{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:24:19Z","timestamp":1783013059452,"version":"3.54.6"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"abstract":"\n Background<\/jats:title>\n \n APOL1<\/jats:italic>\n polymorphisms are a significant risk factor of kidney disease including HIV-associated nephropathy (HIVAN), but a comprehensive understanding of the pathogenic mechanism remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n APOL1<\/jats:italic>\n transgenic models expressing\n APOL1<\/jats:italic>\n -G0 and the kidney disease risk-associated\n APOL1<\/jats:italic>\n -G1 variant were intercrossed with the Tg26 mouse model of HIVAN. Since all these transgenic models are hemizygous, crosses produced offspring of four genotypes: wildtype mice,\n APOL1<\/jats:italic>\n , Tg26, and dual transgenic mice expressing both\n APOL1<\/jats:italic>\n and Tg26 transgenes. Kidney function, pathology and transgene expression patterns were examined in addition to podocyte and glomerular densities.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The wildtype and\n APOL1<\/jats:italic>\n G0 or G1 mice did not develop kidney disease, whereas Tg26 and dual transgenic mice developed severe kidney disease consistent with the Tg26 HIVAN phenotype. The outcome of the G1\/Tg26 intercross was expressed during pregnancy with neonatal complications that included a preeclampsia-like phenotype, low fetal\/placental weight ratios, low birth weights and fewer dual transgenic offspring that survived to adulthood. Some adult offspring from the G1\/Tg26 intercross also had reduced podocyte densities and fewer glomeruli. This included the wildtype and\n APOL1<\/jats:italic>\n -G1 mice, suggesting a systemic effect of the preeclampsia phenotype on the entire litter. The G0\/Tg26 intercross also demonstrated kidney pathology and albuminuria similar to the G1\/Tg26 intercross.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Co-expression of G0 in the Tg26 mouse model was not protective against kidney disease. In addition, the G1-associated pregnancy complications, reduced podocyte and glomerular densities, suggesting a second mechanism by which\n APOL1<\/jats:italic>\n risk variant expression may impact long-term kidney function.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000001253","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:00:36Z","timestamp":1783011636000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Impact of APOL1-Associated Pregnancy Complications on Kidney Disease Phenotypes in a HIV-Associated Nephropathy Mouse Model"],"prefix":"10.34067","author":[{"given":"Zhenzhen","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-7344","authenticated-orcid":false,"given":"Timur","family":"Azhibekov","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cleveland Clinic Children's, Cleveland, OH, USA"},{"name":"Case Western Reserve University School of Medicine, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfa","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-4942","authenticated-orcid":false,"given":"Jane K.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Diagnostics Institute, Cleveland Clinic, Cleveland, OH"},{"name":"Department of Kidney Medicine, Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0738-111X","authenticated-orcid":false,"given":"Korey R.","family":"Bartolomeo","sequence":"additional","affiliation":[{"name":"Department of Kidney Medicine, Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6440-7975","authenticated-orcid":false,"given":"Oliver","family":"Wessely","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland, OH, USA"},{"name":"Case Western Reserve University School of Medicine, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"O'Toole","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland, OH, USA"},{"name":"Department of Kidney Medicine, Cleveland Clinic, Cleveland, OH, USA"},{"name":"Case Western Reserve University School of Medicine, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6780-9168","authenticated-orcid":false,"given":"John R.","family":"Sedor","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland, OH, USA"},{"name":"Department of Kidney Medicine, Cleveland Clinic, Cleveland, OH, USA"},{"name":"Case Western Reserve University School of Medicine, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5874-705X","authenticated-orcid":false,"given":"Leslie A.","family":"Bruggeman","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland, OH, USA"},{"name":"Case Western Reserve University School of Medicine, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,2]]},"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.34067\/KID.0000001253","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:00:36Z","timestamp":1783011636000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.34067\/KID.0000001253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":0,"URL":"https:\/\/doi.org\/10.34067\/kid.0000001253","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"assertion":[{"value":"2026-02-15","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-17","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}