Real-World Analysis of Outcomes and Economic Burden in Patients with Chronic Kidney Disease with and without Secondary Hyperparathyroidism among a Sample of the Italian Population.

This real-world analysis evaluated the clinical and economic burden of non-dialysis-dependent CKD patients with and without secondary hyperparathyroidism (sHPT) in Italy. An observational retrospective study was conducted using administrative databases containing a pool of healthcare entities covering 2.45 million health-assisted individuals. Adult patients with hospitalization discharge diagnoses for CKD stages 3, 4, and 5 were included from 1 January 2012 to 31 March 2015 and stratified using the presence/absence of sHPT. Of the 5710 patients, 3119 were CKD-only (62%) and 1915 were CKD + sHPT (38%). The groups were balanced using Propensity Score Matching (PSM). Kaplan-Meier curves revealed that progression to dialysis and cumulative mortality had a higher incidence in the CKD + sHPT versus CKD-only group in CKD stage 3 patients and the overall population. The total direct healthcare costs/patient at one-year follow-up were significantly higher in CKD + sHPT versus CKD-only patients (EUR 8593 vs. EUR 5671, p < 0.001), mostly burdened by expenses for drugs (EUR 2250 vs. EUR 1537, p < 0.001), hospitalizations (EUR 4628 vs. EUR 3479, p < 0.001), and outpatient services (EUR 1715 vs. EUR 654, p < 0.001). These findings suggest that sHPT, even at an early CKD stage, results in faster progression to dialysis, increased mortality, and higher healthcare expenditures, thus indicating that timely intervention can ameliorate the management of CKD patients affected by sHPT.

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

BACKGROUND: Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT. METHODS: Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure. RESULTS: Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk. CONCLUSION: Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.

Health Care Costs in Patients with and without Secondary Hyperparathyroidism in Spain.

OBJECTIVE: To analyze the economic burden of secondary hyperparathyroidism (sHPT) in Spain by quantifying differences in costs of pharmacological treatments and associated cardiovascular events (CVE) between renal patients with and without sHPT. METHODS: We used data collected in the NEFRONA cohort study and obtained treatment and CVE costs from the BOT PLUS database and Hospital Discharge Records in the Spanish Health System (CMBD-H), respectively. We examined data from 2445 renal patients followed during 2 years for chronic kidney disease (CKD) progression and 4 years for CVE, stratifying by presence of sHPT. Patient characteristics, administered treatments and CVE were directly extracted from NEFRONA registries. Dosage for each treatment regimen was assumed based on guidelines and multiplied by official unit costs to obtain treatment costs. Costs of CVE were based on ICD-9-CM. RESULTS: Prevalence of sHPT in the cohort was 65.6% (63.6; 67.6). Average yearly pharmacological costs for patients without sHPT were 610.33€, while costs were 1483.17€ for sHPT patients (average increase of 143.0%). Two hundred three patients registered CVE, resulting in 4-year average costs of 582.57€ for non-sHPT patients compared to 941.87€ for sHPT patients (61.7% average increase). Bivariate analyses considering presence of dialysis, hypercalcemia or hyperphosphatemia and stratified by sHPT showed higher costs for sHPT patients. CONCLUSIONS: These results show that sHPT is associated with substantially higher costs of both, pharmacological treatments and associated CVEs. Preventing the development of sHPT with early management in the course of CKD could possibly lead to better health outcomes and cost balance for health care systems.

Timing of parathyroidectomy for tertiary hyperparathyroidism with end-stage renal disease: A cost-effectiveness analysis.

BACKGROUND: Tertiary hyperparathyroidism associated with end-stage renal disease is characterized by progression from secondary hyperparathyroidism to an autonomous overproduction of parathyroid hormone that leads to adverse health outcomes. Rates of parathyroidectomy (PTX) have decreased with the use of calcimimetics. Optimal timing of PTX in relation to kidney transplant remains controversial. We aimed to identify the most cost-effective strategy for patients with tertiary hyperparathyroidism undergoing kidney transplant. METHODS: We constructed a patient level state transition microsimulation to compare 3 management schemes: cinacalcet with kidney transplant, cinacalcet with PTX before kidney transplant, or cinacalcet with PTX after kidney transplant. Our base case was a 55-year-old on dialysis with tertiary hyperparathyroidism awaiting kidney transplant. Outcomes, including quality-adjusted life years, surgical complications, and mortality, were extracted from the literature, and costs were estimated using Medicare reimbursement data. RESULTS: Our base case analysis demonstrated that cinacalcet with PTX before kidney transplant was dominant, with a lesser cost of $399,287 and greater quality-adjusted life years of 10.3 vs $497,813 for cinacalcet with PTX after kidney transplant (quality-adjusted life years 9.4) and $643,929 for cinacalcet with kidney transplant (quality-adjusted life years 7.4). CONCLUSION: Cinacalcet alone with kidney transplant is the least cost-effective strategy. Patients with end-stage renal disease-related tertiary hyperparathyroidism should be referred for PTX, and it is most cost-effective if performed prior to kidney transplant.

