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Serum β-Crosslaps as Predictor of long-term Parathyroid Hormone Levels in Haemodialysis Patients

This paper is available in a repository.
This paper is available in a repository.

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Abstract

Surrogate bone chemical markers, such as serum calcium (Ca 2+), phosphate (PO 4 -), alkaline phosphatase (ALP) and mainly plasma levels of intact parathyroid hormone (PTH), are commonly used in the management of CKD-MBD in clinical settings. Usually single PTH measurements are performed every 3-6 months and patients are treated according to well-established thresholds of PTH levels, while recent evidences show a very high biological variability of PTH in hemodialysis (HD) patients. On this basis, it has been proposed that absolute measurements of PTH at determined time-points is not the ideal tool to modulate therapy but would be better to evaluate PTH variability over time, or search for new surrogate markers of variability. The aim of our study was to evaluate the ability of serum β-Crosslaps (CTX), the Cross-linked C-terminal telopeptides of type I collagen, a validated marker of bone reabsorption, to estimate backward PTH levels according to different time intervals in a cohort of HD patients. Furthermore, we aimed to investigate the potential role of CTX as indicator of a target level of PTH maintenance. PATIENTS AND METHODS Out of the 98 patients recruited from two HD units of Catanzaro (Italy) 46 fulfilled inclusion criteria. Admission criteria included HD age >21 months and PTH values recorded every three months over the last 21 months. All patients were receiving regular, standard (4-hour, thrice a week) renal replacement treatment with standard bicarbonate dialysis. All patients were treated as recommended by current K/DOQI Clinical Practice Guidelines for CKD-MBD. Data of the backward quarter PTH values over the last 21 months were collected from clinical records. PTH measurements were carried out uniformly in all patients: fasting, in the morning and before starting a mid-week HD session after a short inter-dialytic period. The degradation products of C-terminal telopeptides of Type I collagen (CTX) was measured, in a fasting state, within one month by the Serum CrossLaps® ELISA test. In order to evaluate the relationship between CTX value and the maintenance of PTH in the short-and long-term, seven time intervals (3, 6, 9, 12, 15, 18 and 21-month) were individuated and the mean of PTH measured within each interval calculated for every patient (Figure 1). RESULTS We found: 1) positive correlation between mean PTH in each time interval and β-Crosslaps with a progressive increase of the correlation coefficient (highest value for the 12-and 21-month intervals); 2) significant differences between tertiles of β-Crosslaps at 6, 9, 12, 15, 18 and 21-month intervals, with a progressively growing value of the test coefficient; 3) after computation of receiver operating characteristic (ROC) curves, β-Crosslaps showed to significantly estimate threshold PTH values with the highest AUCs (AUC=0.763, 95%CI 0.625-0.901 for PTH <150 pg/ml; AUC=0.774, 95%CI 0.614-0.934 for PTH >300 pg/ml) and best value of both sensitivity and specificity at the 12-month time interval (82 and 72% for PTH <150 pg/ml, 78 and 79% for PTH >300 pg/ml)