Hydroxyurea interferes with point-of-care creatinine testing in children with sickle cell anemia

Objective: To evaluate the performance of the point-of-care i-STAT device for creatinine measurement in Ugandan children with sickle cell anemia (SCA), and to determine the clinical impact of hydroxyurea-associated assay interference. Results description: This secondary analysis was nested within a randomized clinical trial involving 248 Ugandan children with SCA. The mean age at enrollment was 32 months, and 115/248 (46.2%) initiated hydroxyurea during 12 months of follow-up as part of routine clinical care. At enrollment, creatinine values measured by i-STAT and reference laboratory testing were clinically comparable. At follow-up, children receiving hydroxyurea had significantly higher creatinine values measured by i-STAT than by reference laboratory testing (mean difference + 0.19 mg/dL; p = 0.006), with several i-STAT results falling within the clinically abnormal range. No such discrepancy was observed among children not receiving hydroxyurea. In a subset of samples, serum hydroxyurea concentrations measured by high-performance liquid chromatography accounted for 73% of the variability in i-STAT creatinine values. These findings demonstrate clinically meaningful interference of hydroxyurea with enzymatic point-of-care creatinine testing, which may result in misclassification of kidney function and inappropriate clinical decision-making in children with SCA receiving hydroxyurea. ClinicalTrials.gov identifier: NCT03528434 (date registered: May 7^th, 2018).