The Experts below are selected from a list of 1458 Experts worldwide ranked by ideXlab platform

Daniel Batlle - One of the best experts on this subject based on the ideXlab platform.

  • Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 ckd
    American Journal of Kidney Diseases, 2006
    Co-Authors: Daniel W Coyne, Muralidhar Acharya, Ping Qiu, Laura A Williams, Daniel Batlle, Hanna E Abboud, Steven J Rosansky, Stephen Z Fadem, Barton S Levine, Dennis L Andress
    Abstract:

    Background: The safety and efficacy of Paricalcitol injection have been well established for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 5. The capsule form of Paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD. Methods: Three randomized, placebo-controlled, phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT. Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m 2 (0.25 and 1.00 mL/s/1.73 m 2 ), an average of 2 consecutive intact parathyroid hormone (iPTH) levels greater than 150 pg/mL (ng/L), 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL (2.00 and 2.50 mmol/L), and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less (≤1.68 mmol/L). Two studies used a thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24 weeks. Dosing was based on serum iPTH, calcium, and phosphorus levels. The primary efficacy end point is 2 consecutive decreases in iPTH levels greater than 30% from baseline. Results: Two hundred twenty patients participated (n = 107, Paricalcitol; n=113, placebo). At least 2 consecutive decreases in iPTH levels of 30% or greater from baseline occurred in 91% of Paricalcitol versus 13% of placebo patients ( P Conclusion: Paricalcitol capsule was well tolerated and effectively decreased iPTH levels with minimal or no impact on calcium levels, phosphorus balance, and kidney function in patients with stages 3 and 4 CKD.

  • antiproteinuric effect of oral Paricalcitol in chronic kidney disease
    Kidney International, 2005
    Co-Authors: Rajiv Agarwal, Muralidhar Acharya, Jin Tian, Richard Hippensteel, Joel Z Melnick, Ping Qiu, Laura A Williams, Daniel Batlle
    Abstract:

    Antiproteinuric effect of oral Paricalcitol in chronic kidney disease. Background Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients. Methods In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral Paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral Paricalcitol ( N = 107, mean dose 9.5 μg/week) or placebo ( N = 113) and followed for up to 24 weeks. In conjunction with other safety measures, proteinuria was measured by dipstick and read by an automated reader at the beginning and end of trial. We subsequently analyzed the dipstick data to evaluate the effect of Paricalcitol on proteinuria. Results At baseline, proteinuria was present in 57 patients randomized to oral Paricalcitol and 61patients randomized to placebo (NS). At the final visit, 29/57 (51%) of the Paricalcitol patients compared to 15/61 (25%) placebo patients had reduction in proteinuria, P = 0.004 (odds for reduction in proteinuria 3.2 times greater for Paricalcitol patients, 95% CI 1.5-6.9). For the patients who had both proteinuria at baseline and parathyroid hormone (PTH) suppression (end point defined as 2 consecutive ≥30% decreases in iPTH from baseline), 27/51 (53%) patients had a reduction in the proteinuria in the Paricalcitol group and 0/7 (0%) had a reduction in proteinuria in the placebo group. Reduction of proteinuria favored patients on Paricalcitol, regardless of age, sex, race, diabetes mellitus, hypertension, or use of therapies to block the renin-angiotensin-aldosterone system (RAAS). Conclusion Our results demonstrate that the reduction in proteinuria was associated with Paricalcitol treatment, and the reduction in proteinuria was independent of concomitant use of agents that block the RAAS. Paricalcitol as a potential pharmacologic means of reducing proteinuria in CKD patients warrants further investigation.

  • Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism
    Kidney International, 2003
    Co-Authors: Michael Amdahl, Francisco Llach, Daniel Batlle, Stuart M Sprague, Carol Taccetta
    Abstract:

    Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Background Management of secondary hyperparathyroidism has included the use of active vitamin D or vitamin D analogs for the suppression of parathyroid hormone (PTH) secretion. Although, these agents are effective, therapy is frequently limited by hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus (Ca × P) product. In clinical studies, Paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia as compared to placebo. A comparative study was undertaken in order to determine whether Paricalcitol provides a therapeutic advantage to calcitriol. Methods A double-blind, randomized, multicenter study comparing the safety and effectiveness of intravenous Paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients was performed. A total of 263 randomized patients were enrolled at domestic and international sites. Following the baseline period, patients with serum Ca × P Results Paricalcitol-treated patients achieved a ≥50% reduction from baseline PTH significantly faster than did the calcitriol-treated patients ( P = 0.025) and achieved a mean reduction of PTH into a desired therapeutic range (100 to 300 pg/mL) at approximately week 18, whereas the calcitriol-treated patients, as a group, were unable to achieve this range. Moreover, Paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and/or increased Ca × P product than calcitriol patients ( P = 0.008). Conclusion Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca × P product than calcitriol therapy.

  • Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism
    Kidney International, 2003
    Co-Authors: Michael Amdahl, Francisco Llach, Daniel Batlle, Stuart M Sprague, Carol Taccetta
    Abstract:

    BACKGROUND: Management of secondary hyperparathyroidism has included the use of active vitamin D or vitamin D analogs for the suppression of parathyroid hormone (PTH) secretion. Although, these agents are effective, therapy is frequently limited by hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus (Ca x P) product. In clinical studies, Paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia as compared to placebo. A comparative study was undertaken in order to determine whether Paricalcitol provides a therapeutic advantage to calcitriol. METHODS: A double-blind, randomized, multicenter study comparing the safety and effectiveness of intravenous Paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients was performed. A total of 263 randomized patients were enrolled at domestic and international sites. Following the baseline period, patients with serum Ca x P or =300 pg/mL were randomly assigned to receive either Paricalcitol or calcitriol in a dose-escalating fashion for up to 32 weeks. Dose adjustments were based on laboratory results for PTH, calcium, and Ca x P. The primary end point was the greater than 50% reduction in baseline PTH. Secondary end points were the occurrence of hypercalcemia and elevated Ca x P product. RESULTS: Paricalcitol-treated patients achieved a > or =50% reduction from baseline PTH significantly faster than did the calcitriol-treated patients (P = 0.025) and achieved a mean reduction of PTH into a desired therapeutic range (100 to 300 pg/mL) at approximately week 18, whereas the calcitriol-treated patients, as a group, were unable to achieve this range. Moreover, Paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and/or increased Ca x P product than calcitriol patients (P = 0.008). CONCLUSION: Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca x P product than calcitriol therapy.

  • suppression of parathyroid hormone secretion in hemodialysis patients comparison of Paricalcitol with calcitriol
    American Journal of Kidney Diseases, 2001
    Co-Authors: Stuart M Sprague, Edgar V Lerma, Daniel Mccormmick, Mohan Abraham, Daniel Batlle
    Abstract:

    Abstract Paricalcitol was introduced recently as an effective alternative to calcitriol for the suppression of parathyroid hormone (PTH) in patients with end-stage renal disease. An international, multicenter, double-blinded, randomized, comparative study of intravenous Paricalcitol and calcitriol was performed. Results from 38 patients at dialysis units affiliated with the Northwestern University Medical School (Chicago and Evanston, IL) are reported here while a report of the full clinical trial is being completed. Results were evaluated in terms of obtaining the following end points: decrease of at least 50% in baseline PTH concentration and the occurrence of hypercalcemia and hyperphosphatemia. Paricalcitol therapy was started at a dose of 0.04 μg/kg and increased by 0.04-μg/kg increments every 4 weeks to a maximum allowable dose of 0.24 μg/kg or until there was at least a 50% decrease in serum PTH concentration. Calcitriol therapy was started at a dose of 0.01 μg/kg and increased by 0.01-μg/kg increments every 4 weeks to a maximum allowable dose of 0.06 μg/kg or until there was at least a 50% decrease in serum PTH concentration. Mean baseline serum PTH, calcium, and phosphorus concentrations were similar. Reductions in PTH occurred more rapidly in subjects administered Paricalcitol compared with calcitriol, with no difference in serum calcium levels throughout the study between groups. The percentage of subjects experiencing severe hyperphosphatemia (serum phosphorus >8.0 mg/dL) was greater in those administered calcitriol compared with Paricalcitol. In conclusion, our data suggest that Paricalcitol reduces PTH levels more rapidly, with fewer episodes of hyperphosphatemia, than intravenous calcitriol.

Stuart M Sprague - One of the best experts on this subject based on the ideXlab platform.

  • a randomized multicenter trial of Paricalcitol versus calcitriol for secondary hyperparathyroidism in stages 3 4 ckd
    Clinical Journal of The American Society of Nephrology, 2014
    Co-Authors: Daniel W Coyne, Seth Goldberg, Mark D Faber, Cybele Ghossein, Stuart M Sprague
    Abstract:

    Background and objectives Calcitriol is used to treat secondary hyperparathyroidism in patients with CKD. Paricalcitol is less calcemic and phosphatemic in preclinical studies and in some trials in dialysis patients, but head-to-head comparisons in nondialysis patients are lacking. A large meta-analysis of trials concluded that these agents did not consistently reduce parathyroid hormone (PTH) and increased the risk of hypercalcemia and hyperphosphatemia. Therefore, the objective of this multicenter trial was to compare the rate of hypercalcemia between calcitriol and Paricalcitol, while suppressing PTH 40%–60%. Design, setting, participants, & measurements Patients with stages 3–4 CKD ( n =110) with a PTH level >120 pg/ml were recruited and randomized to 0.25 μ g/d of calcitriol or 1 μ g/d of Paricalcitol between April 2009 and July 2011. Subsequent dose adjustments were by protocol to achieve 40%–60% PTH suppression below baseline. The primary endpoint was the rate of confirmed hypercalcemia of >10.5 mg/dl between groups. Results Forty-five patients in each group completed the 24 weeks of treatment. Both agents suppressed PTH effectively (−52% with Paricalcitol and −46% with calcitriol; P =0.17), although the Paricalcitol group reached a 40% reduction in PTH sooner at a median 8 weeks (interquartile range [IQR], 4, 12) versus 12 weeks (IQR, 8, 18; P =0.02) and had a lower pill burden of 240 (IQR, 180, 298) versus 292 (IQR, 231, 405; P =0.01). Confirmed hypercalcemia was very low in both groups (three with Paricalcitol and one with calcitriol) and was not significantly different ( P =0.36). Both groups had small increases in calcium and phosphorus levels (0.3–0.4 mg/dl in each electrolyte) and significant decreases in alkaline phosphatase, a marker of high bone turnover, with no significant differences between groups. Conclusions These results show that both calcitriol and Paricalcitol achieved sustained PTH and alkaline phosphatase suppression in stages 3–4 CKD, with small effects on serum calcium and phosphorus and a low incidence of hypercalcemia.

