{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T14:00:45Z","timestamp":1782136845532,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23HL157554"],"award-info":[{"award-number":["K23HL157554"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Progressive kidney injury is a major cause of morbidity and mortality in sickle cell anemia (SCA). The high risk\n                    <jats:italic>APOL1<\/jats:italic>\n                    G1\/G2 variants contribute to the development of kidney disease in individuals of African ancestry, including those with SCA. However, few studies have evaluated the longitudinal effect of\n                    <jats:italic>APOL1<\/jats:italic>\n                    variants in children and young adults. We analyzed the association of\n                    <jats:italic>APOL1<\/jats:italic>\n                    risk variants with kidney function in 494 individuals aged 1 to 25 in the Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>\n                    #NCT02098863). Before age 10,\n                    <jats:italic>APOL1<\/jats:italic>\n                    G1\/G2 alleles were not associated with time to CKD (hazard ratio [HR]\u2009=\u20091.87;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.14), hyperfiltration (HR\u2009=\u20090.96;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.88), or continuous eGFR (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u2009\u22120.0090;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.71). However, after age 10,\n                    <jats:italic>APOL1<\/jats:italic>\n                    G1\/G2 variants were associated with higher baseline eGFR (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>APOL1<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.098;\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>APOL1<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.016), a steeper downward slope of eGFR over time (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>APOL1<\/jats:italic>\n                      xAge\n                    <\/jats:sub>\n                    \u2009=\u2009\u22120.014;\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>APOL1<\/jats:italic>\n                      xAge\n                    <\/jats:sub>\n                    \u2009=\u20091.60\u2009\u00d7\u200910\n                    <jats:sup>\u221210<\/jats:sup>\n                    ), and increased odds of having an accelerated rate of eGFR decline (individual\u2010specific eGFR slopes in the most negative tertile; odds ratio [OR]\u2009=\u20092.18;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.040). Among 111 individuals with measurements before and after 10\u2009years of age, those with hyperfiltration before age 10 or\n                    <jats:italic>APOL1<\/jats:italic>\n                    risk alleles were at increased risk of having an accelerated rate of eGFR decline (OR\u2009=\u20092.96;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.019). These findings support the hypothesis that genetic risk stratification and early renal surveillance can help identify patients most at risk for the progression of kidney injury.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Clinicaltrials.gov #NCT02098863.\n                  <\/jats:p>","DOI":"10.1002\/ajh.70290","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T15:04:54Z","timestamp":1774278294000},"page":"1341-1350","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Longitudinal Effect of\n                    <scp>\n                      <i>APOL1<\/i>\n                    <\/scp>\n                    Risk Alleles on Sickle Cell Anemia\u2010Associated Kidney Function"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5542-6891","authenticated-orcid":false,"given":"Sara R.","family":"Rashkin","sequence":"first","affiliation":[{"name":"Department of Hematology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6102-0115","authenticated-orcid":false,"given":"Guolian","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2832-6884","authenticated-orcid":false,"given":"Clifford M.","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Department of Hematology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-3036","authenticated-orcid":false,"given":"Mitchell J.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Hematology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4501-9982","authenticated-orcid":false,"given":"Kenneth I.","family":"Ataga","sequence":"additional","affiliation":[{"name":"Center for Sickle Cell Disease University of Tennessee Health Sciences Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8584-4194","authenticated-orcid":false,"given":"Santosh L.","family":"Saraf","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology University of Illinois Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5011-1022","authenticated-orcid":false,"given":"Jeffrey","family":"Lebensburger","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3631-7195","authenticated-orcid":false,"given":"Rima S.","family":"Zahr","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology and Hypertension University of Tennessee Health Science Center  Memphis Tennessee 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