Abstract: PO1764
Kidney Thrombotic Microangiopathy Associated to Lupus Nephritis Is Mediated by the Activation of the Alternative Complement Pathway
Session Information
- Glomerular Diseases: Lupus and Membranous
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Mejia, Juan M., Department of Nephrology and Mineral Metabolism. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran., Mexico City, CDMX, Mexico
- Gómez Ruiz, Ismael Antonio, Department of Nephrology and Mineral Metabolism. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran., Mexico City, CDMX, Mexico
- Méndez, Rossa Angelica, Department of Nephrology and Mineral Metabolism. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran., Mexico City, CDMX, Mexico
- Cruz, Cristinoc, Department of Nephrology and Mineral Metabolism. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran., Mexico City, CDMX, Mexico
- Morales-Buenrostro, Luis E., Department of Nephrology and Mineral Metabolism. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran., Mexico City, CDMX, Mexico
- Correa-Rotter, Ricardo, Department of Nephrology and Mineral Metabolism. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran., Mexico City, CDMX, Mexico
Background
Thrombotic microangiopathy (TMA) in the context of lupus nephritis is a rare disease whose pathogenesis has been linked to complement activation. This study aimed to evaluate complement pathway activation products in plasma and urine from patients with LN associated TMA (LN-TMA) and to compare its levels to patients with active LN (aLN), patients with inactive lupus (iSLE) and kidney donors (KD).
Methods
Plasma and urine samples were obtained from 19 patients with acute LN-TMA and 19 patients with biopsy-proven aLN matched by histologic activity index. Patients with iSLE (n=16) and kidney donors (n=10) were included as controls. Complement activation fragments C3a, C4a, C5a, Ba, C5bC9, and factor H were assessed by ELISA. Kidney C4d deposition was detected by immunohistochemistry. After 12 months, complement activation products were re-assessed after treatment.
Results
Both, the acute LN-TMA and aLN patients had increased plasma Ba and C5bC9 along with decreased plasma C3, C4, C4a, and factor H. Urine C5a, Ba, and C5bC9 were higher in patients with acute LN-TMA than in aLN. The levels of the urine complement fragment correlated with the degree of interstitial inflammation, interstitial fibrosis, and tubular atrophy in the kidney biopsy. After treatment, the levels of circulating C3, C4, and factor H increased, and the levels of urine C5bC9 decreased. In two patients with repeated LN-TMA episodes, factor H and urine C5a levels decreased, while urine Ba and C5bC9 increased after treatment in each episode. There was no difference in C4d fragment deposition in glomerular capillaries, tubular basement membrane, peritubular capillaries, and arterioles, between patients with aLN and those with acute LN-TMA.
Conclusion
The levels of plasma and urine complement activation products suggest that the pathogenesis of acute LN-TMA is mediated through activation of the complement alternative pathway.
Levels of plasma factor H (A), urine complement fragment Ba (B) and urine complement fragment C5a (C) in the studied groups.
Funding
- Government Support - Non-U.S.