Hydroxychloroquine Induces Remission for IgA Nephropathy With Mild to Moderate Proteinuria: A Single-Centered Retrospective Analysis

Abstract

Background: Hydroxychloroquine (HCQ) influences both toll-like receptor (TLR) signaling and leukocyte activation, which are speculated to play a role in the pathogenesis of IgA nephropathy (IgAN).

Methods: This is a single-centered retrospective study involving 426 IgAN patients diagnosed from May 2016 to August 2020. All patients were matched according to a propensity score matching (PSM) to produce three groups: renin-angiotensin-aldosterone system inhibitors (RAASi) group (RAASi only), corticosteroids group (corticosteroids only or combined with RAASi), and HCQ group (HCQ only or combined with RAASi), consisting of 63 patients for each group.

Results: After PSM, the median urine protein/creatinine ratio (UPCR) of overall patients was 0.91 g/g, while their median serum creatinine was 87.00 μmol/L. After the median follow-up period of 11.03 months, the total remission rates of the RAASi group, corticosteroids group, and HCQ groups were 49.21% (n = 31), 74.60% (n = 47), and 52.38% (n = 33), respectively (p = 0.017). Thirteen (6.88%) patients experienced a decline in estimated glomerular filtration rate (eGFR) of more than 25% from baseline, including six (9.52%) patients in the RAASi group, three (4.76%) patients in the corticosteroids group, and four (6.35%) patients in HCQ group (p = 0.677). One (1.59%) patient in the HCQ group had blurred vision and continued to use HCQ after ruling out retinal lesions by ophthalmic examination.

Conclusion: HCQ is effective in inducing remission and well-tolerated in IgAN patients with mild to moderate proteinuria.

Keywords: adverse events; hydroxychloroquine; iga nephropathy; remission rate; retrospective analysis.

Figure 1. The flow chart of patient screening and enrollment

IgAN: IgA nephropathy; HCQ: Hydroxychloroquine; RAASi: Renin-angiotensin-aldosterone system inhibitors; eGFR: Estimated glomerular filtration rate.

Figure 2. Changes in UPCR (A), urinary blood cell count (B), eGFR (C), SCr (D) during follow-up in the RAASi, corticosteroids, and HCQ groups after PSM

RAASi: Renin-angiotensin-aldosterone system inhibitors; HCQ: Hydroxychloroquine; UPCR: Urine protein/creatinine ratio; eGFR: Estimated glomerular filtration rate; SCr: Serum creatinine; PSM: Propensity score matching. ^{a, b, c}: p < 0.05 compared with baseline in the RAASi, corticosteroids, and HCQ groups, respectively. ^{A, B, C}: p < 0.05 of each time-point compared with the one preceding it in the RAASi, corticosteroids, and HCQ groups, respectively.

Figure 3. Changes in TG (A) and TC (B) during follow-up in the RAASi, corticosteroids, and HCQ groups after PSM

RAASi: Renin-angiotensin-aldosterone system inhibitors; HCQ: Hydroxychloroquine; TG: Triglycerides; TC: Total cholesterol; PSM: Propensity score matching. ^{a, b}: p < 0.05 compared with baseline in the corticosteroids and HCQ groups, respectively. ^{A, B}: p < 0.05 of each time-point compared with the one preceding it in the corticosteroids and HCQ groups, respectively.

Figure 4. Accumulated total remission (A) and CR (B) rates in the RAASi, corticosteroids, and HCQ groups after PSM

RAASi: Renin-angiotensin-aldosterone system inhibitors; HCQ: Hydroxychloroquine; HR: Hazard ratio; CI: Confidence interval.

Figure 5. A nomogram for predicting remission of IgA nephropathy after treatment

RAASi: Renin-angiotensin-aldosterone system inhibitors; HCQ: Hydroxychloroquine.

Figure 6. The calibration curves for predicting patient non-remission probability at six months (A) and one year (B) in the internal verification

Figure 7. Performance of nomogram to predict non-remission probability in IgAN

AUC: Area under curve; IgAN: IgA nephropathy.