{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:16:36Z","timestamp":1791825396519,"version":"4.3.4"},"reference-count":78,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reduced red cell mass is a poor prognostic indicator in chronic kidney disease (CKD) patients. Whilst overt anaemia impacts on the quality of life of patients with CKD, lowered red cell mass may also compromise oxygen delivery to proximal tubular cells and contribute to progressive kidney injury. Epidemiological data from cats with CKD support this hypothesis although controlled interventional studies involving drugs that raise red cell mass in trials designed to test this hypothesis are lacking in both human and veterinary medicine. Recombinant analogues of erythropoietin (EPO) are currently standard of care for human CKD patients where low red cell mass impacts on their quality of life. Resistance to EPO is encountered in 20% to 40% of patients treated, probably due to functional iron deficiency, reflecting the difficulties of managing iron deficiency associated with the chronic inflammation of CKD. Similar issues are likely faced in managing anaemia in feline CKD although published data on the use of human EPO analogues are limited as such treatment in cats risks antibody formation resulting in red cell aplasia and transfusion dependency and so is reserved for late stage cases only. This article reviews the recent alternative therapeutic approach to increase red cell mass using HIF\u2010prolyl hydroxylase inhibitors and explains their mode of action and theoretical advantages over EPO analogues in the context of iron metabolism. The results of human clinical trials and the potential benefit of adopting this approach in feline CKD patients are discussed.<\/jats:p>","DOI":"10.1111\/jvp.13127","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T10:44:45Z","timestamp":1681123485000},"page":"145-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Therapeutics of managing reduced red cell mass associated with chronic kidney disease \u2013 Is there a case for earlier intervention?"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-6590","authenticated-orcid":false,"given":"Jonathan","family":"Elliott","sequence":"first","affiliation":[{"name":"Department of Comparative Biomedical Sciences Royal Veterinary College London NW1 0TU UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfx133"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1777"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(97)90339-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfab191"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019020213"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.12600"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000139113"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985815622975"},{"issue":"5","key":"e_1_2_12_10_1","first-page":"R1002","article-title":"Single\u2010nephron adaptations to partial renal ablation in cats","volume":"269","author":"Brown S. A.","year":"1995","journal-title":"The American Journal of Physiology"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399407000531"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00227.2005"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2011.00874.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfms.2011.07.016"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2011.00864.x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.13385"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105341"},{"issue":"4","key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.2460\/javma.1998.212.04.521","article-title":"Use of recombinant human erythropoietin for management of anemia in dogs and cats with renal failure","volume":"212","author":"Cowgill L. D.","year":"1998","journal-title":"Journal of the American Veterinary Medical Association"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2020.11.034"},{"issue":"9","key":"e_1_2_12_20_1","first-page":"1196","article-title":"Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973\u20101984)","volume":"190","author":"DiBartola S. P.","year":"1987","journal-title":"Journal of the American Veterinary Medical Association"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-5827.1998.tb03598.x"},{"key":"e_1_2_12_22_1","unstructured":"EMA. (2021).Evrenzo(Roxadustat).https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/evrenzo[last accessed 23\/01\/2023]"},{"issue":"4","key":"e_1_2_12_23_1","first-page":"H545","article-title":"Effects of hematocrit variations on regional hemodynamics and oxygen transport in the dog","volume":"238","author":"Fan F. C.","year":"1980","journal-title":"The American Journal of Physiology"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020081150"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-149773"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.35353"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00410.2014"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.13625"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.13630"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.vh.2019.01.002"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26581"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2021.06.004"},{"key":"e_1_2_12_33_1","unstructured":"IRIS. (2023).Treatment Recommendations for cats.http:\/\/www.iris\u2010kidney.com\/pdf\/IRIS_CAT_Treatment_Recommendations_2023.pdf[last accessed 23\/01\/2023]"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.1c02923"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.14661"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.06.037"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.20.4190"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules201119717"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12661"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105256"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gft033"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-022-01783-3"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.34.24147"},{"key":"e_1_2_12_44_1","first-page":"127","article-title":"Feline chronic renal failure: Questions, answers, questions","volume":"14","author":"Lulich J. P.","year":"1992","journal-title":"Compendium on Continuing Education for the Practising Veterinarian"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059538"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2011-0221"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601283103"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1057206"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80425-6"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2180373"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-117812"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.05.020"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000636200"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01584"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/1098612X14536176"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.16656"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31370"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.642296"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2015.12.020"},{"issue":"28","key":"e_1_2_12_60_1","first-page":"E3738","article-title":"Maternal intestinal HIF\u20102\u03b1 is necessary for sensing iron demands of lactation in mice","volume":"112","author":"Ramakrishnan S. K.","year":"2015","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.32.20055"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985815600500"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI122359"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011043"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.12.12.5447"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.12.012"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfab057"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(03)00468-1"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2017.1301680"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.2002.220.1799"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.701516"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80571-7"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.2.680"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00736.2009"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00415.2005"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI159839"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7SC02103H"},{"issue":"22","key":"e_1_2_12_78_1","first-page":"5830","article-title":"Overexpression of hypoxia\u2010inducible factor 1\u03b1 in common human cancers and their metastases","volume":"59","author":"Zhong H.","year":"1999","journal-title":"Cancer Research"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)11179-0"}],"container-title":["Journal of Veterinary Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.13127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T23:47:57Z","timestamp":1729208877000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvp.13127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,10]]},"references-count":78,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1111\/jvp.13127"],"URL":"https:\/\/doi.org\/10.1111\/jvp.13127","archive":["Portico"],"relation":{},"ISSN":["0140-7783","1365-2885"],"issn-type":[{"value":"0140-7783","type":"print"},{"value":"1365-2885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,10]]},"assertion":[{"value":"2023-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}