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valsartan (160mg/d) and Hydroxychloroquine Sulfate ( 400mg/d, twice daily)

Hydroxychloroquine Sulfate

RUITONG GAO, MD

Ruitong Gao, MD

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world.There is to date no curative therapy for patients with IgAN.It is considered that dendritic cells, Toll-like receptor (TLR) 9 and cytokines interleukin-6 (IL-6), and interferon-alpha (IFN-a) and tumor necrosis factor-alpha (TNF-α), play an important role in the aberrant mucosal response. Hydroxychloroquine 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 plasmacytoid dendritic cells, reduced production of inflammatory cytokines including interferon alpha, IL-6 and TNF alpha. Recent studies showed hydroxychloroquine had a benefit for renal remission and could retard the onset of renal damage in patients with lupus nephritis. hydroxychloroquine may have the potential effect in IgA nephropathy, alleviated the proteinuria and had the renal protect effect. This will be a single center, prospective, randomized, controlled study to assess the utility of hydroxychloroquine in IgAN patients.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Its estimated frequency is at least 2.5 cases per year per 100,000 adults. The glomerulopathy usually progressed slowly leading to end stage renal disease (ESRD). ESRD developed in 20%-40% of patients after 20 years. Given its complex and as yet incompletely understood pathogenetic mechanisms, there is to date no curative therapy for patients with IgAN.

Although pathogenesis of IgAN is still obscure, underglycosylated IgA-containing immune-complex including IgG or IgA antibodies against the hinge region of IgA1 are key factors for IgA nephropathy. Aberrant mucosal immune response might lead to increased production of underglycosylated IgA1. It is considered that dendritic cells, Toll-like receptor (TLR)9, and cytokines interleukin-6 (IL-6), , interferon-alpha (IFN-a) and tumor necrosis factor-alpha (TNF-α), play an important role in the aberrant mucosal response.

Hydroxychloroquine 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 plasmacytoid dendritic cells, reduced production of inflammatory cytokines including interferon alpha, IL-6 and TNF alpha. Recent studies showed hydroxychloroquine had a benefit for renal remission and could retard the onset of renal damage in patients with lupus nephritis.

Therefore, hydroxychloroquine, targeting dendritic cells, TLR, IL-6, IFN-α and TNF-α，may have the potential effect in IgA nephropathy, alleviated the proteinuria and had the renal protect effect. This will be a single center, prospective, randomized, controlled study to assess the utility of hydroxychloroquine added to valsartan in IgAN patients.

Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy

Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy:a Single Center Prospective Randomized Controlled Study

CR: proteinuria \<0.3 g/24 hr with no worsening of renal function (\<15% estimated glomerular filtration rate(eGFR) reduction from Baseline).PR: proteinuria \<3.5g/24 hrs but ≥0.3g/24 hrs and a decrease of \>50% from Baseline based on 24 hours pooled urine, with no worsening of renal function(\<15% eGFR reduction from Baseline). eGFR at Baseline will be defined as the Day 0 values.

Proteinuria is being assessed at Weeks 0, 4, 12, 24 follow-up visits. Proteinuria is based on 24 hours pooled urine. Baseline is defined as the Day 0 values. The ratio is defined as the post-Baseline value divided by the Baseline value.

Serum creatinine is being assessed at Weeks 0, 4, 12, 24 follow-up visits. Baseline is defined as the Day 0 values. The ratio is defined as the post-Baseline value divided by the Baseline value.

eGFR is being assessed from levels of creatinine using the 4 variable version of the modification of diet in renal disease (MDRD) equation as recommended by national kidney foundation-chronic kidney disease (NKF-CKD) guidelines. eGFR is calculated at Weeks 0, 4, 12, 24 follow-up visits. Baseline is defined as the Day 0 values. The ratio is defined as the post-Baseline value divided by the Baseline value.

IgA levels in serum are being analyzed at Weeks 0, 4, 12, 24 follow-up visits. Baseline is defined as the Day 0 value. The ratio is defined as the post-Baseline value divided by the Baseline value.

Interleukin-6 levels in serum are being analyzed at Weeks 0, 4, 12, 24 follow-up visits by means of enzyme linked immunosorbent assay (ELISA). Baseline is defined as the Day 0 value. The ratio is defined as the post-Baseline value divided by the Baseline value.

Interferon alfa levels in serum are being analyzed at Weeks 0, 4, 12, 24 follow-up visits by means of enzyme linked immunosorbent assay (ELISA). Baseline is defined as the Day 0 value. The ratio is defined as the post-Baseline value divided by the Baseline value.

Tumor necrosis factor alpha levels in serum are being analyzed at Weeks 0, 4, 12, 24 follow-up visits by means of enzyme linked immunosorbent assay (ELISA). Baseline is defined as the Day 0 value. The ratio is defined as the post-Baseline value divided by the Baseline value.

Peking Union Medical College Hospital

Spots Global Cancer Trial Database for primary iga nephropathy