Kidney Week

Abstract: FR-PO497

Genetic Determinants of Ultrafiltration With Peritoneal Dialysis

Session Information

• Peritoneal Dialysis: Current Topics
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 702 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

• Stanaway, Ian Byrell, University of Washington School of Medicine, Seattle, Washington, United States

Ian Byrell Stanaway,

• Devuyst, Olivier, University of Zurich, Zurich, Switzerland

Olivier Devuyst,

• Perl, Jeffrey, University of Toronto, Toronto, Ontario, Canada

Jeffrey Perl,

• Lambie, Mark, Keele University, Keele, Staffordshire, United Kingdom

Mark Lambie,

• Morelle, Johann, Cliniques Universitaires Saint-Luc, Brussels, Belgium

Johann Morelle,

• Jarvik, Gail P., University of Washington School of Medicine, Seattle, Washington, United States

Gail P. Jarvik,

• Jain, Arsh, London Health Sciences Center, London, Ontario, Canada

Arsh Jain,

• Himmelfarb, Jonathan, University of Washington School of Medicine, Seattle, Washington, United States

Jonathan Himmelfarb,

• Heimburger, Olof, Karolinska Universitetssjukhuset, Stockholm, Sweden

Olof Heimburger,

• Johnson, David W., Princess Alexandra Hospital, Woolloongabba, Queensland, Australia

David W. Johnson,

• Pirkle, James L., Wake Forest University, Winston-Salem, North Carolina, United States

James L. Pirkle,

• Robinson, Bruce M., Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Bruce M. Robinson,

• Stenvinkel, Peter, Karolinska Universitetssjukhuset, Stockholm, Sweden

Peter Stenvinkel,

• Davies, Simon J., Keele University, Keele, Staffordshire, United Kingdom

Simon J. Davies,

• Mehrotra, Rajnish, University of Washington School of Medicine, Seattle, Washington, United States

Rajnish Mehrotra,

Group or Team Name

• Bio-PD Consortium

Background

The inter-individual variability in the peritoneal dialysis (PD) ultrafiltration (UF) capacity is largely unexplained by demographic and clinical variables. We tested the hypothesis that common genetic variants are associated with variability in UF.

Methods

The Bio-PD study enrolled participants from 69 centers in 6 countries. The phenotype of UF volume at 4 hours was obtained from the 1^st peritoneal equilibration test (PET) when starting PD. Genotyping was done with the Illumina InfiniumOmni2-5 array and imputed using the Michigan Imputation Server. Heritability was estimated using genomic-restricted maximum likelihood analysis, genome-wide association was performed for single nucleotide variants (SNVs) with minor allele frequency >2%, and gene-wise analyses were done with the Generalized Berk-Jones test. Analyses were adjusted for sex, age, body mass index, country, diabetes, dialysate dextrose concentration, interval between PD start and PET, and principal components of ancestry. Additional analyses included 4-h Dialysate/Plasma (D/P) creatinine ratio as covariate.

Results

Analysis included 2413 participants (64% men, 32% diabetes, 82% White). The PETs were done at a median of 63 days (IQR 36-121) from PD start, 78% were completed with 2.5% dextrose, with a mean 4-h D/P creatinine of 0.70 and a median UF of 250mL (IQR 0-494). The heritability of UF was estimated at 58% and 42% in models without and with 4-h D/P creatinine, respectively (p=6x10^-4 and 0.01). No SNV reached genome-wide significance using 7,052,235 SNVs. Analyses testing association with 18,330 genes showed significant association of 3 genes at a false discovery rate (FDR) <10% (PTGES FDR=0.02, GPHN FDR=0.04, SLC24A3 FDR=0.05). Further adjustment for 4-h D/P creatinine showed association with 2 genes remained significant (PTGES and SLC24A3).

Conclusion

Common genetic variants account for a substantial proportion of the variability in UF and these analyses suggest a potential association with variation in PTGES and SLC24A3 genes.

Funding

• NIDDK Support