PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (843840)

Clipboard (0)
None

Related Articles

1.  Cost Effectiveness of Paricalcitol Versus Cinacalcet with Low-Dose Vitamin D for Management of Secondary Hyperparathyroidism in Haemodialysis Patients in the USA 
Clinical Drug Investigation  2013;34(2):107-115.
Background
The IMPACT SHPT [Improved Management of Intact Parathyroid Hormone (iPTH) with Paricalcitol-Centered Therapy Versus Cinacalcet Therapy with Low-Dose Vitamin D in Hemodialysis Patients with Secondary Hyperparathyroidism] study compared the effectiveness of paricalcitol and cinacalcet in the management of secondary hyperparathyroidism in haemodialysis patients but did not report the costs or cost effectiveness of these treatments.
Aim
The aim of this study was to compare the cost effectiveness of a paricalcitol-based regimen versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients from a US payer perspective, using a 1-year time horizon.
Methods
This was a post hoc cost-effectiveness analysis of data collected for US patients enrolled in the IMPACT SHPT study—a 28-week, randomized, open-label, phase 4, multinational study (ClinicalTrials.gov identifier: NCT00977080). Patients eligible for the IMPACT SHPT study were aged ≥18 years with stage 5 chronic kidney disease, had been receiving maintenance haemodialysis three times weekly for at least 3 months before screening and were to continue haemodialysis during the study. Only US patients who reached the evaluation period (weeks 21–28) were included in this secondary analysis. US subjects in the IMPACT SHPT study were randomly assigned to receive intravenous paricalcitol, or oral cinacalcet plus fixed-dose intravenous doxercalciferol, for 28 weeks. Patients in the paricalcitol group could also receive supplemental cinacalcet for hypercalcaemia. The primary effectiveness endpoint in the IMPACT SHPT study was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) level of 150–300 pg/mL during the evaluation period. In this secondary analysis, we estimated the incremental cost-effectiveness ratio (ICER), comparing paricalcitol-treated patients with cinacalcet-treated patients on the basis of this primary endpoint and several secondary endpoints. Costs were estimated by examining the dosage of the study drug (paricalcitol or cinacalcet) and phosphate binders used by each participant during the trial. Nonparametric bootstrap analysis was used to examine the accuracy of the ICER point estimates.
Results
The percentages of patients achieving the treatment goal of a mean iPTH level between 150–300 pg/mL during weeks 21–28 of therapy were 56.9 % in the paricalcitol group and 34.0 % in the cinacalcet group (a difference of 23 %, p = 0.0235). Paricalcitol was also more effective for each of the secondary endpoints. When annualized, the total drug costs were US$10,153 in the paricalcitol group and US$15,967 in the cinacalcet group, a difference of US$5,814 (57.3 %, p = 0.0053). Because the paricalcitol-based treatment was less expensive and more effective, it was ‘dominant’, compared with cinacalcet, in this cost-effectiveness analyses. In our bootstrap analysis, 99.1 % of bootstrap replicates for the ICER of the primary endpoint fell within the lower right quadrant of the cost-effectiveness plane—where paricalcitol is considered dominant. For all of the other endpoints, paricalcitol was dominant in 100 % of replicates.
Conclusion
On the basis of dosing and effectiveness data from US patients in the IMPACT SHPT study, we found that a regimen of intravenous paricalcitol was more cost effective than cinacalcet plus low-dose vitamin D in the management of iPTH in patients with SHPT requiring haemodialysis.
doi:10.1007/s40261-013-0151-4
PMCID: PMC3899451  PMID: 24214232
2.  Treatment of secondary hyperparathyroidism in haemodialysis patients: a randomised clinical trial comparing paricalcitol and alfacalcidol 
BMC Nephrology  2009;10:28.
Background
Secondary hyperparathyroidism is a common feature in patients with chronic kidney disease. Its serious clinical consequences include renal osteodystrophy, calcific uremic arteriolopathy, and vascular calcifications that increase morbidity and mortality.
Reduced synthesis of active vitamin D contributes to secondary hyperparathyroidism. Therefore, this condition is managed with activated vitamin D. However, hypercalcemia and hyperphosphatemia limit the use of activated vitamin D.
In Denmark alfacalcidol is the primary choice of vitamin D analog.
A new vitamin D analog, paricalcitol, may be less prone to induce hypercalcemia and hyperphosphatemia.
However, a randomised controlled clinical study comparing alfacalcidol and paricalcitol has never been performed.
The primary objective of this study is to compare alfacalcidol and paricalcitol. We evaluate the suppression of the secondary hyperparathyroidism and the tendency towards hyperphosphatemia and hypercalcemia.
Methods/Design
This is an investigator-initiated cross-over study. Nine Danish haemodialysis units will recruit 117 patients with end stage renal failure on maintenance haemodialysis therapy.
Patients are randomised into two treatment arms. After a wash out period of 6 weeks they receive increasing doses of alfacalcidol or paricalcitol for a period of 16 weeks and after a further wash out period of 6 weeks they receive the contrary treatment (paricalcitol or alfacalcidol) for 16 weeks.
Discussion
Hyperparathyroidism, hypercalcemia and hyperphosphatemia are associated with increased cardiovascular mortality in patients with chronic kidney disease.
If there is any difference in the ability of these two vitamin D analogs to decrease the secondary hyperparathyroidism without causing hypercalcemia and hyperphosphatemia, there may also be a difference in the risk of cardiovascular mortality depending on which vitamin D analog that are used. This has potential major importance for this group of patients.
Trial registration
ClinicalTrials.gov NCT004695
doi:10.1186/1471-2369-10-28
PMCID: PMC2760547  PMID: 19778452
3.  Comparison of oral and intravenous Alfacalcidol in chronic hemodialysis patients 
BMC Nephrology  2014;15:27.
Background
Activated vitamin D is the mainstay of treatment for secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients. However, the optimal route of administration is still debated. The aim of our study was to compare efficacy of oral vs intravenous (IV) administration of alfacalcidol in hemodialysis. A secondary objective was to determine the cost-effectiveness advantage of oral administration.
Methods
Eighty-eight chronic hemodialysis patients receiving IV alfacalcidol three times a week were included in the study. All were switched to the same dose of alfacalcidol given orally three times a week during the hemodialysis session. A budget impact analysis was performed.
