Severe secondary hyperparathyroidism in patients on haemodialysis is associated with a high initial serum parathyroid hormone and beta-CrossLaps level: Results from an incident cohort

<div><p>Background</p><p>Secondary hyperparathyroidism (SHPT) is a frequent complication of renal disease and most commonly occurs in patients on haemodialysis (HD) with metabolic, vascular, endocrine, and bone complications. The aim of this study was to analyze the evolution of mineral metabolism parameters during the first 36 months of HD treatment and identify the initial factors associated with severe SHPT.</p><p>Methods</p><p>Serum parathyroid hormone (PTH), calcium and phosphate levels were measured monthly; bone-specific alkaline phosphatase (b-ALP) and beta-CrossLaps (CTX) were measured biannually. Severe SHPT was defined as the need for cinacalcet treatment. Patients with less than 24 months of follow-up were excluded.</p><p>Results</p><p>One hundred thirty-three incident HD patients were included. Baseline mean PTH was 275 ± 210 pg/mL. After an initial drop at the third month (172 ± 133 pg/mL), the serum PTH level progressively increased to the maximum at 36 months (367 ± 254 pg/mL). This initial drop was associated with the initial correction of both hypocalcaemia and hyperphosphataemia. Serum CTX and b-ALP revealed no significant changes over time. Severe SHPT was observed in 18% of patients and was associated with higher mean calcaemia and phosphataemia. In logistic regression, the initial factors associated with the risk of severe SHPT were: female sex, higher baseline PTH and CTX values. A receiver operation characteristic curve analysis identified a cut-off value of >374 pg/mL for baseline PTH and >1.2 μg/L for CTX for increased risk of developing severe SHPT. The relative risk of developing severe SHPT was 3.7 (1.8–7.5, p = 0.002) for high baseline CTX, 4.9 (2.4–9.7, p = 0.001) for high baseline PTH, and 7.7 (3.6–16, p< 0.0001) when both criteria were present.</p><p>Conclusion</p><p>After an initial drop, a progressive increase in the serum PTH level during the first 3 years of HD treatment was observed despite aggressive therapy. High baseline levels of PTH and CTX increased the risk of developing severe SHPT.</p></div

Kinetics of the serum b-ALP level from baseline according to the patient group.

<p>Mean ± SEM.</p

Logistic regression analysis of the baseline factors which were associated with the risk of developing severe SHPT.

<p>Age, diabetes, cardiac disease, cancer, phosphataemia and sevelamer use were not significantly associated with the risk for severe SHPT.</p

Baseline characteristics of the patients stratified according to a future severe SHPT occurring during the study period.

<p>Mean ± SD except for serum CRP and PTH: Median (IQR).</p

Kinetics of the serum CTX level from baseline according to the patient group.

<p>Mean ± SEM. *: p<0.05 = difference with previous value.</p

Kinetics of the serum calcium level according to the patient group.

<p>*: p< 0.05 with previous month. Mean ± SEM.</p

Kinetics of the serum phosphate level according to the patient group.

<p>*: p<0.05 with previous month. Mean ± SEM.</p

Relative risk of future severe SHPT according to the baseline CTX or / and PTH values.

<p>High CTX: > 1.2 μg/L; high PTH: > 374 pg/ml. ** p< 0.001; *** p< 0.0001.</p

Kinetics of the serum PTH level according to the patient group.

<p>*: p< 0.05 with previous month. Mean ± SEM.</p

Newborn morphology and growth of BSP+/+ and BSP−/− mice.

<p>(A) general aspect of BSP+/+ (+/+) and BSP −/− (−/−) newborn mice. (B) Kinetics of weight gain during the growth of BSP+/+ and BSP−/− mice. M, males; F, females. Data are Mean±SEM of N = 4 to 31 mice. Note the log scale.</p