A genome-wide association study suggests correlations of common genetic variants with peritoneal solute transfer rates in patients with kidney failure receiving peritoneal dialysis

• Published in: Kidney international Vol. 100; no. 5; pp. 1101 - 1111
• Main Authors: Mehrotra, Rajnish, Stanaway, Ian B., Jarvik, Gail P., Lambie, Mark, Morelle, Johann, Perl, Jeffrey, Himmelfarb, Jonathan, Heimburger, Olof, Johnson, David W., Imam, Talha H., Robinson, Bruce, Stenvinkel, Peter, Devuyst, Olivier, Davies, Simon J., Pisoni, Ronald, Johnson, David, Cho, Yeoungjee, Wong, Muh Geot, Mather, Amanda, Cooper, Bruce, Goffin, Eric, Bammens, Bert, Bovy, Philippe, Margetts, Peter, Taylor, Paul, Jain, Arsh, Jassal, Vanita, Kuan, Ying, Harron, Camille, Dasgupta, Indranil, Stoves, John, Akbani, Habib, Abeygunasekara, Sumith, Sharples, Edward, Mead, Paul, Hayat, Amer, Morgan, Neal, Cramp, Hilary, Robertson, Susan, Fielding, Richard, Brown, Edwina, Collinson, Helen, Ande, Pravene, Doulton, Tim, MacDougall, Iain, Cairns, Hugh, Vilar, Enric, Vardhan, Anand, Chess, James, Sandhu, Kanwaljit, Wilkie, Martin, McHaffie, Gavin, Lewis, Robert, Kamesh, Lavanya, Buck, Kate, Peel, Robert, Taylor, Jo, Johnston, Paul, Leung, Janson, Bingham, Coralie, Anijeet, Hameed, Ranakrishna, Satish, Nair, Sunita, Iggo, Neil, Lewis, David, Udayaraj, Uday, Dawson, Susan, Woordrow, Graham, Chandrasekar, Thangavelu, Hamer, Rizwan, Davies, Simon, Donovan, Kieron, Jones, Colin, Ynares, Christina, Dukes, Carl, Corapi, Kristin, Nigwekar, Sagar, Khawar, Osman, Weiner, Daniel, Lau, Wei Ling, Harley, Kevin, Ghaffari, Arshia, Saxena, Ramesh, Abraham, Josephine, Cavanaugh, Kerri L., Golper, Thomas A., Burkart, John M., Pirkle, James L., Miller, Brent, Jang, Judy, Turner, Jeffrey
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2021
• Subjects: Creatinine; Dialysis Solutions; epithelial mesenchymal transition; genetics; Genome-Wide Association Study; Humans; kidney failure; Kidney Failure, Chronic; Medicin och hälsovetenskap; peritoneal dialysis; Peritoneal Dialysis - adverse effects; peritoneal solute transfer rate; Peritoneum; Renal Insufficiency; kidney failure; epithelial mesenchymal transition; peritoneal dialysis; genetics; peritoneal solute transfer rate; genome-wide association study
• ISSN: 0085-2538; 1523-1755; 1523-1755
• DOI: 10.1016/j.kint.2021.05.037

Movement of solutes across the peritoneum allows for the use of peritoneal dialysis to treat kidney failure. However, there is a large inter-individual variability in the peritoneal solute transfer rate (PSTR). Here, we tested the hypothesis that common genetic variants are associated with variability in PSTR. Of the 3561 participants from 69 centers in six countries, 2850 with complete data were included in a genome-wide association study. PSTR was defined as the four-hour dialysate/plasma creatinine ratio from the first peritoneal equilibration test after starting PD. Heritability of PSTR was estimated using genomic-restricted maximum-likelihood analysis, and the association of PSTR with a genome-wide polygenic risk score was also tested. The mean four-hour dialysate/plasma creatinine ratio in participants was 0.70. In 2212 participants of European ancestry, no signal reached genome-wide significance but 23 single nucleotide variants at four loci demonstrated suggestive associations with PSTR. Meta-analysis of ancestry-stratified regressions in 2850 participants revealed five single-nucleotide variants at four loci with suggestive correlations with PSTR. Association across ancestry strata was consistent for rs28644184 at the KDM2B locus. The estimated heritability of PSTR was 19%, and a permuted model polygenic risk score was significantly associated with PSTR. Thus, this genome-wide association study of patients receiving peritoneal dialysis bolsters evidence for a genetic contribution to inter-individual variability in PSTR. [Display omitted]