Treatment strategy of end stage renal disease-related hyperparathyroidism before, during, and after the era of calcimimetics.

BACKGROUND: Since 2004, end-stage renal disease related hyperparathyroidism patients are treated mainly with cinacalcet, which ceased to be subsidized through the Australian Pharmaceutical Benefits Scheme in 2015. We aimed to investigate the impact of these changes on the treatment strategy in the Australian end-stage renal disease population. METHODS: The following groups were formed according to the date of parathyroidectomy: A, before calcimimetics; B, during the era of calcimimetics; and C, after cinacalcet removal by the Australian Pharmaceutical Benefits Scheme. The primary outcome was time from start of dialysis to parathyroidectomy. Regression analysis was used to examine trends in parathyroidectomy rates. RESULTS: Between 1998 and 2016, 195 parathyroidectomies were performed. Median time to referral was 69 (33-123), 67 (31-110) and 44 (23-102) months for groups A, B, and C, respectively (P = .55). Parathyroidectomy rates increased throughout the years (CI 0.09-1.13, R2=0.27, P = .02). A trend toward a dip in parathyroidectomy rates was seen during the era of cinacalcet (P = .08). Median preoperative parathyroid hormone levels increased significantly (842 [418-1,553] versus 1,040 [564-1,810] versus 1,350 [1,037-1,923] pg/mL, for groups A, B, and C, respectively [P < .01]). CONCLUSION: Parathyroidectomy rates seem to vary according to the availability of cinacalcet. This change in treatment strategy is accompanied with increased preoperative parathyroid hormone levels, reflecting delayed surgery and increased disease severity.

Reforming medicare's dialysis payment policies: implications for patients with secondary hyperparathyroidism.

OBJECTIVE: To demonstrate how expanding services covered by a "bundled payment" can also expand variation in the costs of treating patients under the bundle, using the Medicare dialysis program as an example. DATA SOURCES/STUDY SETTING: Observational claims-based study of 197,332 Medicare hemodialysis beneficiaries enrolled for at least one quarter during 2006-2008. STUDY DESIGN: We estimated how resource utilization (all health services, dialysis-related services, and medications) changes with intensity of secondary hyperparathyroidism (sHPT) treatment. DATA EXTRACTION METHODS: Using Medicare claims, a patient-quarter level dataset was constructed, including a measure of sHPT treatment intensity. PRINCIPAL FINDINGS: Under the existing, narrow dialysis bundle, utilization of covered services is relatively constant across treatment intensity groups; under a broader bundle, it rises more rapidly with treatment intensity. CONCLUSIONS: The broader Medicare dialysis bundle reimburses providers uniformly, even though patients treated more intensively for sHPT cost more to treat. Absent any payment adjustments or efforts to ensure quality, this flat payment schedule may encourage providers to avoid high-intensity patients or reduce their treatment intensity. The first incentive harms efficiency. The second may improve or worsen efficiency, depending on whether it reduces appropriate or inappropriate treatment.

Cinacalcete para o tratamento de pacientes com hiperparatireoidismo secundário à doença renal, em diálise e refratários à terapia convencional / Cinacalcete for the treatment of patients with hyperparathyroidism secondary to renal disease, on dialysis and refractory to conventional therapy

