New assays for parathyroid hormone (PTH) and the relevance of PTH fragments in renal failure.
BACKGROUND
Immunometric assays for parathyroid hormone (PTH) are used extensively to assess bone and mineral metabolism in patients with end-stage renal disease (ESRD) who are treated with dialysis. Results generally correspond to bone histology as documented by bone biopsy, and they are useful in monitoring disease progression. Recent work has shown, however, that older, first-generation immunometric PTH assays detect not only full-length PTH(1-84), but also other amino-terminally-truncated PTH fragments (ntPTH) that may have inhibitory effects on bone cell metabolism and/or contribute to the development of adynamic renal osteodystrophy. New second-generation immunometric PTH assays, by contrast, detect PTH(1-84) exclusively. The diagnostic value of plasma PTH determinations using second-generation immunometric PTH assays and the utility of estimates of the concentration of ntPTH in plasma in patients with ESRD has been assessed only recently.


METHODS
Results were reviewed from three published studies that examined the relationship between bone histology and plasma PTH levels as measured both by first- and by second-generation immunometric PTH assays in patients with ESRD. In all three studies, the concentration of ntPTH was estimated from the numerical difference between the results obtained with each assay and a ratio of PTH(1-84)/ntPTH was calculated.


RESULTS
In one report, all patients with adynamic renal osteodystrophy had PTH(1-84)/ntPTH ratio values <1.0, although some patients with high-turnover skeletal lesions also had values <1.0. Estimates of the ratio of PTH(1-84)/ntPTH were found to be a better predictor of adynamic bone than PTH values measured by either assay. By contrast, two other studies failed to confirm these observations. One made use of the same second-generation immunometric PTH assay employed in the original report, whereas the other used a different assay with similar specificity for PTH(1-84). Plasma PTH levels obtained by first- and second-generation assays were highly correlated in these two independent reports.


CONCLUSIONS
Plasma PTH levels, as determined by first-generation and second-generation immunometric assays, are highly correlated and have similar diagnostic value for the non-invasive assessment of renal osteodystrophy. The contention that ntPTH estimates and values for the PTH(1-84)/ntPTH ratio are useful in the diagnostic assessment of renal osteodystrophy has yet to be confirmed.
Goodman
William G
WG
Department of Medicine, Division of Nephrology, UCLA School of Medicine, Los Angeles, California 90095, USA. wgoodman@ucla.edu
D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007118:Immunoassay / Q000639:trends*; D010281:Parathyroid Hormone / Q000032:analysis* / Q000097:blood*; D051437:Renal Insufficiency / Q000097:blood
D010281:Parathyroid Hormone