Low estimated glomerular filtration rate is an independent risk factor for higher hydroxychloroquine concentration

Abstract

Background The aim of this study was to analyze the relationship of the estimated glomerular filtration rate (eGFR) to hydroxychloroquine (HCQ) blood concentrations in systemic lupus erythematosus (SLE) patients. Method Patients with SLE who had been taking HCQ for more than 12 months were recruited. All subjects gave written informed consent. Various clinical characteristics and laboratory values were examined. The blood concentration of HCQ was measured by high-performance liquid chromatography, and the relationship of eGFR to HCQ blood concentration was mainly investigated. Result In total, 115 patients with SLE receiving long-term HCQ therapy were included in the study. The median concentration of HCQ was 1096 ng/ml (range 116–8240 ng/ml). The eGFR was strongly associated with blood concentration of HCQ (P = 0.011, P < 0.05), when adjusted for age, sex, body mass index (BMI), weight-adjusted dose, prednisone use and immunosuppressive drug use. No statistically significant association were found between age, duration, BMI, weight-adjusted HCQ dose, corticosteroid use, immunosuppressant use and blood concentrations of HCQ. Conclusion We provided novel evidence that impaired renal function influenced the blood concentration of HCQ. Patients with low eGFR need to adjust the HCQ dosage according to the monitoring results of HCQ blood concentrations. Key points• A higher HCQ blood concentration was associated with low eGFR.• This finding reinforces the importance of routine HCQ measurement to maintain normal blood concentrations.• HCQ blood monitoring will be useful for dose modification in patients with renal dysfunction.

Therapeutic Drug Monitoring in Patients with Systemic Lupus Erythematosus: Utility and Gaps

“…More studies are required to enable clinicians to individualise these therapies via TDM in SLE. -Age [25] -Gender [25] -CYP450 polymorphisms [26,27] -Renal function [23,30] -Ethnicity [52] -Renal function [53] -Liver function [51] -Serum albumin levels [51] -Concomitant drugs (e.g., proton pump inhibitors, iron oxide) [51] -CYP3A inhibitors or inducers including dietary polyphenols -CYP3A5 polymorphisms [70] -Xanthine oxidase inhibitor -TPMT/NUDT15 polymorphisms [84] Utility of monitoring -Identify non-adherence, which predicts damage [39] and mortality -Predicts lupus flares and treatment failure [34,35] -Predicts thrombotic events [40] -Predicts HCQ retinopathy [41] Determine…”

“…Yet, blood HCQ concentrations are profoundly affected by renal function. Several studies including the PLUS study found an inverse correlation between the estimated glomerular filtration rate (eGFR) and blood HCQ concentrations [23,30]. The Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) guidelines recommend that the maximum dosing of HCQ is 5 mg/kg/day, and that the dose be reduced by 50% when eGFR < 30 mL/min [31].…”