Tecnologia: Cinacalcete (Mimpara®). Indicação: Hiperparatireoidismo secundário em pacientes com doença renal estágio final, submetidos à diálise e refratários ao tratamento convencional. Demandante: Laboratório Químico Bergamo Ltda. Contexto: O hiperpar atireoidismo secundário (HPTS) à doença crônica renal é caracterizado por elevados níveis séricos do paratormônio (PTH), hiperplasia das glândulas paratireóides e uma doença óssea de alto remanejamento. O nível de PTH considerados adequado está situado entre 150 a 300 pg/ml ou duas a nove vezes o valor limite do método de dosagem. Segundo o censo da Sociedade Brasileira de Nefrologia, em 2011, aproximadamente 30,6% dos pacientes em tratamento por diálise no Brasil apresentavam valores acima de 300 pg/ml (população com HPTS), representando cerca de 28.000 pacientes. Com base nas diretrizes internacionais, o tratamento de HPTS e doença óssea relacionada está centrado no controle dos níveis de fósforo, cálcio e PTH. Para a redução dos níveis do PTH, estão disponíveis no mercado brasileiro três classes de medicamentos: ativadores não seletivos do VDR (calcitriol e alfacalcidol), ativadores seletivos de VDR (paricalcitol) e calcimiméticos (cinacalcete). Dos medicamentos supracitados, o SUS disponibiliza calcitriol oral e intravenoso e alfacalcidol oral. Pergunta: O uso do cinacalcete é eficaz, seguro e custo-efetivo em pacientes com Hiperparatireoidismo secundário à DRC, refratários à terapia convencional, quando comparado ao tratamento padrão disponível no SUS? Evidências científicas: Foram analisados quatro estudos para avaliar o uso do cinacalcete para indicação proposta, dois apresentados pelo demandante (uma metanálise e um estudo observacional) e dois incluídos pela Secretaria Executiva da Conitec (uma metanálise e um estudo clínico). As duas metanálises apontaram que os pacientes tratados com cinacalcete apresentaram melhora estatisticamente significante em relação aos parâmetros bioquímicos (PTH, Ca, CaxP) em comparação ao grupo controle. Uma das metanálises avaliou desfechos clínicos e não observou diferença estatisticamente significante para mortalidade por todas as causas. Um estudo observacional avaliou sobrevida em pacientes com HPTS que usaram cinacalcete, concluindo que, tanto no modelo ajustado, quanto no não ajustado, a taxa de mortalidade por todas causas e por causas cardiovasculares foi estatisticamente menor no grupo tratado com cinacalcete. Discussão: A incorporação do cinacalcete ao SUS foi solicitada para uso em pacientes com HPTS e doença renal em estágio final, submetidos à diálise, refratários à terapia convencional. Os critérios para definir refratariedade não foram estabelecidos, e, desta forma, não há clareza se a população elegível utilizada no estudo de custo-efetividade e no impacto orçamentário refletem a população alvo de acordo com a solicitação de incorporação. Decisão: Pelo exposto, a Conitec recomendou a não incorporação ao SUS do medicamento cinacalcete para Hiperparatireoidismo secundário em pacientes com doença renal estágio final, submetidos à diálise, refratários ao tratamento convencional. Considerou-se que a população-alvo para indicação proposta não está bem delimitada, o que compromete seu alinhamento no estudo econômico e no impacto orçamentário apresentados. Após discussão sobre as contribuições da consulta pública, um total de 603, o plenário da Conitec manteve a recomendação de não incorporar ao SUS o medicamento cinacalcete conforme solicitação do demandante. Quando da revisão dos Protocolos Clínicos e Diretrizes Terapêuticas do MS ligados ao HPTS, o cinacalcete será novamente avaliado quanto ao seu potencial benefício clínico a um grupo específico e bem delimitado de pacientes com HPTS.

Paricalcitol para tratamento e prevenção do hiperparatireoidismo secundário (HPTS) associado à insuficiência renal crônica / Paricalcitol for treatment and prevention of secondary hyperparathyroidism (HPTS) associated with chronic renal failure

