Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy

Abstract

ImportanceThe role of mycophenolate mofetil (MMF) in management of immunoglobulin A nephropathy (IgAN) remains highly controversial.ObjectiveTo evaluate the efficacy and safety of MMF in patients with IgAN at high risk of kidney function loss.Design, Setting, and ParticipantsThis randomized clinical trial with open-label, blinded end-point design was conducted among adults with IgAN, proteinuria greater than 1.0 g/d, and estimated glomerular filtration rate (eGFR) greater than 30 and less than 60 mL/min/1.73m2 or with persistent hypertension from September 2013 to December 2015. During a 3-month run-in period, 238 patients received optimized supportive care (SC), including losartan. Patients with a urinary protein excretion rate of 0.75 g/d or greater despite of 3 months optimized SC were enrolled into the trial for 3 years. Survivors of the trial who did not receive dialysis or transplant were followed up after the trial for a median (IQR) of 60 (47-76) months. Data were analyzed from March through June 2022.InterventionsA total of 170 participants were randomized in a 1:1 ratio to receive MMF (initially, 1.5 g/d for 12 months, maintained at 0.75-1.0 g for at least 6 months) plus SC or SC alone.Main Outcomes and MeasuresThe primary outcomes were (1) a composite of doubling of serum creatinine, end-stage kidney disease (dialysis, transplant, or kidney failure without receiving kidney replacement therapy), or death due to kidney or cardiovascular cause and (2) progression of chronic kidney disease.ResultsAmong 170 randomized patients (mean [SD] age 36.6 [9.4] years; 94 [55.3%] male patients), 85 patients received MMF with SC and 85 patients received SC alone. The mean (SD) eGFR was 50.1 (17.9) mL/min/1.73m2 and mean (SD) proteinuria level was 1.9 (1.7) g/d; 168 patients (98.8%) completed the trial, and 157 participants (92.4%) survived and did not receive dialysis or transplant. Primary composite outcome events occurred in 6 patients (7.1%) in the MMF group and 18 patients (21.2%) in the SC group (adjusted hazard ratio [aHR], 0.23; 95% CI, 0.09-0.63). Progression of chronic kidney disease occurred in 7 participants (8.2%) in the MMF group and 23 participants (27.1%) in the SC group (aHR, 0.23; 95% CI, 0.10-0.57). The effect of MMF treatment on primary outcomes was consistent across prespecified subgroups, with no significant interaction per subgroup. During posttrial follow-up, annual loss of eGFR accelerated after discontinuation of MMF; mean (SD) annual eGFR loss during the study period was 2.9 (1.0) mL/min/1.73m2 in the MMF group and 6.1 (1.2) mL/min/1.73m2 among 66 patients in the MMF group who discontinued MMF after the trial. Serious adverse events were not more frequent with MMF vs SC alone.Conclusions and RelevanceThis study found that addition of MMF to SC compared with SC alone significantly reduced risk of disease progression among patients with progressive IgAN.Trial RegistrationClinicalTrials.gov Identifier: NCT01854814

Considering the Treatment of IgA Nephropathy

“…, mycophenolate with or without corticosteroids, average exposure 18 months). Consistent with recent randomized control trials of methylprednisolone or of mycophenolate in China, 4,6 they find an impressive 35% risk reduction (HR [hazard ratio] unadjusted 0.64 [0.53–0.79], adjusted 0.60 [0.48–0.75]) in these hard end points with immunosuppressive therapy, either examined overall or by individual class of medication. As in other reports, the authors show that adverse events leading to hospital stays were greater with these interventions (3% with immunosuppression, 1% without, higher in immunosuppressed patients with eGFR <60 ml/min, 5%).…”

Clinicopathological Features and Outcomes of IgA Nephropathy with Serum Antineutrophil Cytoplasmic Autoantibody Positivity

“…ANCA-positive IgAN patients were more frequently treated with immunosuppressants in our study, and the use of immunosuppressants may influence prognosis. But the efficacy of immunosuppressants in the treatment of IgAN is still controversial in randomized controlled trials [26, 27]. This is only an observational study, so the efficacy of immunosuppressants in the treatment of IgAN with ANCA positivity is uncertain.…”

Treatment of IgA Nephropathy: A Rapidly Evolving Field

“…8 The more recent Effect of Mycophenolate Mofetil on Renal Outcomes in Advanced Immunoglobulin A Nephropathy trial, performed in patients with proteinuria .1 g/d, hematuria, and eGFR between 30 and 60 ml/min per 1.73 m 2 or with persistent hypertension, revealed that 18-month MMF reduced the risk of a composite end point of doubling of serum creatinine, ESKD, or death due to kidney or cardiovascular cause by 77% after 3 years of follow-up. 50 Interestingly, pathologic findings at presentation (41% C1, 55% T2, 62% glomerulosclerosis .50%) suggested already advanced disease. Furthermore, subgroup analyses showed that patients with eGFR 30-50 ml/min per 1.73 m 2 benefited equally or more from MMF compared with those with eGFR .50 ml/min per 1.73 m 2 .…”