Results
Mean patient age was 64 years old and 43% were males. The mean alfacalcidol dose administered was 2.1 μg three times a week. After three months, serum parathormone (PTH) levels decreased from 80 to 59 pmol/L (p = 0.001) and total serum calcium levels increased from 2.34 to 2.40 mmol/L (p = 0.002). After six months, total serum calcium levels were still significantly higher. Alfacalcidol dosage was significantly decreased during study period; the mean reduction was 0.44 μg per dose. Finally, oral administration was associated with an annual cost reduction of 197 678$CAN and an annual nursing time reduction of 25 days.
Conclusion
Our findings support that switching IV to oral administration of alfacalcidol during hemodialysis sessions may lead to a similar control of SHPT with lower doses of activated vitamin D. This is a good strategy for optimizing compliance and may allow a dose reduction because of a greater efficacy to suppress PTH. Oral administration also has significant cost-effectiveness advantages.
doi:10.1186/1471-2369-15-27
PMCID: PMC3915223  PMID: 24495277
Alfacalcidol administration; End-stage renal failure; Hyperparathyroidism
4.  Meta-Analysis: The Efficacy and Safety of Paricalcitol for the Treatment of Secondary Hyperparathyroidism and Proteinuria in Chronic Kidney Disease 
BioMed Research International  2012;2013:320560.
Introduction. Previous studies have demonstrated the safety and efficacy of using Paricalcitol for the treatment of secondary hyperparathyroidism (SHPT) in patients on dialysis. The aim of the current meta-analysis was to assess the safety and efficacy of Paricalcitol for the management of SHPT in patients with chronic kidney disease (CKD) not yet on dialysis. A secondary aim was to determine if sufficient data was available to assess the effect of Paricalcitol for the management of proteinuria. Methods. A meta-analysis was conducted using the Cochrane Collaboration's RevMan 4.2 software. Results. Paricalcitol is effective in lowering PTH in patients with CKD not yet on dialysis and is also effective in lowering proteinuria in diabetic CKD patients. However, we uncovered a safety signal identifying an elevated calcium phosphate product and a trend towards the development of hypercalcemia. A phosphate elevation was not demonstrated because the target used in the clinical studies was a P > 5.5 mg/dl, a value appropriate for dialysis patients and not CKD patients. Conclusion. Although Paricalcitol is effective in lowering PTH, we advise caution in the use of any active Vitamin D analogues in patients with CKD because of the potential risk of exacerbating vascular calcification.
doi:10.1155/2013/320560
PMCID: PMC3591146  PMID: 23509710
5.  Effects of paricalcitol on calcium and phosphate metabolism and markers of bone health in patients with diabetic nephropathy: results of the VITAL study 
Nephrology Dialysis Transplantation  2013;28(9):2260-2268.
Background
Chronic kidney disease (CKD) is associated with elevations in serum phosphate, calcium–phosphorus product and bone-specific alkaline phosphatase (BAP), with attendant risks of cardiovascular and bone disorders. Active vitamin D can suppress parathyroid hormone (PTH), but may raise serum calcium and phosphate concentrations. Paricalcitol, a selective vitamin D activator, suppressed PTH in CKD patients (stages 3 and 4) with secondary hyperparathyroidism (SHPT) with minimal changes in calcium and phosphate metabolism.
Methods
The VITAL study enrolled patients with CKD stages 2–4. We examined the effect and relationship of paricalcitol to calcium and phosphate metabolism and bone markers in a post hoc analysis of VITAL. The study comprised patients with diabetic nephropathy enrolled in a double-blind, placebo-controlled, randomized trial of paricalcitol (1 or 2 μg/day). Urinary and serum calcium and phosphate, serum BAP, and intact PTH (iPTH) concentrations were measured throughout the study.
Results
Baseline demographics and calcium, phosphate, PTH (49% with iPTH <70 pg/mL), and BAP concentrations were similar between groups. A transient, modest yet significant increase in phosphate was observed for paricalcitol 2 μg/day (+0.29 mg/dL; P < 0.001). Dose-dependent increases in serum and urinary calcium were observed; however, there were few cases of hypercalcemia: one in the 1-μg/day group (1.1%) and three in the 2-μg/day group (3.2%). Significant reductions in BAP were observed that persisted for 60 days after paricalcitol discontinuation (P < 0.001 for combined paricalcitol groups versus placebo). Paricalcitol dose-dependent reductions in iPTH were observed. Paricalcitol in CKD patients (±SHPT) was associated with modest increases in calcium and phosphate.
Conclusion
Paricalcitol reduces BAP levels, which may be beneficial for reducing vascular calcification.
Trial registration
Trial is registered with ClinicalTrials.gov, number NCT00421733.
doi:10.1093/ndt/gft227
PMCID: PMC3769981  PMID: 23787544
bone-specific alkaline phosphatase; calcitriol; hypercalcemia; hyperphosphatemia; paricalcitol; vitamin D receptor activation
6.  The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study 
BMC Nephrology  2014;15:130.
Background
The risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined.
Methods
In 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin-A, NT-proBNP, hs-Crp, IL-6 and TNF-α, during 16 weeks of treatment.
Results
NT-proBNP and osteoprotegerin increased comparably in the paricalcitol and alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol-treated group compared with the paricalcitol-treated group (difference 32.84 μmol/l (95% C.I.; range 0.21–67.47)) during the first treatment period. No difference was found between the groups during the second treatment period, and IL-6, TNF-α and hs-Crp were unchanged in both treatment groups.
Conclusions
Paricalcitol and alfacalcidol modulate regulators of vascular calcification. Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We did not find any anti-inflammatory effect or difference in changes of NT-proBNP.
Trial registry
ClinicalTrials.gov NCT00469599 May 3 2007.
doi:10.1186/1471-2369-15-130
PMCID: PMC4136403  PMID: 25112372
Cardiovascular disease; Heart failure; Hemodialysis; Vascular calcification; Vitamin D
7.  An LRP5 Receptor with Internal Deletion in Hyperparathyroid Tumors with Implications for Deregulated WNT/β-Catenin Signaling 
PLoS Medicine  2007;4(11):e328.
