Effectiveness of cinacalcet in patients with recurrent/persistent secondary hyperparathyroidism following parathyroidectomy: results of the ECHO study

Nephrology Dialysis Transplantation, Jun 2011

Background. Progressive secondary hyperparathyroidism (sHPT) is characterized by parathyroid gland hyperplasia which may ultimately require parathyroidectomy (PTX). Although PTX is generally a successful treatment for those patients subjected to surgery, a significant proportion develops recurrent sHPT following PTX. ECHO was a pan-European observational study which evaluated the achievement of KDOQITM treatment targets with cinacalcet use in patients on dialysis. Previously published results showed that cinacalcet plus flexible vitamin D therapy lowered serum PTH, phosphorus and calcium in the clinical practice with similar efficacy as seen in phase III trials.

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Effectiveness of cinacalcet in patients with recurrent/persistent secondary hyperparathyroidism following parathyroidectomy: results of the ECHO study

Nephrol Dial Transplant Effectiveness of cinacalcet in patients with recurrent/persistent secondary hyperparathyroidism following parathyroidectomy: results of the ECHO study Emanuel Zitt 2 3 Marianne Rix 1 2 Pablo Ureña Torres 0 2 Denis Fouque 2 7 Stefan H. Jacobson 2 6 Frank Pétavy 2 5 Bastian Dehmel 2 5 Miroslav Ryba 2 4 0 Service de Nephrologie-Dialyse, Clinique de l'Orangerie , Aubervilliers , France 1 Department of Nephrology, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark 2 The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions , please 3 Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch , Feldkirch , Austria 4 Nephrology, Krajska Nemocnice Liberec , Liberec , Czech Republic 5 Amgen (Europe) GmbH , Zug, Switzerland and Uxbridge , UK 6 Nephrology Clinic, Danderyd University Hospital , Stockholm , Sweden 7 Hopital Edouard Herriot , University Lyon 1 , France Background. Progressive secondary hyperparathyroidism (sHPT) is characterized by parathyroid gland hyperplasia which may ultimately require parathyroidectomy (PTX). Although PTX is generally a successful treatment for those patients subjected to surgery, a significant proportion develops recurrent sHPT following PTX. ECHO was a pan-European observational study which evaluated the achievement of KDOQITM treatment targets with cinacalcet use in patients on dialysis. Previously published results showed that cinacalcet plus flexible vitamin D therapy lowered serum PTH, phosphorus and calcium in the clinical practice with similar efficacy as seen in phase III trials. Methods. This subgroup analysis of ECHO describes the real-world cinacalcet treatment effect in patients with recurrent or persistent sHPT after PTX (n = 153) compared to sHPT patients without prior history of PTX (n = 1696). Results. Both groups of patients had substantially elevated serum PTH with comparable sHPT severity at baseline. After 12 months of cinacalcet treatment, 20.3% (26/128) of patients with prior PTX and 18.2% (253/1388) of patients without prior PTX achieved serum PTH and Ca × P values within the recommended KDOQITM target ranges. Conclusions. Our data support the successful use of cinacalcet in patients with recurrent/persistent sHPT after PTX. cinacalce; clinical practice; parathyroidectomy; secondary hyperparathyroidism; observational study Introduction Secondary hyperparathyroidism (sHPT) is part of the mineral metabolism and bone disorder observed in patients with chronic kidney disease (CKD-MBD) and usually coupled with alterations in calcium (Ca) and phosphorus (P) metabolism. sHPT is characterized by abnormally elevated levels of parathyroid hormone (PTH) and is associated with an increased risk of cardiovascular morbidity and mortality in patients on dialysis [ 1–6 ]. Consistent control of these biochemical parameters has been shown to improve survival [7] and reduce the risk of cardiovascular and all-cause mortality [ 6 ]. Persistently increased serum PTH levels > 800 pg/mL (88.0 pmol/L) in the presence of hypercalcaemia or hyperphosphataemia refractory to medical therapy are an indication for surgery [ 8 ]. Subtotal and total parathyroidectomy (PTX) with forearm autograft arose as a treatment option in the 1990s [ 9 ], and PTX continues to be a primary therapeutic option for refractory sHPT in both Europe and the USA. Rates of PTX increased for US patients on haemodialysis from 1998 to 2002 despite an increase in therapeutic options [ 10 ]. The frequency of PTX across Europe has remained relatively stable since the mid-1980s [ 11 ] and is lower in older patients [ 12 ]. PTX offers the highest percentage cure for sHPT, compared to all other medical and surgical treatments. However, recurrent hyperparathyroidism can be observed in 10–70% of patients dependent on follow-up time [ 13– 15 ]. What remains unclear is whether the optimal level or target range of serum PTH for patients with prior PTX is equivalent to that of uraemic patients without prior PTX [ 16 ]. Uraemic patients with sHPT with or without prior PTX have reduced vitamin D receptor (VDR), Casensing receptor (CaSR), Klotho and FGFR1 expression in hyperplastic parathyroid tissue [ 9,17–19 ]. This complicates the control of PTH secretion. Due to the surgical limitations and diff iculties of re-PTX, a pharmacological approach to the treatment of recurrent sHPT seems to be a good alternative to control and possibly prevent its systemic impact. Calcimimetics are allosteric modulators of the CaSR that sensitize the receptor to extracellular Ca. This results in reduced PTH secretion and inhibited parathyroid cell proliferation [ 20,21 ]. This decrease in serum PTH is accompanied by control of serum Ca and P levels in patients with sHPT as well as a halt or regression of parathyroid gland hyperplasia [22]. Inhibited parathyroid gland growth slows disease progression and reduces t (...truncated)


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Zitt, Emanuel, Rix, Marianne, Ureña Torres, Pablo, Fouque, Denis, Jacobson, Stefan H., Pétavy, Frank, Dehmel, Bastian, Ryba, Miroslav. Effectiveness of cinacalcet in patients with recurrent/persistent secondary hyperparathyroidism following parathyroidectomy: results of the ECHO study, Nephrology Dialysis Transplantation, 2011, pp. 1956-1961, Volume 26, Issue 6, DOI: 10.1093/ndt/gfq641