{"id":730,"date":"2026-07-10T16:02:22","date_gmt":"2026-07-10T16:02:22","guid":{"rendered":"https:\/\/valutednews.com\/?p=730"},"modified":"2026-07-10T16:02:22","modified_gmt":"2026-07-10T16:02:22","slug":"apol1-status-may-refine-long-term-kidney-donor-risk","status":"publish","type":"post","link":"https:\/\/valutednews.com\/?p=730","title":{"rendered":"APOL1 Status May Refine Long-Term Kidney Donor Risk"},"content":{"rendered":"
\"APOL1<\/div>

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Black living kidney donors who carried high-risk apolipoprotein LI1 (APOL1<\/em>) genotypes had a substantially increased risk for long-term kidney dysfunction than donors without these variants, according to a new study.<\/p>\n

Nearly two decades after nephrectomy, donors with these genotypes were more than twice as likely to have an estimated glomerular filtration rate (eGFR) < 45 mL\/min\/1.73 m2<\/sup>, a threshold associated with clinically significant kidney impairment.<\/p>\n

\u201cWe think that, given the size of the association \u2014 which is almost certainly causal, since we know that APOL1<\/em> causes CKD [chronic kidney disease<\/a>] in other settings \u2014 Black potential kidney donors should be screened for this genotype,\u201d lead author Chi-yuan Hsu, MD, MS, Dr. Robert W. Schrier Distinguished Professor in Nephrology and chief of the Division of Nephrology at the University of California, San Francisco, told Medscape Medical News<\/em>.<\/p>\n

The findings were published<\/a> in JAMA Internal Medicine<\/em>.<\/p>\n

Better Long-Term Risk Assessment Is Needed\u00a0<\/h2>\n

Living kidney donation is a unique medical procedure in which the primary beneficiary is the recipient rather than the donor, the study authors noted. Accurate estimates of long-term donor risk are therefore essential for donor evaluation, selection, and informed consent. However, relatively few studies have assessed long-term kidney health after living donation.<\/p>\n

Earlier studies were limited by relatively short follow-up and underrepresentation of racial and ethnic minorities at higher risk for kidney disease. Nevertheless, some previous analyses have reported Black donors have a two- to three-fold higher risk for CKD or end-stage kidney disease (ESKD) after donation than White donors.<\/p>\n

In an accompanying editorial<\/a>, Adnan Sharif, MD, consultant nephrologist and transplant physician at University Hospitals Birmingham and an honorary professor at the University of Birmingham in Birmingham, England, explained that APOL1<\/em> protects against African trypanosomiasis<\/a> (sleeping sickness<\/a>) and likely evolved to counteract parasite resistance. Variants of the APOL1<\/em> gene (G1 and G2) occur almost exclusively in people of African or Caribbean ancestry.<\/p>\n

Individuals carrying two APOL1<\/em> alleles (G1\/G1, G1\/G2, or G2\/G2) are considered to have a high-risk genotype, which has been associated with a 51% increased risk for CKD and approximately double the risk for progression to kidney failure compared with carrying one or no risk alleles, Sharif noted.<\/p>\n

The National Institutes of Health-sponsored APOL1<\/em> Long-term Kidney Transplantation<\/a> Outcomes Network (APOLLO) was established to prospectively assess<\/a> kidney allograft survival according to donor and recipient APOL1\u00a0<\/em>genotype. The current LETO study was designed to complement APOLLO by examining long-term kidney health among living donors.<\/p>\n

Hsu described LETO as \u201ca standalone APOLLO ancillary study, but thematically very linked.\u201d<\/p>\n

Robust and Relevant\u00a0<\/h2>\n

The LETO study included 445 Black living kidney donors (66% women; mean age, 38 years) and 208 White donors (68% women; mean age, 44 years). Among Black donors, 15.3% carried high-risk APOL1<\/em> genotypes.<\/p>\n

The primary outcome was eGFR < 45 mL\/min\/1.73 m2<\/sup>. Secondary outcomes included eGFR < 60 mL\/min\/1.73 m2<\/sup> and urinary albumin<\/a>–creatinine<\/a> ratio of \u2265 30 or \u2265 300 mg\/g.<\/p>\n

Participants completed home-based research visits a median of 18.5 years after donation. Investigators measured height, weight, waist circumference, blood pressure, serum creatinine, and urinary albumin levels, collected DNA samples, and administered health status questionnaires.<\/p>\n

By follow-up, three Black donors had developed ESKD, one of whom carried a high-risk APOL1<\/em> genotype, and all three had undergone a kidney transplantation<\/a>.<\/p>\n

Overall, 7.6% of Black donors developed the primary outcome. The rate was significantly higher among donors with high-risk APOL1<\/em> genotypes than among those without (14.7% vs 6.4%; P<\/em> = .02).<\/p>\n

Compared with Black donors without high-risk genotypes, those with high-risk APOL1<\/em> genotypes had more than twice the risk of developing the primary outcome (relative risk, 2.31; P<\/em> = .02).<\/p>\n