Tecnologia: Paricalcitol (Zemplar®). Indicação: Tratamento e prevenção do hiperparatireoidismo secundário (HPTS) associado à insuficiência renal crônica. Demandante: Abbott Laboratórios do Brasil Ltda. Contexto: O hiperparatireoidismo secundário (HPTS) à doença crônica renal é caracterizado por elevados níveis séricos de paratormônio (PTH), hiperplasia das glândulas paratireoides e uma doença óssea de alto remanejamento. O nível de PTH considerado adequado está situado entre 150 e 300 pg/ml ou duas a nove vezes o valor limite do método de dosagem. Segundo o censo da Sociedade Brasileira de Nefrologia, em 2011, aproximadamente 30,6% dos pacientes em tratamento dialítico no Brasil apresentavam valores acima de 300 pg/ml, representando, assim, cerca de 28.000 pacientes com HPTS. Com base nas diretrizes internacionais, o tratamento de HPTS e doença óssea relacionada está centrado no controle dos níveis de fósforo, cálcio e PTH. Para a redução dos níveis do PTH, estão disponíveis no mercado brasileiro três classes de medicamentos: ativadores não seletivos do receptor de vitamina D/VDR (calcitriol e alfacalcidol), ativadores seletivos de VDR (paricalcitol) e calcimiméticos (cinacalcete). Dos medicamentos supracitados, o SUS disponibiliza calcitriol oral e intravenoso e alfacalcidol oral. O calcitriol é utilizado desde a década de 80 para reduzir os níveis de PTH, entretanto apresenta como efeitos não desejáveis hipercalcemia e hiperfosfatemia. Assim, o demandante solicita a substituição do calcitriol intravenoso pelo paricalcitol intravenoso, visto que esse pode apresentar efeito menos calcêmico. Pergunta: O uso do paricalcitol intravenoso é eficaz, seguro e custo-efetivo em pacientes com hiperparatireoidismo secundário à insuficiência renal crônica quando comparado ao calcitriol intravenoso? Evidências científicas: O principal estudo clínico apresentado pelo demandante concluiu que os pacientes que usaram paricalcitol atingiram redução de 50% nos níveis do PTH oito semanas antes do grupo que usou calcitriol, além de terem apresentado um número menor de episódios de hipercalcemia e/ou elevação do produto cálcio x fósforo. A incidência de hiperfosfatemia foi comparável entre os dois grupos. A revisão sistemática da Cochrane analisada não encontrou evidências desuperioridade dos novos compostos de vitamina D sobre os estabelecidos (calcitriol ou alfacalcidol) para nenhum desfecho avaliado nos estudos que os compararam diretamente, tanto desfechos clínicos ou bioquímicos (níveis séricos de cálcio e fósforo). Como conclusão desse estudo, os novos compostos de vitamina D não podem ser considerados superiores aos tratamentos existentes, pois ainda não há informações suficientes para determinar o efeito menos calcêmico ou não calcêmico em relação ao calcitriol ou alfacalcidol. Dois estudos observacionais avaliaram mortalidade em pacientes recebendo paricalcitol vs. calcitriol, sendo que um deles mostrou diferença estatística entre os grupos, e o outro apresentou diferença, porém, não estatisticamente significativa. Um terceiro estudo observacional avaliou o desfecho hospitalização, concluindo, que, pacientes que usaram paricalcitol apresentaram menos dias/ano de hospitalização e menos risco para hospitalização. Avaliação econômica: Foi realizado um estudo de custo-efetividade comparando paricalcitol intravenoso com calcitriol intravenoso. Discussão: As evidências científicas apresentadas pelo demandante não são definitivas em termos da superioridade do paricalcitol em comparação ao calcitriol no tratamento de HPTS. Além disso, as limitações do estudo econômico e do impacto orçamentário não permitem concluir que a incorporação do paricalcitol no SUS seria custo-efetiva e que traria redução de custos ao SUS, conforme afirma o demandante. Decisão: Pelo exposto, a Conitec recomendou a não incorporação ao SUS do medicamento paricalcitol intravenoso em substituição ao calcitriol intravenoso para tratamento e prevenção de HPTS associado à insuficiência renal crônica. Considerou-se que as evidências científicas apresentadas pelo demandante não são definitivas em termos da superioridade do paricalcitol intravenoso em relação ao calcitriol intravenoso na prevenção e tratamento de HPTS. Na consulta pública foram recebidas 406 contribuições.Após discussão sobre as contribuições, o plenário da Conitec manteve a recomendação de não incorporação ao SUS do medicamento paricalcitol intravenoso conforme solicitação do demandante. Os membros da CONITEC presentes na 17ª reunião do plenário do dia 04/07/2013 deliberaram, por unanimidade, por não recomendara incorporação ao SUS do medicamento paricalcitol intravenoso em substituição ao calcitriol intravenoso para tratamento e prevenção do hiperparatireoidismo secundário associado à insuficiência renal crônica.

[Chronic kidney disease (CKD) and bone. Control of CKD-MBD from the viewpoint of the medical cost].

