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Long-term clinical practice experience with cinacalcet for treatment of hypercalcemic hyperparathyroidism after kidney transplantation.

Thiem U, Gessl A, Borchhardt K - Biomed Res Int (2015)

Bottom Line: It significantly decreased total serum calcium (-0.30 (-0.34 to -0.26) mmol/L, P < 0.001) and parathyroid hormone levels (-79 (-103 to -55) pg/mL, P < 0.001).Serum levels of inorganic phosphate (Pi) and renal tubular reabsorption of phosphate to glomerular filtration rate (TmP/GFR) increased simultaneously (Pi: 0.19 (0.15-0.23) mmol/L, P < 0.001, TmP/GFR: 0.20 (0.16-0.23) mmol/L, P < 0.001).In summary, cinacalcet effectively controlled hypercalcemic hyperparathyroidism in KTRs in the long-term and increased low Pi levels without causing hyperphosphatemia, pointing towards a novel indication for the use of cinacalcet in KTRs.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.

ABSTRACT
Within this prospective, open-label, self-controlled study, we evaluated the long-term effects of the calcimimetic cinacalcet on calcium and phosphate homeostasis in 44 kidney transplant recipients (KTRs) with hypercalcemic hyperparathyroidism by comparing biochemical parameters of mineral metabolism between pre- and posttreatment periods. Results are described as mean differences (95% CIs) between pre- and posttreatment medians that summarize all repeated measurements of a parameter of interest between the date of initial hypercalcemia and cinacalcet initiation (median of 1.6 (IQR: 0.6-3.8) years) and up to four years after treatment start, respectively. Cinacalcet was initiated after 1.8 (0.8-4.7) years posttransplant and maintained for 6.2 (3.9-7.6) years. It significantly decreased total serum calcium (-0.30 (-0.34 to -0.26) mmol/L, P < 0.001) and parathyroid hormone levels (-79 (-103 to -55) pg/mL, P < 0.001). Serum levels of inorganic phosphate (Pi) and renal tubular reabsorption of phosphate to glomerular filtration rate (TmP/GFR) increased simultaneously (Pi: 0.19 (0.15-0.23) mmol/L, P < 0.001, TmP/GFR: 0.20 (0.16-0.23) mmol/L, P < 0.001). In summary, cinacalcet effectively controlled hypercalcemic hyperparathyroidism in KTRs in the long-term and increased low Pi levels without causing hyperphosphatemia, pointing towards a novel indication for the use of cinacalcet in KTRs.

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Parathyroid hormone levels in kidney transplant recipients treated with cinacalcet for hypercalcemic hyperparathyroidism. Variations of intact parathyroid hormone levels before and after initiation of cinacalcet (t = 0) are plotted over time. Starting point of the pretreatment period is the date when the patients initially presented with hypercalcemia following transplantation. For both pre- and posttreatment period, quarterly median values were obtained for each patient by summarizing all repeated measurements over a three-month period starting from t = 0. Values were excluded if a patient received active vitamin D in addition to cinacalcet. Data are presented as medians and interquartile ranges.
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fig4: Parathyroid hormone levels in kidney transplant recipients treated with cinacalcet for hypercalcemic hyperparathyroidism. Variations of intact parathyroid hormone levels before and after initiation of cinacalcet (t = 0) are plotted over time. Starting point of the pretreatment period is the date when the patients initially presented with hypercalcemia following transplantation. For both pre- and posttreatment period, quarterly median values were obtained for each patient by summarizing all repeated measurements over a three-month period starting from t = 0. Values were excluded if a patient received active vitamin D in addition to cinacalcet. Data are presented as medians and interquartile ranges.

Mentions: Comparison of the patients' pre- and posttreatment median values of total serum calcium revealed that cinacalcet effectively controlled hypercalcemia in our population of kidney transplant recipients with hypercalcemic hyperparathyroidism (Figure 2(a)). The mean difference between pre- and posttreatment medians of total serum calcium was −0.30 mmol/L (−0.34 to −0.26 mmol/L, P < 0.001, n = 41). The decrease in total serum calcium levels was accompanied by an increase in urinary fractional calcium excretion (0.24 (0.06 to 0.42)%, P < 0.05, n = 40) (Figure 2(b)). Importantly, urolithiasis did not occur in any of the participants. Moreover, serum levels of inorganic phosphate and TmP/GFR simultaneously increased during the first year after treatment start, then reaching a plateau (Figures 3(a) and 3(b)). The mean difference between pre- and posttreatment medians was 0.19 mmol/L (0.15 to 0.23 mmol/L, P < 0.001, n = 41) for serum levels of inorganic phosphate and 0.20 mmol/L (0.16 to 0.23 mmol/L, P < 0.001, n = 40) for TmP/GFR. Variations in intact PTH levels over time are depicted in Figure 4. The mean difference between pre- and posttreatment median values of intact PTH was −79 pg/mL (−103 to −55 pg/mL, P < 0.001, n = 41). Four patients continuously received active vitamin D analogues in addition to cinacalcet starting within three months after initiation of cinacalcet. Another four patients temporarily received active vitamin D analogues in addition to cinacalcet later in the course. After excluding these values from the analysis of intact PTH, the mean difference between pre- and posttreatment medians was smaller, but still significant (−66 (−91 to −41) pg/mL, P < 0.001, n = 37). None of the participants underwent parathyroidectomy during the entire observation period.