Black donors carrying high-risk genotypes also had higher serum creatinine concentrations at the time of donation than those without high-risk genotypes (1.01 vs 0.93 mg\/dL; P<\/em> \u2009= .01).<\/p>\n

Adjusting for baseline eGFR weakened the association between APOL1<\/em> genotypes and the risk of developing low eGFR, although significant associations persisted for secondary kidney outcomes.<\/p>\n

Age-stratified analyses found that the association between APOL1\u00a0<\/em>genotypes and reduced kidney function was stronger among donors older than a median age of 38 years at donation.<\/p>\n

Can APOL1\u00a0<\/em>Replace Race in Algorithms?\u00a0<\/h2>\n

\u201cRight now, many centers don\u2019t do APOL1<\/em> genotyping for Black donor candidates,\u201d Hsu said.<\/p>\n

\u201cWe think that now that we have data specific to this population, it\u2019s hard to defend not checking. We didn\u2019t speculate on which donors with high-risk genotype should or should not donate, but we do think that all Black potential kidney donors should be screened.\u201d<\/p>\n

Hsu emphasized that identifying a high-risk genotype should not automatically exclude someone from donation, as many may have no other risk factors.<\/p>\n

\u201cSome people think that testing for this would reduce the pool of donors, when there\u2019s a great need for African American patients on dialysis to get living donors,\u201d he said. \u201cHowever, we think there might be the opposite effect, which is that you identify people at low-risk and therefore provide reassurance to proceed.\u201d<\/p>\n

He acknowledged that race is a complicated issue, with both social and biologic components, noting that several models<\/a> incorporate race to predict long-term outcomes among living kidney donors.<\/p>\n

\u201cThe APOL1<\/em> genotype has the potential \u2014 I\u2019m not saying it\u2019s ready at this point, but it could be one day \u2014 to replace race in these algorithms.\u201d<\/p>\n

Rather than treating all Black donor candidates as having similar risk, APOL1<\/em> testing \u201cidentifies higher- and lower-risk groups,\u201d he added.<\/p>\n

Informing Rather Than Prohibiting Donation\u00a0<\/h2>\n

Commenting for Medscape Medical News<\/em>, Sharif said the findings have immediate implications but also warrant caution.<\/p>\n

\u201cThese results are important for counseling and risk stratification of Black living kidney donor candidates with two APOL1\u00a0<\/em>alleles but carry the risk of worsening access to kidney transplantation for Black kidney transplant candidates who already face disadvantages due to structural and\/or societal inequities,\u201d he said.<\/p>\n

The LETO study \u201cprovides important data for immediate clinical translation\u201d while clinicians await results from the prospective APOLLO study, Sharif added.<\/p>\n

\u201cIt highlights the need to avoid using Black race as a crude risk factor for living kidney donor outcomes and suggests greater clarity can be provided with APOL1<\/em> genotyping.\u201d<\/p>\n

However, he emphasized that APOL1<\/em> testing alone should not serve an absolute contraindication to living kidney donation.<\/p>\n

\u201cUntil further data emerges, Black living kidney donor candidates should be appropriately counseled regarding their personal risks using APOL1<\/em> genotyping to inform, not prohibit, decision-making.\u201d<\/p>\n

The LETO study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Hsu reported receiving grants from the National Institutes of Health\/National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study. The other authors\u2019 disclosures are listed on the original publication. Sharif reported no relevant financial relationships.\u00a0<\/em><\/p>\n

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as<\/em> Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).<\/em><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Black living kidney donors who carried high-risk apolipoprotein LI1 (APOL1) genotypes had a substantially increased risk for long-term kidney dysfunction than donors without these variants, according to a new study. Nearly two decades after nephrectomy, donors with these genotypes were more than twice as likely to have an estimated glomerular filtration rate (eGFR) < 45…<\/p>\n","protected":false},"author":1,"featured_media":731,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"fifu_image_url":"https:\/\/img.medscape.com\/thumbnail_library\/Social_Facebook_806x806.jpg","fifu_image_alt":"","footnotes":""},"categories":[18],"tags":[1538,1542,1541,1540,1539,1543,424],"class_list":["post-730","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health","tag-apol1","tag-donor","tag-kidney","tag-longterm","tag-refine","tag-risk","tag-status"],"_links":{"self":[{"href":"https:\/\/valutednews.com\/index.php?rest_route=\/wp\/v2\/posts\/730","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/valutednews.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/valutednews.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/valutednews.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/valutednews.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=730"}],"version-history":[{"count":0,"href":"https:\/\/valutednews.com\/index.php?rest_route=\/wp\/v2\/posts\/730\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/valutednews.com\/index.php?rest_route=\/wp\/v2\/media\/731"}],"wp:attachment":[{"href":"https:\/\/valutednews.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=730"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/valutednews.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=730"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/valutednews.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=730"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}