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Abstract: TH-PO615

Interplay between Immune Deposits, Complement Activation, and APOL1 Renal Risk Variants in Patients with FSGS

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Caliskan, Yasar, Saint Louis University, St Louis, Missouri, United States
  • Royal, Virginie, Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Troyanov, Stephan, Hopital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada
  • Bonnefoy, Arnaud, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
  • Merlen, Clémence, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
  • Schnitzler, Mark, Saint Louis University, St Louis, Missouri, United States
  • Edwards, John C., Saint Louis University, St Louis, Missouri, United States
  • Laurin, Louis-Philippe, Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Lentine, Krista L., Saint Louis University, St Louis, Missouri, United States
Background

The mechanisms by which APOL1 renal risk variants (RRVs) carry a worse prognosis in FSGS is debated. Whether glomerular immune deposits and complement activation participate in APOL1 mediated FSGS is unknown. Using the large CureGN cohort, we evaluated the association APOL1 RRVs and immunofluorescence (IF) findings and urinary complement fragment measurements (sC5b9).

Methods

We studied the associations of glomerular IgG, IgM and C3 localization and intensity, biopsy findings, urinary sC5b9 and clinical data in CureGN FSGS cohort, regardless of self-reported race. Patients were categorized by two APOL1 RRVs [high risk (HR)] versus zero to one risk alleles [low risk (LR)] groups. The association between histopathological findings, urinary sC5b9 levels and APOL1 RRVs were analyzed.

Results

Of 175 participants, 148 (85%) had genetic testing, among whom 31 were HR and 117 were LR participants. The percentage of patients with active disease (UPCR>1 g/g) at enrollment was higher in HR patients compared to LR patients (74% vs 51%, p=0.07). Collapsing FSGS is the dominant type in HR group (45% vs 11%, p<0.001). Mesangial IgG deposition was significantly more frequent in HR group compared to LR group [10 (32%) vs 4 (3%), p<0.001]. Interstitial fibrosis/tubular atrophy and tubular microcystic changes were found at a significantly higher rate in HR group (84% vs 64%, p=0.033; 29% vs 12%, p<0.001, respectively). Urinary sC5b9 levels (median, IQR) were higher in HR patients enrolled within 6 months of biopsy compared to LR group [0.15 (0.08-0.31) vs 0.03 (0-0.20) μg/g, p=0.08] (Fig.1). Proteinuria levels were similar in both groups (p=0.79).

Conclusion

Patients with FSGS and high-risk APOL1 genotype have more frequent mesangial IgG deposition and a trend towards higher urinary membrane attack complex levels compared to patients with non-risk genotype.