Hydroxyurea's Effects on Kidney Function
Hydroxyurea may affect kidney function, requiring dose adjustment in patients with renal impairment, but has potential renoprotective effects in sickle cell disease patients when properly monitored. 1, 2
Pharmacokinetics and Renal Handling
- Hydroxyurea is primarily excreted by the kidneys, with approximately 40% of an oral dose recovered in urine in patients with sickle cell anemia 1
- Patients with impaired renal function (creatinine clearance <60 mL/min) and those with end-stage renal disease (ESRD) experience 64% higher drug exposure compared to patients with normal renal function 1
- As renal insufficiency worsens, systemic exposure to hydroxyurea increases while urinary recovery decreases 2
Dosing Considerations in Renal Impairment
- Dose reduction is required for patients with creatinine clearance <60 mL/min or ESRD following hemodialysis 1
- For sickle cell disease patients with CrCl <60 mL/min, an initial dosing regimen of 7.5 mg/kg/day (half the standard dose) is recommended 2
- Close monitoring of hematologic parameters is essential when administering hydroxyurea to patients with renal impairment 1
Potential Renoprotective Effects in Sickle Cell Disease
- Hydroxyurea treatment has been associated with a lower prevalence of albuminuria in adults with sickle cell disease 3
- In a cross-sectional study of 149 adult sickle cell patients, those using hydroxyurea were less than one-third as likely to exhibit albuminuria compared to non-users (34.7% versus 55.4%) 3
- The BABY HUG clinical trial demonstrated that hydroxyurea treatment in infants with sickle cell anemia was associated with:
- Better urine concentrating ability (higher urine osmolality)
- Less renal enlargement
- No significant effect on glomerular filtration rate (GFR) 4
Combination Therapy in Sickle Cell Nephropathy
- For sickle cell disease patients with chronic kidney disease and worsening anemia, the American Society of Hematology (ASH) suggests combination therapy with hydroxyurea and erythropoiesis-stimulating agents 5
- This recommendation is based on evidence that erythropoiesis-stimulating agents may allow for more aggressive hydroxyurea dosing in patients with mild renal insufficiency 5
- The safety profile of this combination therapy appears favorable, with only 1.8% of patients experiencing worsening sickle cell symptoms in available studies 5
Monitoring Recommendations
- Regular assessment of renal function is important for patients on hydroxyurea, particularly elderly patients who are more likely to have decreased renal function 1
- For patients with sickle cell disease receiving combination therapy with erythropoiesis-stimulating agents, hemoglobin levels should not exceed 10 g/dL (hematocrit of 30%) to reduce the risk of vaso-occlusive complications 5
- Patients with subclinical renal dysfunction should be identified by measuring plasma creatinine levels before initiating hydroxyurea therapy 6
Clinical Pearls and Caveats
- Elderly patients may be more sensitive to the effects of hydroxyurea and may require a lower dose regimen due to age-related decline in renal function 1
- Hydroxyurea has been used experimentally in the management of struvite stones by blocking urease activity, suggesting potential benefits beyond its primary indications 7
- The ASH guideline panel identified the need for more research on the effects of hydroxyurea on kidney function, particularly studies examining its potential to slow progression of end-organ damage 5