immunoglobulin A (IgA) nephropathy (Berger disease) is the most frequent primary glomerulonephritis worldwide. This disease accounts for about 5% of the causes of end stage renal disease in France, representing a major public health issue. Its pathophysiology seems to be triggered by mucosal immunity abnormalities leading to the systemic misaddressing of mucosal IgA, generation of circulating immunoglobulin A1 (IgA1) immune complexes finally deposited in renal glomeruli leading to renal tissue inflammation and scarring processes. Among this pathogeny, innate immunity is involved at several steps, including mucosal immunity.

In this regard, hydroxychloroquine has been shown to generate a global anti-inflammatory effect, particularly through its action on Toll like receptors and dendritic cells. This drug is well tolerated, widely used for other auto-immune diseases (e.g. Systemic Lupus Erythematosus) and very low priced.

One randomized controlled study conducted in China has recently shown a significant drop in proteinuria of IgA nephropathy patients treated with hydroxychloroquine (-48.4%) compared to the placebo group (+10.0%), after a quite short-term follow-up (6 months) and a moderate statistical power (30 patients in each group).

Considering (i) the potential mechanism of therapeutic effect on this disease, (ii) the well documented safety profile of the drug for rheumatologic indications and posologies, and its low cost (iii) its efficacy in reducing proteinuria in IgA nephropathy patients in a preliminary Chinese randomized control study, the investigators aim in this study at establishing the beneficial impact of hydroxychloroquine on IgA nephropathy in a double blind randomized controlled trial on a Caucasian French population with harder outcomes and a longer follow-up compared to the Chinese preliminary study.

Inclusion Criteria:

• Social security affiliation
• Signed informed consent
• With biopsy proven IgA nephropathy (any vintage)
• With at least one Oxford lesion (M, E, S, T, C) on last available kidney biopsy - With urine albumin/creatinine > 300mg/g,
• under maximal tolerated labeled dose of renin-angiotensin-aldosterone system (RAAS) inhibitors for at least 3 months
• Sodium-Glucose Transport Protein 2 (SGLT-2) inhibitors initiated at least 1 month before inclusion visit
• Only patients treated with SGLT2i and RAAS dual therapy before inclusion
• With estimate GFR above 15 mL/min/1,73m² (Chronic Kidney Disease - EPIdemiology collaboration CKD-EPI formula)
• Woman in childbearing with a highly effective method of contraception
• Agreement of woman in childbearing potential (WOCBP) to perform a urine pregnancy test every month until three months after the end of study treatment
• Agreement of fertile male with WOCBP partner to use a condom for the duration of the study treatment up to 3 months after treatment the end of study treatment.

Exclusion Criteria:

• Secondary IgA nephropathy (Henoch Schonlein purpura, cirrhosis, inflammatory bowel disease)
• Corticosteroid or immunosuppressive therapies in the past year before screening
• Contra-indication to hydroxychloroquine (retinopathy, maculopathy, history of intolerance to hydroxychloroquine…)
• Uncontrolled hypertension (systolic blood pression> 160 mmHg and/or diastolic blood pression >110 mmHg )
• Long QT interval and/or QT prolonging medicines
• Pregnancy or lactation