#5827 MYCOPHENOLATE MOFETIL AS IMMUNOSUPPRESSIVE THERAPY IN IGA NEPHROPATHY
Authors: Barrington-White Henry , Pomeranc Abigail , Murphy Conor , Ghalli Farid 
Published: June 2023

Abstract

Background and Aims
IgA Nephropathy is the commonest cause of primary Glomerulonephritis in developed countries. It is characterised by IgA-dominant deposits in the mesangium on renal biopsy. Classically presenting with asymptomatic non-visible haematuria or episodic visible haematuria 24-48 hours after an upper respiratory tract infection, raised BP and Proteinuria. End-stage renal disease (ESRD) can occur in up to 20-50% of patients. Treatment with ACEI/ARB has strong evidence in managing IgA. If there is evidence of progression, steroids and immunosuppression are recommended. Mycophenolate Mofetil's effectiveness in IgA nephropathy is controversial. KGIGO guidelines authors suggest not to use it. In this work, we reviewed immunosuppression with mycophenolate Mofetil (MMF) retrospectively in IgA nephropathy patients managed at Sussex Kidney unit – Brighton -UK.

Method
We retrospectively reviewed 25 patients who had a diagnosis of IgA nephropathy and were treated with mycophenolate mofetil as immunosuppression for IgA nephropathy under the care of the Sussex Renal Unit at University Hospitals Sussex. Patients reviewed, had been diagnosed between 2011-2020. Data collected from our department's electronic system, including laboratory results, histopathology reports, clinic letters and medications. Data were collected until January 2023 for patients who had renal survival. For patients who started on renal replacement therapy (RRT), data were collected until the start of RRT. The work aimed at looking at MMF efficacy in IgA nephropathy. The primary measures were renal survival without the need for RRT and proteinuria reduction to &gt; 50% of the baseline at diagnosis.

Results
We reviewed 25 patients, 13 male and 12 female. Twenty-four patients (96%) were of white Caucasian ethnicity while one patient (4%) was Asian. The mean age was 42.4± 16 years. All the patients were diagnosed with both clinical pictures and renal biopsies. Oxford classification score showed M1 (21) patients, E (5 patients), S (19 patients), T (1 = 10 patients, 2 = 4 patients), and C (1 = 15 patients, 2 = 4 patients). On presentation, 5 patients presented with a sore throat, 8 with skin rash and 7 with macroscopic haematuria. Seventeen patients (60%) presented with AKI. Eleven patients (44%) had nephrotic range proteinuria on presentation. The average duration of the disease was 6.1 years at the time of assessment. MMF was used in the 25 patients, five of them had prednisolone and cyclophosphamide for 3 months followed by MMF maintenance. Twenty patients were treated with MMF alone or in combination with steroids (17 patients) from the start. The average duration of treatment was 2 years, and the average dose was 1 gm twice daily. Five patients (20%) progressed to ESRD and three of them had renal transplantation while twenty patients (80%) maintained renal survival. For the 80% who maintained renal survival the mean eGFR at diagnosis was 45.6± 34.1 and at the time of assessment was 56.1±26.6. Of the 17 patients presented with AKI, five patients (29.4%) recovered to normal renal function, five patients had ESRD (29.4%) and four had improvements of eGFR while three patients showed a decrease of eGFR (Mean 45.6± 1.1 ml/min) to eGFR (Mean 32± 8.2 ml/min). In total, 70.6% of AKI patients recovered either to normal or to CKD level and 80% of the total patients had renal survival without RRT during the time of review. Twenty patients (80%) achieved more than 50% reduction of proteinuria, with five patients (20%) having proteinuria less than 0.3 g/24 hours and 9 (36%) patients less than 0.5 g/24 hours. Comparison between the proteinuria at diagnosis and at the time of assessment was significant (P&lt;0.001).

Conclusion
Mycophenolate mofetil was effective in maintaining renal survival and improving proteinuria in IgA nephropathy patients who were indicated for immunosuppression based on histopathology and risk of progression. It was well tolerated by patients. A randomised controlled trial is needed to compare the MMF effect in comparison with currently available therapies.