Kidney Week

Abstract: TH-PO826

Complement Activation in Renal Thrombotic Microangiopathy Associated to Systemic Lupus Erythematosus: An Exploratory Analysis

Session Information

• Glomerular Diseases: Immunology and Inflammation - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Gómez Ruiz, Ismael Antonio, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

Ismael Antonio Gómez Ruiz,

• Nuñez alvarez, Carlos, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

Carlos Nuñez alvarez,

• Cruz, Cristinoc, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

Cristinoc Cruz,

• Morales-Buenrostro, Luis E., Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

Luis E. Morales-Buenrostro,

• Correa-Rotter, Ricardo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

Ricardo Correa-Rotter,

• Mejia-Vilet, Juan M., Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

Juan M. Mejia-Vilet,

Background

Renal thrombotic microangiopathy (TMA) in SLE is a rare and severe manifestation with dismal prognosis. While complement participation in lupus nephritis (LN) has been studied, its role in SLE renal TMA remains lesser explored.

Methods

To study complement proteins we included patients with SLE-renal TMA (n=12), active biopsy-proven LN (n=12), inactive SLE patients (n=9) and living kidney donors (n=5). Renal TMA patients were divided into acute TMA (aTMA) or chronic TMA (cTMA) according to histopathology. Terminal complement pathway activation was evaluated by a soluble C5b-C9 ELISA. Alternative pathway urine C3d fragment was evaluated with a specific monoclonal antibody. Groups were compared by Kruskal-Wallis test and correlations obtained by Spearman's rho.

Results

Of 12 patients with SLE renal TMA, 3 (25%) had positivity for aPL antibodies and 9 corresponded to aHUS. Renal TMA patients presented with higher arterial pressure, serum creatinine and dsDNA titers; while hemoglobin, platelets and haptoglobin levels were lower than in active LN. Notably, renal TMA patients had few systemic manifestations of microangiopathic hemolytic anemia. Renal TMA biopsies showed higher global sclerosis, interstitial fibrosis and tubular atrophy. Plasma and urine sC5b-C9 titers in both renal TMA and active LN groups were higher than in inactive LN and kidney donors. Urine sC5b-C9 titers were higher in renal aTMA compared to cTMA (Figure A). In the Figure B we present the case of a patient with SLE and 2 renal TMA episodes. As shown, urine and plasma sC5b-C9 titers rose during the acute event and diminished after treatment. There was a trend for higher urine C3d fragment in aTMA compared to cTMA and active LN. There was a correlation between urine sC5b-C9 titers and serum creatinine (r=0.308, p=0.017) and proteinuria (r=0.686, p<0.001).

Conclusion

There is activation of complement pathway in renal TMA evidenced by the elevation of complement protein's fragments. It should be further explored if these tests may be of use to follow-up the course of the disease.