Long-term clinical practice experience with cinacalcet for treatment of hypercalcemic hyperparathyroidism after kidney transplantation.

Thiem U, Gessl A, Borchhardt K - Biomed Res Int (2015)

Parathyroid hormone levels in kidney transplant recipients treated with cinacalcet for hypercalcemic hyperparathyroidism. Variations of intact parathyroid hormone levels before and after initiation of cinacalcet (t = 0) are plotted over time. Starting point of the pretreatment period is the date when the patients initially presented with hypercalcemia following transplantation. For both pre- and posttreatment period, quarterly median values were obtained for each patient by summarizing all repeated measurements over a three-month period starting from t = 0. Values were excluded if a patient received active vitamin D in addition to cinacalcet. Data are presented as medians and interquartile ranges.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4377458&req=5

fig4: Parathyroid hormone levels in kidney transplant recipients treated with cinacalcet for hypercalcemic hyperparathyroidism. Variations of intact parathyroid hormone levels before and after initiation of cinacalcet (t = 0) are plotted over time. Starting point of the pretreatment period is the date when the patients initially presented with hypercalcemia following transplantation. For both pre- and posttreatment period, quarterly median values were obtained for each patient by summarizing all repeated measurements over a three-month period starting from t = 0. Values were excluded if a patient received active vitamin D in addition to cinacalcet. Data are presented as medians and interquartile ranges.
Mentions: Comparison of the patients' pre- and posttreatment median values of total serum calcium revealed that cinacalcet effectively controlled hypercalcemia in our population of kidney transplant recipients with hypercalcemic hyperparathyroidism (Figure 2(a)). The mean difference between pre- and posttreatment medians of total serum calcium was −0.30 mmol/L (−0.34 to −0.26 mmol/L, P < 0.001, n = 41). The decrease in total serum calcium levels was accompanied by an increase in urinary fractional calcium excretion (0.24 (0.06 to 0.42)%, P < 0.05, n = 40) (Figure 2(b)). Importantly, urolithiasis did not occur in any of the participants. Moreover, serum levels of inorganic phosphate and TmP/GFR simultaneously increased during the first year after treatment start, then reaching a plateau (Figures 3(a) and 3(b)). The mean difference between pre- and posttreatment medians was 0.19 mmol/L (0.15 to 0.23 mmol/L, P < 0.001, n = 41) for serum levels of inorganic phosphate and 0.20 mmol/L (0.16 to 0.23 mmol/L, P < 0.001, n = 40) for TmP/GFR. Variations in intact PTH levels over time are depicted in Figure 4. The mean difference between pre- and posttreatment median values of intact PTH was −79 pg/mL (−103 to −55 pg/mL, P < 0.001, n = 41). Four patients continuously received active vitamin D analogues in addition to cinacalcet starting within three months after initiation of cinacalcet. Another four patients temporarily received active vitamin D analogues in addition to cinacalcet later in the course. After excluding these values from the analysis of intact PTH, the mean difference between pre- and posttreatment medians was smaller, but still significant (−66 (−91 to −41) pg/mL, P < 0.001, n = 37). None of the participants underwent parathyroidectomy during the entire observation period.

Bottom Line: It significantly decreased total serum calcium (-0.30 (-0.34 to -0.26) mmol/L, P < 0.001) and parathyroid hormone levels (-79 (-103 to -55) pg/mL, P < 0.001).Serum levels of inorganic phosphate (Pi) and renal tubular reabsorption of phosphate to glomerular filtration rate (TmP/GFR) increased simultaneously (Pi: 0.19 (0.15-0.23) mmol/L, P < 0.001, TmP/GFR: 0.20 (0.16-0.23) mmol/L, P < 0.001).In summary, cinacalcet effectively controlled hypercalcemic hyperparathyroidism in KTRs in the long-term and increased low Pi levels without causing hyperphosphatemia, pointing towards a novel indication for the use of cinacalcet in KTRs.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.

ABSTRACT
Within this prospective, open-label, self-controlled study, we evaluated the long-term effects of the calcimimetic cinacalcet on calcium and phosphate homeostasis in 44 kidney transplant recipients (KTRs) with hypercalcemic hyperparathyroidism by comparing biochemical parameters of mineral metabolism between pre- and posttreatment periods. Results are described as mean differences (95% CIs) between pre- and posttreatment medians that summarize all repeated measurements of a parameter of interest between the date of initial hypercalcemia and cinacalcet initiation (median of 1.6 (IQR: 0.6-3.8) years) and up to four years after treatment start, respectively. Cinacalcet was initiated after 1.8 (0.8-4.7) years posttransplant and maintained for 6.2 (3.9-7.6) years. It significantly decreased total serum calcium (-0.30 (-0.34 to -0.26) mmol/L, P < 0.001) and parathyroid hormone levels (-79 (-103 to -55) pg/mL, P < 0.001). Serum levels of inorganic phosphate (Pi) and renal tubular reabsorption of phosphate to glomerular filtration rate (TmP/GFR) increased simultaneously (Pi: 0.19 (0.15-0.23) mmol/L, P < 0.001, TmP/GFR: 0.20 (0.16-0.23) mmol/L, P < 0.001). In summary, cinacalcet effectively controlled hypercalcemic hyperparathyroidism in KTRs in the long-term and increased low Pi levels without causing hyperphosphatemia, pointing towards a novel indication for the use of cinacalcet in KTRs.

Show MeSH
Related in: MedlinePlus