Background
Hyperparathyroidism (HPT) is a common endocrine disorder with incompletely understood etiology, characterized by enlarged hyperactive parathyroid glands and increased serum concentrations of parathyroid hormone and ionized calcium. We have recently reported activation of the Wnt signaling pathway by accumulation of β-catenin in all analyzed parathyroid tumors from patients with primary HPT (pHPT) and in hyperplastic parathyroid glands from patients with uremia secondary to HPT (sHPT). Mechanisms that may account for this activation have not been identified, except for a few cases of β-catenin (CTNNB1) stabilizing mutation in pHPT tumors.
Methods and Findings
Reverse transcription PCR and Western blot analysis showed expression of an aberrantly spliced internally truncated WNT coreceptor low-density lipoprotein receptor–related protein 5 (LRP5) in 32 out of 37 pHPT tumors (86%) and 20 out of 20 sHPT tumors (100%). Stabilizing mutation of CTNNB1 and expression of the internally truncated LRP5 receptor was mutually exclusive. Expression of the truncated LRP5 receptor was required to maintain the nonphosphorylated active β-catenin level, transcription activity of β-catenin, MYC expression, parathyroid cell growth in vitro, and parathyroid tumor growth in a xenograft severe combined immunodeficiency (SCID) mouse model. WNT3 ligand and the internally truncated LRP5 receptor strongly activated transcription, and the internally truncated LRP5 receptor was insensitive to inhibition by DKK1.
Conclusions
The internally truncated LRP5 receptor is strongly implicated in deregulated activation of the WNT/β-catenin signaling pathway in hyperparathyroid tumors, and presents a potential target for therapeutic intervention.
Gunnar Westin and colleagues report the expression of an aberrantly spliced LRP5 receptor in primary and spontaneous parathyroid tumors and implicate it in the deregulated activation of the Wnt/β-catenin signaling pathway.
Editors' Summary
Background.
The parathyroid glands—four rice-sized glands in the neck—maintain a normal calcium balance in the body, to maintain strong bones and essential cellular functions. The glands release parathyroid hormone as a response to a decrease in blood calcium level. By stimulating calcium release from bone and its absorption in the gut, parathyroid hormone restores the blood calcium level. However, 100,000 new individuals in the US develop hyperparathyroidism (HPT) annually, characterized by enlarged, overactive parathyroid glands and high blood levels of calcium. Primary HPT (pHPT) is usually caused by a benign tumor (a non-life-threatening growth) in one of the parathyroid glands. Secondary HPT (sHPT) occurs in response to calcium regulatory disturbances, linked to vitamin D deficiency, and more or less invariably develops in patients with uremic kidney disease.
Why Was This Study Done?
HPT is usually treated by surgical removal of the enlarged parathyroid glands, which is done with great efficiency. However, ideally, doctors would like to know what drives the overgrowth of the parathyroid glands to be able to develop drugs for treatment or disease prophylaxis. Researchers recently reported that the cells in enlarged parathyroid glands from patients with HPT contain high amounts of β-catenin. This protein is part of the Wnt signaling pathway, which has been found to be disrupted in many tumor entities in other organs. In the absence of Wnt proteins, a group of proteins called the β-catenin destruction complex marks β-catenin so that it is rapidly destroyed. When Wnt proteins bind to a cell-surface receptor called Frizzled and a coreceptor called LRP5, the destruction complex is inhibited and β-catenin accumulates. This accumulation induces the production of other proteins (in particular, c-Myc) that stimulate cell growth and division. The accumulation of β-catenin in the enlarged parathyroid glands of patients with HPT could, therefore, significantly contribute to the overgrowth of their glands—but what causes β-catenin accumulation? In this study, the researchers have investigated this question to try to identify a target for drugs to treat HPT.
What Did the Researchers Do and Find?
The researchers looked for genetic changes (mutations) in β-catenin that stabilize the protein and measured the expression of LRP5 in abnormal parathyroid gland tissue from 37 patients with pHPT and 20 with uremia and sHPT. All the samples contained high levels of β-catenin, but only four contained a β-catenin–stabilizing mutation. All the sHPT samples and 32 pHPT samples (but none of the samples containing the β-catenin stabilizing mutation) expressed a mutated LRP5, with the central region deleted. To investigate the functional consequences of this internally deleted LRP5 protein, the researchers used a technique called RNA interference to block its expression in a human parathyroid tumor cell line. They found that expression of the mutated, short LRP5 is required for accumulation of β-catenin, expression of c-Myc, and continued growth of the cell line in test tubes and in animals.
What Do These Findings Mean?
The accumulation of β-catenin in all the enlarged parathyroid glands examined so far strongly implicates abnormal Wnt/β-catenin signaling in the development of pHPT and sHPT. These new findings identify which part of the signaling pathway is altered. The expression data and functional data together suggest that an internally deleted LRP5 coreceptor is often responsible for the accumulation of β-catenin. The functional data also show that expression of shortened LRP5 is necessary for the abnormal growth of parathyroid tumor cells. Exactly how the internally deleted coreceptor activates β-catenin signaling in parathyroid gland cells, or why a shorter-than-normal LRP5 is made, are not yet known. However, because these findings indicate that internally deleted LRP5 has a fundamental role in activating Wnt signaling in HPT, drugs that inactivate this aberrant protein but leave the normal protein unscathed might provide a nonsurgical treatment for this common hormone disorder.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040328.
edlinePlus has encyclopedia pages on hyperparathyroidism, primary hyperparathyroidism, and secondary hyperparathyroidim (in English and Spanish)
Information is available for patients from the US National Institute of Diabetes and Digestive and Kidney Diseases on hyperparathyroidism, which includes links to organizations that help people with hyperparathyroidism
Wikipedia maintains pages on Wnt signaling pathway and on β-catenin (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.0040328
PMCID: PMC2082644  PMID: 18044981
8.  Effect of paricalcitol on renin and albuminuria in non-diabetic stage III-IV chronic kidney disease: a randomized placebo-controlled trial 
BMC Nephrology  2013;14:163.
Background
Vitamin D receptor activators reduce albuminuria, and may improve survival in chronic kidney disease (CKD). Animal studies suggest that these pleiotropic effects of vitamin D may be mediated by suppression of renin. However, randomized trials in humans have yet to establish this relationship.
