Low-Dose, Short-Course Corticosteroids Combined with Delayed Mycophenolate Mofetil is Safer for Treating IgA Nephropathy

Although the efficacy of low-dose corticosteroids (CS) combined with mycophenolate mofetil (MMF) in treating IgA nephropathy (IgAN) has been established, safety remains a concern. Whether the regimen of low-dose, short-course CS combined with delayed MMF initiation can reduce adverse events while maintaining good efficacy remains elusive.

This multi-center, retrospective study included 160 adults with biopsy-proven IgAN in Jiangxi Province, China (Jan 2022-Jun 2023), with a follow-up period of 18 months. Key inclusion criteria were persistent urinary protein (UP) ≥ 0.75 g/day despite renin-angiotensin system blockade for 1-month and estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m². Patients were assigned to two groups: the delayed MMF group (n=79) received low-dose, short-course CS (a total of three months, initially 0.4-0.6 mg/kg/day, reducing by 20% every two weeks, and maintained at 0.1 mg/kg/day), with MMF (1.25-1.5 g/day for six months and subsequently maintained at 0.75-1.0 g/day until follow-up finished) introduced only when the CS dose reached 0.2-0.3 mg/kg/day; the Recommended MMF group (n=81) started both CS and MMF initiated concurrently from the outset, following the same dosing and tapering schedules as above. Propensity score matching (PSM, 1:1, caliper=0.2) adjusted for age, gender, eGFR, UP, and MESTC score, yielding 63 balanced pairs.

After PSM, both groups showed comparable clinical and pathological characteristics (all P >0.05, Table 1). Efficacy outcomes were not significantly different (Table 2). Specifically, the CR rates at 6, 12, and 18 months were similar (at 6-month: 30.2% vs. 28.6%, P = 0.845; at 12-month: 44.4% vs. 39.7%, P = 0.588; at 18-month: 57.7% vs. 57.1%, P = 0.875). The OR rates at 6, 12, and 18 months were also comparable (at 6-month: 58.7% vs. 50.8%, P = 0.371; at 12-month: 77.8% vs. 74.6%, P = 0.676; at 18-month: 81.0% vs. 81.0%, P = 1.000, Table 2). Kaplan-Meier analyses confirmed no difference in cumulative CR (P = 0.730, Figure 2B), OR (P = 0.630, Figure 2D), or composite event-free survival (P = 0.640, Figure 2F).

Subgroup analyses across key baseline characteristics generally revealed no significant interactions between treatment assignment and most subgroups, except for T. T1 was associated with HR = 1.54 (95% CI: 0.79-3.00). A significant interaction was observed (P = 0.003). Furthermore, longitudinal data revealed comparable improvements in UP, ALB, and eGFR between both groups over the 18-month follow-up, with no significant intergroup differences (P = 0.835 for UP, P = 0.922 for ALB, P = 0.051 for eGFR; Figure 4). Multivariable Cox regression confirmed that the treatment group was not associated with CR (HR 0.86, 95% CI 0.55-1.34, P = 0.513, Table 3). Regarding Safety, the Delayed MMF group had a significantly lower incidence of total AEs (44.4% vs 63.5%, P = 0.032) and notably fewer infections (28.6% vs 50.8%, P = 0.011, Table 4).

Table 1: Clinical and pathologic features of participants at baseline before and after propensity score matching

Notes: Values for categorical variables were given as count (percentage); values for continuous variables, as mean ± standard deviation or median (IQR).

Abbreviations: ALB, albumin; eGFR, estimated glomerular filtration rate; RASB, renin-angiotensin system blockers; CCB, calcium channel blocke.

Table 2: Primary and secondary outcome in this study before and after propensity score matching