What is the current drug of choice for managing hypertension in patients with Chronic Kidney Disease (CKD) stage 5?

Drug of Choice for Hypertension in CKD Stage 5

Loop diuretics (furosemide 20-80 mg twice daily or torsemide 5-10 mg daily) combined with ACE inhibitors or ARBs represent the preferred initial approach for hypertension management in CKD Stage 5 patients, with loop diuretics being essential as thiazides are ineffective at GFR <30 mL/min. 1, 2

First-Line Therapy Selection

Loop Diuretics as Foundation

• Loop diuretics are the preferred diuretic class in CKD Stage 5 because thiazide and thiazide-like diuretics lose effectiveness when GFR falls below 30 mL/min 1, 2
• Furosemide 20-80 mg twice daily or torsemide 5-10 mg once daily should be initiated to address volume overload, which is the primary driver of hypertension in advanced CKD 1, 2
• Achievement of dry weight and reduction of extracellular fluid volume should be aggressively pursued, though this may not be effective in every patient 1

ACE Inhibitors or ARBs as Add-On Therapy

• ACE inhibitors or ARBs should be added or optimized at maximal tolerated doses if not contraindicated by hyperkalemia or symptomatic hypotension 1, 2
• In observational studies, ACE inhibitor use has been associated with decreased mortality in CKD Stage 5 patient cohorts 1
• These agents provide cardiovascular protection beyond blood pressure reduction, which is critical given the high cardiovascular mortality in this population 1

Blood Pressure Targets

Primary Target

• Target blood pressure of 140/90 mmHg (predialysis measurement in sitting position) is reasonable for most CKD Stage 5 patients, provided there is no substantial orthostatic hypotension or symptomatic intradialytic hypotension 1
• An alternative acceptable range is SBP 130-139 mmHg, which is considered safe in CKD Stage 5 2

Intensive Target Considerations

• An intensive target of SBP <120 mmHg may be considered if tolerated, based on SPRINT trial cardiovascular benefits, though this must use standardized office BP measurement 2
• However, lack of high-quality data impedes firm recommendations for specific BP targets in CKD Stage 5, as most major trials including SPRINT excluded patients with advanced CKD 1, 3

Algorithmic Treatment Approach

Step 1: Volume Management

• Initiate loop diuretic therapy and pursue dry weight achievement through dialysis optimization (if on dialysis) 1, 2
• Emphasize continuous salt restriction as an integral lifestyle modification 1

Step 2: Add RAAS Blockade

• If volume management alone is unsuccessful, add ACE inhibitor or ARB as first-line antihypertensive agent 1, 2
• Monitor serum creatinine and potassium within 2-4 weeks of initiating or increasing dose 2
• Continue therapy if creatinine rises ≤30% from baseline, as this reflects hemodynamic changes rather than harm 2

Step 3: Additional Agents for Resistant Hypertension

• Beta-blockers should be preferred in patients with previous myocardial infarction or established coronary artery disease, as exposure to beta-blockers is associated with decreased mortality in CKD 1
• Calcium channel blockers (both dihydropyridine and non-dihydropyridine) should be added if BP remains uncontrolled 1, 3
• Observational studies suggest CCBs are associated with decreased total and cardiovascular mortality 1

Step 4: Severe Resistant Hypertension

• If BP remains above 140/90 mmHg despite dry weight achievement and three antihypertensive agents of different classes, evaluate for secondary causes of resistant hypertension 1
• If no evident cause is found and patient remains hypertensive after trial with minoxidil, consider continuous ambulatory peritoneal dialysis (CAPD) 1
• If CAPD proves ineffective, surgical or embolic nephrectomy should be considered 1

Critical Monitoring Parameters

Electrolyte Surveillance

• Check serum potassium regularly when using ACE inhibitors/ARBs, as there is increased risk of hyperkalemia in CKD 1, 2
• Avoid potassium supplements and potassium-sparing diuretics when using RAAS inhibitors 1

Renal Function Monitoring

• Monitor serum creatinine within 2-4 weeks of initiating or dose-adjusting ACE inhibitors/ARBs 2
• Up to 30% creatinine increase is acceptable and expected, representing hemodynamic changes rather than nephrotoxicity 2
• Further GFR decline beyond 30% should prompt investigation for volume contraction, nephrotoxic agents, or renovascular disease 3

Orthostatic Assessment

• Inquire about postural symptoms when assessing patients receiving BP-lowering medications, particularly in elderly patients 1
• Ensure target BP levels are not associated with substantial symptomatic intradialytic hypotension in dialysis patients 1

Common Pitfalls to Avoid

Dual RAAS Blockade

• Never combine ACE inhibitor + ARB, as this increases adverse events (hyperkalemia, acute kidney injury) without additional benefit 1, 2
• Avoid any combination of ACE inhibitor, ARB, and direct renin inhibitor 1

Inappropriate Diuretic Selection

• Do not use thiazide or thiazide-like diuretics as monotherapy in CKD Stage 5, as they are ineffective at GFR <30 mL/min 1, 2
• Potassium-sparing diuretics (amiloride, triamterene) should be avoided in patients with significant CKD (GFR <45 mL/min) 1

Premature Discontinuation of RAAS Inhibitors

• Do not discontinue ACE inhibitor/ARB for modest creatinine increases up to 30%, as this is an expected hemodynamic effect 2
• The controversy about whether ACE inhibitors/ARBs should be discontinued in CKD Stage 5 because they compromise residual kidney function remains unresolved, but current evidence favors continuation for cardiovascular protection 1

Inadequate Volume Assessment

• Failure to achieve dry weight is a common reason for resistant hypertension in CKD Stage 5 1
• Volume control may require loop diuretics in patients with signs of volume overload and nephrotic-range proteinuria 1