Methods
In a randomized, placebo-controlled, double-blinded crossover study, the effect of oral paricalcitol (2 μg/day) was investigated in 26 patients with non-diabetic, albuminuric stage III-IV CKD. After treatment, plasma concentrations of renin (PRC), angiotensin II (AngII) and aldosterone (Aldo) were measured. GFR was determined by 51Cr-EDTA clearance. Assessment of renal NO dependency was performed by infusion of NG-monomethyl-L-arginine (L-NMMA). Albumin excretion rate (AER) was analyzed in 24-h urine and during 51Cr-EDTA clearance.
Results
Paricalcitol did not alter plasma levels of renin, AngII, Aldo, or urinary excretion of sodium and potassium. A modest reduction of borderline significance was observed in AER, and paricalcitol abrogated the albuminuric response to L-NMMA.
Conclusions
In this randomized, placebo-controlled trial paricalcitol only marginally decreased AER and did not alter circulating levels of renin, AngII or Aldo. The abrogation of the rise in albumin excretion by paricalcitol during NOS blockade may indicate that favourable modulation of renal NO dependency could be involved in mediating reno-protection and survival benefits in CKD.
Trial registration
ClinicalTrials.gov identifier: NCT01136564
doi:10.1186/1471-2369-14-163
PMCID: PMC3729723  PMID: 23889806
Albuminuria; Chronic kidney disease; Nitric oxide; Vitamin D; Renin-angiotensin system
9.  Inflammation and Albuminuria in HIV-infected Patients Receiving Combination Antiretroviral Therapy 
Background:
The observed higher prevalence of albuminuria among HIV-infected patients has been strongly associated with cardiovascular disease and higher mortality. In HIV-seronegative patients with metabolic syndrome, malignancies and infections, pro-inflammatory cytokines, and acute phase reactants have been associated with albuminuria. However, the pathophysiology of albuminuria in HIV-seropositive individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected patients on combination antiretroviral therapy.
Methods:
This is a cross-sectional analysis of the entry data of the participants enrolled in the Hawai‘i Aging with HIV-Cardiovascular Cohort. Participants were ≥ 40 years old, lived in Hawai‘i, documented HIV-positive, and had been on antiretroviral therapy for at least 6 months prior to recruitment. Albuminuria was defined as urine albumin-to-creatinine ratio (ACR) of 30 mg/g or higher, as assessed from single random urine collection. Microalbuminuria was defined as urine ACR between 30 and 300 mg/g and macroalbuminuria as urine ACR more than 300 mg/g. Plasma inflammatory biomarkers were assessed by multiplexing using Milliplex Human Cardiovascular Disease panels. Differences in clinical and laboratory characteristics between subjects with and without albuminuria were compared using a non-parametric Wilcoxon rank test for continuous variables and a chi-squared test for categorical variables. Univariate and multivariate logistic regression analyses were utilized to assess the association between presence of albuminuria as the dependent variable and plasma biomarkers as independent variables. Log-transformed plasma inflammatory biomarkers with P-value less than .1 in univariate logistic regression analysis were selected for examination in separate multivariate logistic regression models, adjusting for previously reported risk factors for albuminuria (age, gender, race, diabetes, hypertension, CD4 percent, current ritonavir, and tenofovir use).
Results:
Among a cohort of 111 HIV-infected patients (median age of 52 (Q1: 46, Q3: 57); male 86%; diabetes 6%; hypertension 33%; median CD4 count of 489 cells/mm3(Q1:341, Q3: 638); HIV RNA PCR < 48 copies/ml 85%), eighteen subjects (16.2%) had microalbuminuria, and two subjects (1.8%) had macroalbuminuria. There was no significant difference in CD4 count and HIV viral loads between patients with and without albuminuria. In univariate logistic regression analysis, higher levels of log-transformed soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule 1 (sVCAM-1), tissue plasminogen activator inhibitor-1 (tPAI-1), C-reactive protein (CRP), serum amyloid A (SAA), serum amyloid P (SAP), interleukin-1β, interleukin-8, and tumor necrosis factor-α (TNF-α) were associated with albuminuria (P < .10). In multivariate logistic regression models, sE-selectin, sVCAM-1, tPAI-1, CRP, and SAP remained significant (P < .05) even after adjustment for previously reported risk factors for albuminuria.
Conclusions:
This study has shown an association between inflammation and albuminuria independent of previously reported risk factors for albuminuria in HIV-infected subjects on stable combination antiretroviral therapy. Chronic low-grade inflammation despite potent antiretroviral treatment may be one of the factors causing higher rates of albuminuria among HIV-infected patients. Future studies are needed to further elucidate the pathophysiologic mechanisms of chronic inflammation in HIV and its impact on kidney disease.
PMCID: PMC4175929
10.  Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. 
BMJ : British Medical Journal  1995;310(6976):358-363.
OBJECTIVE--To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. DESIGN--Double blind, prospective, randomised, placebo controlled study. SETTING--17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. SUBJECTS--176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. INTERVENTIONS--Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. MAIN OUTCOME MEASURES--Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. RESULTS--132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. CONCLUSION--Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.
PMCID: PMC2548761  PMID: 7677827
11.  Three-Year Successful Cinacalcet Treatment of Secondary Hyperparathyroidism in a Patient with X-Linked Dominant Hypophosphatemic Rickets: A Case Report 
Case Reports in Endocrinology  2014;2014:479641.
Hypophosphatemic rickets (HR) is a rare inherited disorder characterized by a classic rickets phenotype with low plasma phosphate levels and resistance to treatment with vitamin D. Development of secondary hyperparathyroidism (SHPT) as a direct consequence of treatment is a frequent complication and a major clinical challenge, as this may increase risk of further comorbidity. Cinacalcet, a calcimimetic agent that reduces the secretion of PTH from the parathyroid glands, has been suggested as adjuvant treatment to SHPT in patients with HR. However, only two papers have previously been published and no data are available on effects of treatment for more than six months. We now report a case of 3-year treatment with cinacalcet in a patient with HR complicated by SHPT. A 53-year-old woman with genetically confirmed X-linked dominant hypophosphatemic rickets developed SHPT after 25 years of conventional treatment with alfacalcidol and phosphate supplements. Cinacalcet was added to her treatment, causing a sustained normalization of PTH. Ionized calcium decreased, requiring reduction of cinacalcet, though asymptomatical. Level of phosphate was unchanged, but alkaline phosphatase increased in response to treatment. Cinacalcet appeared to be efficient, safe, and well tolerated. We recommend close control of plasma calcium to avoid hypocalcemia.
