P0287LONG-TERM CLINICAL OUTCOMES IN IDIOPATHIC MEMBRONOUS NEPHROPATHY TREATED BY CYCLOSPORINE AND PREDNISOLONE
Authors: Ito Chiharu , OTSUKA Yasuhiro , Takeda Asami 
Published: June 2020

Abstract

Background and Aims
Membranous nephropathy (MN) is the most common primary glomerular disease diagnosed in older patients. MN in adults is most often idiopathic, and risk factors of clinical findings for progressive idiopathic MN (iMN) seems to be older age at onset, male sex, and nephrotic-range proteinuria persisting for several months. Immunosuppressive therapy should be applied to the patients with iMN who have risk factors for progression, however little is known about the most effective regimen of immunosuppressive therapy. In addition, long-term prognosis of iMN for each immunosuppressive regimen is unclear. Most of the patients with iMN at our center were treated by prednisolone (PSL) and cyclosporine (CYA) combination therapy, and commencement of therapy was around the time of renal biopsy. The objective of this study is to assess medium to long-term outcome of treated iMN patients with CYA at our center.

Method
Retrospective data were collected from January 2000 to December 2014 on all consecutive 1080 native renal biopsy at our center. 102 cases were diagnosed as MN. Of 102 MN cases, 43 cases were iMN, which was IgG4 dominant or codominant in immunofluorescence of IgG subclass. Secondary MN is diagnosed by clinical history of possible drug use, the presence of malignancy, positive serologic tests for both infection and connective tissue diseases, hepatitis B or hepatitis C virus positive, and full house immunofluorescence.

Results
Of 43 iMN cases, there were 4 cases who were treated with only nonimmunosuppressive therapies, 5 cases who were treated with PSL, and 34 cases who were treated with CYA combination. Immunosuppressive therapy commenced within one month before and after renal biopsy. Immunosuppressive regimen was determined by each doctor. CYA was administered once-daily, and the area under the concentration-time curve up to 4 hour after administration of CYA (AUC0-4h) was determined in each patient. No infectious complications were found. The duration of CYA use was 194.7±848.9 days (median 786.5 days), and follow-up period of CYA group was 3026.4±1608.0 days.
There were no significant differences between PSL group and CYA group in age (53.4±20.6 years vs. 64.1±10.6 years, p=0.162), sex (1 male 4 female vs. 23 male 11 female ,p=0.162), urinary protein (1.37±0.65 g/gCre vs. 5.44±3.64 g/gCre, p=0.0679), serum creatinine at the time of renal biopsy (0.66±0.19 mg/dl vs. 1.09±0.57 mg/dl, p=0.352), a 30% eGFR decline (0 cases vs. 2 cases), cases achieved complete remission (CR) (5 cases vs. 26 cases, p=0.196), and time from commencement of immunosuppressive therapy to CR (748.2±795.5 days vs. 422.2±379.9 days, p=0.242).
There were no significant differences between non-remission cases in CYA group (8 cases) and remission cases in CYA group (26 cases) in age, sex, and urinary protein, but serum creatinine was significantly greater in non-remission cases than remission cases in CYA group (1.75±1.01 mg/dL vs. 0.94±0.29mg/dL, p=0.0251).
There were no significant differences between non-recurrent cases in CYA group (16 cases) and recurrent cases (10 cases) in CYA group in age, sex, urinary protein, and serum creatinine at the time of renal biopsy.

Conclusion
Between PSL group and CYA group, there were no significant differences in age, and sex at the time of biopsy, and there was a trend that urinary protein was greater in CYA group than in PSL group (p=0.0679). Due to the tendency that urinary protein at the biopsy was greater in CYA group, no significant differences were seen in the remission rate and the time from commencement of immunosuppressive therapy to remission between PSL group and CYA group. Despite long duration of CYA use, infectious complications and renal function deterioration were not seen, so CYA can use safely by dose adjustment by AUC0-4h. Further study is needed to provide enough evidence of effectiveness of CYA combination therapy.