How to manage new onset hypertension in a patient with End-Stage Renal Disease (ESRD) receiving Erythropoietin (EPO) therapy?

Management of New Onset Hypertension in ESRD Patients on EPO Therapy

For ESRD patients with new onset hypertension while on erythropoietin therapy, implement a three-pronged approach: optimize antihypertensive medications, intensify ultrafiltration if volume overload is present, and consider reducing the EPO dose if there has been a rapid hemoglobin rise. 1, 2

Understanding the Mechanism

Hypertension is the most common side effect of erythropoietin therapy in ESRD patients, occurring in approximately 23% of treated patients 1, 2. The pathophysiology involves:

• Increased vascular wall reactivity
• Hemodynamic changes from increasing red blood cell mass
• Increased ratio of plasma endothelin to proendothelin
• Elevated cytosolic ionic calcium and nitric oxide resistance
• Enhanced alpha-adrenergic sensitivity (nearly 4-fold increase) 3

Importantly, this hypertensive response is unique to renal patients and is not observed in anemic patients without renal disease who receive EPO 1.

Management Algorithm

Step 1: Assess and Monitor

• Monitor blood pressure closely, particularly during the first 4 months of EPO therapy when risk is highest 4
• Evaluate for rapid hemoglobin/hematocrit rise (>3 g/dL or >8 percentage points per month)
• Assess volume status

Step 2: Implement Treatment

1. Antihypertensive Medication Management:

   • Initiate or increase antihypertensive medications 1, 2
   • ACE inhibitors, ARBs, and beta-blockers are reasonable first-line agents 5
   • Consider medication removal with dialysis when selecting agents:
     • For patients prone to intradialytic hypotension: use medications removed by dialysis
     • For patients with intradialytic hypertension: use non-dialyzable medications 5

2. Volume Management:

   • Intensify ultrafiltration if evidence of extracellular volume expansion exists 1
   • Implement dietary sodium and fluid restriction 6

3. EPO Dose Adjustment:

   • If hemoglobin/hematocrit has increased rapidly (>3 g/dL or >8 percentage points per month), reduce weekly EPO dose by 25% 1
   • Do not discontinue EPO therapy unless hypertension is refractory to aggressive management 1

Step 3: Special Considerations

• If hypertensive encephalopathy occurs (with or without seizures), discontinue EPO until clinical stability is achieved 1, 2
• For persistent hypertension despite above measures, temporarily discontinue EPO therapy 4

Important Caveats

• The incidence of hypertension with EPO is not associated with the dose of EPO or whether a normal hematocrit is achieved 1
• Hypertension typically develops during the first 4 months of therapy and usually stabilizes thereafter 4
• Prevention is better than treatment - consider initiating EPO at lower doses with slow increases to prevent rapid hematocrit rise 6
• There is no evidence that increased blood pressure associated with EPO should be treated differently than hypertension in dialysis patients not on EPO 1

By following this structured approach, the increased cardiovascular morbidity and mortality risk associated with uncontrolled hypertension in ESRD patients can be effectively managed while maintaining the benefits of EPO therapy for anemia correction.