolled on ACE inhibitor/ARB plus diuretic:

• Add a dihydropyridine calcium channel blocker (amlodipine or nifedipine) as third-line therapy. 3, 2
• Consider beta-blockers as an alternative third agent. 1
• The typical effective regimen consists of: ACE inhibitor or ARB + loop diuretic + dihydropyridine CCB. 3

Monitoring Parameters

Check serum creatinine and potassium within 2-4 weeks of initiating or increasing the dose of ACE inhibitor or ARB. 1, 3, 2

• Continue the RAS inhibitor unless creatinine rises >30% within 4 weeks, as increases ≤30% reflect hemodynamic changes and do not indicate harm. 1, 3
• For hyperkalemia during RAS inhibitor therapy, manage with dietary potassium restriction, diuretic optimization, sodium bicarbonate (if acidotic), or potassium binders—do not reduce or stop the RAS inhibitor unless hyperkalemia remains uncontrolled despite these measures. 1, 3

Novel Adjunctive Therapy

Consider adding an SGLT2 inhibitor for all patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m², as this provides kidney protection, cardiovascular benefit, and modest additional blood pressure lowering. 2 Continue SGLT2 inhibitor even if eGFR falls below 20 mL/min once initiated, unless not tolerated. 2

Lifestyle Modifications

• Restrict dietary sodium to <2.3 g/day to enhance diuretic efficacy and optimize medication effectiveness. 3, 2
• Advise tobacco cessation in all patients who use tobacco products. 1
• Recommend 150 minutes per week of moderate-intensity physical activity. 2

Common Pitfalls to Avoid

• Do not use thiazide diuretics as monotherapy in advanced CKD (eGFR <30 mL/min)—they are ineffective and loop diuretics are required. 3
• Do not stop ACE inhibitor/ARB for modest creatinine increases up to 30%—this is an expected hemodynamic effect. 1, 3
• Do not combine ACE inhibitor + ARB + direct renin inhibitor—this triple combination increases adverse events without benefit. 3
• Do not underdose RAS inhibitors—the renoprotective effects require maximal tolerated doses. 1, 2

Special Considerations for CKD Stage 5

If the patient progresses to CKD Stage 5 (eGFR <15 mL/min), consider reducing the dose or discontinuing ACE inhibitors/ARBs only if symptomatic hypotension, uncontrolled hyperkalemia despite medical treatment, or uremic symptoms develop. 3