doi:10.1155/2014/479641
PMCID: PMC3934321  PMID: 24660072
12.  Oral Paricalcitol for the Treatment of Secondary Hyperparathyroidism in Chronic Kidney Disease 
Secondary hyperparathyroidism (SHPT) is commonly seen in patients with chronic kidney disease (CKD). Even in early CKD, parathyroid hormone (PTH) levels are elevated, maintaining mineral homeostasis at the cost of long-term bone health. One potent stimulus for PTH secretion is a deficiency of active vitamin D. Replacement with calcitriol, the active form of vitamin D, lowers PTH but often raises calcium and phosphorus levels, predisposing patients to an increased risk of ectopic calcifications. Paricalcitol is a vitamin D analog designed to treat SHPT without raising serum calcium and phosphorus levels. The intravenous preparation of paricalcitol is used routinely in the hemodialysis population and has demonstrated a survival benefit over calcitriol in hemodialysis patients. A new oral preparation has now been developed for use in the pre-dialysis CKD population. Thus far, oral paricalcitol has been shown to reduce PTH by an average of 42% in CKD patients, while having minimal effects on serum calcium and phosphorus. While long term effects of the oral preparation have yet to be studied, emerging evidence suggests that paricalcitol mediates a variety of beneficial effects through the activation of vitamin D receptors which may result in improved survival.
PMCID: PMC1936265  PMID: 18360604
paricalcitol; secondary hyperparathyroidism; chronic kidney disease
13.  Evaluating targets and costs of treatment for secondary hyperparathyroidism in incident dialysis patients: the FARO-2 study 
Background
The aim of this analysis was to estimate biochemical parameters and the costs of treatment of secondary hyperparathyroidism (SHPT) in a subpopulation of the FARO-2 study.
Methods
The FARO-2 observational study aimed at evaluating the patterns of treatment for SHPT in naïve hemodialysis patients. Data related to pharmacological treatments and biochemical parameters (parathyroid hormone [PTH], calcium, phosphate) were recorded at entry to hemodialysis (baseline) and 6 months later (second survey). The analysis was performed from the Italian National Health Service perspective.
Results
Two prominent treatment groups were identified, ie, one on oral calcitriol (n=105) and the other on intravenous paricalcitol (n=33); the intravenous calcitriol and intravenous paricalcitol + cinacalcet combination groups were not analyzed due to low patient numbers. At baseline, serum PTH levels were significantly higher in the intravenous paricalcitol group (P<0.0001). At the second survey, the intravenous paricalcitol group showed a higher percentage of patients at target for PTH than in the oral calcitriol group without changing the percentage of patients at target for phosphate. Moreover, between baseline and the second survey, intravenous paricalcitol significantly increased both the percentage of patients at target for PTH (P=0.033) and the percentage of patients at target for the combined endpoint PTH, calcium, and phosphate (P=0.001). The per-patient weekly pharmaceutical costs related to SHPT treatment, erythropoietin-stimulating agents and phosphate binders accounted for 186.32€ and 219.94€ at baseline for oral calcitriol and intravenous paricalcitol, respectively, while after 6 months, the costs were 180.51€ and 198.79€, respectively. Either at the beginning of dialysis or 6 months later, the total cost of SHPT treatment was not significantly lower in the oral calcitriol group compared with the intravenous paricalcitol group, with a difference among groups that decreased by 46% between the two observations. The cost of erythropoietin stimulating agents at the second survey was lower (−22%) in the intravenous paricalcitol group than in the oral calcitriol group (132.13€ versus 168.36€, respectively).
Conclusion
Intravenous paricalcitol significantly increased the percentage of patients at target for the combined endpoint of PTH, calcium, and phosphate (P=0.001). The total cost of treatment for the patients treated with intravenous paricalcitol 6 months after entry to dialysis was not significantly higher than the cost for patients treated with oral calcitriol.
doi:10.2147/IJNRD.S72011
PMCID: PMC4274130  PMID: 25565880
cost consequences analysis; therapeutic costs; outcomes; SHPT treatments; secondary hyperparathyroidism
14.  Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD 
Nephrology Dialysis Transplantation  2011;27(6):2198-2205.
Background.
Secondary hyperparathyroidism (sHPT) represents an adaptive response to progressively impaired control of calcium, phosphorus and vitamin D in chronic kidney disease (CKD). It is characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Parathyroid hyperplasia in uremic rats can be prevented by calcium-sensing receptor (CaSR) activation with the calcimimetic cinacalcet (Sensipar®/Mimpara®); however, it is unknown, how long the effects of cinacalcet persist after withdrawal of treatment or if cinacalcet is efficacious in uremic rats with established sHPT.
Methods.
We sought to determine the effect of cinacalcet discontinuation in uremic rats and whether cinacalcet was capable of influencing parathyroid hyperplasia in animals with established sHPT.
Results.
Discontinuation of cinacalcet resulted in reversal of the beneficial effects on serum PTH and parathyroid hyperplasia. In rats with established sHPT, cinacalcet decreased serum PTH and mediated regression of parathyroid hyperplasia. The cinacalcet-mediated decrease in parathyroid gland size was accompanied by increased expression of the cyclin-dependent kinase inhibitor p21. Prevention of cellular proliferation with cinacalcet occurred despite increased serum phosphorus and decreased serum calcium.
Conclusions.
The animal data provided suggest established parathyroid hyperplasia can be reversed by modulating CaSR activity with cinacalcet and that continued treatment may be necessary to maintain reductions in PTH.
