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Abstract: TH-PO811

APOL1, Bone Lead, and Kidney Disease: A Pilot Study Using Recall by Genotype

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Saha, Aparna, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Chan, Lili, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Horowitz, Carol, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Cooper, Richard, Loyola University Chicago, Maywood, Illinois, United States
  • Nadkarni, Girish N., Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

The APOL1 high-risk genotype is frequent (14%) in African Americans (AAs) and is associated with increased risk of chronic kidney disease (CKD). However, only a fraction of individuals with the genotype have CKD indicating the presence of modifiers of disease risk (‘second hits’). Nephrotoxic metals, including lead (Pb) are associated with kidney disease risk. We sought to assess whether APOL1 genetic risk and bone lead concentration interact for CKD.

Methods

We recalled AA participants with APOL1 high risk and low risk genotype from the BioMe Biobank and matched them on age, sex, most estimated glomerular filtration rate (eGFR) and socio-demographics. We then measured tibia Pb indicating body lead burden (BLB) using X ray fluoroscopy. We then estimated the difference in BLB by APOL1 risk for a given eGFR using non-parametric tests.

Results

We recalled 30 AA participants (15 with APOL1 high risk and 15 with APOL1 low risk). The median age was 56, 66% were female and median eGFR was 59 ml/min. The median Pb was 9.2 gm/gm of bone (IQR 2.7-12) and was correlated with lower eGFR (R2=-0.19). There was a trend towards lower Pb in individuals with APOL1 high risk vs. low risk (median 6.9 vs. 10.6 gm/gm; p=0.10). This was more evident in individuals (n=10) with eGFR≤45 ml/min (median 3 vs. 11.5 gm/gm; p=0.07). (Figure 1)

Conclusion

Conditional on low eGFR, Individuals with APOL1 high risk have lower BLB compared to those with APOL1 low risk. Although larger studies are needed, this may suggest that CKD risk is potentiated by BLB at lower exposure levels in persons with APOL1 high risk. Finally, this also serves as a proof-of-concept study using ‘recall by genotype’ for deep phenotyping of environmental exposures.

Funding

  • NIDDK Support