Hydroxycloroquine Blood Concentration in Lupus Nephritis

A Determinant of Disease Outcome?

Cátia Cunha; Suceena Alexander; Damien Ashby; Janet Lee; Gary Chusney; Tom D Cairns; Liz Lightstone


Nephrol Dial Transplant. 2018;33(9):1604-1610. 

In This Article

Abstract and Introduction


Background: Hydroxychloroquine (HCQ) is a recommended drug in systemic lupus erythematosus (SLE). It has a long terminal half-life, making it an attractive target for therapeutic drug monitoring. The aim of this study was to establish a relationship between blood HCQ concentration and lupus nephritis activity.

Methods: We conducted a retrospective observational study with data collected from clinical and laboratory records. Inclusion criteria were patients followed in the lupus clinic with biopsy-proven International Society of Nephrology/Renal Pathology Society Classes III, IV or V lupus nephritis on HCQ for at least 3 months (200–400 mg daily) and with HCQ levels measured during treatment. Exclusion criteria were patients on renal replacement therapy at baseline or patients lost to follow-up.

Results: In 171 patients, the HCQ level was measured in 1282 samples. The mean HCQ blood level was 0.75±0.54mg/L and it was bimodally distributed. An HCQ level <0.20 mg/L [232 samples (18.1%)] appeared to define a distinct group of abnormally low HCQ levels. For patients in complete or partial remission at baseline compared with those remaining in remission, patients with renal flare during follow-up had a significantly lower average HCQ level (0.59 versus 0.81 mg/L; P= 0.005). Our data suggest an HCQ target level to reduce the likelihood of renal flares >0.6 mg/L (600 ng/mL) in those patients with lupus nephritis.

Conclusion: HCQ level monitoring may offer a new approach to identify non-adherent patients and support them appropriately. We propose an HCQ minimum target level of at least 0.6 mg/L to reduce the renal flare rate, but this will require a prospective study for validation.


Lupus nephritis is a major complication of systemic lupus erythematosus (SLE), occurring in up to two-thirds of SLE patients. Renal remission is important, with those patients that enter complete remission having a higher renal and overall survival compared with those patients in whom remission is not achieved.[1] Even a partial remission in lupus nephritis is associated with a significantly better patient and renal survival compared with no remission.[2–5] Renal flares average ~8 per 100 patient-years for the first 5 years after attaining remission.[6] Severe disease at baseline, a delay in reaching remission and attainment of partial compared to complete remission are some of the factors predisposing to renal flares.[6–8] Non-adherence to lupus nephritis treatment is the most important factor for non-remission or renal relapses.[9–11]

Hydroxychloroquine (HCQ) is currently recommended long term for all patients with SLE provided no contraindications exist. There is evidence of multiple beneficial effects, including control of disease activity by its immunomodulatory effects, reduction of cardiovascular events, lipid- and glucose-lowering effects, antithrombotic effects and improved survival.[12–16]

HCQ has a long terminal half-life of >40 days and a steady-state level in blood with small daily fluctuation,[17] making it an attractive target for therapeutic drug monitoring to evaluate adherence to medication as well as efficacy.

A pharmacokinetic/pharmacodynamic relation for blood HCQ concentration has been found in rheumatoid arthritis and cutaneous lupus.[18–20] For SLE, low whole-blood HCQ concentrations suggest non-adherence and may predict disease exacerbations, with one study showing that a cut-off of 1 mg/L had a negative predictive value of 96% for a systemic flare during follow-up.[21] There is also evidence of a protective effect of HCQ in retarding renal damage occurrence in SLE,[22] but there are no reports, to our knowledge, looking specifically at HCQ blood levels in patients with lupus nephritis.

The aim of this study was to establish a relationship between blood HCQ concentration and lupus nephritis activity, including its relation with time to remission and risk of renal flares.