EXTENDED USE OF MYCOPHENOLATE MOFETIL IMPROVES REMISSION RATES IN C3GN ALBEIT CONCERNS OF INFECTION EPISODES AND DISEASE PROGRESSION

C3 glomerulonephritis (C3GN) belongs to a rare group of disorders with complement pathway dysregulation. While complement factor inhibitors are currently undergoing trials, steroids and mycophenolate mofetil (MMF/Std) are the mainstay of treatment over the last decade. Though the guideline from Kidney Disease: Improving Global Outcomes suggesting a course of MMF/Std  for six months, the evidence for the duration of immunosuppression and withdrawing MMF in patients who do not achieve remission is yet unclear. We present our single center experience using combination of steroids with mycophenolate mofetil beyond six months in patients with C3GN. 

In the present retrospective, single-center, observational study, records of patients with C3GN on biopsy and following up in the study center between August 2015 and July 2025 were extracted (n=112). Patients who had spontaneous remissions (n=4), received only steroids (n= 26), received cyclophosphamide with steroids (n=27) or received conservative management due to biopsy findings such as diffuse global glomerulosclerosis on biopsy (n= 17), were excluded from the analysis. The patients who received both cyclophosphamide and mycophenolate sequentially (n=3), and those who received plasma exchange or rituximab in addition, were also excluded (n= 4).  

The present analysis included a total of 31 patients (median age 19 (14-27) years, 38.7% females) who received mycophenolate mofetil in addition to steroids (MMF/Std) with a median follow-up of 15 (10-41) months. Presentation as nephrotic, nephritic and nephroto-nephritic syndromes, was nearly equally distributed (9, 10, 11 patients, respectively). Overall, any remissions (complete and partial) occurred in 64.5% of patients receiving MMF/Std, however, only 7% achieved any remission by 6 months, and another 38.7% achieved any remission between 6 and 12 months. In a subgroup of eight patients with crescents on biopsy, the remission rate was much lower, at 25%. Trends of serum creatinine from baseline to 6,12 months and last follow-up, are depicted in Figure 1, among patients with remission and in those with progressive disease. Progressive GFR loss took place in 19.4% of patients on MMF/Std. Endstage kidney disease developed in 9.7% of those on MMF/Std. A total of 11 hospitalizations were recorded in 8 patients (26%). all of which were due to suspected/proven infection-related (2 were episodes of lower respiratory infection, 2 with urinary tract infection, 3 with raised procalcitonin levels and unclear primary source, 2 with pulmonary and disseminated tuberculosis, 2 with SARS-Cov2 pneumonia, and one mortality due to disseminated tuberculosis. Repeat kidney biopsies were undertaken in 7 patients with progressive renal failure and/or nephrotic proteinuria, all of whom received > 12 months of MMF/Std. (Figure 2) Increase in globally sclerosed glomeruli by a median of 17.6% (inter-quartile range 3-25%) and increase in severity grade of tubular atrophy by 1 (inter-quartile range 0-1) were the only notable changes, with zero median change in percentage of mesangial and endocapillary hypercellularity, segmental sclerosis, crescents and grade of interstitial fibrosis. 

Combination of mycophenolate mofetil and steroids beyond 6 months was efficacious in effecting remissions in nearly two-thirds of the study population with continued usage, making this an effective treatment option. However, risks of infection-related hospitalization (26%) and progressive renal failure (19%) raise concerns. Repeat kidney biopsies among patients receiving > 12 months of combination immunosuppression, showed predominantly increase in global glomerulosclerosis and tubular atrophy, suggesting mechanisms other than glomerular inflammation, might underlie progression of renal failure in these patients.