Tripterygium wilfordii Hook F Treatment for Stage IV Diabetic Nephropathy: Protocol for a Prospective, Randomized Controlled Trial

BACKGROUND: Diabetic nephropathy (DN) is a major cause of chronic kidney disease (CKD). There are no effective treatments to prevent or reverse the progression of DN. A preliminary study showed that Tripterygium glycosides from Tripterygium wilfordii Hook F (TwHF) with valsartan decrease proteinuria in patients with DN. OBJECTIVES: The objective of the present study is to investigate the efficacy and safety of Tripterygium glycosides from TwHF, a traditional Chinese medicine, for the treatment of DN. Methods and Analysis. This is a prospective, single-center randomized controlled trial. Seventy participants diagnosed with DN were recruited and randomized 1 : 1 to two groups: (1) angiotensin receptor blocker (ARB) combined with TwHF and (2) ARB-only. The treatment period is 48 weeks. The primary endpoint is 24 h proteinuria decreased level (reduction of 30% vs. baseline) after 48 weeks of treatment. The secondary endpoints are (1) all-cause and cardiovascular-related mortality, (2) development of ESRD (serum creatinine > 530.4 μmol/L or estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m(2)), (3) the need for renal replacement therapy, and (4) increased serum creatinine (2-fold higher than the baseline value or ≥442 μmol/L, with confirmation of the initial results after 4 weeks). A health economics analysis will be carried out. Discussion. A meta-analysis of RCTs carried out in patients with stage 4 (Mogensen classification) diabetic CKD showed that TwHF combined with an ARB was more effective than an ARB alone when considering 24 h proteinuria and serum albumin, but with an increase in adverse event (AE) frequency of 8%. This is a prospective clinical trial that may provide information on a safe and effective novel method for the treatment of DN, especially for patients with macroproteinuria. Ethics and Dissemination. The protocol is approved by the ethics committee of Beijing Hospital (2016BJYYEC-059-02). The results will be disseminated through peer-reviewed publications and international conferences. This trial is registered with ChiCTR-IOR-17010623.