The impact of cinacalcet in the mineral metabolism markers of patients on dialysis with severe secondary hyperparathyroidism

Abstract Introduction: Treating secondary hyperparathyroidism (SHPT), a common condition associated with death in patients with chronic kidney disease, is a challenge for nephrologists. Calcimimetics have allowed the introduction of drug therapies no longer based on phosphate binders and active vitamin D. This study aimed to assess the safety and effectiveness of cinacalcet in managing chronic dialysis patients with severe SHPT. Methods: This retrospective study included 26 patients [age: 52 ± 12 years; 55% females; time on dialysis: 54 (4-236) months] on hemodialysis (N = 18) or peritoneal dialysis (N = 8) with severe SHPT (intact parathyroid hormone (iPTH) level > 600 pg/mL) and hyperphosphatemia and/or persistent hypercalcemia treated with cinacalcet. The patients were followed for 12 months. Their serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and iPTH levels were measured at baseline and on days 30, 60, 90, 180, and 365. Results: Patients with hyperphosphatemia (57.7%), hypercalcemia (23%), or both (19.3%) with iPTH > 600 pg/mL were prescribed cinacalcet. At the end of the study, decreases were observed in iPTH (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0.001), Ca (9.5 ± 1.0 vs. 9.1 ± 0.6 mg/dl; p = 0.004), P (6.0 ± 1.3 vs. 4.9 ± 1.1 mg/dl; p < 0.001), and ALP (202 ± 135 vs. 155 ± 109 IU/L; p = 0.006) levels. Adverse events included hypocalcemia (26%) and digestive problems (23%). At the end of the study, 73% of the patients were on active vitamin D and cinacalcet. Three (11.5%) patients on peritoneal dialysis did not respond to therapy with cinacalcet, and their iPTH levels were never below 800 pg/mL. Conclusion: Cinacalcet combined with traditional therapy proved safe and effective and helped manage the mineral metabolism of patients with severe SHPT.

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Dynamic changes in calcium and phosphate plasma concentrations in the patients on peritoneal dialysis

Vojnosanitetski pregled ◽

10.2298/vsp0601027j ◽

2006 ◽

Vol 63 (1) ◽

pp. 27-30

Author(s):

Natasa Jovanovic ◽

Mirjana Lausevic ◽

Biljana Stojimirovic

Keyword(s):

Vitamin D ◽

Renal Failure ◽

Peritoneal Dialysis ◽

End Stage Renal Disease ◽

Calcium Concentration ◽

Phosphate Binders ◽

Active Vitamin ◽

Active Vitamin D ◽

Stage Renal Disease ◽

End Stage

Background/Aim. The disturbances of active forms of vitamin D synthesis and disturbances in calcium and posphate metabolism develop early in chronic renal failure, when creatinine clearance is about 30 ml/min. Chronic hemodialysis and peritoneal dialysis only partially correct the biochemical environment of patients on chronic renal replacement therapy because of end-stage renal disease. These dialysis modalities can?t significantly affect the endocrine disturbances of chronic renal failure and they have minimal modulatory effect. The management of disturbed calcium (Ca) and phosphate (P) metabolism and the maintainance of Ca ? P product below 4.4 mmol/l thanks to the use of dialysate solutions with the appropriate calcium concentration and the careful dosage of phosphate binders, calcium and active vitamin D metabolits, are extremely important for the prevention of renal osteodystrophy, secondary hyperparathyroidism as well as low-bone turnover disease. The aim of the study was to analyze the plasma levels of calcium, phosphate, albumin, alkaline phosphatase and parathormon (PTH) in 58 patients who were treated with continuous ambulatory peritoneal dialysis (CAPD) from March to August 2003. The use of phosphate binders and the substitution with active vitamin D metabolits were also analyzed. Methods. We examined 58 patients, 30 males and 28 female, mean-age 52 years (range, 26-78 years), affected by end-stage renal disease of the different leading cause. The average time on peritoneal dialysis program was 20 months (2-66 months). Most of the patients were treated by CAPD, while only few of them performed automatic, cyclic or intermittent peritoneal dialysis. Most of the patients used a dialysate with 1.75 mmol/l calcium concentration. Results. The study showed that our patients on chronic CAPD program during several months had normal calcemia, phosphatemia and the level of alkaline phosphatase, and that they had Ca ? P product in the recommended range. PTH serum level ranged from 16 to 490 pg/l in our patients. Conclusion. The study showed that a balanced diet and a correct dosage of phosphate binders, as well as a careful substitution with active vitamin D metabolits render a good control of calcium and phosphate serum balance, as well as an effective prevention of renal osteodystrophy development in the patients on chronic peritoneal dialysis treatment.