Pharmacoeconomics (PE) , which contribute to the decisions on the population rather than the patient level such as policy making, provides us with the cost and value of a given drug. In the midst of terrible economic climate, medications for CKD-MBD are reviewed from the viewpoint of PE in this manuscript. DCOR trial is the only study in maintenance hemodialysis patients with mortality as a primary endpoint, which compared expensive sevelamer hydrochloride and economical calcium containing phosphate binders, showing no difference in mortality between these drugs. This means that calcium containing phosphate binders are more cost-effective. Cost utility analysis from the United States revealed that parathyroidectomy became more cost-effective at 16 months than cinacalcet hydrochloride, which theoretically have to be continued throughout life. The effect of active vitamin D on mortality is controversial, since there has not been any prospective randomized controlled trial. Taking these findings into account, cinacalcet should be indicated only in those patients who have secondary hyperparathyroidism refractory to conventional therapy and for whom parathyroidectomy is not a good indication. Furthermore, when cinacalcet have to be used, we should give priority to calcium containing phosphate binders rather than expensive sevelamer from the viewpoint of the medical cost. Moreover, the doses of cinacalcet should be minimized by administering inexpensive vitamin D concomitantly.

Impact of secondary hyperparathyroidism on disease progression, healthcare resource utilization and costs in pre-dialysis CKD patients.

BACKGROUND AND OBJECTIVES: Secondary hyperparathyroidism (SHPT) can lead to significant morbidity, mortality, and additional healthcare resource utilization in chronic kidney disease (CKD) stage 5. The objective of this study was to examine healthcare costs and utilization, and the risks of dialysis or mortality, among pre-dialysis CKD patients with and without SHPT. RESEARCH DESIGN AND METHODS: This retrospective cohort study examined insurance claims from 66 644 adult, pre-dialysis, CKD patients with and without SHPT during a 72-month period. Annualized estimates of healthcare costs and utilization, and disease progression to dialysis or death following index CKD diagnosis were compared. RESULTS: Post-index annualized costs and inpatient healthcare resource utilization was higher in those with SHPT in both unadjusted and adjusted (controlling for gender, age, plan type, payer type, geographic region, physician specialty, pre-index co-morbidities, and pre-index total healthcare costs), and unmatched and matched analyses. Kaplan-Meier analysis demonstrated that the rate of progression to dialysis or death was higher for CKD with SHPT compared to CKD without SHPT, and Cox proportional hazard models suggested that CKD patients with SHPT were more than four to five times as likely to initiate dialysis or die as compared to CKD without SHPT. CONCLUSION: SHPT in pre-dialysis CKD patients is associated with significantly greater healthcare costs, inpatient hospitalizations, and a faster rate of disease progression compared to pre-dialysis CKD without SHPT. Since observational studies are designed to demonstrate associations rather than causality, further investigation is required to confirm these findings.

Differences in corrective mode for divalent ions and parathyroid hormone between standard- and low-calcium dialysate in patients on continuous ambulatory peritoneal dialysis--result of a nationwide survey in Japan.

BACKGROUND: In patients on continuous ambulatory peritoneal dialysis (CAPD), dialysate calcium concentration has a strong influence on correction of serum calcium, phosphorus, and parathyroid hormone (PTH); however, the optimal concentration of Ca in PD solution is still uncertain. The aim of the survey reported here was to evaluate the prevalence of patients treated with standard- [SCD (approximately 3.25 - 4.0 mEq/L)] or low-calcium [LCD (approximately 1.8 - 2.5 mEq/L)] dialysate and differences in the clinical effects for correction of abnormalities in divalent ions and PTH. MATERIALS AND METHODS: We used a questionnaire to survey 333 peritoneal dialysis facilities nationwide in Japan. Then, we analyzed serum Ca, P, and PTH levels and the prescription rates for CaCO(3) as a P binder and for vitamin D (VitD) analogs. RESULTS: The 2384 CAPD patients enrolled in this analysis had a mean age of 60.5 +/- 14.2 years and a mean duration of CAPD of 44.1 +/- 39.2 months. The prevalences of SCD, LCD, and combination of SCD and LCD were, respectively, 49%, 50%, and 1% at initiation, and 40%, 38%, and 22% at the time of the survey. In 735 and 876 patients respectively, LCD and SCD had been prescribed from initiation to the time of the survey. In these two groups, we observed no difference in initiation and current serum levels of Ca and P. But prescription rates for CaCO(3) and VitD analogs were higher in the LCD group than in the SCD group, and PTH levels were higher in the LCD group than in the SCD group. CONCLUSIONS: A beneficial effect of LCD was revealed in the increased doses of CaCO(3) and VitD analogs seen in that group without the occurrence of hypercalcemia; however, PTH levels in that group were not maintained within an acceptable range. The survey suggests that more serious attention should be paid to the Ca concentration in peritoneal dialysate so as to lessen mineral and PTH disorders in CAPD.