doi:10.1093/ndt/gfr589
PMCID: PMC3363978  PMID: 22036941
calcimimetics; cinacalcet; parathyroid hormone; parathyroid hyperplasia; secondary hyperparathyroidism
15.  Eldecalcitol reduces the risk of severe vertebral fractures and improves the health-related quality of life in patients with osteoporosis 
Eldecalcitol reduces the risk of vertebral fractures in comparison to alfacalcidol in osteoporotic patients under vitamin D repletion. The aim of this study was to evaluate the effects of eldecalcitol on the spinal location of incident vertebral fractures, the severity of the fractures, and the changes in health-related quality of life (HRQOL) compared with those of alfacalcidol. The post hoc analysis has been performed on the data from the three-year, double-blind, randomized, head-to-head clinical trial of eldecalcitol versus alfacalcidol conducted in Japan. A total of 1054 patients were enrolled and randomized to take 0.75 μg eldecalcitol or 1.0 μg alfacalcidol daily for 3 years. The incidence of vertebral fractures was re-evaluated based on the location on the spine (upper T4–T10; lower T11–L4). The severity of vertebral fractures was determined by the semi-quantitative method, and the change in HRQOL was analyzed by using the Medical Outcomes Study Short Form 36-item questionnaire. The incidence of vertebral fracture at the lower spine was less in the eldecalcitol group than in the alfacalcidol group (p = 0.029). The incidence of severe vertebral fracture (Grade 3) was 3.8 % in the eldecalcitol group and 6.7 % in the alfacalcidol group, demonstrated a significant difference between the 2 groups (p = 0.036). Both eldecalcitol and alfacalcidol improved HRQOL in osteoporotic patients. Although no significant differences in each HRQOL scores were observed between eldecalcitol and alfacalcidol during the observational period, overall improvement from baseline of HRQOL scores were clearly observed in the eldecalcitol group. In conclusion, the incidences of lower spinal vertebral fractures and severe vertebral fractures were reduced further by eldecalcitol compared to alfacalcidol in the 3-year clinical trial. Daily treatment with eldecalcitol is effective in improving HRQOL, possibly owing to the reduced risk of lower spinal vertebral fractures and/or severe vertebral fractures.
doi:10.1007/s00774-012-0397-6
PMCID: PMC3590407  PMID: 23129180
Eldecalcitol; Health-related quality of life; Osteoporosis; Vertebral fracture
16.  Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study 
Nephrology Dialysis Transplantation  2012;27(8):3270-3278.
Background
Optimal treatment for secondary hyperparathyroidism (SHPT) has not been defined. The IMPACT SHPT (ClinicalTrials.gov identifier: NCT00977080) study assessed whether dose-titrated paricalcitol plus supplemental cinacalcet only for hypercalcaemia is superior to cinacalcet plus low-dose vitamin D in controlling intact parathyroid hormone (iPTH) levels in patients with SHPT on haemodialysis.
Methods
In this 28-week, multicentre, open-label Phase 4 study, participants were randomly selected to receive paricalcitol or cinacalcet plus low-dose vitamin D. Randomization and analyses were stratified by mode of paricalcitol administration [intravenous (IV) or oral]. The primary efficacy end point was the proportion of subjects who achieved a mean iPTH value of 150–300 pg/mL during Weeks 21–28.
Results
Of 272 subjects randomized, 268 received one or more dose of study drug; 101 in the IV and 110 in the oral stratum with two or more values during Weeks 21–28 were included in the primary analysis. In the IV stratum, 57.7% of subjects in the paricalcitol versus 32.7% in the cinacalcet group (P = 0.016) achieved the primary end point. In the oral stratum, the corresponding proportions of subjects were 54.4% for paricalcitol and 43.4% for cinacalcet (P = 0.260). Cochran–Mantel–Haenszel analysis, controlling for stratum, revealed overall superiority of paricalcitol (56.0%) over cinacalcet (38.2%; P = 0.010) in achieving iPTH 150–300 pg/mL during Weeks 21–28. Hypercalcaemia occurred in 4 (7.7%) and 0 (0%) of paricalcitol-treated subjects in the IV and oral strata, respectively. Hypocalcaemia occurred in 46.9% and 54.7% of cinacalcet-treated subjects in the IV and oral strata, respectively.
Conclusion
Paricalcitol versus cinacalcet plus low-dose vitamin D provided superior control of iPTH, with low incidence of hypercalcaemia.
doi:10.1093/ndt/gfs018
PMCID: PMC3408938  PMID: 22387567
cinacalcet hydrochloride; paricalcitol; secondary hyperparathyroidism; kidney disease; haemodialysis
17.  The importance of early referral for the treatment of chronic kidney disease: a Danish nationwide cohort study 
BMC Nephrology  2012;13:108.
Background
Many patients with advanced chronic kidney disease are referred late to renal units. This is associated with negative aspects. The purpose of the present study was to characterize late versus early referrals for renal replacement therapy including their renal disease, health care contacts and medical treatment before renal replacement therapy (RRT) and the consequences for RRT modality and mortality.
Methods
Nationwide cohort study including 4495 RRT patients identified in the Danish Nephrology Registry 1999–2006. The cohort was followed to end 2007 by linkage to other national registries. Late referral: follow-up ≤16 weeks in renal unit before RRT start. Cox proportional hazards models were used to estimate the relative risk of mortality or waiting list status within 365 days in late referrals versus early referrals.
Results
A total of 1727 (38%) incident RRT patients were referred late. Among these, 72% were treated in non-nephrology hospital departments and 91% in general practice 2 years to 16 weeks before RRT start. Fewer late referrals received recommended pre-RRT treatment as judged by renin-angiotensin-system blockade: 32% versus 57% or the D-vitamin analogue alfacalcidol: 5% versus 30% (P < .001). Primary RRT modality was peritoneal dialysis: 18% in late versus 32% in early referrals (P < .001), 7% versus 30%, respectively, had an arteriovenous dialysis-fistula (P < .001) and 0.2% versus 6% were on the waiting-list for renal transplantation (P < .001) before RRT start. One-year-mortality was higher in late referrals: hazard ratio 1.55 (CI 95% 1.35–1.78). In a subgroup, 30% (CI 95% 25–35%) late and 9% (CI 95% 6–12%) early referrals had plasma creatinine ≤150% of upper reference limit within 1 to 2 years before RRT start (P < .001).