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Calcimimetics for the Treatment of Secondary Hyperparathyroidism in Peritoneal Dialysis Patients

Peritoneal Dialysis International ◽

10.1177/089686080802802s08 ◽

2008 ◽

Vol 28 (2_suppl) ◽

pp. 42-46 ◽

Cited By ~ 2

Author(s):

Jean Francis ◽

David B. Simon ◽

Peter Jeurgensen ◽

Fredric O. Finkelstein

Keyword(s):

Vitamin D ◽

Peritoneal Dialysis ◽

Secondary Hyperparathyroidism ◽

Hormone Secretion ◽

Phosphate Binders ◽

Serum Phosphate Level ◽

Dialysis Patients ◽

Intravenous Vitamin ◽

Stage Renal Disease ◽

End Stage

Secondary hyperparathyroidism is a common complication in patients with end-stage renal disease. It has been associated with increased cardiovascular events and mortality. Traditional therapy has been based on vitamin D analogs and phosphate binders; but these therapies often do not control secondary hyperparathyroidism, particularly in peritoneal dialysis patients for whom phosphate clearances are limited and intravenous vitamin D is impractical. Cinacalcet, a calcimimetic, suppresses parathormone secretion by interacting with the calcium-sensing receptor on the surface of parathyroid gland cells. The resulting suppression of parathyroid hormone secretion produces a reduction in serum phosphate level and CaxPO4 product. The present paper reviews the efficacy of cinacalcet in the management of secondary hyperparathyroidism in peritoneal dialysis patients.

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Pharmacotherapy in chronic kidney disease hyperphosphatemia – effects on vascular calcification and bone health

Macedonian Pharmaceutical Bulletin ◽

10.33320/maced.pharm.bull.2017.63.01.001 ◽

2017 ◽

Vol 63 (01) ◽

pp. 3-24

Author(s):

Dimce Dzingarski ◽

Kristina Mladenovska

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Kidney Disease ◽

Bone Health ◽

Mineral Metabolism ◽

Phosphate Binders ◽

Active Vitamin ◽

Bone Disorders ◽

Active Vitamin D ◽

Active Vitamin D Sterols

Hyperphosphatemia (HP) in patients with chronic kidney disease (CKD) leads to complications such as renal osteodistrophy, cardiovascular calcification and hemodynamic abnormalities, all of them having a serious impact on the survival rate and quality of life. Also, HP is a key pathogenic factor in the development of secondary hyperparathyroidism (SHPT) in CKD. Having in regard the significance of controlling serum phosphorus levels (Pi), in this paper, the needs and obstacles to successful pharmacological management of HP in CKD are presented, with an overview of major classes of phosphate binders (PBs) and other drugs affecting Pi level, such as active vitamin D sterols and calcimimetics (CMs). In addition, their effects on progression of cardiovascular calcification and bone health are elaborated. In this regard, a PubMed search was carried out to capture all abstracts and articles relevant to the topic of CKD, HP and mineral metabolism, bone disorders and vascular/valvular calcification (VC), published from January 2007 to August 2017. The search was limited to English language, with the search terms including drug name AND hyperphosphatemia or cardiovascular calcification or bone disorder. Comparative studies, clinical studies/trials and meta-analyses related to different classes/representatives of PBs, vitamin D analogues and CMs were reviewed and research data related to their efficacy and safety compared. Keywords: chronic kidney disease, hyperphosphatemia, phosphate binders, active vitamin D sterols, calcimimetics, bone disorders, cardiovascular calcification

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Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics

Nutrients ◽

10.3390/nu13082559 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2559

Author(s):

María Dolores Arenas Jimenez ◽

Emilio González-Parra ◽

Marta Riera ◽

Abraham Rincón Bello ◽

Ana López-Herradón ◽

...

