{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:11:02Z","timestamp":1780758662748,"version":"3.54.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Early intervention and management of anemia, particularly the commonly used measures of hemoglobin (Hb) and hematocrit (HCT), are important in slowing and preventing the progression of chronic kidney disease (CKD). However, the optimal range for regulating Hb and HCT levels remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this study was to elucidate the intrinsic relationship between Hb and HCT and the short- and long-term prognosis of CKD, and determine optimal ranges for Hb and HCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively collected demographic and clinical data over a 6-year follow-up period in Lingnan, China, to show the long-term characteristics of Hb and HCT, and studied the association between Hb, HCT, and the prognosis of patients with CKD stages 3\u20134. We constructed Cox and group-based trajectory modeling (GBTM) models to examine Hb\u2019s and HCT\u2019s associations with short- and long-term risk of composite outcomes in patients with CKD stages 3\u20134.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 730 individuals were included, with a median age of 59.30 (48.47, 68.63) years, 306 (41.92%) were women, and median eGFR was 39.24 (26.26, 50.67) mL\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      . A multivariate time-dependent Cox model revealed mean_Hb and mean_HCT as independent protective factors for the composite outcome {hazard ratio (HR) (95% confidence interval [CI]): 0.851 (0.786, 0.921) g\/L,\n                      <jats:italic>p=<\/jats:italic>\n                      0.000; 0.578% (0.441%, 0.758%),\n                      <jats:italic>p=<\/jats:italic>\n                      0.000}. Optimized GBTM models categorized Hb and HCT into four groups. Group 1 (\u201clower and decreasing\u201d) (Hb&amp;lt;100 g\/L, HCT approximately 30%) served as the reference. Groups 2 (\u201clower and growing slightly\u201d) (Hb 110\u2013120 g\/L, HCT approximately 35%), 3 (\u201chigher and growing slightly\u201d) (Hb 125\u2013135 g\/L, HCT approximately 40%), and 4 (\u201chigher and growing steadily\u201d) (Hb 145\u2013160 g\/L, HCT approximately 45%) served as independent protective factors for patients with CKD stages 3\u20134 for the composite outcome (\n                      <jats:italic>p=<\/jats:italic>\n                      0.000;\n                      <jats:italic>p<\/jats:italic>\n                      for trend&amp;lt;0.000). Subgroup analyses showed interactions between mean_Hb and sex (\n                      <jats:italic>p<\/jats:italic>\n                      for interaction=0.034), as well as between Hb trajectory group 2 and CKD stage (\n                      <jats:italic>p<\/jats:italic>\n                      for interaction=0.015).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Maintenance of stable and higher Hb levels of 110\u2013130 g\/L and HCT levels of 35%\u201340% in patients with CKD stages 3\u20134 is both protective and reliable in delaying CKD progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1642307","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T05:24:29Z","timestamp":1761801869000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Time-updated patterns of hemoglobin and hematocrit and the risk of CKD progression"],"prefix":"10.3389","volume":"16","author":[{"given":"Li-zhe","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-fen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-han","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-long","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-xuan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-wei","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-sheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-fan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2019.01.001","article-title":"US renal data system 2018 annual data report: epidemiology of kidney disease in the United States","volume":"73","author":"Saran","year":"2019","journal-title":"Am J Kidney Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2021.01.011","article-title":"International Society of Nephrology Global Kidney Health Atlas: structures, organization and services for the management of kidney failure in North and East Asia","volume":"11","author":"Zhang","year":"2021","journal-title":"Kidney Int Suppl (2011)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1001\/jamainternmed.2022.6817","article-title":"Prevalence of chronic kidney disease in China: results from the sixth China chronic disease and risk factor surveillance","volume":"183","author":"Wang","year":"2023","journal-title":"JAMA Intern Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-039653","article-title":"Cost-effectiveness analysis of renal replacement therapy strategies in Guangzhou city, southern China","volume":"11","author":"Yang","year":"2021","journal-title":"BMJ Open"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfv233","article-title":"Cost of renal replacement: how to help as many as possible while keeping expenses reasonable","volume":"31","author":"Vanholder","year":"2016","journal-title":"Nephrol