Targets for parathyroid hormone in secondary hyperparathyroidism: is a "one-size-fits-all" approach appropriate? A prospective incident cohort study

Abstract

Background: Recommendations for secondary hyperparathyroidism (SHPT) consider that a "one-size-fits-all" target enables efficacy of care. In routine clinical practice, SHPT continues to pose diagnosis and treatment challenges. One hypothesis that could explain these difficulties is that dialysis population with SHPT is not homogeneous.

Methods: EPHEYL is a prospective, multicenter, pharmacoepidemiological study including chronic dialysis patients (≥ 3 months) with newly SHPT diagnosis, i.e. parathyroid hormone (PTH) ≥ 500 ng/L for the first time, or initiation of cinacalcet, or parathyroidectomy. Multiple correspondence analysis and ascendant hierarchical clustering on clinico-biological (symptoms, PTH, plasma phosphorus and alkaline phosphatase) and treatment of SHPT (cinacalcet, vitamin D, calcium, or calcium-free calcic phosphate binder) were performed to identify distinct phenotypes.

Results: 305 patients (261 with incident PTH ≥ 500 ng/L; 44 with cinacalcet initiation) were included. Their mean age was 67 ± 15 years, and 60% were men, 92% on hemodialysis and 8% on peritoneal dialysis. Four subgroups of SHPT patients were identified: 1/ "intermediate" phenotype with hyperphosphatemia without hypocalcemia (n = 113); 2/ younger patients with severe comorbidities, hyperphosphatemia and hypocalcemia, despite SHPT multiple medical treatments, suggesting poor adherence (n = 73); 3/ elderly patients with few cardiovascular comorbidities, controlled phospho-calcium balance, higher PTH, and few treatments (n = 75); 4/ patients who initiated cinacalcet (n = 43). The quality criterion of the model had a cut-off of 14 (>2), suggesting a relevant classification.

Conclusion: In real life, dialysis patients with newly diagnosed SHPT constitute a very heterogeneous population. A "one-size-fits-all" target approach is probably not appropriate. Therapeutic management needs to be adjusted to the 4 different phenotypes.

Figure 1

Disposition of patients. ^aParathyroid hormone.

Figure 2

Distribution of parathyroid hormone (PTH) according to multiples of the upper normal limit for the assays in the EPHEYL study.

Figure 3

Identification of four distinct subgroups of dialysis patients with secondary hyperparathyroidism (SHPT) using multiple correspondence analyses. The horizontal axis defined the presence or absence of calcium supplementation, the presence or absence of treatment with cinacalcet, and serum PTH below or above 500 ng/L. The vertical axis defined a normophosphatemia, a hyperphosphatemia, the absence or presence of phosphorus binders, high or low level of alkaline phosphatases, the presence or absence of vitamin D supplementation, the presence or absence of calcium suplementation. Each patient is identified by a number and a color according to the following code: black for group 1 (“intermediate”), green for group 2 (younger with severe cardiovascular comorbidities), blue for group 3 (elderly patients with few cardiovascular comorbidities), pink for group 4 (“cinacalcet prescription”).