Keyword(s):

Vitamin D ◽

Mortality Rate ◽

Secondary Hyperparathyroidism ◽

Cox Regression ◽

Serum Vitamin ◽

Hemodialysis Patients ◽

Active Vitamin ◽

Cox Regression Analysis ◽

Active Vitamin D ◽

The Impact

Background. In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. Methods. A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. Results. The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6–27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97–1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. Conclusions. Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.

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Intraperitoneal Calcitriol for Treatment of Severe Hyperparathyroidism in Children with Chronic Kidney Disease: A Therapy Forgotten

Peritoneal Dialysis International ◽

10.3747/pdi.2015.00215 ◽

2016 ◽

Vol 36 (6) ◽

pp. 688-690 ◽

Cited By ~ 2

Author(s):

Rahul Chanchlani ◽

Susan Ackerman ◽

Elizabeth Piva ◽

Elizabeth Harvey

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Peritoneal Dialysis ◽

Kidney Disease ◽

Secondary Hyperparathyroidism ◽

Active Vitamin ◽

Active Vitamin D ◽

Oral Formulations ◽

Active Vitamin D Sterols ◽

Intravenous Formulation

Active Vitamin D sterols such as calcitriol and alfacalcidol are quite effective in the treatment of mineral bone disease secondary to chronic kidney disease. However, some children on peritoneal dialysis (PD) are resistant to oral formulations of active Vitamin D, and use of an intravenous formulation in such patients is inconvenient. In these children, intraperitoneal (IP) calcitriol has been shown to be effective in the treatment of secondary hyperparathyroidism. However, its use has declined. We report 2 children, aged 1 and 9.5 years, on chronic cycler PD with severe secondary hyperparathyroidism refractory to oral active Vitamin D who were successfully treated with IP calcitriol for a period of 12 and 4 months, respectively. We also discuss the published literature on the efficacy of IP calcitriol for treatment of secondary hyperparathyroidism and specific considerations for its use in PD patients.

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MO1020EFFICACY OF CALCITRIOL COMPARING TO ALFACALCIDOL FOR THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN CHILDREN ON PERITONEAL DIALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab108.0017 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Marina Khvan ◽

Samat Issakov ◽

Nazym Nigmatullina ◽

Saltanat Rakhimzhanova ◽

Venera Altynova

Keyword(s):

Vitamin D ◽

Peritoneal Dialysis ◽

Secondary Hyperparathyroidism ◽

Initial Dose ◽

Plasma Calcium ◽

T Test ◽

Active Vitamin ◽

Active Vitamin D ◽

The Mean ◽

Pth Level

Abstract Background and Aims Active vitamin D analogues are used routinely for the treatment of secondary hyperparathyroidism in children with end-stage renal disease (ESRD) on peritoneal dialysis (PD). Calcitriol is preferred active form of vitamin D, while data on efficacy of alfacalcidol in children on PD are limited. The aim of this study was to compare the efficacy of these two active vitamin D analogues for the treatment of secondary hyperparathyroidism in children on PD. Method This retrospective cohort study included data from 26 pediatric patients under 18 years of age with ESRD on PD who were treated at the National Research Center for Maternal and Child Health, Astana, Kazakhstan. Patients were allocated by initial treatment into two groups: oral alfacalcidol (n=21) and oral calcitriol (n=5). The first step of the study was to compare the efficacy of treatment between this two groups 3 and 6 months after. The second step was to compare the efficacy of calcitriol in subgroup of patients from alfacalcidol group who were switched to calcitriol later (n=12). The following characteristics were analyzed: parathyroid hormone (PTH), total plasma calcium, ionized plasma calcium, plasma phosphorus, initial dose of active vitamin D and corrected dose of vitamin D after 3 months. Independent t-test and repeated measures Anova were used for comparison between alfacalcidol and calcitriol groups. To compare data in subgroup between baseline and 3 months after conversion from alfacalcidol to calcitriol we used paired Student t-test. Results The mean age and baseline characteristics were no different between alfacalcidol and calcitriol groups (Table 1). The initial dose of alfacalcidol was 2.42±1.03 µg/week (0.157±0.097 µg/kg/week) and 2.09±0.74 µg/week (0.105±0.039 µg/kg/week) for calcitriol were not significantly different (P=0.5 and P=0.25 respectively). After 3 months of treatment there was statistically significant decrease of PTH level in calcitriol group 180±168 pmol/L comparing to alfacalcidol group 869±670 pmol/L (P=0.006). After 6 months, there was statistically significant decrease of PTH level in calcitriol group 261±259 pmol/L in contrast with alfacalcidol group 1080±716 pmol/L (P=0.047) and rise in total calcium in calcitriol group 2.46±0.17 mmol/L compared with alfacalcidol group 2.09±0.25mmol/L (P=0.035). The mean dose of calcitriol was also significantly lower as opposed to alfacalcidol dose: 0.04±0.039 µg/kg/week and 0.17±0.076 µg/kg/week respectively (P=0.002). The median age of children who were switched from alfacalcidol to calcitriol were significantly younger comparing with those who continued alfacalcidol (5±4.6 and 10±4.3 years of age respectively (P=0.022)). 3 months after conversion there was significant increase in ionized calcium level and decrease in PTH level comparing with baseline (Table 2). The dose of alfacalcidol before and dose of calcitriol after switch were differed (0.18±0.1 µg/kg/week and 0.13±0.05 µg/kg/week respectively, P=0.025) Conclusion Calcitriol showed superior efficacy for the treatment of secondary hyperparathyroidism in children on PD with the dose 4.25 times lower that of alfacalcidol. Alfacalcidol had limited efficacy for the treatment of secondary hyperparathyroidism in younger children when prescribed in recommended doses.

