Abelmoschus manihot – a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial

Abstract

BackgroundIgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN.MethodsWe will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks.DiscussionThis study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN.Trial registrationClinicalTrials.gov, identifier: NCT02231125. Registered on 30 August 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1774-6) contains supplementary material, which is available to authorized users.

Inhibition of Akt/mTOR/p70S6K Signaling Activity With Huangkui Capsule Alleviates the Early Glomerular Pathological Changes in Diabetic Nephropathy

“…HKC and its bioactive component hyperoside (HYP) can ameliorate proteinuria and renal dysfunction for patients and animal models with the early chronic kidney disease (CKD) (Chen et al, 2015 ; Ge et al, 2016 ). Recently, the increasing clinical evidences in China have been suggested that HKC at the safe and effective dose of 7.5 g/kg/day can reduce micro-urinary albumin (micro-UAlb) in the early DN patients and the IgA nephropathy patients (Liu et al, 2010 ; Li et al, 2017 ), and that its therapeutic action may be concerned with regulating transforming growth factor-β1 (TGF-β1) signaling in vivo (Tu et al, 2013 ), and inhibiting high-glucose (HG)-induced renal tubular epithelial-mesenchymal transition in vitro (Cai et al, 2017 ). In addition, our previous animal experiment as the first step revealed that, after the drug-intervention for 8 weeks, 2 g/kg/day dose of HKC can significantly attenuate the advanced renal fibrosis in the DN model rats induced by the unilateral nephrectomy combined with the intraperitoneal injection of streptozotocin (STZ) through regulating oxidative stress and p38 mitogen-activated protein kinase/Akt pathways (Mao et al, 2015 ).…”

Traditional Uses, Chemical Constituents, Biological Properties, Clinical Settings, and Toxicities of Abelmoschus manihot L.: A Comprehensive Review

“…This suggests that HKC might be a promising agent for patients with primary kidney disease and moderate proteinuria, especially in CKD stages 1 and 2 ( Carney, 2014 ; Zhang et al., 2014 ). Li et al. (2017) assessed the efficacy and safety of HKC for treating immunoglobulin A (IgA) nephropathy in a multicenter, prospective, double-blind, and double-dummy randomized controlled clinical trial by enrolling approximately 1600 patients with biopsy-proven IgA nephropathy at 100 centers and following them for up to 48 weeks.…”

“…The results of this study indicated that HKC (at a dose of 2.5 g [i.g.] three times per day) markedly decreased 24 h urinary protein and the estimated glomerular filtration rate with respect to baseline after treatment for 48 weeks ( Li et al., 2017 ). In addition, two systematic reviews and a meta-analysis were conducted to determine the safety and efficacy of HKC for the treatment of DN and type 2 DN, respectively.…”

“…Furthermore, Huangkui capsule (HKC), a Chinese patent medicine, is a single plant-based drug extracted from the dry flowers of A. manihot . HKC was approved by the State Food and Drug Administration of China (Z19990040) in 1999 for the treatment of CKD, such as DN, chronic glomerulonephritis, membranous nephropathy, and other inflammatory diseases, in clinical practice ( Zhang et al., 2014 ; Du L. Y. et al., 2015 ; Li et al., 2017 ). Its main mechanisms of action include improving the immune response, decreasing inflammation, improving renal fibrosis, and protecting renal tubular epithelial cells ( Chen et al., 2012 ).…”

Zhen-Wu-Tang Protects IgA Nephropathy in Rats by Regulating Exosomes to Inhibit NF-κB/NLRP3 Pathway

“…More and more traditional Chinese medicine (TCM) has been used for prevention and treatment of IgAN and gradually approved worldwide ( Li et al., 2017 ; Li and Li, 2020 ). Zhen-wu-tang (ZWT) is a classical prescription of Treatise on Febrile Diseases written by Zhongjing Zhang, composed of Aconiti Lateralis Radix Praeparata, Poria, Atractylodis Macrocephalae Rhizoma, Paeoniae Radix Alba and Zingiberis Rhizoma Recens .…”