How to manage hypertension in a patient with advanced chronic kidney disease (eGFR <15) and impaired renal function?

Management of Hypertension in Advanced CKD (eGFR <15)

For patients with advanced CKD (eGFR <15) not yet on dialysis, target a blood pressure <130/80 mmHg using standardized measurement, prioritize volume management with loop diuretics, and use ACE inhibitors or ARBs cautiously with close monitoring for hyperkalemia and acute kidney injury. 1

Blood Pressure Target

• Target BP <130/80 mmHg for patients with CKD stages 4-5 not on dialysis, though evidence is weaker than for earlier CKD stages 1
• The 2021 KDIGO guideline suggests targeting SBP <120 mmHg using standardized office measurement, but this recommendation is controversial and based primarily on SPRINT trial data that excluded most patients with eGFR <20 1
• Apply the <130/80 mmHg target to routine clinic measurements rather than the more aggressive <120 mmHg target, as the latter requires standardized measurement conditions rarely achievable in practice and may increase risk of adverse events in advanced CKD 1
• Monitor for symptomatic hypotension and orthostatic changes, as aggressive BP lowering in advanced CKD may accelerate need for dialysis 1

Volume Management as First-Line Therapy

• Achieve euvolemia through dietary sodium restriction (<2g sodium/day) and loop diuretics as the cornerstone of BP management in advanced CKD 1, 2
• Loop diuretics are necessary in stage 4-5 CKD due to reduced effectiveness of thiazide diuretics at low eGFR 1
• Consider adding chlorthalidone 25mg daily to loop diuretics for synergistic diuretic effect and additional BP lowering, even at eGFR <30, with close monitoring of electrolytes 1
• Check electrolytes within 2-4 weeks after initiating or escalating diuretic therapy 1

Pharmacologic Management

First-Line Agents

• Start ACE inhibitor or ARB if albuminuria is present (moderately or severely increased), as these provide renoprotection beyond BP lowering 1
• Use the highest tolerated dose to achieve proven benefits from clinical trials 1
• For patients without significant albuminuria, any first-line antihypertensive class is reasonable, though ACE inhibitors/ARBs may still be considered 1

Critical Monitoring with RAS Blockade

• Check serum creatinine and potassium within 2-4 weeks after initiating or increasing ACE inhibitor/ARB dose 1
• Continue therapy unless creatinine rises >30% within 4 weeks of initiation or dose increase 1
• Reduce dose by half if potassium rises to >5.5 mmol/L; discontinue immediately if ≥6.0 mmol/L 1, 3
• Consider dose reduction or discontinuation if symptomatic hypotension, uncontrolled hyperkalemia despite medical management, or to reduce uremic symptoms at eGFR <15 1

Second and Third-Line Agents

• Add long-acting dihydropyridine calcium channel blocker (e.g., amlodipine) as second-line therapy for additional BP lowering 1, 4
• Amlodipine maintains effectiveness in renal impairment without dose adjustment, though elderly patients may need lower initial doses 4
• Add beta-blocker as third-line agent, particularly if history of myocardial infarction or coronary artery disease 2
• Beta-blockers are associated with decreased mortality in CKD patients with cardiovascular disease 2

Resistant Hypertension Management

• Define resistant hypertension as BP >140/90 mmHg despite euvolemia and three appropriate antihypertensive agents at optimal doses 2
• Evaluate for secondary causes of hypertension before escalating therapy 1, 2
• Add spironolactone 25mg daily for resistant hypertension, but monitor potassium closely given high risk of hyperkalemia at eGFR <15 1, 5
• The combination of chlorthalidone with spironolactone may mitigate hyperkalemia risk while improving BP control, but requires intensive monitoring 5
• For severe resistant hypertension unresponsive to medical therapy, consider minoxidil as a potent vasodilator 2

Monitoring Strategy

• Check basic metabolic panel within 2-4 weeks after any medication initiation or dose adjustment 1
• Implement home blood pressure monitoring to avoid hypotension (SBP <110 mmHg) during medication titration 1
• Follow-up every 6-8 weeks until BP goal achieved, then every 3-6 months once stable 1
• Train patients to hold or reduce antihypertensive doses during volume depletion (vomiting, diarrhea, decreased oral intake) to prevent acute kidney injury 1

Critical Pitfalls to Avoid

• Never combine ACE inhibitor with ARB - this dual RAS blockade increases hyperkalemia and acute kidney injury risk without improving outcomes 1
• Do not automatically discontinue thiazide diuretics when eGFR falls below 30; chlorthalidone specifically may remain effective and can be combined with loop diuretics 1
• Avoid aggressive BP lowering in elderly patients with isolated systolic hypertension and low diastolic BP due to arterial stiffness 1
• Do not use potassium-rich salt substitutes or DASH diet in advanced CKD due to hyperkalemia risk 1
• Recognize that in advanced CKD, the risk of acute kidney injury with RAS blockade is higher than in earlier stages, requiring more cautious monitoring 1

Special Considerations for Transition to Dialysis

• Once eGFR <15 and dialysis is imminent, consider reducing or discontinuing ACE inhibitor/ARB to reduce uremic symptoms, though this should be balanced against cardiovascular benefits 1
• After dialysis initiation, target predialysis BP of 140/90 mmHg with continued emphasis on achieving dry weight through ultrafiltration 2
• ACE inhibitors or ARBs remain first-line agents for most dialysis patients, with particular benefit for preserving residual kidney function 2, 3