Clinical, Histologic, and Serological Predictors of Renal Function Loss in Lupus Nephritis

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OBJECTIVE: Kidney survival is the ultimate goal in lupus nephritis (LN) management, but long-term predictors remain inadequately studied, requiring long-term follow-up. This study aimed to identify baseline and early longitudinal predictors of kidney survival in the Accelerating Medicines Partnership LN longitudinal cohort. METHODS: We performed time-to-event analyses of clinical, centrally scored histologic, and serological predictors of kidney function loss (sustained ≥40% estimated glomerular filtration rate [eGFR] decline or progression to end-stage kidney disease) in 172 LN patients with a median follow-up of 4.6 years (range 0.5-7.8). RESULTS: Kidney function loss occurred in 57 of 172 (33%) patients. Baseline lower eGFR, non-first kidney biopsy, and higher National Institutes of Health (NIH) chronicity index were associated with eGFR loss. Chronicity index was the strongest predictor, but no clear threshold defined higher risk. NIH activity index and International Society of Nephrology (ISN) class were not predictive. Proteinuria at 12 months was prognostic, with urine protein-to-creatinine ratio <0.7 g/g associated with lower risk; however, no single threshold ensured protection, and lower levels had better outcomes. Lack of complete clinical response at 3, 6, or 12 months predicted future eGFR loss, whereas partial response conferred intermediate risk. Serological markers were not associated with eGFR loss. CONCLUSION: Low baseline eGFR and chronic histologic damage, but not activity or ISN class, predicted eGFR loss. Proteinuria <0.7 g/g at one year was associated with better outcomes but did not ensure protection. Because proteinuria does not reflect intrarenal inflammation, these results suggest current response definitions serve better as prognostic indicators than true measures of treatment efficacy, and better biomarkers are needed.

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