Yaotong Shi, Ye Wang, Nan Li, Qiuyuan Shao, Chunming Jiang, Ting Yang, Jing Liu
{"title":"Pharmacokinetic Aspects of Hydroxychloroquine and Its Relationship to Efficacy in Immunoglobulin A Nephropathy.","authors":"Yaotong Shi, Ye Wang, Nan Li, Qiuyuan Shao, Chunming Jiang, Ting Yang, Jing Liu","doi":"10.1159/000543131","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Hydroxychloroquine (HCQ) is recommended for Chinese patients with immunoglobulin A nephropathy (IgAN). This study aimed to investigate the pharmacokinetics of HCQ in the treatment of IgAN and its relationship with therapeutic efficacy.</p><p><strong>Methods: </strong>This prospective study included 49 IgAN patients treated with HCQ, who were divided into effective and ineffective groups based on HCQ treatment efficacy after 6 months, defined as a reduction in proteinuria of at least 50% from baseline. The concentrations of HCQ and its metabolites were measured by high-performance liquid chromatography-tandem mass spectrometry. The relationships between the concentrations of HCQ and its metabolites and therapeutic efficacy were analyzed using linear correlation analysis and logistic regression. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of HCQ and its metabolite concentrations.</p><p><strong>Results: </strong>Following 6 months of treatment with HCQ, patients in the effective group exhibited increased concentrations of HCQ (<i>p</i> = 0.022) and desethylchloroquine (DCQ) (<i>p</i> = 0.015). The results of the Spearman's correlation analysis indicated a positive correlation between alterations in proteinuria and concentrations of HCQ (<i>r</i> = 0.328, <i>p</i> < 0.05) and DCQ (<i>r</i> = 0.267, <i>p</i> < 0.05). Univariate and multivariate logistic regression analyses indicated that efficacy was significantly correlated with HCQ (odds ratio 1.008, 95% CI: 1.001-1.014) and DCQ (odds ratio 1.064, 95% CI: 1.010-1.121) concentrations. ROC curves indicated that an HCQ concentration of 442.6 ng/mL and a DCQ concentration of 42.7 ng/mL exhibited the optimal capacity to predict efficacy (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>The blood concentrations of HCQ and its metabolite DCQ may be significant factors for evaluating therapeutic efficacy in IgAN patients.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"38-48"},"PeriodicalIF":3.2000,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842063/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000543131","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Hydroxychloroquine (HCQ) is recommended for Chinese patients with immunoglobulin A nephropathy (IgAN). This study aimed to investigate the pharmacokinetics of HCQ in the treatment of IgAN and its relationship with therapeutic efficacy.
Methods: This prospective study included 49 IgAN patients treated with HCQ, who were divided into effective and ineffective groups based on HCQ treatment efficacy after 6 months, defined as a reduction in proteinuria of at least 50% from baseline. The concentrations of HCQ and its metabolites were measured by high-performance liquid chromatography-tandem mass spectrometry. The relationships between the concentrations of HCQ and its metabolites and therapeutic efficacy were analyzed using linear correlation analysis and logistic regression. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of HCQ and its metabolite concentrations.
Results: Following 6 months of treatment with HCQ, patients in the effective group exhibited increased concentrations of HCQ (p = 0.022) and desethylchloroquine (DCQ) (p = 0.015). The results of the Spearman's correlation analysis indicated a positive correlation between alterations in proteinuria and concentrations of HCQ (r = 0.328, p < 0.05) and DCQ (r = 0.267, p < 0.05). Univariate and multivariate logistic regression analyses indicated that efficacy was significantly correlated with HCQ (odds ratio 1.008, 95% CI: 1.001-1.014) and DCQ (odds ratio 1.064, 95% CI: 1.010-1.121) concentrations. ROC curves indicated that an HCQ concentration of 442.6 ng/mL and a DCQ concentration of 42.7 ng/mL exhibited the optimal capacity to predict efficacy (p < 0.05).
Conclusion: The blood concentrations of HCQ and its metabolite DCQ may be significant factors for evaluating therapeutic efficacy in IgAN patients.
期刊介绍:
''Kidney Diseases'' aims to provide a platform for Asian and Western research to further and support communication and exchange of knowledge. Review articles cover the most recent clinical and basic science relevant to the entire field of nephrological disorders, including glomerular diseases, acute and chronic kidney injury, tubulo-interstitial disease, hypertension and metabolism-related disorders, end-stage renal disease, and genetic kidney disease. Special articles are prepared by two authors, one from East and one from West, which compare genetics, epidemiology, diagnosis methods, and treatment options of a disease.