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Observational Study
. 2018 Sep 1;33(9):1604-1610.
doi: 10.1093/ndt/gfx318.

Hydroxycloroquine blood concentration in lupus nephritis: a determinant of disease outcome?

Cátia Cunha  1 , Suceena Alexander  2 , Damien Ashby  3 , Janet Lee  4 , Gary Chusney  4 , Tom D Cairns  3 , Liz Lightstone  3   5
Affiliations
Observational Study

Hydroxycloroquine blood concentration in lupus nephritis: a determinant of disease outcome?

Cátia Cunha et al. Nephrol Dial Transplant. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Statement

None declared.

Figures

Figure 1
Figure 1
Variation in hydroxychloroquine levels according to patient weight.
Figure 2
Figure 2
Distribution of total HCQ blood levels. Black: daily HCQ dosage of 200 mg; grey: daily HCQ dosage of 400 mg.
Figure 3
Figure 3
Consistency of HCQ blood levels over time per patient.
Figure 4
Figure 4
Average HCQ blood level by follow-up status (complete remission versus flare during follow-up in those in complete or partial remission at baseline).
Figure 5
Figure 5
Percentage of lupus nephritis flare during follow-up for patients in complete/partial remission at baseline per average HCQ blood level quintiles. Q1:<0.31 mg/L, Q2: 0.31–0.62 mg/L, Q3: 0.63–0.81 mg/L, Q4: 0.81–1.12 mg/L, Q5: >1.12 mg/L.
See this image and copyright information in PMC

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