Hydroxychloroquine Remains a Mainstay in Lupus Nephritis

Why was this study done?

Hydroxychloroquine (HCQ) is the cornerstone in lupus management, but its specific impact on long-term kidney outcomes in lupus nephritis has not been well quantified in real-world settings. With the great debate around HCQ dosing and concerns for safety in patients with kidney disease, lower adoption of HCQ or delays in starting HCQ in lupus nephritis have been noted.

What were the study methods?

This study leverages data from longitudinal inception and prevalent lupus nephritis cohorts with up to 20 years of follow-up data. This study uses robust statistical modeling with time-varying Cox proportional hazard modeling and linear mixed effects modeling using random slope and intercept to shed new evidence on the timing of HCQ’s initiation and the impact of early use of HCQ in preventing kidney function decline in lupus nephritis to ensure early and universal use of HCQ in patients with lupus nephritis.

What were the key findings?

HCQ use was independently associated with a significantly lower risk of sustained estimated glomerular filtration rate (eGFR) decline in lupus nephritis. The magnitude of benefit was notable: time-varying HCQ use had a 61–73% lower risk of kidney function decline. Additionally, we are the first to show a significant reduction in kidney function slope decline with HCQ use, which was a striking finding. Our study uniquely highlights a 5.12 mL/min/1.73m² per year slower eGFR decline in HCQ users within the first five years of lupus nephritis diagnosis than in HCQ non-users.

What are the main conclusions of this study?

These findings reinforce HCQ’s protective role in lupus nephritis and encourage care team members and patients with lupus nephritis to feel confident in decisions to start HCQ early as part of their initial lupus nephritis therapy and continue HCQ during the disease course.

What are the implications for patients and clinicians?

This study offers firsthand, real-world evidence to support patients and clinicians in shared decision making to start HCQ as part of initial therapy in all patients with lupus nephritis by: 1) highlighting the benefits of using HCQ to preserve kidney function; 2) showing the early use of HCQ is associated with slower kidney function slope decline; and 3) demonstrating the lower risk of kidney function decline (30% or 40%) over time, thereby potentially reducing kidney failure chances and improving survival.

Future studies should explore optimal HCQ dosing strategies that balance efficacy and safety, particularly in patients with chronic kidney disease, given that 65% of HCQ is cleared by the kidneys.

The study

Garg S, Rovin B, Astor BC, et al. Hydroxychloroquine associated with lower glomerular filtration rate decline in lupus nephritis. Arthritis Care Res (Hoboken). 2025 Jul 20. Epub ahead of print.

Reprinted and adapted from an article in The Rheumatologist, November 2025.