Clinical Profile and Outcomes of Patients with Membranous Nephropathy Resistant to Modified Ponticelli Regimen

ABSTRACT

Introduction: Membranous nephropathy is one of the most common causes of nephrotic syndrome. Among the available treatment options, the tried and tested regimen is the modified Ponticelli regimen. Despite adequate therapy, studies have shown that close to one-quarter of patients fail to attain complete remission. However, data is limited regarding patients who are resistant to this regimen. Method(s) This was an ambispective, observational study conducted in Madras Medical College, Chennai, India between April 2021 to August 2022. All patients with biopsy-proven primary membranous nephropathy resistant to modified Ponticelli regimen were included. Complete remission was defined as proteinuria < 0.5g/day combined with a stable eGFR. Partial remission was defined as reduction of proteinuria by 50% to < 3.5g/day but >0.5g/day. Resistance to therapy was defined as the failure to attain at least partial remission, 12 months after completion of modified Ponticelli regimen. Result(s) A total of 13 patients were enrolled in the study. The median age was 41 years (IQR 38-49) with a male preponderance (n=9;69%). Serum MPLA2R antibody was positive for 9 patients. All patients were negative for ANA and serology for hepatitis B, hepatitis C and HIV were negative. The most common clinical presentation was with nephrotic syndrome, seen in nine patients (69.23%). Renal failure was seen at presentation in 4 patients (30.76%), with one patient warranting initiation of hemodialysis. At 12 months, post completion of modified Ponticelli regimen, the median quantum of proteinuria was 8.7 grams per day. Due to trend towards normalisation of serum albumin and immunological remission, 3 patients were managed with optimised RAS inhibition after modified Ponticelli regimen. Currently, they are in partial remission. Four patients were treated with a second course of modified Ponticelli regimen. Of them one patient is in partial remission, while two patients had progressed to end-stage renal disease and are currently on maintenance hemodialysis. One patient who was resistant to the second course, was managed with a trial of calcineurin inhibitors (CNI) therapy followed by 4 doses of Rituximab (500mg each) due to persistent proteinuria. However, he was lost to follow up during the COVID pandemic and presented with end stage renal disease warranting hemodialysis. A trial of CNI therapy was given to 6 patients. All patients had nephrotic-range proteinuria 12 months post CNI therapy initiation. Five patients were then given Rituximab, among whom, two patients attained complete remission, while three patients have attained immunological and clinical remission. One patient was given a second trial of modified Ponticelli regimen following CNI therapy and is currently in complete remission. Two of these patients developed thrombotic complications - one patient diagnosed with coronary artery disease and one patient with renal vein thrombosis. Conclusion(s) Rituximab is a promising option for patients with primary membranous nephropathy who do not respond to modified Ponticelli regimen. No conflict of interestCopyright © 2023