Dial Transplant"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-023-01849-9","article-title":"A novel scenario in the therapeutic management of anemia of chronic kidney disease: placement and use of roxadustat","volume":"8","author":"Locatelli","year":"2024","journal-title":"J Nephrol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.19891220","article-title":"Fatigue in CKD: epidemiology, pathophysiology, and treatment","volume":"16","author":"Gregg","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003967.pub2","article-title":"Haemoglobin and haematocrit targets for the anaemia of chronic kidney disease","author":"Strippoli","year":"2006","journal-title":"Cochrane Database Syst Rev"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfac004","article-title":"New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: a multicohort observational study","volume":"15","author":"Minutolo","year":"2022","journal-title":"Clin Kidney J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.16191020","article-title":"Efficacy and cardiovascular safety of roxadustat for treatment of anemia in patients with non-dialysis-dependent CKD: pooled results of three randomized clinical trials","volume":"16","author":"Provenzano","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019020213","article-title":"Iron deficiency in chronic kidney disease: updates on pathophysiology, diagnosis, and treatment","volume":"31","author":"Batchelor","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.270","article-title":"Summary of the KDIGO guideline on anemia and comment: reading between the (guide)line(s)","volume":"82","author":"Dr\u00fceke","year":"2012","journal-title":"Kidney Int"},{"key":"B13","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1186\/s12882-017-0688-1","article-title":"Renal association clinical practice guideline on Anaemia of Chronic Kidney Disease","volume":"18","author":"Mikhail","year":"2017","journal-title":"BMC Nephrol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.1001-7097.2018.11.012","article-title":"Expert consensus on the diagnosis and treatment of renal anaemia (2018 revised edition)","volume":"34","year":"2018","journal-title":"Chin J Nephrol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s10157-022-02282-1","article-title":"Hematological parameters of anemia and prognosis of non-dialysis-dependent chronic kidney disease: the Fukushima CKD cohort study","volume":"27","author":"Saito","year":"2023","journal-title":"Clin Exp Nephrol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065485","article-title":"Correction of anemia with epoetin alfa in chronic kidney disease","volume":"355","author":"Singh","year":"2006","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062276","article-title":"Normalization of hemoglobin level in patients with chronic kidney disease and anemia","volume":"355","author":"Dr\u00fceke","year":"2006","journal-title":"N Engl J Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","year":"2024","journal-title":"Kidney Int"},{"key":"B19","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1007\/BF02924688","article-title":"Multiple imputation for nonresponse in surveys","volume":"31","author":"Toutenburg","year":"1990","journal-title":"Stat Papers"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0236132","article-title":"Prevalence of anemia in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB)","volume":"15","author":"Sofue","year":"2020","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfab195","article-title":"Contemporary outcomes of anemia in US patients with chronic kidney disease","volume":"15","author":"Wittbrodt","year":"2021","journal-title":"Clin Kidney J"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038881","article-title":"Possible mechanism of hematocrit elevation by sodium glucose cotransporter 2 inhibitors and associated beneficial renal and cardiovascular effects","volume":"139","author":"Sano","year":"2019","journal-title":"Circulation"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1525-139X.2007.00329.x","article-title":"The optimal hemoglobin in dialysis patients- a critical review","volume":"21","author":"Singh","year":"2008","journal-title":"Semin Dial"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.295","article-title":"Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved haemoglobin outcomes","volume":"74","author":"Szczech","year":"2008","journal-title":"Kidney Int"},{"key":"B25","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1053\/j.ajkd.2007.06.008","article-title":"KDOQI clinical practice guideline and clinical practice recommendations for anaemia in chronic kidney disease, 2007 update of haemoglobin target","volume":"50","year":"2007","journal-title":"Am J Kidney Dis"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1642307\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T05:24:32Z","timestamp":1761801872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1642307\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":25,"alternative-id":["10.3389\/fendo.2025.1642307"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1642307","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]},"article-number":"1642307"}}