CINACALCET (SENSIPAR) Calcimimetic Agents in CKD | ESRD | Dialysis and Hemodialysis Patients
Patients with chronic kidney disease have special issues in regulating mineral metabolism.
The kidneys actively hold onto necessary minerals and excrete or get rid of minerals thought to be in excessive supply.
Some of these minerals necessary for cellular functions include sodium, potassium, calcium and phosphorous.
The kidneys play a unique role in calcium regulation due to the fact that healthy kidneys activate a form of Vitamin D. Vitamin D in turn facilitates absorption of Calcium from the intestines from the food or from bones.
Other important glands in this metabolic system are the parathyroids. These small glands in the neck secrete a hormone called PTH or parathyroid hormone that boosts the absorption of calcium from the intestine or bones if the body is deemed to have too little calcium.
Patients with abnormal, or scarred kidneys do not make sufficient active Vitamin D. Chronic kidney disease (CKD) patients or end stage renal disease (ESRD) patients
therefore may be deficient in calcium and have an elevated parathyroid level. This elevated PTH level is called secondary hyperparathyrodism.
There are several methods of helping to control mineral metabolism in ESRD and CKD patients. Some of these methods include diet, Vitamin D supplementation and drugs which help absorb excessive minerals from the intestine. A relatively new medication acts to help decrease parathyroid hormone production by making the parathyroid gland more sensitive to calcium. This new class of medication is called a calcimimetic because it mimics the effects of calcium on the parathyroid glands.
The articles reference below discuss calcimemetics in CKD and ESRD.
David M. Spiegel, Lesley McPhatter, Ann Allison, Joanne C. Drumheller, and Robert Lockridge
CJASN CJN.08170811; published ahead of print February 2012 doi:10.2215/CJN.08170811
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Ikee R, Tsunoda M, Sasaki N, Sato N, Hashimoto N.
Nephrology (Carlton). 2011 Nov 24.
doi: 10.1111/j.1440-1797.2011.01545.x.
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Author Interview: J. Andrew Lee, PhD, ScM
A Study of the Association between Cinacalcet Adherence and Biochemical Outcomes
Abstract: [TH-PO263]
Andrew Lee, PhD, Vasily Belozeroff, PhD, Richard Mutell, T. Christopher Bond, PhD, William G. Goodman, MD. Amgen Inc; DaVita Clinical Research. |
Author Interview: Dr. Jesús Montenegro
Efficacy and safety of cinacalcet for the treatment of secondary hyperparathyroidism in patients with advanced chronic kidney disease before initiation of regular dialysis.
Montenegro J, Cornago I, Gallardo I, García-Ledesma P, Hernando A, Martinez I, Muñoz RI, Romero MA.
Servicio de Nefrología, Hospital de Galdakao-Usansolo, Galdakao, Vizcaya, Spain.
Nephrology (Carlton). 2011 Oct 25. doi: 10.1111/j.1440-1797.2011.01530.x.
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Author Interview: Dr. Giuseppe Cianciolo
VDR Expression on Circulating Endothelial Progenitor Cells in Dialysis Patients Is Modulated by 25(OH)D Serum Levels and Calcitriol Therapy.
Cianciolo G, La Manna G, Cappuccilli ML, Lanci N, Della Bella E, Cuna V, Dormi A, Todeschini P, Donati G, Alviano F, Costa R, Bagnara GP, Stefoni S.
Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University Hospital, Bologna, Italy.
Blood Purif. 2011 Jul 9;32(3):161-173.
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Battistella M, Richardson RM, Bargman JM, Chan CT.
Division of Nephrology, Department of Medicine, University Health Network, Toronto, ON, Canada.
Clin Nephrol. 2011 Aug;76(2):99-103.
