Role of Repeat Kidney Biopsy after 6 Months of Treatment in Proliferative Lupus Nephritis

Objective To characterise histological response following induction therapy in a real-world cohort of patients with proliferative lupus nephritis (LN) undergoing per-protocol repeat kidney biopsy; to assess the concordance between clinical and histological response and to identify baseline factors associated with changes in activity and chronicity indices. Methods We conducted a retrospective observational study including 20 adult patients with systemic lupus erythematosus and biopsy-proven proliferative LN who underwent a protocolised repeat kidney biopsy at 6 months (±3 months) after induction therapy. Clinical, laboratory and histopathological data were collected at both biopsy time points. Associations between baseline parameters and histological outcomes were explored. Results After a median of 7.5 months, proteinuria significantly decreased while estimated glomerular filtration rate and complement levels significantly improved. The histological activity index (AI) decreased significantly, with improvement observed in 90% of patients. Chronicity index (CI) increased in 50% of patients, without reaching statistical significance. At 6 months, 55% of patients achieved primary efficacy renal response, whereas 45% achieved histological response. Notably, discordance between clinical and histological responses was frequent: 45% of clinical responders exhibited persistent histological activity and 33% of histological responders failed to meet clinical response criteria. Lower baseline proteinuria and better baseline renal function were observed among patients with AI improvement. Likewise, patients with an increase in CI had a lower baseline CI and tended to have a better baseline renal function. Histological outcomes did not differ according to the type of immunosuppressive therapy used during induction. Conclusions In this real-world cohort of proliferative LN, substantial discordance between clinical and histological response was observed following induction therapy. While histological activity improved in most patients, chronic damage progressed in half of the cohort despite favourable clinical evolution. These findings should be interpreted as exploratory and hypothesis-generating rather than as definitive associations and highlight the need for prospective studies to define its role in personalised LN management.