Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial

Frisch, Gershon; Lin, Julie; Rosenstock, Jordan L.; Markowitz, Glen S.; D’Agati, Vivette D.; Radhakrishnan, Jai; Preddie, Dean C.; Crew, John R.; Valeri, Anthony M.; Appel, Gerald B.

doi:10.1093/ndt/gfh974

Cited by 192 publications

(151 citation statements)

References 16 publications

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“…No curative treatment is available 67. In the present study, pulse methylprednisolone therapy followed by oral corticosteroids plus azathioprine or cyclosporine was used in cases of crescentic glomerulonephritis with acute renal failure.…”

Section: Discussionmentioning

confidence: 99%

“…Therapeutic efforts have been directed at either reducing or preventing antigen entry, as well as altering the abnormal immune response and its consequences. However, the appropriate therapy for IgAN remains uncertain, and curative therapy is still not available 67. The aim of this study was to review cases of IgAN treated at our institution over a 5-year period and to study the spectrum of clinical presentation and histopathological findings.…”

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confidence: 99%

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Clinical and histopathological spectrum of IgA nephropathy in Kuwait

Ghani

Waheeb

Homoud

et al. 2011

Annals of Saudi Medicine

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BACKGROUND:Little is known about the nature and the course of IgA nephropathy (IgAN) in Arab countries. The aim of this work was to study the spectrum of clinical presentation and histopathological findings at our institution.DESIGN AND SETTING:Retrospective review, all renal biopsies at the Mubarak Al Kabeer Hospital between January 2000 and December 2004.METHODS:Cases of IgA nephropathy were selected, and their medical records and biopsy findings were reviewed.RESULTS:Eighty patients (9.2% of all native kidney biopsies) were diagnosed to have IgAN nephropathy. Sixty-nine biopsies were included in the study;11 were excluded. Forty-three (62.3%) patients were male and 26 (37.7) patients were female. Fifty (72.5%) patients were below the age of 40 years. Mean (SD) duration of follow-up was 3.6 (1.3) years. The first presentation included nephritic-range proteinuria (49.3%) and renal impairment (50.7%). During the follow-up period, 56 (81.2%) patients were stable or improved. Hass classification of biopsies showed 36.2% had class I, 27.5% had class II, 13.0% had class III, 5.8% had class IV, and 17.4% had class V IgAN. Females had milder forms of the disease than males. Macroscopic hematuria and renal impairment at presentation were seen more in patients with class IV and V IgAN. The presenting serum creatinine and uric acid values were higher in those with Hass classes III to V. Deterioration of renal function during the follow-up period was more significant in the presence of hypertension, renal impairment, or macroscopic hematuria at the time of biopsy .CONCLUSION:The prevalence of IgAN in Kuwait is about 9.2%. Renal impairment or macroscopic hematuria at presentation was seen in patients with more aggressive renal lesions and contributed to poor outcome.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Clinical and histopathological spectrum of IgA nephropathy in Kuwait

Ghani

Waheeb

Homoud

et al. 2011

Annals of Saudi Medicine

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“…To date only four RCTs have compared MMF with placebo [4][5][6][7]11] and results have been conflicting. All studies have been small (between 17 and 22 patients receiving MMF monotherapy) and have utilised different inclusion criteria, ethnic populations and durations of follow up.…”

Section: Discussionmentioning

confidence: 99%

“…Current research has produced conflicting data about the benefit of mycophenolate mofetil (MMF) therapy in IgAN [4][5][6][7][8][9][10]. Four small randomised controlled trials have been performed, with a range of results reported.…”

Section: Introductionmentioning

confidence: 99%

“…Four small randomised controlled trials have been performed, with a range of results reported. Some have demonstrated no benefit from MMF therapy [4,5,7], particularly in advanced fibrotic disease [5], while others have described a reduction in proteinuria and long term renoprotection following treatment with MMF [6,11]. Previous studies looking at outcomes in IgAN have been limited by a lack of specific histological inclusion and exclusion criteria.…”

Section: Introductionmentioning

confidence: 99%

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Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment

Beckwith

Medjeral-Thomas

Galliford

et al. 2017

Nephrology Dialysis Transplantation

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Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy

et al. 2023

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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

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Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial

Abstract: No benefit was seen in patients who received MMF in this high risk group, probably reflecting the relatively advanced stage of disease of our population. We conclude that MMF is probably not effective in patients with IgAN who already have moderate renal insufficiency.

Cited by 192 publications

References 16 publications

Clinical and histopathological spectrum of IgA nephropathy in Kuwait

Clinical and histopathological spectrum of IgA nephropathy in Kuwait

Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment

Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy

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