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Sensipar(R) Patents Upheld By District Court
Injunction Prohibits Teva and Barr from Marketing Generic Versions of Amgen's Sensipar Through 2018 Patent Expiry
THOUSAND OAKS, Calif., Jan. 7, 2011
A U.S. District Court in Delaware today granted an injunction preventing Teva Pharmaceuticals USA, Inc., Teva Pharmaceuticals Industries Ltd., and Barr Laboratories, Inc. from commercializing generic versions of Amgen's (Nasdaq: AMGN) Sensipar(R) (cinacalcet) until expiration of the drug's U.S. patents. The latest Sensipar expiry is in 2018. Sensipar is approved for the treatment of secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) on dialysis and for the treatment of elevated levels of calcium in patients with parathyroid carcinoma. |
Nephron Clin Pract. 2010 Aug 10;117(2):c151-c159.
Schumock GT, et al
Center for Pharmacoeconomic Research, Department of Pharmacy Practice, and Department of Pharmacy Administration, University of Illinois at Chicago, Chicago, Ill.
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Calcimimetic Agents in CKD ESRD Dialysis and Hemodialysis Patients
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Sensipar (Cinacalcet) is made by Amgen. The Sensipar website has a number of educational resource, including prescribing and safety information.
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J Nephrology. 2010 May 2. pii: 8E39C3E1-CF8D-4F2A-94D3-D72F4B99DFFC.
Guerra R, Auyanet I, Fernández EJ, Pérez MA, Bosch E, Ramírez A, Suria S, Checa MD.
Department of Nephrology, Hospital Insular de Gran Canaria, Las Palmas de Gran Canaria - Spain. |
Calcimimetic inhibits late-stage cyst growth in ADPKD.
Journal of the American Society of Nephrology. 2009 Jul;20(7):1527-32.
Gattone VH 2nd, Chen NX, Sinders RM, Seifert MF, Duan D, Martin D, Henley C, Moe SM.
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, Indiana 46202, USA. vgattone@iupui.edu
Comment in:
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J Am Soc Nephrol. 2009 Jul;20(7):1421-5.
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Author Interviews: hemodialysis
- Dialysis - ESRD - CKD |
| Predictors of eGFR Decline in Type 2 Diabetes & Preserved Kidney Function: Dr. Chonchol CJASN |
| Tenecteplase for improvement of blood flow in dysfunctional hemodialysis catheters: Dr. Goldman Clin Neph |
| Religious coping, psychological distress and quality of life in hemodialysis: Dr. Carvalho J Psychosom Res. |
| Effect of captopril on recuperation from ischemia/reperfusion-induced AKI Nephrology Dialysis Transplant |
| Restless legs syndrome in dialysis: comparison of hemodialysis & CAPD: Dr. Merlino Neurol Sci. |
| International practice patterns & non-conventional hemodialysis utilization : Dr. Sood BMC Nephrology |
| Decreased PON1 in hemodialyzed & renal transplanted patients. Dr. Paragh Nephrol. Dial. Transplant |
| Preoperative Proteinuria & Long-Term Progression to Chronic Dialysis & Mortality after CABG: Drs. Chao & Ko : PLoS ONE |
| Creatinine generation is reduced in CVHD & predicts mortality: Dr. Wilson: Nephrology Dialysis Transplant |
Importance of normohydration for the long-term survival in hemodialysis : Dr. Wabel
Nephrology Dialysis Transplant |
| Local Tissue Renin-Angiotensin System Activation in Cardiorenal Metabolic Syndrome & Type 2 Diabetes: Dr.Hayden Cardiorenal Med |
| Group I nonreciprocal inhibition in restless legs syndrome secondary to CKD : Dr. Marconi Parkinsonism & Related Disorders |
Low-Dose ESAs and CV Geometry in CKD: Is Darbepoetin-α More Effective than Expected? Dr. Di Lullo
Cardiorenal Med |
Pharmacotherapy to improve outcomes in vascular access surgery: Dr. Jackson
Nephrology Dialysis Transplant |
