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Abstract
Background Lupus nephritis (LN) is characterized by glomerular and tubulointerstitial (TI) inflammation that presumably must resolve with treatment to achieve remission. Here we sought to document the trajectory of histologic resolution using protocol kidney biopsies during LN treatment.
Methods A cohort (n=110) of proliferative LN patients was prospectively followed during treatment with standard (glucocorticoids plus MMF or cyclophosphamide) therapy. Patients underwent a diagnostic kidney biopsy (Bx1), a biopsy within the first treatment year (Bx2, 9.7 months), and a biopsy after ≥3 years of total immunosuppression (Bx3, 42.6 months). At each biopsy NIH activity and chronicity indices (AI, CI) were calculated.
Results Patients were followed for a median of 109 months. Treatment was successful. At last follow-up only 2 patients had ESKD and only 5 developed new CKD (eGFR <60 ml/min/1.73m²). AI decline was biphasic, rapidly falling immediately after starting treatment and then slowing (figure 1). At Bx2 the percent of biopsies positive for cellular crescents (CC), fibrinoid necrosis (FN), and neutrophil infiltration (NEU) fell precipitously, while endocapillary hypercellularity (EH) and hyaline deposits (HD) declined gradually. At Bx3 fewer than 5% of biopsies had residual CC, FN, NEU, or interstitial inflammation, but 25% still had EH and HD (figure 1). Over 90% of diagnostic biopsies had IgG and complement components C3 and C1q. At Bx3 only 30–40% of biopsies continued to show IF for complement, but IgG persisted in 66% of biopsies. Chronicity increased in most patients after Bx1. The rate of increase of glomerulosclerosis, tubular atrophy, and interstitial fibrosis was greatest from Bx1 to Bx2 and slowed between Bx2 and Bx3 (figure 1).
Conclusions The most inflammatory LN lesions respond rapidly to conventional immunosuppression, but EH and HD are more resistant. Complement deposition resolves quickly, but IgG can persist in glomeruli for years. Despite rapid improvement in inflammation, chronic damage accumulates early
The change in the activity index/chronicity index (A), and prevalence of activity index (B) and chronicity index (C) histologic components over time during successful treatment of lupus nephritis
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