Corticosteroids and mycophenolic acid analogues in immunoglobulin A nephropathy with progressive decline in kidney function

Abstract

Background A randomized controlled trial (RCT) demonstrated a beneficial effect of corticosteroids (CS) plus cyclophosphamide followed by azathioprine in progressive IgA nephropathy (IgAN). Although treatment with CS and mycophenolic acid analogs (MPAA) remains controversial in IgAN, there is no information about their effect in progressive IgAN. Methods Patients with progressive IgAN, defined by a decrease in estimated glomerular filtration rate (eGFR) of at least 10 ml/min/1.73 m2 in the 12 months prior to the start of treatment, proteinuria ≥ 0.75 g/24h despite maximum tolerated doses of renin-angiotensin system blockers (RASB) and persistent hematuria, who had received treatment with CS+MPAA were included in this retrospective study. The main outcome was the difference between the eGFR slope from the start of treatment with CS+MPAA to the last visit with this treatment with respect to the eGFR slope during the 12 months prior to start of treatment. Results Twenty-five patients were included in the study. Mean duration of CS+MPAA treatment was 24.7±15.2 months. In the 12 months prior to treatment the median rate of kidney function decline was -23 [-32 to -16] ml/min/1.73 m2 per year. After the onset of treatment, the median eGFR slope was +5 [+3 to +9] ml/min/1.73 m2 per year (P = 0.001 with respect to the 12 months prior to treatment). Proteinuria decreased from 1.8 (1.0-2.5) g/day at baseline to 0.6 (0.3-1.2) g/day at the end of treatment (P = 0.01) and hematuria disappeared in 40% of the patients. There were no serious adverse effects requiring treatment discontinuation. Conclusions CS + MPAA is an effective treatment in IgAN patients with a sustained decline in kidney function accompanied by persistent proteinuria and hematuria despite optimized conservative treatment. Prospective studies are needed to confirm these results.

Crescents and IgA Nephropathy: A Delicate Marriage

“…A recently published Argentinian-Spanish retrospective study assessed the impact of steroids plus mycophenolate in a cohort of 25 patients with progressive IgAN [54]. Progressive IgAN was defined by a decrease in eGFR of at least 10 mL/min in the 12 months prior to the start of treatment and proteinuria ≥0.75 g/day despite maximum tolerated doses of RAS blockade, and hematuria (≥5 red blood cells per high power field) at the beginning of treatment.…”

Efficacy and safety of sequential immunosuppressive treatment for severe IgA nephropathy: A retrospective study

“…Simultaneously, the results of a prospective study in Hong Kong showed that for IgAN patients with moderate renal insufficiency and proteinuria >1.8 g/d, the use of MMF resulted in a significant decrease in urinary protein and a higher 6-year renal survival rate ( Tang et al, 2005 ). Not long ago, scholars reported that corticosteroids + MMF is an effective treatment in IgAN patients with a sustained decline in kidney function accompanied by persistent proteinuria and haematuria despite optimized conservative treatment ( Huerta et al, 2022 ). However, foreign prospective studies have not found that MMF has a renoprotective effect on IgAN ( Zheng et al, 2018 ).…”

Clinical Practice Patterns in IgA Nephropathy: A Global Questionnaire-Based Survey

“…Whether patients with proliferative lesions such as E1 and C1 should be initiated on immunosuppression immediately after diagnosis irrespective of their proteinuria levels to prevent fibrosis or one should wait to assess response to RAAS blockade for 3 months, which may actually increase the risk of progressive chronic disease remains debatable. 16 , 17 Again, whether patients with persistent proteinuria >1 g/d due to secondary glomerulosclerosis and hyperfiltration should receive immunosuppression as per KDIGO guidelines or continued on optimized nephroprotective supportive therapy also remains controversial and needs to be investigated.…”

“…The use of long-term immunosuppression (low dose, maintenance) to prevent relapsing proteinuria and progression of disease was not investigated, which is also a gap not addressed by the KDIGO guidelines. The use of the International IgAN network tool 16 to prognosticate patients was not assessed in our survey. Most of the respondents were mainly from Asia and South America, and other regions were underrepresented.…”