Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy

Inclusion Criteria

• •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• •1. Stated willingness to comply with all study procedures and availability for the duration of the study
• •2. Male or female, \>= 18 years of age
• •3. Nephrotic range proteinuria that persists for at least 6 months post diagnosis of membranous nephropathy greater than 3.5 grams /24 hours (based on 24-hour urine collection).
• •a. If the subject s renal function rapidly declines in less than 6 months could proceed with immunosuppression therapy sooner such as complications of the nephrotic syndrome that are not controlled with supportive therapy or evidence of decline in glomerular filtration rate or proteinuria \>8 grams/day. Subjects with declining renal function and/or high-grade proteinuria due to MN are considered "high risk" subjects and have a higher probability of progression to end stage kidney disease.
• •4. Nephrotic range proteinuria (\>3.5 g/24 hours) that persists despite angiotensin antagonist therapy (ACE inhibitor or ARB) for at least 2 months unless intolerant.
• •a. The rationale is that blockade of the renin angiotensin system (RAAS) is widely considered to be part of the standard of care treatment for subjects with the nephrotic syndrome. Nephrotic range proteinuria will be defined as an estimated average proteinuria \>3.5 g/24 hours in adults based on at least two 24-hour urine protein excretions obtained prior to initiating therapy. Incomplete urine
• •collections (based on inadequate creatinine excretion) will be excluded.
• •5. Renal biopsy within the past 24 months must reveal typical changes of membranous nephropathy by light and electron microscopy or a positive anti-PLA2R antibody test in the serum. There has been a change in the management strategies for MN such that a renal biopsy is not absolutely required for diagnosis if patient has positive circulating anti-PLA2R antibody.
• •a. Based on published KDIGO 2021 Clinical Practice Guidelines 3.1.1 patients with MN who are positive for anti-PLA2R do not require renal biopsy as long as renal function is normal (eGFR \>60) and has not had immunosuppression as it has been demonstrated that results of the biopsy have not altered clinical approach and management. If not PLA2R positive, renal biopsy within 24 months is still required.
• •6. Blood pressure \<=140/90 on \>75% of measurement while on anti-hypertensive treatment for at least 1-2 months.
• •7. There is no evidence to suggest secondary forms of membranous nephropathy.
• •8. Ability to take oral medication and be willing to adhere to the cyclosporine regimen
• •9. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for 12 months after the last Rituximab infusion.
• •10. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
• •11. Ability of subject to understand and the willingness to sign a written informed consent document.