Effect of Hydroxychloroquine on Proteinuria and Inflammatory Markers in Chronic Glomerulopathy: A Proof-of-Concept Randomized Controlled Trial (HCQ-CGN Trial)
- 1Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
Abstract
Introduction: Hydroxychloroquine (HCQ) has immunomodulatory and anti-inflammatory properties that may provide additional benefit in chronic proteinuric glomerulopathy (CGN). This study aimed to evaluate the short-term effects of adjunctive HCQ on proteinuria and inflammatory biomarkers in patients with stable CGN receiving optimized supportive therapy.
Methods: In this single-center, double-blind, placebo-controlled proof-of-concept randomized trial, 43 patients with CGN (urine protein-to-creatinine ratio of ≥0.5 g/g and estimated glomerular filtration rate [eGFR] of >20 mL/min/1.73 m2) were randomized to receive eGFR-adjusted HCQ (n = 21) or placebo (n = 22) for 4 months. The primary outcome was change in proteinuria; secondary outcomes included interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), eGFR, and safety.
Results: After 4 months, the median percentage change in proteinuria was −27.9% (IQR, −55.1 to −15.5) with HCQ versus +20.7% (IQR, −6.9 to +45.4) with placebo. In mixed-effects maximum-likelihood regression adjusted for systolic blood pressure, HCQ was associated with a greater reduction in proteinuria than placebo (β, −118.55; 95% CI, −208.07 to −29.03; p = 0.009). A ≥30% reduction in proteinuria occurred more frequently with HCQ than placebo (50.0% vs. 14.3%; p = 0.014). IL-6 and hsCRP were also reduced with HCQ. No significant between-group difference in eGFR or serious adverse events was observed.
Conclusion: Adjunctive HCQ was associated with a short-term reduction in proteinuria in patients with stable chronic proteinuric glomerulopathy receiving optimized supportive therapy. Exploratory reductions in IL-6 and hsCRP were also observed. These proof-of-concept findings support further evaluation of HCQ in larger, longer, biopsy-based, disease-specific randomized trials.
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BibTeX
@article{supasil2026effect,
title = {{Effect of Hydroxychloroquine on Proteinuria and Inflammatory Markers in Chronic Glomerulopathy: A Proof-of-Concept Randomized Controlled Trial (HCQ-CGN Trial)}},
author = {Thitirat Supasil and Paramat Thimachai and Ouppatham Supasyndh and Bancha Satirapoj},
journal = {Glomerular Diseases},
year = {2026},
month = sep,
doi = {10.1159/gdz/acyag005},
url = {https://doi.org/10.1159/gdz/acyag005},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effect of Hydroxychloroquine on Proteinuria and Inflammatory Markers in Chronic Glomerulopathy: A Proof-of-Concept Randomized Controlled Trial (HCQ-CGN Trial)
AU - Thitirat Supasil
AU - Paramat Thimachai
AU - Ouppatham Supasyndh
AU - Bancha Satirapoj
PY - 2026
DA - 2026/09/29
JO - Glomerular Diseases
DO - 10.1159/gdz/acyag005
UR - https://doi.org/10.1159/gdz/acyag005
AB - Introduction: Hydroxychloroquine (HCQ) has immunomodulatory and anti-inflammatory properties that may provide additional benefit in chronic proteinuric glomerulopathy (CGN). This study aimed to evaluate the short-term effects of adjunctive HCQ on proteinuria and inflammatory biomarkers in patients with stable CGN receiving optimized supportive therapy. Methods: In this single-center, double-blind, placebo-controlled proof-of-concept randomized trial, 43 patients with CGN (urine protein-to-creatinine ratio of ≥0.5 g/g and estimated glomerular filtration rate [eGFR] of >20 mL/min/1.73 m2) were randomized to receive eGFR-adjusted HCQ (n = 21) or placebo (n = 22) for 4 months. The primary outcome was change in proteinuria; secondary outcomes included interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), eGFR, and safety. Results: After 4 months, the median percentage change in proteinuria was −27.9% (IQR, −55.1 to −15.5) with HCQ versus +20.7% (IQR, −6.9 to +45.4) with placebo. In mixed-effects maximum-likelihood regression adjusted for systolic blood pressure, HCQ was associated with a greater reduction in proteinuria than placebo (β, −118.55; 95% CI, −208.07 to −29.03; p = 0.009). A ≥30% reduction in proteinuria occurred more frequently with HCQ than placebo (50.0% vs. 14.3%; p = 0.014). IL-6 and hsCRP were also reduced with HCQ. No significant between-group difference in eGFR or serious adverse events was observed. Conclusion: Adjunctive HCQ was associated with a short-term reduction in proteinuria in patients with stable chronic proteinuric glomerulopathy receiving optimized supportive therapy. Exploratory reductions in IL-6 and hsCRP were also observed. These proof-of-concept findings support further evaluation of HCQ in larger, longer, biopsy-based, disease-specific randomized trials.
SN - 2673-3625
SN - 2673-3633
ER -