Sex Differences Across Corticosteroid Response and Outcomes in IgA Nephropathy

The impact of sex on treatment response and outcomes in IgA nephropathy (IgAN) remains uncertain. This analysis of the Therapeutic Effects of Steroids in IgAN Global (TESTING) trial aimed to evaluate the following: (i) the effect of sex on corticosteroid response and (ii) the association between sex and kidney outcomes in IgAN.

Participants with IgAN were randomized to 6 to 9 months of oral methylprednisolone or placebo. The primary outcome was a composite of 40% decline in estimated glomerular filtration rate (eGFR), kidney failure, or death because of kidney disease. The interaction between sex and treatment on the risk of the primary outcome, relative change in proteinuria, and total eGFR slope was tested. Cox models were used to estimate the risk of the primary outcome in males versus females. Sex differences in total eGFR slope were also estimated.

Overall, there were 305 males (61%) and 198 females (39%). The mean follow-up period was 4.2 years. Compared with placebo, methylprednisolone lowered the risk of the primary outcome in both males (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.35-0.74) and females (HR: 0.64, 95% CI: 0.38-1.09) (P-interaction = 0.47), and reduced proteinuria from baseline at 12 months and slowed the rate of total eGFR decline, with no sex differences (P-interaction = 0.28 and 0.81, respectively). Males had a greater risk of the primary outcome than females (HR: 1.44, 95% CI: 1.05-1.97, P = 0.03). Total eGFR rate of decline over 2 years was greater in males compared with females by 3.13 ml/min per 1.73 m²/yr (95% CI: 0.92-5.34, P = 0.006).

Methylprednisolone improves kidney outcomes in IgAN, regardless of sex; however, males experience poorer kidney outcomes than females.