[Basic and clinical aspects of calcimimetics. Calcimimetics from the viewpoint of medical cost].

Cinacalcet hydrochrolide has now become available in Japan after a three-year interval from its introduction to Western countries. The clinical use of this drug should certainly bring benefit to the treatment of secondary hyperparathyroidism among dialysis patients. But, at the same time, it should increase the medical cost, as shown in the cost utility analyses reported previously in Western countries. Moreover, the longevity of Japanese hemodialysis patients might increase the difference between the cost of parathyroidectomy (PTX) and that of cinacalcet treatment which theoretically should be continued throughout their life. From the viewpoint of the cost, the intervention techniques, such as PTX and percutaneous ethanol injection therapy, should be encouraged. When sevelamer hydrochloride was first introduced in Japan, the abrupt and complete transition from calcium containing phosphate binder to large amount of sevelamer brought about severe constipation among Japanese dialysis patients, resulting in unwillingness or reluctance to take this agent and low compliance. Looking back on this bitter experience and again from the viewpoint of the cost, it is reasonable in Japan to administer small dose of cinacalcet with concomitant vitamin D therapy.

Outcomes of secondary hyperparathyroidism in chronic kidney disease and the direct costs of treatment.

BACKGROUND: There has been an emphasis over the last several years to identify and treat chronic kidney disease (CKD) and its complications as they evolve rather than waiting until the patient reaches end-stage renal disease (ESRD), also known as CKD stage 5. The number of patients who will be identified and prescribed therapies for complications such as secondary hyperparathyroidism (SHPT) is greater than initially proposed. OBJECTIVE: To review the pathways, complications, management, and estimated treatment costs of CKD-related SHPT. METHODS: An electronic literature search of MEDLINE (January 1980 through January 2007) was conducted for English-language publications using the base search term secondary hyperparathyroidism. To refine subsequent searches, the authors added Boolean operators to the following secondary and tertiary search terms: parathyroid hormone, chronic kidney disease, renal osteodystrophy, adynamic bone disease, vascular calcification, cardiovascular disease, vitamin D, vitamin D analogs, hypercalcemia, hyperphosphatemia, calcimimetics, costs, prevalence, and economics. RESULTS: The initial MEDLINE search produced 278 relevant articles. After refining the search terms, the authors triaged the results for English-language publications relevant to the discussion of SHPT and its complications in CKD, eliminating 149 publications. The remaining 129 publications were accepted for review. These articles represent a growing body of primarily observational evidence that demonstrates that elevated intact parathyroid hormone (PTH) levels cause deleterious physiological results across a variety of organ systems, including the cardiovascular and skeletal systems. Specific complications associated with SHPT are left ventricular hypertrophy (LVH), renal osteodystrophy (ROD), and extraskeletal calcification. Medical management of the PTH/vitamin D/calcium and phosphorus imbalances in SHPT focus on regulating PTH levels via vitamin D therapy. The class of calcimimetics is a newer treatment modality that has favorable effects on biochemical laboratory values, such as serum calcium and phosphorus levels, but current data do not show differences on hard endpoint patient-oriented outcomes compared with standard generic agents. The direct drug costs in April 2007 U.S. dollars of treating CKD-associated elevations in PTH in predialysis patients range from $8.40 per patient per week ($437 per year) for oral generic calcitriol to $88.90 per patient per week ($4,623 per year) for oral paricalcitol (expressed as 85% of average wholesale price [AWP] for brand drugs or 70% of AWP for generic drugs). The direct drug costs of treating SHPT in hemodialysis patients range from $80.20 per patient per week ($4,170 per year) for generic calcitriol (IV) to $278.46 per patient per week ($14,480 per year) for oral cinacalcet. CONCLUSIONS: SHPT causes skeletal and cardiovascular complications in CKD patients. Calcitriol therapy is effective in managing PTH levels, but efforts to reduce the associated hypercalcemia and hyperphosphatemia have led to the development of newer, yet more expensive, vitamin D analogs. With the lack of evidence to support comparative superior outcomes in end-organ disease among SHPT therapy alternatives, future research is still needed to clearly identify which newer agents are most competitive with the historical gold standard of calcitriol therapy.

