{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:52:39Z","timestamp":1789843959617,"version":"4.0.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>High levels of Proenkephalin A 119\u2013159 (PENK) have been associated with decreased glomerular filtration rate (GFR) in subjects with preserved kidney function, yet its clinical utility in patients with end-stage kidney disease (ESKD) remains to be established. This study aimed to investigate the correlation between PENK and GFR, and evaluate the clearance of PENK during hemodialysis (HD) in ESKD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center prospective cohort study enrolled adult patients with ESKD undergoing maintenance HD. Plasma PENK levels were determined before (baseline) and after a single HD session using a double-antibody sandwich enzyme-linked immunosorbent assay. The associations of PENK with estimated GFR (eGFR), and other markers of kidney function and heart failure were analyzed at baseline. Furthermore, changes in PENK levels during HD were evaluated to assess its dialytic clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 100 ESKD patients were enrolled. At baseline, the median eGFR and PENK level were 6.30\u202fmL\/min\/1.73\u202fm\n                      <jats:sup>2<\/jats:sup>\n                      and 4.88\u202fng\/mL, respectively. In the entire cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f100), no significant correlations were observed between PENK and eGFR (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f\u22120.00,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.99), BUN (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f0.16,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.10), SCr (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f0.18,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.08), NT-proBNP (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f\u22120.06,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.58), or LVEF (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f0.12,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.26). Among patients with residual urine output (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f56), PENK and eGFR also exhibited no significant correlation (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f\u22120.15,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.28). Although significant clearance was observed for BUN (12.59 vs. 3.68\u202fmmol\/L,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001) and SCr (458.70 vs. 165.85\u202f\u03bcmol\/L,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), PENK levels remained unchanged during HD (4.88 vs. 4.80\u202fng\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.85), with the stability unaffected by residual urine output, dialysis vintage, dialysis frequency, or comorbidities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this cohort of ESKD patients, plasma PENK levels showed no significant correlation with eGFR, and negligible clearance of PENK was observed during HD. These preliminary results suggested limited value of PENK for evaluating residual kidney function and dialysis adequacy in patients with ESKD. Further studies are required to clarify the mechanisms by which PENK is involved in kidney impairment and to characterize PENK kinetics during HD in this patient population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1762412","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:20:40Z","timestamp":1776140440000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Proenkephalin a 119\u2013159 for evaluating glomerular filtration rate and hemodialysis adequacy in patients with end-stage kidney disease: a prospective cohort study"],"prefix":"10.3389","volume":"13","author":[{"given":"Luobei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University","place":["Wuhan, Hubei, China"]},{"name":"Hubei Clinical Research Center for Critical Care Medicine","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Gong","sequence":"additional","affiliation":[{"name":"Hubei Clinical Research Center for Critical Care Medicine","place":["Wuhan, Hubei, China"]},{"name":"Department of Critical Care Medicine, Jiayu Hospital Zhongnan Hospital of Wuhan University, Xianning","place":["Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University","place":["Wuhan, Hubei, China"]},{"name":"Hubei Clinical Research Center for Critical Care Medicine","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University","place":["Wuhan, Hubei, China"]},{"name":"Hubei Clinical Research Center for Critical Care Medicine","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University","place":["Wuhan, Hubei, China"]},{"name":"Hubei Clinical Research Center for Critical Care Medicine","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Clinical Research Center for Critical Care Medicine","place":["Wuhan, Hubei, China"]},{"name":"School of Basic Medical Sciences, Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Hou","sequence":"additional","affiliation":[{"name":"Hubei Clinical Research Center for Critical Care Medicine","place":["Wuhan, Hubei, China"]},{"name":"School of Basic Medical Sciences, Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Tong","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, Department of Medicine, Zhongnan Hospital of Wuhan University","place":["Xianning, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University","place":["Wuhan, Hubei, China"]},{"name":"Hubei Clinical Research Center for Critical Care Medicine","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University","place":["Wuhan, Hubei, China"]},{"name":"Hubei Clinical Research Center for Critical Care Medicine","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1016\/s0140-6736(25)01853-7","article-title":"Global, regional, and national burden of chronic kidney disease in adults, 1990-2023, and its attributable risk factors: a systematic analysis for the global burden of disease study 2023","volume":"406","year":"2025","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2502","DOI":"10.1093\/ndt\/gfp071","article-title":"Residual renal function improves outcome in incremental haemodialysis despite reduced dialysis dose","volume":"24","author":"Vilar","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1053\/ajkd.2001.25198","article-title":"Residual renal function and mortality risk in hemodialysis 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