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Abstract: SA-PO753

Targeted Genetic Testing with Broad Panel Informs Secondary Genetic Factors in Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Caliskan, Yasar, Saint Louis University Department of Internal Medicine, Saint Louis, Missouri, United States
  • Bastani, Bahar, Saint Louis University Department of Internal Medicine, Saint Louis, Missouri, United States
  • Abu Al Rub, Fadee, Saint Louis University Department of Internal Medicine, Saint Louis, Missouri, United States
  • Miyata, Kana N., Saint Louis University Department of Internal Medicine, Saint Louis, Missouri, United States
  • Mosman, Amy, Saint Louis University Department of Internal Medicine, Saint Louis, Missouri, United States
  • Vo, Thanh-Mai Nguyen, Saint Louis University Department of Internal Medicine, Saint Louis, Missouri, United States
  • Philipneri, Marie D., Saint Louis University Department of Internal Medicine, Saint Louis, Missouri, United States
  • Lentine, Krista L., Saint Louis University Department of Internal Medicine, Saint Louis, Missouri, United States
  • Edwards, John C., Saint Louis University Department of Internal Medicine, Saint Louis, Missouri, United States
Background

Currently, a major obstacle in autosomal dominant polycystic kidney disease (ADPKD) research is the low number of African American (AA) patients in clinical studies and lack of studies evaluating a potential interaction of APOL1-related nephropathy with ADPKD. In this pilot study, we aimed to identify the causal and secondary variants in a cohort including AA patients.

Methods

Genetic testing was performed using a commercially available next-generation sequencing-based 382 gene kidney disease panel. Pathogenic (P), likely pathogenic (LP) variants and variant of uncertain significance (VUS) were reported. Demographic data and urine protein creatinine ratio (UPCR) were obtained from electronic medical reports.

Results

Genetic testing was performed for 13 ADPKD patients (9 men and 4 women, mean age 56±10 yrs, Table 1). Five individuals were found to have heterozygous PKD1 mutations (2 with P variants, 1 with LP variant, 2 VUSs). Two individuals were found to be heterozygous for a PKD2 P variant. Six individuals had no identified P, LP variants or VUS in PKD1 or PKD2. There were 5 AA patients and all have APOL1 renal risk variants. Mean UPCR of AA patients were significantly higher than European American patients (2.15±1.27 vs 0.57±0.95 g/g, p=0.035). Of these AA patients, one had two APOL1 risk alleles (G1/G2), one with homozygous G1/G1 and 3 had heterozygous APOL1 G0/G1 risk allele.

Conclusion

Use of broad panel genetic testing in patients with PKD identifies factors underlying disease variability and progression. This preliminary data suggests the importance of genetic testing for APOL1 risk variants in AA ADPKD patients. Proteinuria may be an important sign of APOL1 associated kidney disease in AA ADPKD patients.

Funding

  • Private Foundation Support