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Abstract: FR-PO845

Angiotensin II Type 1 Receptor Agonist Antibodies Are Prevalent in Lupus Nephritis Patients and May Be Associated with Vascular Damage

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Carranza, Carlos A, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico, Mexico
  • Mejia-Vilet, Juan M., Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico, Mexico
  • Cruz, Cristinoc, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico, Mexico
  • Trujeque, Mariedel, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico, Mexico
  • Morales-Buenrostro, Luis E., Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico, Mexico
Background

Angiotensin type II receptor antibodies (AT1R-Ab) have been linked to hypertension, vascular inflammation and atherosclerosis in human diseases. The aim of this study was to determine the association between AT1R-Ab and intima-media thickness (IMT), microvascular damage and lupus nephritis (LN) activity.

Methods

Plasma AT1R-Ab were evaluated in 107 patients with biopsy proven LN. Then 80 patients were prospectively followed for one-year. Plasma AT1R-Ab, double-strand DNA antibodies (dsDNA-Ab), complement C3 and C4 were assayed in plasma samples obtained at 3, 6 and 12-months from the start of treatment. Morphometric analysis of the kidney biopsy vessels was performed to determine intimal fibrosis and medial layer thickness. Carotid IMT was evaluated by USG at the time of biopsy and then at one-year in 22 AT1R-Ab patients. The comparisons between AT1R-Ab+ and AT1R-Ab- patients were performed by Chi-square and Mann-Whitney's U. Association between the AT1R-Ab course and other parameters was evaluated by linear mixed models.

Results

AT1R-Ab were positive in 58 (54%) patients and higher than in inactive LN patients and kidney donors. AT1R-Ab+ patients had higher dsDNA-Ab (287 UI/ml [97-814] Vs. 26 UI/ml [26-182], p<0.001), lower complement C3 (62mg/dl [43-80] Vs. 74mg/dl [50-101], p=0.016), higher histologic activity index (5 [3-11] Vs. 2 [1-7], p=0.020), more segmental lesions (67% Vs. 43%, p=0.013) and more class III LN (43% Vs. 20%, p=0.019) than AT1R-Ab- patients. The prevalence of subintimal fibrosis >10% was 47% and the percentage of subintimal fibrosis was higher in AT1R-Ab+ patients (12% [6-20] Vs. 7% [3-16%], p=0.025). The area of medial layer hyperplasia was greater in AT1R+ patients (72um2 [61-88] Vs. 55um2 [42-66]). On multivariate analysis, AT1R-Ab titers were independently associated with the degree of medial hyperplasia. The course of AT1R-Ab on follow-up was associated with the course of dsDNA-Ab (r=+0.454, p<0.001), complement C3 (r=-0.185, p=0.049) and C4 (r=-0.281, p=0.013). There were no significant changes in IMT after 12 months of follow-up between AT1R-Ab+ and AT1R-Ab- patients.

Conclusion

AT1R-Ab are associated with vascular medial hyperplasia and segmental glomerular damage in LN patients and are associated with serological biomarkers.