Relationship between blood bone metabolic biomarkers and anemia in CKD patients

Introduction Blood bone metabolic biomarkers are non-invasive indexes for evaluating renal osteodystrophy (ROD). Here the relationships between blood bone metabolic biomarkers and anemia in chronic kidney disease (CKD) patients are investigated, the effects of parathyroidectomy (PTX) on above indices are analyzed. Methods In this cross-sectional study, 100 healthy controls and 239 CKD patients, including 46 secondary hyperparathyroidism (SHPT) subgroup with PTX, were enrolled. A prospective study with 28 PTX patients was followed up. The degree of anemia was classified as mild, moderate, and severe based on the tertiles of hemoglobin (Hb) levels of the anemic CKD patients, with cutoff values of 83g/L and 102g/L. Bone metabolic biomarkers, including calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23) and α-klotho were tested. Results The mean eGFR in CKD patients was 25.74±35.99 ml/min/1.73 m2 and 84.10% patients had anemia. The baseline Hb levels in the mild, moderate, and severe anemia subgroups were 110.86±5.99g/L, 92.71±5.96g/L and 67.38±10.56g/L, respectively. CKD patients had higher adjusted Ca, P, ALP, iPTH and FGF23 levels, and lower α-klotho levels than controls. Baseline adjusted Ca, P, iPTH and α-klotho levels were associated with Hb in CKD patients. Blood adjusted Ca, P, iPTH levels were correlated with anemia severity. After PTX (median interval: 6.88 months), anemia and high blood adjusted Ca, P, iPTH and FGF23 levels were ameliorated, while α-klotho levels increased. Conclusions Blood adjusted Ca, P, iPTH and α-klotho levels were correlated with Hb in CKD patients, correcting ROD is supposed to be therapeutic targets for anemia. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by the National Natural Science Foundation of China [81270408, 81570666]; International Society of Nephrology (ISN) Clinical Research Program [1801-0247]; CKD Anemia Research Foundation from China International Medical Foundation [Z-2017-24-2037]; Construction Program of Jiangsu Provincial Clinical Research Center Support System [BL2014084]; Chinese Society of Nephrology [13030300415]; Jiangsu Province Key Medical Personnel Project [RC201162, ZDRCA2016002]; Outstanding Young and Middle-aged Talents Support Program of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethics Committee of the First Affiliated Hospital of Nanjing Medical University gave ethical approval for this work (2015-SR-146). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.