| Parathyroidectomy for the attainment of NKF-K/DOQI™ and KDIGO recommended values for bone & mineral metabolism in dialysis with uncontrollable secondary hyperparathyroidism. Langenbecks Arch Surg |
| Bisphosphonate Therapy, Death, and Cardiovascular Events Among Female Patients With CKD: Dr. Perkins |
| Losartan prevents the development of the pro-inflammatory monocytes CD14+CD16+ in hemodialysis : Dr. Merino Nephrology Dialysis Transplant |
| Does Dialysis Modality Influence the Oxidative Stress of Uremia? Dr. Capusa Kidney Blood Press Res |
| Treatment of Periodontal Diseases Reduces Inflammation in Hemodialysis : Dr. Siribamrungwong |
| Declining Rates of Deceased Donor Renal Transplantation in the US Over Successive Years of Listing: Dr. Trivedi |
| When Is the Best Moment to Assess the Ankle Brachial Index: Pre- or Post-Hemodialysis?Dr. RM Elias |
| Role of Race and Poverty on Steps to Kidney Transplantation in the Southeastern US |
| Validity & Reliability of the MUST and MST Nutrition Screening Tools in Renal Inpatients : C. Lawson |
| Target-Orientated Algorithm for Regional Citrate-Calcium Anticoagulation in Extracorporeal Therapies: Dr. Brandl |
| Evaluation of bone microarchitecture by HR-pQCT in hemodialysis : Dr. Negri |
| Erectile Dysfunction in Chronic Hemodialysis : Dr. Strippoli |
| Have Renal Dietitians Successfully Implemented Evidence-Based Guidelines Into Practice? E. Joy |
| Regional Citrate Versus Heparin Anticoagulation for CRRT: Drs. Tam & Wu |
| von Willebrand factor predicts mortality in CRRT : Dr. Péquériaux |
| Clinical Outcome of Twice-Weekly Hemodialysis Patients in Shanghai | Dr. Qian |
| Persistently low intact PTH levels predict aortic arch calcification progression in hemodialysis patients : Dr. Song |
| Lack of Awareness among Future Medical Professionals about the Risk of Consuming Hidden Phosphate-Containing Processed Food & Drinks : Dr. Razzaque |
| 51Cr-EDTA plasma & urinary clearance as a measure of residual renal function in dialysis :Dr. Kjaergaard |
| Obesity and Mortality Risk among Younger Dialysis Patients: Dr. Hoogeveen |
| Solar-Assisted Hemodialysis: Dr. Agar |
| Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by activating AMP-activated protein kinase in renal epithelial cells Drs. Lee & Kasinath |
| Mineral, bone disorders, survival in hemodialysis with & without PKD : Drs. Molnar & Kalantar-Zadeh |
| Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by activating AMP-activated protein kinase in renal epithelial cells Drs. Lee & Kasinath |
| Mineral, bone disorders, survival in hemodialysis with & without PKD : Drs. Molnar & Kalantar-Zadeh |
| Downregulation of the renal & hepatic hydrogen sulfide-producing enzymes and capacity in CKD - Dr. Vaziri |
| A predictive algorithm for management of anemia in hemodialysis based on ESA pharmacodynamics : Dr. Lines |
| Factors Associated With Intradialytic Systolic Blood Pressure Variability: Dr. Flythe |
| Safety and predictors of complications of renal biopsy in the outpatient setting : Dr. Jiang |
| Heparin induced antibodies in chronic hemodialysis patients and cardiac surgery patients: Dr. Shavit |
| Atrial Fibrillation in Medicare/Medicaid-eligible dialysis patients: Dr. Wetmore |
| Newly identified anorexigenic adipokine nesfatin-1 in hemodialysis patients: J. Saldanha |
| Correction of Post kidney Transplant Anemia Reduces Progression of Allograft Nephropathy: Dr. Choukrou |
| Mild and moderate pre-dialysis CKD is associated with increased coronary artery calcium: Dr. Budoff |
| Endogenous factors modified by hemodialysis and accuracy of blood glucose-measuring device: Dr. Ogawa |
| Narrow-band UVV increases serum vitamin D levels in hemodialysis patients Dr. Ala-Houhala |
| Predicting hospital cost in CKD patients through blood chemistry values: Dr. Bessette |
