title: The relationship between intact PTH and biointact PTH (1-84) with bone and mineral metabolism in pre-dialysis chronic kidney disease (CKD).
abstract: OBJECTIVE
  Abnormalities in PTH are implicated in the pathogenesis of bone abnormalities in chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD). PTH concentrations are important in clinical decision and management. This emphasises the importance of providing an assay which measures biologically active PTH. We compared concentrations of intact PTH with biointact PTH (1-84) in CKD and end stage renal disease (ESRD) and investigated the relationship between the 2 PTH assays with bone and mineral laboratory parameters and bone mineral density (BMD) in CKD.
  
  
  METHODS
  We assessed 140 patients (61 in ESRD and 79 with CKD stages 1-4) in this cross-sectional study. We measured biointact PTH (1-84) as well as routine biochemical parameters on all subjects. In the CKD cohort, bone turnover markers; bone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase (TRACP)-5b and bone mineral density (BMD) were also determined.
  
  
  RESULTS
  In ESRD, intact PTH concentration was significantly higher compared to biointact PTH (1-84) (422 [443] v/s 266 [251] pg/mL, (p<0.001) with an average bias of 60%. In CKD, intact PTH concentration was also higher compared to biointact PTH (1-84) (79[55] v/s 68[49] pg/mL p<0.001) with an average bias of 18%. Only the biointact PTH (1-84) assay showed any significant correlation with serum calcium concentrations (r=-0.26, p<0.05) and phosphate (r=0.25, p<0.05) in CKD. Following multilinear regression analysis and adjustment for all significant co-variables, only eGFR, BAP and 25 (OH)vitamin remained significantly associated with intact PTH and biointact PTH (1-84). The strength of association was stronger between BAP and biointact PTH (1-84) (biointact PTH (1-84): p=0.007, intact PTH: p=0.01). In adjusted analyses, only biointact PTH (1-84) was significantly associated with BMD at the fore-arm (FARM) (p=0.049).
  
  
  CONCLUSIONS
  The study confirms the differences between intact PTH and biointact PTH (1-84) in ESRD. Whilst there may be similarities in the diagnostic ability of both intact and biointact PTH (1-84), our data suggest that biointact PTH (1-84) assay may better reflect bone metabolism and BMD in CKD. Further longitudinal studies are needed.
authors.affiliation: Department of Clinical Chemistry, GSTS Pathology, St Thomas' Hospital, London SE1 7EH, UK. Electronic address: deeoflaherty@hotmail.com.
authors.forename: D
authors.initials: D
authors.lastname: O'Flaherty
authors.forename: A
authors.initials: A
authors.lastname: Sankaralingam
authors.forename: P
authors.initials: P
authors.lastname: Scully
authors.forename: P
authors.initials: P
authors.lastname: Manghat
authors.forename: D
authors.initials: D
authors.lastname: Goldsmith
authors.forename: G
authors.initials: G
authors.lastname: Hampson
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D018488:Bone Demineralization, Pathologic / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D015519:Bone Density; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010710:Phosphates / Q000097:blood; D006435:Renal Dialysis; D012720:Severity of Illness Index; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007527:Isoenzymes; D010281:Parathyroid Hormone; D010710:Phosphates; C083610:1,25-dihydroxy-19-norvitamin D3; D000469:Alkaline Phosphatase; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol
keywords: Biointact PTH (1–84); Bone mineral density; Bone turnover; Chronic kidney disease; End stage renal disease; Intact PTH