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Abstract: FR-PO638

Are Immunosuppression Treatments for Glomerular Disease Associated With Increased Cardiovascular Risk?

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Atiquzzaman, Mohammad, BC Provincial Renal Agency, Vancouver, British Columbia, Canada
  • Canney, Mark, University of Ottawa, Ottawa, Ontario, Canada
  • Zheng, Yuyan, BC Provincial Renal Agency, Vancouver, British Columbia, Canada
  • Er, Lee, BC Provincial Renal Agency, Vancouver, British Columbia, Canada
  • Zhao, Yinshan, The University of British Columbia, Vancouver, British Columbia, Canada
  • Induruwage, Dilshani, BC Provincial Renal Agency, Vancouver, British Columbia, Canada
  • Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
Background

The risk of cardiovascular disease (CVD) associated with immunosuppression (IS) treatments for glomerular disease is currently unknown. This was investigated in a population-level cohort of patients with glomerular diseases from British Columbia, Canada after adjusting for eGFR and proteinuria over time as measures of disease activity.

Methods

All adults with IgA nephropathy, FSGS, membranous nephropathy or minimal change disease on a kidney biopsy between January 2000 & December 2012 were identified from a provincial registry, excluding those with ESKD prior to the biopsy date or no available follow-up. IS medications were categorized as antimetabolites, calcineurin inhibitors, corticosteroids or cyclophosphamide, and quantified using defined daily doses (DDD) or grams, as appropriate. The primary outcome was acute cardiovascular events and urgent revascularization after biopsy date, evaluated using extended Cox regression models to determine the association with time-varying IS exposure after adjusting for eGFR & proteinuria over time, type of glomerular disease & CV risk factors.

Results

Amongst 1,912 patients with median follow-up 6.8 years, 212 (11.1%) patients developed a CV outcome event. In multivariable models, prednisone and antimetabolite exposures were not associated with CV risk. However, modest (150-300 DDD) & high (≥300 DDD) cumulative doses of calcineurin inhibitors were both associated with >2-fold higher risk of CV events, and each 10g of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of CV events (Table).

Conclusion

Calcineurin inhibitors and cyclophosphamide used for the treatment of glomerular diseases are both associated with increased risk of CV events independent of treatment effects on disease activity. These results can inform the selection of therapies in clinical practice with less CVD morbidity.