Can aliskiren be used in end‑stage kidney disease (eGFR < 15 mL/min/1.73 m² or on chronic dialysis) for hypertension?

Aliskiren Should Not Be Used in End-Stage Kidney Disease

Aliskiren is not recommended for patients with end-stage kidney disease (eGFR <15 mL/min/1.73 m² or on chronic dialysis) due to lack of efficacy, increased risk of adverse events, and contraindication when combined with ACE inhibitors or ARBs—which are the preferred agents in this population. 1

Primary Contraindications and Safety Concerns

Dual RAS Blockade is Contraindicated

• The FDA issued a contraindication in April 2012 against using aliskiren with ACE inhibitors or ARBs in patients with diabetes due to increased risk of kidney impairment, hypotension, and hyperkalemia 1
• The ALTITUDE trial was stopped early due to therapeutic futility and increased risk of stroke, hyperkalemia, hypotension, and ESRD or death from kidney disease when aliskiren was combined with ACE inhibitors or ARBs 1
• The 2017 ACC/AHA guidelines explicitly state: "Do not use in combination with ACE inhibitors or ARBs" and note increased risk of hyperkalemia in CKD patients 1

Lack of Efficacy in Dialysis Patients

• In a randomized controlled trial of 83 hemodialysis patients with refractory hypertension, aliskiren 150 mg failed to significantly reduce pre-dialysis clinic blood pressure or home blood pressure, while amlodipine successfully lowered blood pressure 2
• Aliskiren did suppress the renin-angiotensin system and reduce ANP, but these biochemical changes did not translate into meaningful blood pressure reduction in the dialysis population 2

Heart Failure Considerations

• The 2019 ESC guidelines explicitly state that aliskiren (direct renin inhibitor) in heart failure with reduced ejection fraction and diabetes is not recommended (Class III recommendation) 1
• This is particularly relevant since many ESRD patients have concurrent heart failure

Pharmacokinetic Data Does Not Support Safety

While pharmacokinetic studies show that:

• Aliskiren exposure (AUC) is 41-61% higher in ESRD patients compared to healthy subjects 3
• Only 10-12% of the drug is removed by a typical 4-hour hemodialysis session 3
• The FDA label states "no dose adjustment is warranted in ESRD patients receiving hemodialysis" 4

These pharmacokinetic findings do not override the clinical trial evidence showing lack of efficacy and increased adverse events in advanced CKD and ESRD populations 1, 2

Preferred Alternatives in ESRD

First-Line Agents

• ACE inhibitors or ARBs remain the preferred agents and should be continued even at eGFR <15 mL/min/1.73 m² unless symptomatic hypotension, uncontrolled hyperkalemia, or uremic symptoms develop 5, 6, 7
• Long-acting dihydropyridine calcium channel blockers (such as amlodipine) are effective for blood pressure control in dialysis patients 2

Blood Pressure Targets

• Target systolic blood pressure of 120-130 mm Hg for patients with eGFR <30 mL/min/1.73 m², individualized based on tolerability 5

Critical Clinical Pitfalls to Avoid

1. Never combine aliskiren with ACE inhibitors or ARBs in any CKD patient, especially those with diabetes or advanced kidney disease 1
2. Do not assume that acceptable pharmacokinetics in ESRD equate to clinical benefit—the ALTITUDE trial definitively showed harm 1
3. Do not use aliskiren as monotherapy in dialysis patients expecting blood pressure reduction comparable to calcium channel blockers 2
4. Recognize that aliskiren increases risk of hyperkalemia in CKD patients, particularly when combined with potassium supplements or potassium-sparing drugs 1

Summary Algorithm for ESRD Hypertension Management

For patients with ESRD (eGFR <15 mL/min/1.73 m² or on dialysis):

1. Continue or initiate ACE inhibitor or ARB unless contraindicated by symptomatic hypotension, uncontrolled hyperkalemia, or uremic symptoms 5, 6, 7
2. Add long-acting dihydropyridine calcium channel blocker (e.g., amlodipine) for additional blood pressure control 5, 2
3. Add loop diuretic if residual urine output exists 5
4. Never add aliskiren to this regimen 1