Efficacy and safety of HCQ versus spironolactone in treatment of IgA nephropathy based on RAASi: a real-world study

To investigate the efficacy and safety of hydroxychloroquine (HCQ) versus spironolactone in patients with IgA nephropathy based on sufficient renin-angiotensin-aldosterone system inhibitors (RAASi) treatment.

A prospective, non-randomized study was carried out on 172 patients with primary IgA nephropathy admitted in our department from April 2019 to March 2021. They were 56 males and 116 females, at an average age of 37.5±10.7 years. They were divided into HCQ group (n=104) and double RAASi group (n=68) and were followed up for 6 months. The decreasing rate of urine protein creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) were compared between the 2 groups during follow-up, and subgroup analysis was conducted to explore the effects of corticosteroids or immunosuppressants on the outcomes.

Compared with the dual RAASi group, the patients in the HCQ group had worse baseline renal function, lower eGFR and larger proportion of Lee's grades Ⅲ~Ⅳ (P<0.05). At the 6th month of follow-up, the decreasing rate of UPCR was comparable between the 2 groups (-54.7% vs -52.0%, P=0.551), but the decreasing rate of eGFR was significantly lower in the HCQ group than that in the dual RAASi group (-3.3% vs -11.5%, P<0.001). In addition, subgroup analysis found that there was no significant difference between HCQ and spironolactone in reducing urine protein, but for those who did not use corticosteroids or immunosuppressants before and after enrollment, those who did not use corticosteroids or immunosuppressants before enrollment but added them after enrollment, and those who used corticosteroids or immunosuppressants before and after enrollment, the HCQ group had a significantly lower eGFR decline rate at 6 months of follow-up than the dual RAAS group (P<0.05). Moreover, no serious adverse events (SAEs) were observed in either group during the course of the study.

On the basis of sufficient RAASi treatment, HCQ and spironolactone have similar effects in controlling urine protein level in patients with IgA nephropathy whose urine protein does not reach the target level, and there are no serious adverse events. But HCQ has a significantly better renal protective effect of eGFR than spironolactone.