Abstract: SA-PO684
The Trajectory of Glomerular and Tubulointerstitial Lesions After Treatment of Lupus Nephritis
Session Information
- Glomerular Diseases: Clinical, Outcomes, Trials - III
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials
Authors
- Malvar, Ana, Hospital Fernandez, Buenos Aires, Argentina
- Alberton, Valeria Gabriela, Hospital Fernandez, Buenos Aires, Argentina
- Lococo, Bruno Jorge, Hospital Fernandez, Buenos Aires, Argentina
- Lourenco, Maria Cecilia, Hospital Fernandez, Buenos Aires, Argentina
- Martínez, Joaquín, Hospital Fernandez, Buenos Aires, Argentina
- Elencwajg, Mauro, Hospital Fernandez, Buenos Aires, Argentina
- Nagaraja, Haikady N., The Ohio State University, Columbus, Ohio, United States
- Rovin, Brad H., The Ohio State University, Columbus, Ohio, United States
Background
Proliferative lupus nephritis (LN) is characterized histologically by glomerular and tubulointerstitial (TI) inflammation that presumably must resolve with treatment to achieve remission. Here we sought to document the trajectory of lesion resolution using serial kidney biopsies during LN treatment.
Methods
A cohort of proliferative LN patients was prospectively followed during treatment with standard LN therapy. Patients had a diagnostic kidney biopsy (Bx1), a biopsy generally within the first year of treatment (Bx2), and a biopsy after at least 3 years of total immunosuppression (Bx3). The NIH activity and chronicity indices (AI, CI) were calculated at each biopsy.
Results
The cohort (n=110) was followed for a median (range) of 109 (34, 202) months. Patients were treated with either MMF or cyclophosphamide initially. Overall, the patients did very well. Only 2 patients developed ESKD by last follow-up and only 9 patients had CKD (eGFR <60 ml/min/1.73m2), but this was pre-existing in 4 patients. AI followed an exponential decline after starting treatment. At the time of Bx2 (an average 9.7 months after Bx1), the percent of biopsies positive for cellular crescents (CC), fibrinoid necrosis (FN), and neutrophil infiltration NEU) fell precipitously, while the decline of endocapillary hypercellularity (EH) and hyaline deposits (HD) was more gradual. At Bx3 (an average of 42.6 months after Bx1) fewer than 5% of biopsies had residual CC, FN, NEU, or interstitial inflammation, but 25% still had EH and HD. By immunofluorescence microscopy over 90% of Bx1 biopsies had IgG and complement components C3 and C1q. At Bx3 only 30-40% of biopsies continued to show IF for complement, but IgG was still present in 66% of biopsies. The CI increased after Bx1. The rate of increase of all CI components was greatest from Bx1 to Bx2, slowed between Bx2 and Bx3, and actually declined for fibrous crescents.
Conclusion
These data show that the most inflammatory lesions found in proliferative LN are rapidly responsive to immunosuppression, but EH and HD are more resistant. Complement deposition resolves quickly, but IgG is present in glomeruli for a long time. Despite rapid improvement in active inflammation, kidneys sustain chronic damage early in the disease course.
Funding
- Other NIH Support