Conclusions
Late nephrology referrals were well-known to the healthcare system before referral for RRT start and more often had near normal plasma creatinine levels within 2 years before RRT start. They infrequently received available treatment or optimal first RRT modality. An increased effort to identify these patients in the healthcare system in time for proper pre-dialysis care including preparation for RRT is needed.
doi:10.1186/1471-2369-13-108
PMCID: PMC3469388  PMID: 22963236
Chronic kidney failure; Epidemiology; Late diagnosis; Treatment; Renal replacement therapy
18.  Treatment of secondary hyperparathyroidism in kidney disease: what we know and do not know about use of calcimimetics and vitamin D analogs 
There is a growing understanding of the pathophysiology of secondary hyperparathyroidism (SHPT) and a recent emergence of new agents for SHPT treatment in patients with advanced kidney disease. At the same time, appreciation that mineral metabolic derangements promote vascular calcification and contribute to excess mortality, along with recognition of potentially important “non-classical” actions of vitamin D, have prompted the nephrology community to reexamine the use of various SHPT treatments, such as activated vitamin D sterols, phosphate binders, and calcimimetics. In this review, the evidence for treatment of SHPT with calcimimetics and vitamin D analogs is evaluated, with particular consideration given to recent clinical trials that have reported encouraging findings with cinacalcet use. Additionally, several controversies in the pathogenesis and treatment of SHPT are explored. The proposition that calcitriol deficiency is a true pathological state is challenged, the relative importance of the vitamin D receptor and the calcium sensing receptor in parathyroid gland function is summarized, and the potential relevance of non-classical actions of vitamin D for patients with advanced renal disease is examined. Taken collectively, the balance of evidence now supports a treatment paradigm in which calcimimetics are the most appropriate primary treatment for SHPT in the majority of end stage renal disease patients, but which nevertheless acknowledges an important role for modest doses of activated vitamin D sterols.
PMCID: PMC3108756  PMID: 21694914
secondary hyperparathyroidism; vitamin D; vitamin D receptor; calcium sensing receptor; calcimimetics; kidney disease
19.  Calcimimetics or vitamin D analogs for suppressing parathyroid hormone in end-stage renal disease: time for a paradigm shift? 
SUMMARY
Considerable advances have been made in the understanding of the pathogenesis and treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). These include the discovery that the calcium-sensing receptor has an important role in the regulation of parathyroid gland function, the development of calcimimetics to target this receptor, the recognition that vitamin D receptor activation has important functions beyond the regulation of mineral metabolism, the identification of the phosphaturic factor fibroblast growth factor 23 and the contribution of this hormone to disordered phosphate and vitamin D metabolism in CKD. However, despite the availability of calcimimetics, phosphate binders, and vitamin D analogs, control of SHPT remains suboptimal in many patients with advanced kidney disease. In this Review, we explore several unresolved issues regarding the pathogenesis and treatment of SHPT. Specifically, we examine the significance of elevated circulating fibroblast growth factor 23 levels in CKD, question the proposition that calcitriol deficiency is truly a pathological state, explore the relative importance of the vitamin D receptor and the calcium-sensing receptor in parathyroid gland function and evaluate the evidence to support the treatment of SHPT with calcimimetics and vitamin D analogs. Finally, we propose a novel treatment framework in which calcimimetics are the primary therapy for suppressing parathyroid hormone production in patients with end-stage renal disease.
doi:10.1038/ncpneph0977
PMCID: PMC3924719  PMID: 18957950
calcimimetics; calcium-sensing receptor; chronic kidney disease; secondary hyperparathyroidism; vitamin D
20.  Comparison of total parathyroidectomy without autotransplantation and without thymectomy versus total parathyroidectomy with autotransplantation and with thymectomy for secondary hyperparathyroidism: TOPAR PILOT-Trial 
Trials  2007;8:22.
Background
Secondary hyperparathyroidism (sHPT) is common in patients with chronic renal failure. Despite the initiation of new therapeutic agents, several patients will require parathyroidectomy (PTX). Total PTX with autotransplantation of parathyroid tissue (TPTX+AT) and subtotal parathyroidectomy (SPTX) are currently considered as standard surgical procedures in the treatment of sHPT. Recurrencerates after TPTX+AT or SPTX are between 10% and 12% (median follow up: 36 months).
Recent retrospective studies demonstrated a lower rate of recurrent sHPT of 0–4% after PTX without autotransplantation and thymectomy (TPTX) with no higher morbidity when compared to the standard procedures. The observed superiority of TPTX is flawed due to different definitions of outcomes, varying follow up periods and different surgical treatment strategies (with and without thymectomy).
Methods/Design
Patients with sHPT (intact parathyroid hormone > 10 times above the upper limit of normal) on long term dialysis (>12 months) will be randomized either to TPTX or TPTX+AT and followed for 36 months. Outcome parameters are recurrence rates of sHPT, frequencies of reoperations due to refractory hypoparathyroidism or recurrent/persistent hyperparathyroidism, postoperative morbidity and mortality and quality of life. 50 patients per group will be randomized in order to obtain relevant frequencies of outcome parameters that will form the basis for a large scale confirmatory multicentred randomized controlled trial.
Discussion
sHPT is a disease with a high incidence in patients with chronic renal failure. Even a small difference in outcomes will be of clinical relevance. To assess sufficient data about the rate of recurrent sHPT after both methods, a multicentred, randomized controlled trial (MRCT) under standardized conditions is mandatory.
Due to the existing uncertainties the calculated number of patients necessary in each treatment arm (n > 4000) makes it impossible to perform this study as a confirmatory trial. Therefore estimates of different outcomes are performed using a pilot MRCT comparing 50 versus 50 randomized patients in order to establish a hypothesis that can be tested thereafter.
If TPTX proves to have a lower rate of recurrent sHPT, no relevant disadvantages and no higher morbidity than TPTX+AT, current surgical practice may be changed.
Trial registration
International Standard Randomized Controlled Trial Number Registration (ISRCTN86202793)
doi:10.1186/1745-6215-8-22
PMCID: PMC2075519  PMID: 17877805
21.  Impact of cinacalcet introduction on MBD management: the MBD-5D study in Japan 
Kidney International Supplements  2013;3(5):436-441.
