Document resource
Objectives Lupus nephritis (LN) is a highly heterogenous disease with variable risks of end-stage kidney disease (ESKD) across histological classes and ethnic groups. Current remission criteria based on proteinuria remain under debate due to their limited accuracy in distinguishing active disease from irreversible chronic kidney injury. To better capture long-term kidney outcomes, this study applied eGFR’s slope analysis to real-world data to visualize kidney function trajectories in LN and identify the impact of kidney relapse and other clinical- and histopathological factors on its decline.Methods Patients with biopsy-proven LN were retrospectively recruited from the Limburg Renal Registry (1977-2024). Biopsies were classified and scored on activity/chronicity. Outcomes included partial renal remission (PRR), complete renal remission (CRR), ESKD and death. Kidney function trajectories were analyzed using linear mixed-effect model. Changes in chronicity scores were evaluated in repeat biopsies during LN relapse.Results 131 patients were included with a median follow-up of 11.2 years (IQR 3.1–18.9). Most achieved PRR (89%) and CRR (80%) within the first year of treatment, whereas 19% developed ESKD after a median of 10.4 years (IQR 6.2–15.6). Residual proteinuria (more than 100 mg/mmol UPCR at 3 years) was not linked to worse eGFR trajectories. Kidney relapse occurred in 42% after a median of 3.1 (IQR 1.6–7.2) years. Relapsing patients showed a significant decline in eGFR slope of -2.47 (95% CI, -3.73 to -1.21) mL/min/1,73m2/year compared to a stable eGFR in non-relapsing patients. Each single relapse contributed to an additional decline of -1.39 (95% CI, -2.11 to -0.66) mL/min/1,73m2/year. Higher serum creatinine (HR 1.08 per 10 mmol/L increase, p<0.001), histological activity (HR 1.09 per 1-point increase, p=0.024) and chronicity (HR 1.52 per 1-point increase, p<0.001) were independent predictors of ESKD. Kidney relapse greatly reduced the likelihood of PRR and CRR (data not shown).Conclusions In this real-world cohort, high remission rates were achieved with only few patients retaining residual proteinuria. Patients maintaining remission fare well, whereas kidney relapses cause additional yearly eGFR decline. Repeat biopsies reveal progression in chronicity even in remitted patients, highlighting the need for improved disease-monitoring and prevention of kidney relapses through novel therapeutics.