The cost-utility of cinacalcet in addition to standard care compared to standard care alone for secondary hyperparathyroidism in end-stage renal disease: a UK perspective.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common side effect of end-stage renal disease (ESRD) and is associated with increased risk of fracture and cardiovascular events (CV). Current standard treatment includes dietary control, phosphate binders and vitamin D. However, many patients do not have their parathyroid hormone (PTH), calcium and phosphate levels controlled by this regimen. Cinacalcet is the first of a new class of calcimimetic drugs which suppress PTH production. Although there is convincing evidence of the impact of cinacalcet on serum biomarkers, the long-term clinical implications of treatment are less clear. The aim of this study is to estimate the cost-utility of cinacalcet as an addition to standard treatment of SHPT compared with standard treatment alone. METHODS: A Markov model was developed to estimate the incremental cost-utility of cinacalcet. Uncertainty was explored through extensive sensitivity analysis. RESULTS: Compared with standard treatment, cinacalcet incurs average additional lifetime costs of pound21,167 per person and confers an additional 0.34 quality adjusted life years, resulting in an incremental cost-effectiveness ratio of pound61,890 (approximately euro89,000) per quality-adjusted life-year (QALY). Extensive one-way sensitivity analysis showed that cinacalcet was only likely to be considered cost-effective if the relative risk of mortality for people with very high levels of PTH was 2.2 compared with people whose PTH reached target levels, or if drug costs were considerably reduced. Probabilistic sensitivity analysis showed cinacalcet was very unlikely to be cost-effective at usual levels of willingness to pay in the National Health Service (NHS). CONCLUSION: Unless the cost of cinacalcet is considerably reduced, it is unlikely to be considered a cost-effective treatment for people with SHPT.

Early hospital readmission was less likely for hemodialysis patients from facilities with longer median length of stay in the DOPPS study.

The length of hospital stay is considered to influence hospital readmission in general. The Dialysis Outcomes and Practice Patterns Study (DOPPS), an international prospective observational study undertaken to establish a relationship between facility practices and dialysis outcomes, started in 1996. Results suggest that the duration of hospital stay is significantly correlated with the probability of early readmission in dialysis patients. Thus, early hospital readmission was observed to be less likely for hemodialysis patients from facilities with longer median length of stay. The lengths of hospital stay for hemodialysis patients differed in the three continents studied. Although socioeconomic pressures may drive the lengths of hospital stay, the duration of hospitalization should be determined keeping in mind the safety of clinical course for each disease. In this forum, a 47-year-old female hemodialysis patient with severe secondary hyperparathyroidism, who had been treated with hemodialysis for 21 years, was hospitalized with severe clinical symptoms. Although the clinical symptoms disappeared 10 days after total parathyroidectomy with autotransplantation, severe hypocalcemia persisted despite large amounts of intravenous calcium gluconate. This patient was hospitalized for a long duration owing to the large calcium deficit in her body. Had the length of her hospital stay been shortened, either she could have needed rehospitalization or her condition could have worsened.

Assessment of acute parathyroid responsiveness to high calcium dialysate in uremic patients.

The response of the parathyroid glands to dialysis-induced changes in calcium has been studied in 83 normocalcemic patients receiving maintenance hemodialysis. Predialysis concentrations of intact parathyroid hormone (iPTH) were normal in 13 patients; 70 patients had increased iPTH levels of different degrees. All patients had analytically significant changes in total serum calcium (2.3 +/- 0.2 vs 2.8 +/- 0.2 mmol/l) without additional parenteral calcium loading during a standard dialysis session with a dialysis solution of 1.75 mmol calcium chloride. During hemodialysis the concentration of iPTH fell in 77 patients and was normalized in 48 of these patients. The remaining 6 patients showed no or an inadequate response (less than 30% suppression of predialysis iPTH) to the increase in Ca. Parathyroidectomy was performed in patients with refractory iPTH secretion. Histological evidence of marked parathyroid hyperplasia was obtained in all these patients. All patients with normal or partial responsiveness of the parathyroids tolerated at least small doses of 1.25 (OH)2-vitamin D3. Quantification of predialysis and postdialysis iPTH concentrations is a useful and simple method for identifying those uremic patients with true autonomy of the parathyroid glands at an early stage.