Chronic kidney disease-mineral and bone disorder (CKD-MBD) has recently attracted attention in light of its association with clinical outcomes, such as fracture, cardiovascular disease, and mortality. Management of CKD-MBD has therefore come to have a central role in dialysis practice. Cinacalcet, a newly developed drug, has changed prescription patterns in many centers based on different changes in MBD markers than those observed with active vitamin D derivatives. As physicians require real-world evidence to guide their treatment decisions with respect to MBD management, we conducted the Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD-5D), a 3-year observational study involving prevalent hemodialysis patients with secondary hyperparathyroidism (SHPT). Here, we review the results from the MBD-5D and discuss issues of MBD management in the cinacalcet era. Three years since the introduction of cinacalcet, 40% of hemodialysis patients with SHPT have come to use cinacalcet, enjoying marked improvement in management of circulating MBD markers, such as intact parathyroid hormone (PTH), phosphorus, and calcium. Combination therapy with cinacalcet and a vitamin D receptor activator (VDRA) may allow physicians to choose more suitable prescription patterns based on patient characteristics and therapeutic purposes. We observed an additive association between ‘starting cinacalcet' and ‘increased VDRA dose,' with marked improvement in the control of intact PTH levels. Further, the combination pattern of ‘starting cinacalcet' and ‘decreased VDRA dose' was associated with better achievement of target serum phosphorus and calcium levels. Future studies should examine the effect of different prescription patterns for SHPT treatment on clinical outcomes.
doi:10.1038/kisup.2013.91
PMCID: PMC4089738  PMID: 25019026
cinacalcet; dialysis patients; mineral and bone disorder
22.  Cystatin C as an Early Biomarker of Nephropathy in Patients with Type 2 Diabetes 
Journal of Korean Medical Science  2011;26(2):258-263.
This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.
doi:10.3346/jkms.2011.26.2.258
PMCID: PMC3031011  PMID: 21286018
Cystatin C; Diabetic Nephropathies; Albuminuria
23.  Hyperparathyroidism revisited — Old wine in new bottles! 
Aim:
Hyperparathyroidism (HPT) is a condition that occurs due to exacerbated activity of the parathyroid glands. According to the etiology it may be primary, secondary or tertiary hyperparathyroidism (pHPT, sHPT, tHPT). This is a study done to document and evaluate the presentations of primary and secondary HPT, with the associated complications and the approach to management in these patients, at our hospital.
Materials and Methods:
Twenty-one patients with HPT were encountered at Sri Ramachandra Medical College and Research Institute between January 2000 and January 2010. Operative notes, histopathology files, and medical records were used for the retrospective analysis of the patients with HPT. Parathormone, calcium, and phosphate levels were estimated on all the patients, to determine the primary or secondary etiology of this endocrine abnormality. Furthermore, these patients were subjected to ultrasonography (USG) of the neck and Technetium (99 mTc) scan of the neck to identify the parathyroid gland.
Results:
This study revealed that about 76, 19, and 5% of the patients suffered from pHPT, sHPT, and tHPT, respectively, with a female preponderance (62%).The neoplasm in all patients with pHPT was parathyroid adenoma. The patients presented with renal, bony, and menstrual abnormalities. Cases with sHPT had a 15 – 20 year history of chronic kidney disease and they subsequently developed bony abnormalities. Even as all the patients with pHPT were managed with parathyroidectomy, individuals with sHPT were treated conservatively. Postoperative features of hypocalcemia were noted in only one patient.
Conclusion:
This study re-emphasizes that pHPT is more common and is often due to an adenoma. Recent advances in parathormone sampling operatively and minimal access surgery, along with accurate and prompt clinical diagnosis, is necessary for the cure of these patients presenting with obscure abdominal, bony, and renal ailments.
doi:10.4103/2230-8210.83405
PMCID: PMC3156540  PMID: 21897897
Females; hyperparathyroidism; parathyroid adenoma; parathyroidectomy
24.  Efficacy of Alfacalcidol on PEG-IFN/ Ribavirin Combination Therapy for Elderly Patients With Chronic Hepatitis C: A Pilot Study 
Hepatitis Monthly  2013;13(12):e14872.
Background
Serum vitamin D concentration is reported to show a decrease in older age. Patients with chronic hepatitis C (CHC) in Japan are older on average than those in Western countries. Moreover, the outcome of pegylated-interferon (PEG-IFN)/ ribavirin therapy combined with vitamin D in elderly patients is unclear.
Objectives
This pilot study explored the efficacy and safety of alfacalcidol as vitamin D source in PEG-IFN/ ribavirin combination therapy for elderly CHC patients infected with hepatitis C virus genotype 1b.
Patients and Methods
Consecutive twenty CHC patients aged ≥ 65 years were enrolled in this pilot study. Fifteen patients met the inclusion criteria and received PEG-IFN/ ribavirin therapy combined with alfacalcidol. Four-week lead-in of oral alfacalcidol was conducted, and it was subsequently and concurrently administered in PEG-IFN/ ribavirin combination therapy (vitamin D group). Age, gender, and IL28B genotype-matched patients, who received PEG-IFN/ ribavirin alone, were saved as control group (n = 15) to compare the treatment outcome with the vitamin D group.
Results
Subjects consisted of 14 males and 16 females, with a median age of 70 years (65-78). The serum 25 (OH) D3 concentration in females (20 ng/ml, 11-37) was significantly lower than males (27 ng/mL, 13-49) (P = 0.004). Sustained virological response (SVR) rates were 33.3% (5/15) in the control group and 80.0% (12/15) in the vitamin D group, respectively (P = 0.025). While no significant difference was shown in the (SVR) rate between the two groups among males (P = 0.592), in females the SVR rate was significantly higher in the vitamin D group (87.5%, 7/8) than the control group (25.0%, 2/8) (P = 0.041). The relapse rates in the groups with and without alfacalcidol were 7.7% (1/13) and 61.5% (8/13), respectively (P = 0.011). Interestingly, in females, the relapse in the control group was shown in 5 of 7 (71.4%), whereas in the vitamin D group the relapse rate was decreased (1/8, 12.5%) (P = 0.041). No specific adverse events were observed in the vitamin D group.
Conclusions
PEG-IFN/ ribavirin combined with alfacalcidol may be effective and safe in elderly CHC patients. In particular, concomitant administration of alfacalcidol may lead to a reduced relapse rate, and consequently improving the SVR rate in elderly females.
doi:10.5812/hepatmon.14872
PMCID: PMC3877658  PMID: 24403915
1-hydroxycholecalciferol; Vitamin D; Ribavirin; Aged; Hepatitis C, Chronic
25.  Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease 
Mediators of Inflammation  2014;2014:670475.
Paricalcitol, a selective vitamin D receptor (VDR) activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD), has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m2 and an intact parathyroid hormone (PTH) level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours) as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P < 0.01), TNF-α (11.9%, P = 0.01), and IL-6 (7%, P < 0.05), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P = 0.01) and 35.4% (P = 0.01), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.
doi:10.1155/2014/670475
PMCID: PMC3913352  PMID: 24511210

Results 1-25 (843840)