Changes in total parathyroid hormone (PTH), PTH-(1-84) and large C-PTH fragments in different stages of chronic kidney disease.
BACKGROUND
Loss of renal function is accompanied by progressive increase in serum levels of intact parathyroid hormone (iPTH) in patients with end-stage renal disease (ESRD). There is a paucity of data regarding levels of PTH-(1-84) and its large carboxyl-terminal fragments (large C-PTH fragments) and progressive loss of kidney function in patients with chronic kidney disease (CKD). The current study was undertaken to describe the glomerular filtration rate (GFR)-dependent plasma concentrations of PTH-(1-84) and related large C-PTH fragments in adult patients with CKD by using different commercially available PTH assays.


METHODS
We studied 80 Caucasian patients with CKD stages 1-5 without renal replacement therapy. Creatinine clearance was calculated by the Modification of Diet in Renal Disease (MDRD) formula. Levels of iPTH were determined by second-generation assays (iPTH Elecsys system, Roche Diagnostics; DUO total iPTH, Scantibodies Laboratory, Inc.; iPTH, Nichols Institute Diagnostics). Third-generation assays were used to measure PTH-(1-84) (CAP (cyclase activating PTH), Scantibodies; Bio-Intact PTH, Nichols). Levels of large C-PTH fragments and ratios of PTH-(1-84)/large C-PTH fragments were calculated and statistical analyses performed.


RESULTS
Levels of iPTH and PTH-(1-84) showed CKD stage-dependent increases. Variations among the assays increased with progressive loss of kidney function. The assay from Scantibodies showed a GFR-dependent decrease of the ratio 1-84 PTH / large C-PTH fragment that was not observed with the Nichols assay.


CONCLUSIONS
Increasing variations among the assays with progression of CKD emphasize the fact that the interpretation of measurements must take into consideration the specific assay. We found evidence for a possible preferential increase of the level of large C-PTH fragments over 1-84 PTH in a CKD stage-dependent manner (Scantibodies). The clinical implications of this finding have to be further evaluated by bone biopsy studies.
Herberth
J
J
Division of Nephrology, Bone and Mineral Metabolism, Albert B. Chandler Medical Center, University of Kentucky, 800 Rose Street, MN-564, Lexington, KY 40536, USA. jherb2@uky.edu
Fahrleitner-Pammer
A
A
Obermayer-Pietsch
B
B
Krisper
P
P
Holzer
H
H
Malluche
H H
HH
Dobnig
H
H
D000328:Adult; D000368:Aged; D001774:Blood Chemical Analysis / Q000379:methods; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood* / Q000737:chemistry; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry
D010281:Parathyroid Hormone; D010446:Peptide Fragments