IgA nephropathy is the most common primary glomerulonephritis in the world. Because of the poor treatment effect in advanced patients, it is still the main cause of maintenance dialysis. Current immunosuppressive therapy is still controversial, especially to those progressive IgA nephropathy with eGFR<50ml/min. Leflunomide is widely used in the treatment of rheumatic diseases, such as rheumatoid arthritis and lupus nephritis, it's serum concentration will not be affected by renal function, and it also has antiviral effect. There are two randomized controlled trials and a retrospective study suggesting that leflunomide combined with glucocorticoids can effectively control urinary protein compared with glucocorticoids or conservative treatment, but these three studies are not specifically targeted at patients with estimated Glomerular Filtration Rate(eGFR) < 50ml/min.

Investigators will perform a prospective, open-label, randomized, controlled trial to evaluate the efficacy and safety of leflunomide and low dose glucocorticoids therapy in progressive IgA nephropathy with eGFR<50ml/min

all the participants enrolled in the study will be randomly assigned in a 1:1 ratio, the experimental group will receive leflunomide + low dose glucocorticoids therapy on the basis of conservative treatment, while the control group receive conservative treatment only. Conservative treatment is defined as the treatment of delaying the progress of renal function, including low-protein diet supplemented with ketoacid therapy, Renin Angiotensin system (RAS) inhibitor, blood pressure control, lipid-regulating therapy and antiplatelet aggregation therapy. The course of treatment will last one year, then the leflunomide+glucocorticoids group will continue the conservative treatment. Participants will be follow-up at least 98 weeks.

Inclusion Criteria:

• 14 to 65 years old participants, No restrictions on gender or race
• Diagnosis of primary IgA nephropathy
• Renal biopsy within 6 months before screening. Renal pathology shows diffuse IgA deposition in the Mesangial area and dense deposition in the Mesangial area under electron microscope. glomeruli more than 8
• persistent proteinuria ≥ 1 g/24 hr (or urine protein/creatinine ratio ≥ 1.0 mg/g), eGFR at 25-50 ml/min/1.73 m2 (calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula)
• signed written consent; patients under 18 years old need to have legal guardians to sign informed consent at the same time

Exclusion Criteria:

• Secondary IgA nephropathy (such as lupus nephritis, Henoch-Schönlein purpura, hepatitis B associated glomerulonephritis, hepatitis C associated glomerulonephritis, liver cirrhosis and other autoimmune diseases)
• eGFR < 25 ml/min/1.73m2 or eGFR > 50 ml/min/1.73m2 (calculated by CKD-EPI formula)
• Special types of IgA nephropathy need to be excluded, such as crescent IgA glomerulonephritis (defined as the presence of crescents in over 50% of the glomeruli), or minimal lesions with IgA deposition
• Acute kidney injury within 3 months before screening
• Received immunosuppressive therapy within 3 months before screening
• Patients who had acute or chronic infections that need treatment, and the researchers judged that they were not suitable for inclusion in the study
• Pregnancy, lactation or unreliable birth control
• Dialysis treatment before screening
• Allergic or taboo to planned drugs (such as leflunomide, glucocorticoids, etc.)
• Severe acute or chronic diseases that the researchers believe may bring an excessive risk to the subjects
• A history of malignant tumors within 5 years, with the exception of carcinoma in situ and papillary thyroid carcinoma which have been adequately treated
• Participated in other clinical trials and / or used other research drugs within 4 weeks prior to screening

it is a open label trial