Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis

Rheumatology (Oxford). 2020 Nov 1;59(11):3424-3434. doi: 10.1093/rheumatology/keaa129.


Objectives: In patients with LN, clinical and histological responses to treatment have been shown to be discordant. We investigated whether per-protocol repeat kidney biopsies are predictive of LN relapses and long-term renal function impairment.

Methods: Forty-two patients with incident biopsy-proven active proliferative (class III/IV±V) LN from the database of the UCLouvain were included in this retrospective study. Per-protocol repeat biopsies were performed after a median [interquartile range (IQR)] time of 24.3 (21.3-26.2) months. The National Institutes of Health activity index (AI) and chronicity index (CI) scores were assessed in all biopsies.

Results: Despite a moderate correlation between urinary protein/creatinine ratios (UPCR) and AI scores at repeat biopsy (r = 0.48; P = 0.001), 10 patients (23.8%) with UPCR < 1.0 g/g still had a high degree of histological activity (AI > 3). High AI scores (continuous) in repeat biopsies were associated with an increased probability and/or shorter time to renal relapse (n = 11) following the repeat biopsy [hazard ratio (HR) = 1.2, 95% CI: 1.1, 1.3; P = 0.007], independently of proteinuria levels. High CI scores (continuous) in repeat biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR = 1.8, 95% CI: 1.1, 2.9; P = 0.016) through a median (IQR) follow-up time of 131.5 (73.8-178.2) months, being also the case for acute tubulointerstitial inflammation and interstitial fibrosis/tubular atrophy in repeat but not baseline biopsies.

Conclusion: Our results highlight the usefulness of per-protocol repeat biopsies, herein performed after a median time of 24 months from baseline, as an integral part of the treatment evaluation, also in patients showing adequate clinical response.

Keywords: histopathology; long-term outcome; lupus nephritis; renal biopsy; renal function; repeat biopsy; systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Creatinine / urine
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Kidney / pathology*
  • Kidney Tubules / pathology
  • Lupus Nephritis / drug therapy
  • Lupus Nephritis / pathology*
  • Lupus Nephritis / urine
  • Male
  • Methylprednisolone / therapeutic use
  • Mycophenolic Acid / therapeutic use
  • Prognosis
  • Proportional Hazards Models
  • Proteinuria / urine
  • Pulse Therapy, Drug
  • Recurrence
  • Retrospective Studies
  • Rituximab / therapeutic use
  • Young Adult


  • Glucocorticoids
  • Immunologic Factors
  • Immunosuppressive Agents
  • Rituximab
  • Cyclophosphamide
  • Creatinine
  • Mycophenolic Acid
  • Methylprednisolone