| Nutritional vitamin D supplementation in hemodialysis: a potential vascular benefit? D. Mason |
| Volume excess in chronic hemodialysis effects of treatment frequency & treatment spacing : Dr. Schneditz |
| Acid reduction with fruits/veges or bicarb attenuates kidney injury in hypertensive nephropathy with reduced GFR |
Predicting Number of US Medical Graduates Entering Adult Nephrology Fellowships
Using Search Terms Dr. Desai |
| Potential influence of sevelamer hydrochloride on responsiveness to ESAs in hemodialysis patients: Dr. Ikee |
| Anemia Management in Dialysis : ESAs vs Transfusions: Clinical & Economic Consequences :Dr. Naci |
| Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury: Dr. Perkins |
| Filtration Markers May Have Prognostic Value Independent of Glomerular Filtration Rate : Dr. Tangri |
| Stopping Renin-Angiotensin System Inhibitors in Chronic Kidney Disease: Predictors of Response |
| Insights into nephrologist training, clinical practice, and dialysis choice: Dr. Mehrotra |
| Early ACE inhibition in Alport syndrome delays renal failure and improves life expectancy: Dr. Gross |
| Blunted insulinemia using high dialysate glucose concentration during hemodialysis : Dr. Schneditz |
| Prevalence of Inadequate Platelet Inhibition by Clopidogrel in Patients Receiving Hemodialysis: Dr. Alexopoulos |
| Live kidney donation: attitudes towards donor approach, motives and factors promoting donation: Dr. Mazaris |
| High-dose ESAs, inflammatory biomarkers, and soluble erythropoietin receptors : Dr. Inrig |
| Association of AKI with Adverse Outcomes in Burned Military Casualties : Dr. Stewart |
| Sodium Intake, ACE Inhibition, and Progression to ESRD Dr. Ruggenenti |
DOPPS Practice Monitor: Update on Trends in US Hemodialysis Care Following Launch of Bundled Payment System and Revisions to ESA Labels January 6 2011 |
Emerging trends in hemodialysis care through August 2011, based on a sample of US dialysis facilities, are included in the latest update to the DOPPS Practice Monitor (DPM, at http://www.dopps.org/DPM), run by the Dialysis Outcomes and Practice Patterns Study (DOPPS) at Arbor Research Collaborative for Health.
Ongoing Changes in the US Dialysis Environment – Recent changes in dialysis payment and regulatory guidance are expected to affect hemodialysis practice. In January 2011, the Centers for Medicare & Medicaid Services (CMS) launched a new Prospective Payment System (PPS) with the intent to control dialysis costs through bundled payments. In June 2011, the FDA approved revised prescribing information for erythropoiesis-stimulating agents (ESAs), used to treat anemia in most dialysis patients. Previously, the label recommended a hemoglobin target range of 10-12 g/dL. The June 2011 update removed the target range, advising instead to start ESA therapy for dialysis patients at hemoglobin less than 10 g/dL, and to reduce or interrupt the dose when the hemoglobin approaches or exceeds 11 g/dL.
Most Recent Trends in Care – Over the August 2010 to August 2011 time period, many hemodialysis practices have remained stable; examples include nutrition measures and hemodialysis treatment time and dose. There have been notable trends in the following practice areas:
- Anemia: Hemoglobin levels have decreased since the June 2011 ESA label update. While the mean hemoglobin level declined by 0.12 g/dL over 12 months from August 2010 to July 2011, it declined in August 2011 by another 0.10 g/dL to 11.26 g/dL. The percentage of patients with hemoglobin levels greater than 12 g/dL declined sharply (from 28% to 23%) in July/August 2011, while the percentage with hemoglobin levels less than 10 g/dL increased slightly from 8.5% to 10% and the percentage with hemoglobin levels less than 9 g/dL remained under 3%.
