Hydroxychloroquine alleviates persistent proteinuria in IgA nephropathy

Dendritic cells, Toll-like receptor (TLR), interleukin-6 (IFN-alpha), interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) play an important role in the pathogenesis of IgA nephropathy (IgAN). Hydroxychloroquine (HCQ) is an antimalarial agent and had a notable impact on immune activation by the reduction of circulating activated immune cells that including decreased TLR-expressing cells, reduced IFN-secreting DCs, reduced production of cytokines including IFN-alpha,IL-6 and TNF-alpha. We evaluated the efficacy of HCQ in reducing proteinuria in patients with IgAN. Twenty-eight IgAN patients with persistent proteinuria (0.5-2.0 g/24 h) despite treatment with losartan for 3 months were matched to receive HCQ and losartan (group 1) or continue losartan therapy (group 2) for 24 weeks. The primary end point of this prospective, paired case-control study was reduction of proteinuria by 50% or more over entry level. Six patients (42.9%) in group one versus two patients (14.3%) in group 2 reach the primary end point (P = 0.004). By 24 weeks, the mean urinary protein excretion was 65.9 +/- 25.5% (P = 0.002) and 95.3 +/- 30.0% (P = 0.791) that of the corresponding baseline value in group 1 and group 2, respectively. Baseline proteinuria and histologic grades, blood pressure control and changes in serum creatinine and eGFR were not different between the two groups. In selected patients with IgAN, HCQ is effective in ameliorating proteinuria.