ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO1895

APOL1 High-Risk Genotype Is Highly Prevalent Among Brazilian Patients with Collapsing Glomerulopathy, an Association That Manifests from Adolescence to Early Middle Adulthood

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Neves, Precil D., Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Watanabe, Andreia, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Watanabe, Elieser H., Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Cavalcante, Livia Barreira, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Malheiros, Denise M., Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Jorge, Lectícia, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Sampson, Matt G., Boston Children's Hospital, Boston, Massachusetts, United States
  • Onuchic, Luiz F., Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
Background

Collapsing glomerulopathy (CG) is associated with fast progression to ESKD. CG has been linked to specific infections, drugs and immune disorders, the APOL1 high-risk genotype (HRG) and monogenic pathogenic variants.

Methods

70 Brazilian patients of all ages with the diagnosis of idiopathic CG were submitted to APOL1 genotyping and 51 of them to broad genetic evaluation through whole exome sequencing, a 62-gene panel directed to glomerulopathies or Sanger sequencing. Based on retrospective analyses of medical records, the frequency and clinical impact of HRG were analyzed.

Results

Thirty-three (47.1%) patients harbored an HRG. Monogenic pathogenic or likely pathogenic variants were identified in 5 APOL1 low-risk genotype (LRG) individuals, affecting the COL4A5 (2 cases), COQ2, MYH9, and PLCE1 genes. Gender distribution did not differ between the HRG and LRG groups. Patients with HRG were less often self-declared Caucasian than LRG individuals (36.4% vs 89.2%, p<0.001). While the age of disease onset was not significantly different between the HRG and LRG groups [21 (17-33) vs 25 (18-31) years, p=0.755], patients harboring HRG manifested the disease from adolescence to early middle adulthood (10-44 years) more frequently than LRG individuals (97% vs 70.3%; OR=13.54, CI 2.01-150.00; p=0.004). HRG patients reported more often family history of renal disease than individuals with LRG (36.4% vs 10.8%, p=0.01). HRG patients, however, did not differ from individuals with LRG or with monogenic/likely monogenic etiologies with respect to hematuria, hypertension and eGFR decline. The transplant rate did not differ between patients with HRG and individuals with LRG without identified Mendelian disease, whereas the rate of disease relapse in the graft was significantly lower in the first group (0 vs 33.3%, p=0.02).

Conclusion

APOL1 HRG is highly prevalent among Brazilian patients with CG, suggesting a common role of second hits in genetic-environmental interaction in the pathogenesis of this glomerulopathy. Our findings strongly suggest that HRG-associated CG is a disease that manifests primarily from adolescence to early middle adulthood.