Mean prescribed epoetin dose (among patients receiving epoetin) decreased by 15%, from 21,100 units/wk to 17,900 units/wk, from August 2010 to August 2011, with the greatest decline in June-August 2011. Epoetin doses at the higher end of the dose range have decreased most notably. IV iron use increased from August 2010 to August 2011 though has recently stabilized. In keeping with greater IV iron use, serum ferritin levels (indicative of iron stores) continue to rise. Serum ferritin concentration exceeded 500 ng/mL in 65% of patients, 800 ng/mL in 34% of patients, and 1,200 ng/mL in 11% of patients in August 2011.
- Mineral & Bone Disorder: In our last report, we noted a 29% increase in serum parathyroid hormone (PTH) levels through April 2011, and differences by race were described. Since then, PTH levels have remained stable or declined slightly in both black and non-black patients. In August 2011, 22% of black patients and 12% of non-black patients had very high PTH values (defined here as PTH >600 pg/mL). The percentage of hemodialysis patients for whom PTH is measured has declined slightly since August 2010. There have been no clear changes in serum calcium or serum phosphorus levels.
- Clinical Outcomes: Preliminary data indicate that the 30-day hospitalization rate has increased somewhat from August 2010 to August 2011. The DPM does not report yet on trends in red blood cell transfusions, as dialysis units are often unaware of transfusions occurring in the inpatient setting. Additional efforts to comprehensively monitor trends in transfusions are warranted. To date mortality rate has not changed appreciably, though further follow-up time is necessary as we continue to track this outcome.
Future monitoring of these trends, confirmation with national data when eventually available, and understanding their effect on clinical outcomes, if any, is required.
DPM data are aggregated across dialysis organizations and facilities. Aggregated trends may not reflect trends in individual dialysis organizations or facilities, and are not intended to provide oversight of performance in individual dialysis organizations or facilities.
Read the rest of the DOPPS Practice Monitor: Update on Trends in US Hemodialysis Care Following Launch of Bundled Payment System and Revisions to ESA Labels Press Release |
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Hemodialysis Research Interview of the Week |
Author Interview: Dr. Len Usvyat PhD
Clinical Systems Database Senior Analyst
Renal Research Institute
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Seasonal Variations in Mortality, Clinical, and Laboratory Parameters in Hemodialysis Patients: A 5-Year Cohort Study.
Usvyat LA, Carter M, Thijssen S, Kooman JP, van der Sande FM, Zabetakis P,
Balter P, Levin NW, Kotanko P.
Clin J Am Soc Nephrol. 2011 Nov 17.
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What are the main findings of the study? |
We found that mortality of hemodialysis patients followed a seasonal pattern over a five year period with the highest mortality in the winter and lowest mortality in the summer months.
We also observed that many clinical and laboratory parameters follow a seasonal pattern in our patient population.
For example, pre-dialysis systolic blood pressures are highest in winter and lowest in summer months; pre-dialysis body temperatures are highest in summer and lowest in winter months.
Neutrophils are highest in winter and lowest in summer suggesting higher inflammatory markers in the winter.
This phenomena was observed in various geographic regions in US.
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Were any of the findings unexpected? |
It has been previously shown that mortality follows seasonal trends in healthy population however these findings were never extended to dialysis patients.
While it was shown that blood pressures tend to follow a seasonal pattern, to the best of our knowledge, it has not been shown that neutrophils or interdialytic weight gains also follow a seasonal pattern.
Additionally, we applied a cosinor analysis to show whether these patterns are statistically significant.
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What should clinicians and patients take away from this study? |
These findings are particularly important in designing studies -- taking season into account is key.
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What recommendations do you have for future studies as a result of your study? |
Further research into understanding the biologic factors that contribute to this seasonality is important.
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