Reduction of whole PTH/intact PTH ratio as a predictor of bone metabolism in cinacalcet treatment of hemodialysis patients with secondary hyperparathyroidism

Abstract Background and Aims Recently, the importance of osteoporosis and chronic kidney disease-mineral bone disorder (CKD-MBD) has been highlighted as a cause of increased fracture risk in dialysis patients. However, many osteoporosis drugs require careful administration or are contraindicated in dialysis patients, and evidence for their use in dialysis patients is scarce. Here, we administered the new human anti-sclerostin antibody preparation romosozumab to hemodialysis patients with osteoporosis, and examined changes in bone density, bone metabolism markers and other values. Method Romosozumab was administered once per month to 12 hemodialysis patients (mean age: 72.6 ± 9.4 years old; 4 males, 8 females) who were diagnosed with osteoporosis while visiting our hospital and who had no history of cardiovascular complications in the preceding year. Bone density YAM value was measured every 3 months by dual energy X-ray absorptiometry (DXA). TRACP-5b, BAP, P1NP and whole-PTH values were measured every month as bone metabolic markers. Values at the start of observation were regarded as pre-dosing values and the mean values during the 6 months after administration were measured as post-treatment values. The results were then compared. Results At 6 months after the start of treatment, no change was seen in bone density of the proximal femur compared to the pre-dosing value. In contrast, lumbar spine bone density YAM value (%) was significantly improved, from 63.8% ± 9.4% to 70.9% ± 5.2% (P = 0.012). Regarding bone metabolism markers, mean value of bone resorption marker TRACP-5b after the start of administration did not significantly differ from that at the start of observation. BAP value increased significantly from 16.2 ± 8.7 to 25.2 ± 11.0 (p < 0.01) while whole-PTH significantly increased from 103.5 ± 52.8 to 236.1 ± 100.8 (p < 0.01). In addition, serial time changes for each bone metabolic marker, whole-PTH value, and corrected Ca value during the observation period are also reported. Conclusion Romosozumab may improve bone density in dialysis patients with osteoporosis.

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Assessing acute parathyroid responsiveness in hemodialysis patients by measuring intact parathyrin in pre- and post-dialysis serum

Clinical Chemistry ◽

10.1093/clinchem/37.7.1216 ◽

1991 ◽

Vol 37 (7) ◽

pp. 1216-1220 ◽

Cited By ~ 1

Author(s):

Beverly A Dilena ◽

Graham H White

Keyword(s):

Secondary Hyperparathyroidism ◽

Whole Blood ◽

Hemodialysis Patients ◽

Maintenance Hemodialysis ◽

Total Calcium ◽

Dialysis Patients ◽

Intact Pth ◽

Set Point ◽

Patients At Risk ◽

Analytical Imprecision

Abstract We measured pre- and post-dialysis concentrations of ionized calcium (iCa) in whole blood, total calcium (tCa) in plasma, and intact parathyrin (PTH) in serum of 19 patients undergoing maintenance hemodialysis. Plasma tCa was inappropriately increased relative to iCa in 63% of the specimens; the iCa correlated with the PTH concentration in 12 of 19 pre-dialysis specimens, whereas tCa correlated with PTH in only five patients. During dialysis, 16 patients had analytically significant changes in iCa (i.e., exceeded the analytical imprecision of 0.04 mmol/L). Pre- and post-dialysis concentrations of PTH were normal in six patients, four of whom showed a detectable response to changes in iCa. Ten patients had increased PTH in at least one specimen; of these, eight had responsive parathyroid glands. Five of the 16 patients had an increased set point for calcium. The minimal PTH responses of two patients suggested refractory hyperparathyroidism. We conclude that routine estimation of iCa, rather than tCa, in dialysis patients markedly improves the identification of patients at risk for secondary hyperparathyroidism, and that measurement of intact PTH in pre- and post-dialysis serum offers a simple means of assessing parathyroid responsiveness in dialysis patients.

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Decreased expression of calcium-sensing receptor and parafibromin in secondary hyperparathyroidism with an abnormal whole PTH/intact PTH ratio

Clinical Kidney Journal ◽

10.1093/ckj/sft061 ◽

2013 ◽

Vol 6 (4) ◽

pp. 429-432 ◽

Cited By ~ 1

Author(s):

Shunsuke Yamada ◽

Masanori Tokumoto ◽

Masatomo Taniguchi ◽

Hidehisa Kitada ◽

Kazuhiko Tsuruya ◽

...

Keyword(s):

Secondary Hyperparathyroidism ◽

Calcium Sensing Receptor ◽

Intact Pth ◽

Calcium Sensing ◽

Whole Pth

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Long-Term Cinacalcet HCl Treatment Improved Bone Metabolism in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism

American Journal of Nephrology ◽

10.1159/000156717 ◽

2009 ◽

Vol 29 (3) ◽

pp. 230-236 ◽

Cited By ~ 37

Author(s):

Takashi Shigematsu ◽

Tadao Akizawa ◽

Eiji Uchida ◽

Yusuke Tsukamoto ◽

Manabu Iwasaki ◽

...

Keyword(s):

Secondary Hyperparathyroidism ◽

Bone Metabolism ◽

Hemodialysis Patients

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The impact of CASR A990G polymorphism in response to cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism

Scientific Reports ◽

10.1038/s41598-021-97587-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jaruwan Ngamkam ◽

Somratai Vadcharavivad ◽

Nutthada Areepium ◽

Titinun Auamnoy ◽

Kullaya Takkavatakarn ◽

...

Keyword(s):

Secondary Hyperparathyroidism ◽

Hemodialysis Patients ◽

Serum Phosphate ◽

Clinical Factors ◽

Calcium Sensing Receptor ◽

Intact Pth ◽

Baseline Serum ◽

Calcium Sensing ◽

The Impact ◽

Pth Level

AbstractThe objective of this study was to determine the impact of calcium sensing receptor (CASR) A990G genetic polymorphism on parathyroid hormone (PTH) lowering response to cinacalcet treatment when controlling for significant influencing clinical factors. This retrospective study was conducted on 135 Thai hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). CASR A990G genotypes were determined. The patients were identified as either G carriers (heterozygous or homozygous CASR 990G allele carriers) or noncarriers (homozygous CASR 990A carriers). Tested covariates were baseline PTH level (bPTH), baseline serum phosphate (bPhos), baseline serum calcium (bCa), baseline calcitriol equivalent dose (bCtriol), baseline ergocalciferol dose (bErgo), and age. The ANCOVA showed that intact PTH levels after 12 weeks of cinacalcet treatment (PTHw12) was significantly lower among G carriers compared with noncarriers after controlling for bPTH, bPhos, bCtriol, and bErgo (F(1, 127) = 15.472, p < 0.001), with the adjusted mean difference of 253.7 pg/mL. The logistic regression analysis revealed that the odds of a G carrier achieving 30% PTH reduction after 12-week cinacalcet treatment were 3.968 times greater than the odds for a noncarrier after adjusting for bPhos, bCtriol, and age. In conclusion, the CASR A990G polymorphism significantly influences cinacalcet response in HD patients with SHPT.

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