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Trends in Mineral Metabolism Treatment Strategies in Patients Receiving Hemodialysis in the United States

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.04350420 ◽

2020 ◽

Vol 15 (11) ◽

pp. 1603-1613

Author(s):

Rasheeda Hall ◽

Alyssa Platt ◽

Jonathan Wilson ◽

Patti L. Ephraim ◽

Angelina S. Hwang ◽

...

Keyword(s):

Vitamin D ◽

Mineral Metabolism ◽

Treatment Strategies ◽

Practice Variation ◽

Dialysis Initiation ◽

Prescribing Patterns ◽

Sensitivity Analyses ◽

Phosphate Binders ◽

Active Vitamin ◽

Active Vitamin D

Background and objectivesWith multiple medications indicated for mineral metabolism, dialysis providers can apply various strategies to achieve target phosphate and parathyroid hormone (PTH) levels. We describe common prescribing patterns and practice variation in mineral metabolism treatment strategies over the last decade.Design, setting, participants, & measurementsIn a cohort of adults initiating hemodialysis at Dialysis Clinic, Inc. facilities, we assessed prescriptions of vitamin D sterols, phosphate binders, and cinacalcet longitudinally. To identify the influence of secular trends in clinical practice, we stratified the cohort by dialysis initiation year (2006–2008, 2009–2011, and 2012–2015). To measure practice variation, we estimated the median odds ratio for prescribing different mineral metabolism treatment strategies at 12 months post–dialysis initiation across facilities using mixed effects multinomial logistic regression. Sensitivity analyses evaluated strategies used after detection of first elevated PTH.ResultsAmong 23,549 incident patients on hemodialysis, there was a decline in vitamin D sterol–based strategies and a corresponding increase in strategies without PTH-modifying agents (i.e., phosphate binders alone or no mineral metabolism medications) and cinacalcet-containing treatment strategies between 2006 and 2015. The proportion with active vitamin D sterol–based strategies at dialysis initiation decreased across cohorts: 15% (2006–2008) to 5% (2012–2015). The proportion with active vitamin D sterol–based strategies after 18 months of dialysis decreased across cohorts: 52% (2006–2008) to 34% (2012–2015). The odds of using individual strategies compared with reference (active vitamin D sterol with phosphate binder) varied from 1.5- to two-fold across facilities in 2006–2008 and 2009–2011 cohorts, and increased to two- to three-fold in the 2012–2015 cohort. Findings were similar in sensitivity analyses starting from first elevated PTH measurement.ConclusionsOver time, mineral metabolism management involved less use of vitamin D sterol–based strategies, greater use of both more conservative and cinacalcet-containing strategies, and increased practice variation, suggesting growing equipoise.

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