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New data highlight the importance of managing both PTH and phosphate

28 September 2021

Study investigates the independent effects of high PTH, phosphate and calcium levels on negative outcomes in CKD

A 2021 retrospective study sheds light on whether the negative effects of secondary hyperparathyroidism (SHPT) on chronic kidney disease (CKD) patients are linked with hyperphosphataemia and/or hypercalcaemia.1 The results of the investigation can inform clinical decisions and potentially help to improve patient outcomes.

Study goals

SHPT is associated with CKD progression,2,3 cardiovascular (CV) events3,4 and mortality in CKD patients.2–5 However, whether these outcomes are truly due to increases in parathyroid hormone (PTH) levels is unclear, as high levels of calcium, phosphate and calcium–phosphate product are associated with the same outcomes in the same population.6–11

The goals of this study, conducted by Dr Milica Bozic* and colleagues, were to investigate:1

  1. The effect of SHPT on the risks of CKD progression and CV events in CKD patients
  2. Whether hypercalcaemia and/or hyperphosphataemia modify the effect of SHPT

Study design1

CKD patients without previous CV events (N=2,445) were enrolled from NEFRONA, a prospective multicentre cohort study involving 81 Spanish hospitals and dialysis clinics (Table 1).

Table 1. Patient population by CKD stage

Adapted from Bozic M et al. 2021.1

To assess CV events, all patients were followed for 4 years.

To investigate CKD progression (defined as either a 30% decrease of glomerular filtration rate or initiation of dialysis), a patient subgroup (n=1,283) was assessed after 2 years. Dialysis patients were excluded from this analysis.

Patients with SHPT were defined as those with excessive PTH levels (as defined by the Kidney Disease Outcomes Quality Initiative [KDOQI]) or those taking PTH-reducing agents, including cinacalcet and active vitamin D (AVD) compounds. Crucially, the definition did not include patients with hyperphosphataemia or those treated with phosphate binders, allowing the independent effects of high PTH and phosphate levels to be analysed separately.

Study results1

In the whole cohort, the prevalence of SHPT was 65.6%. During the 4 years of follow-up of all patients in the cohort, 203 CV events were recorded.

In the subgroup population that was assessed for CKD progression after 2 years, the prevalence of SHPT was 63.5%. CKD progression was observed in 301 (23.5%) of these patients.

Compared with patients without SHPT, patients with SHPT demonstrated a higher risk of CKD progression and CV events. Hyperphosphataemia was an independent risk factor for both outcomes and did not modify the effect of SHPT. Hypercalcaemia was not associated with the outcomes and did not modify SHPT’s effect.


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Key takeaways

  • SHPT and hyperphosphataemia are independently associated with CKD progression and CV events, unlike hypercalcaemia1
  • To decrease the risks of CKD progression and CV events, the levels of both PTH and phosphate should be managed in non-dialysis CKD patients1
  • Since AVD compounds are known to increase the risk of hyperphosphataemia,12–14 their use in the treatment of progressive SHPT in advanced CKD should be managed carefully

To read the full publication and evaluate the clinical consequences of the results in more detail, visit the Oxford Academic website.

Footnotes and references

*Vascular and Renal Translational Research Group, Biomedical Research Institute, IRBLLEIDA and RedinRen RETIC, ISCIII, Lleida, Spain.

SHPT in stage 3 CKD was defined as PTH >70 pg/mL (>7.4 pmol/L), in stage 4 as >110 pg/mL (>11.7 pmol/L) and in stage 5 or dialysis as >300 pg/mL (>31.8 pmol/L).1

  1. Bozic M et al. Nephrol Dial Transplant. 2021;gfab184.

  2. Schumock G et al. Curr Med Res Opin. 2008;24:3037–48.

  3. Xu Y et al. Clin Kidney J. 2021;sfab006.

  4. Geng G et al. Osteoporos Int. 2019;30:2019–25.

  5. Kovesdy CP et al. Kidney Int. 2008;73:1296–302.

  6. Slinin Y et al. J Am Soc Nephrol. 2005;16(6):1788–93.

  7. Block GA et al. Am J Kidney Dis. 1998;31(4):607–17.

  8. Norris KC et al. J Am Soc Nephrol. 2006;17(10):2928–36.

  9. Voormolen N et al. Nephrol Dial Transplant. 2007;22(10):2909–16.

  10. Kestenbaum B et al. J Am Soc Nephrol. 2005;16(2):520–8.

  11. Palmer SC et al. JAMA. 2011;305(11):1119–27.

  12. Przedlacki J et al. Nephron. 1995;69:433–7.

  13. Coyne DW et al. Nephrol Dial Transplant. 2013;28:2260–8.

  14. Coyne DW et al. Clin J Am Soc Nephrol. 2014;9:1620–6.