Kidney Week

Abstract: SA-PO745

Risk of ESKD in ANCA-Associated Glomerulonephritis at Presentation and during the Disease Course

Session Information

• ANCA-Associated Vasculitis, Anti-GBM Disease, and Other RPGN
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Timmermans, Sjoerd, Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands

Sjoerd Timmermans, MD, PhD

• van Doorn, Daan P.C., Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands

Daan P.C. van Doorn, MD

• Voorde, Floris Ten, Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands

Floris Ten Voorde, DrMed, MSc

• van Paassen, Pieter, Maastricht Universitair Medisch Centrum+, Maastricht, Limburg, Netherlands

Pieter van Paassen, MD, PhD

Group or Team Name

• Limburg Renal Registry; Expert Center for Immune-mediated Kidney Diseases and Vasculitis.

Background

Kidney involvement in ANCA vasculitis is common and impacts quality of life and survival. Tools to determine disease activity and predict risk for ESKD may optimize intensity and duration of immunosuppression. The ANCA kidney risk score (AKRiS) predicts ESKD. The AKRiS, however, is based on cross-sectional data. Here, we validated AKRiS in two well-defined cohorts of patients with de novo ANCA glomerulonephritis (AGN) and studied the effect of kidney recovery and relapsing AGN on kidney survival.

Methods

We analyzed patients with de novo AGN recruited from the Limburg Renal Registry (i.e., historical cohort; n=290) and prospective PROMAVAS cohort (n=36). Kidney recovery at 12 months and slope of eGFR from 12 months onward were studied, using a two-slope mixed-effects linear spline model.

Results

The historical cohort included 126 (63%), 43 (21.5%), 28 (14%), and 3 (1.5%) patients with low, moderate, high, and very high risk, with follow-up of 10 (IQR, 6-15) years. Creatinine was 2.4 (IQR, 1.4-4.5) mg/dL and 164 (82%) patients were treated using a cyclophosphamide-based regimen. Kidney survival varied from 97.5%, 87.9%, 74.5%, to 33.3% at 36 months, validating AKRiS with good discrimination (C statistic, 0.84). The PROMAVAS cohort (creatinine, 2.4; IQR, 1.8-3.5) mg/dL, including 21 (58.3%) patients treated using a rituximab-based regimen, corroborated these observations (C statistic, 0.92). The eGFR improved +10.4 (95%CI, 7.8 to 12.9) mL/min/1.73m² at 12 months, with no differences between patients with an eGFR <30 mL/min/1.73m² as compared to those with better kidney function at presentation. eGFR’s mean annual slope was -1.0 mL/min/1.73m² (95%CI, -1.7 to -0.3) in remitted AGN, contrasting -3.3 mL/min/1.73m² (95%CI, -4.4 to -2.2; P=0.001) in relapsing AGN. ESKD was associated with eGFR <30 mL/min/1.73m² at 12 months.

Conclusion

AKRiS predicts the risk of ESKD in de novo AGN. Moreover, CKD stage at 12 months, and relapsing AGN affect eGFR's slope and progression to ESKD. Treatment should therefore focus on maximal kidney recovery using novel drugs, such as, C5aR inhibition, and prevention of relapsing AGN, particularly in patients with eGFR <30 mL/min/1.73m² at 12 months, to maintain kidney function. Future trials should focus on the effects of treatment on kidney recovery and eGFR's slope.

Funding

• Commercial Support – Vifor Pharma Group