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Abstract: SA-PO790

APOL1-Inflammation and Hypoxia Axis in Ischemic Donor Kidneys

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Caliskan, Yasar, Saint Louis University, Saint Louis, Missouri, United States
  • Kurashima, Kento, Saint Louis University, Saint Louis, Missouri, United States
  • Unes, Meghan Marie, Saint Louis University, Saint Louis, Missouri, United States
  • Portz, Edward L., Saint Louis University, Saint Louis, Missouri, United States
  • Abu Al Rub, Fadee, Saint Louis University, Saint Louis, Missouri, United States
  • Brink, David S., Saint Louis University, Saint Louis, Missouri, United States
  • Nazzal, Mustafa, Saint Louis University, Saint Louis, Missouri, United States
  • Jain, Ajay, Saint Louis University, Saint Louis, Missouri, United States
  • Lentine, Krista L., Saint Louis University, Saint Louis, Missouri, United States
  • Edwards, John C., Saint Louis University, Saint Louis, Missouri, United States
Background

The presence of two APOL1 renal risk variants (RRVs) in donor kidneys negatively impacts kidney allograft survival. We examined the effects of APOL1 RRVs on APOL1 expression and compared the differences in cytokine and APOL1 expression patterns between preservation methods cold storage (CS) and normothermic machine perfusion (NMP).

Methods

Discarded deceased donor kidney pairs underwent 6-hour NMP (n=6) and CS (n=6). Perfusion, biochemical, and histologic parameters were recorded. Paired donor kidneys with different APOL1 genotypes were compared with regard to the aforementioned parameters and gene expression under NMP and CS. DNA is extracted and genotyping for APOL1 RRVs G1 (rs73885319) (rs60910145) and G2 (rs71785313) were performed by Sanger sequencing.

Results

Donor genotyping showed 5 kidney pairs with G0/G0 and a kidney pair with heterozygous G0/G1 RRV. Kidneys were successfully perfused, with improved renal blood flows and resistance over the course of perfusion, and evidence of urine output (Table 1). Transcriptomic analyses showed different expression patterns between APOL1 G0/G0 kidneys and G0/G1 kidney, particularly under NMP (Fig. 1). The kidney with APOL1 G0/G1 showed higher fold increase in expression of APOL1, TGF-β and IFN-γ compared to kidneys with G0/G0 under 6 hrs of NMP. Overall, APOL1 expression was significantly correlated with KIM1 (r=0.87, p<0.001), TGF-β (r=0.83, p=0.001), IFN-γ (r=0.77, p=0.004) and HIF-1α (r=0.81, p<0.001) in all kidney pairs.

Conclusion

Donor kidney with APOL1 G0/G1 RRV demonstrated different transcriptomic response to alternative preservation methods. Further studies needed to clarify the interplay between APOL1, inflammation and kidney injury in the setting of allograft ischemia and reperfusion.

Funding

  • Private Foundation Support