Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy

Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy: a Multicenter, Randomized, Open-label, Parallel Controlled Study

This is a prospective, multicenter, randomized, open-label, parallel controlled study. The purpose of this study is to evaluate the efficacy and safety of Huaier granule on the treatment of idiopathic membranous nephropathy comparing with Ciclosporin soft capsules.

Idiopathic membranous nephropathy (IMN) is a common immune-mediated glomerular disease, accounting for 20% to 36.8% of adult nephrotic syndrome. A third of the patients will experience complete remission spontaneously, and 30%-40% of patients will develop chronic renal failure. The treatment of IMN includes supportive therapy and immunosuppressive therapy. Ciclosporin (CsA) is a kind of calcineurin inhibitor (CNI) recommended by the Kidney disease improving global outcomes (KDIGO) clinical practice guideline for IMN treatment. CsA is effective in inducing remission among patients with steroid-resistant nephrotic IMN, and studies showed the clinical remission rate was 60%-75%. However, it has a high rate of relapse during follow-up in 6-12 months.

Huaier granule is an extract from a medicinal fungus. Previous studies showed that Huaier granule reduced the excretion of proteinuria, inhibited inflammation and cellular transdifferentiation, and protect renal function.

In this study, about 30 research centers will participate. We plan to enroll 480 participants (240 cases in the experimental group and 240 cases in the control group). The planned length of patient recruitment enrolment will be 2 years and the total length of visits be 1 year.

Inclusion Criteria:

• Renal biopsy was performed before randomization and pathologically diagnosed as idiopathic membranous nephropathy;
• Anti-phospholipase a2 receptor (PLA2R) antibody is positive;
• Aged from 18 to 75, either sex;
• Tolerable doses of RASI were received for ≥4 weeks before randomization, nephrotic syndrome was not in remission and 24-hour urinary protein level was ≥3.5g/24h and < 8.0g/24h;
• The eGFR≥45ml/min/1.73m2 (Measured at least twice in 2 weeks);
• The patient is willing to sign the informed consent form.

Exclusion Criteria:

• Diagnosed as secondary membranous nephropathy;
• Rapidly progressive membranous nephropathy (eGFR decreased by 50 % compared with the baseline level within 3 months);
• Receiving renal replacement therapy;
• Diabetes and glycosylated hemoglobin (HbA1c) levels ≥ 7.0%;
• Hypertension is not well controlled (systolic blood pressure>160mmHg or diastolic blood pressure>100mmHg);
• The level of serum albumin≤20g/L;
• Resistance to treatment with CsA or other CNI, rituximab (RTX) or alkylating agents; complete remission or partial remission was obtained after treatment with CNI, RTX, or alkylating agents but there was a history of relapse within 3 months；
• Suspected infection by imaging and/or laboratory tests;
• Infectious diseases, such as hepatitis B, hepatitis C, AIDS, tuberculosis;
• History of malignant tumor;
• Hepatic dysfunction: aspartate aminotransferase (AST) concentration and alanine aminotransferase (ALT) concentration of > 1.5 × upper limit of normal;
• Allergic to Huaier granule or Ciclosporin soft capsules;
• Previous CNI treatment was ineffective;
• Complicate with any diseases that may affect efficacy and safety evaluation;
• Pregnant or lactating women, and patients (male or female) with fertility plans or unwilling to take effective contraceptive measures;
• Participating in other clinical trials or participated in other clinical studies within 3 months;
• According to the researchers, patients have diseases or conditions that increase the difficulty of enrollment or probability of loss to follow-up, such as mental illness, frequent changes in residence and work, etc.