  • Paricalcitol treated patients experience improved hospitalization outcomes compared with calcitriol treated patients in real world clinical settings
    Nephrology Dialysis Transplantation, 2004
    Co-Authors: Deborah Dobrez, Michael Amdahl, Steven E Marx, Joel Z Melnick, Angelo Mathes, Stuart M Sprague
    Abstract:

    BACKGROUND: Abnormalities of serum calcium, phosphorous and intact parathyroid hormone (PTH) are associated with morbidity and mortality in haemodialysis patients. Pharmacologic parenteral vitamin D administration is used to correct these abnormalities; however, the relationship between vitamin D therapies and hospitalizations has never been addressed. METHODS: Healthcare data from January 1999 to November 2001 were analysed for 11,443 adult haemodialysis patients who received at least 10 doses of vitamin D therapy. Multivariate models were used to evaluate the effects of vitamin D therapy on: (i) total number of hospitalizations, (ii) total number of hospital days and (iii) risk of first hospitalization after initiation of vitamin D therapy. RESULTS: When compared with the calcitriol group, the Paricalcitol group had a lower risk of first all-cause hospitalization (14% less likely, P<0.0001), fewer hospitalizations per year (0.642 fewer, P<0.001) and fewer hospital days per year (6.84 fewer, P<0.001). In the Paricalcitol and calcitriol groups, respectively, 5.6 and 41.3% patients switched to another vitamin D compound. For those patients who started and remained on the same vitamin D product, Paricalcitol-treated patients experienced 0.846 fewer hospitalizations per year and 9.17 fewer hospital days per year, P<0.001 for both. The Paricalcitol group also had a lower risk of first PTH-related hospitalizations, fewer PTH-related annual hospitalizations and fewer days per year. CONCLUSION: Paricalcitol-treated patients experienced fewer hospitalizations and hospital days per year when compared with calcitriol-treated patients. Initiating vitamin D therapy with Paricalcitol may result in overall savings of approximately 7600-11,000 US dollars per patient per year. A randomized, controlled, blinded study would be valuable in confirming and understanding these results.

  • Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism
    Kidney International, 2003
    Co-Authors: Michael Amdahl, Francisco Llach, Daniel Batlle, Stuart M Sprague, Carol Taccetta
    Abstract:

    Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Background Management of secondary hyperparathyroidism has included the use of active vitamin D or vitamin D analogs for the suppression of parathyroid hormone (PTH) secretion. Although, these agents are effective, therapy is frequently limited by hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus (Ca × P) product. In clinical studies, Paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia as compared to placebo. A comparative study was undertaken in order to determine whether Paricalcitol provides a therapeutic advantage to calcitriol. Methods A double-blind, randomized, multicenter study comparing the safety and effectiveness of intravenous Paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients was performed. A total of 263 randomized patients were enrolled at domestic and international sites. Following the baseline period, patients with serum Ca × P Results Paricalcitol-treated patients achieved a ≥50% reduction from baseline PTH significantly faster than did the calcitriol-treated patients ( P = 0.025) and achieved a mean reduction of PTH into a desired therapeutic range (100 to 300 pg/mL) at approximately week 18, whereas the calcitriol-treated patients, as a group, were unable to achieve this range. Moreover, Paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and/or increased Ca × P product than calcitriol patients ( P = 0.008). Conclusion Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca × P product than calcitriol therapy.

  • Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism
    Kidney International, 2003
    Co-Authors: Michael Amdahl, Francisco Llach, Daniel Batlle, Stuart M Sprague, Carol Taccetta
    Abstract:

    BACKGROUND: Management of secondary hyperparathyroidism has included the use of active vitamin D or vitamin D analogs for the suppression of parathyroid hormone (PTH) secretion. Although, these agents are effective, therapy is frequently limited by hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus (Ca x P) product. In clinical studies, Paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia as compared to placebo. A comparative study was undertaken in order to determine whether Paricalcitol provides a therapeutic advantage to calcitriol. METHODS: A double-blind, randomized, multicenter study comparing the safety and effectiveness of intravenous Paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients was performed. A total of 263 randomized patients were enrolled at domestic and international sites. Following the baseline period, patients with serum Ca x P or =300 pg/mL were randomly assigned to receive either Paricalcitol or calcitriol in a dose-escalating fashion for up to 32 weeks. Dose adjustments were based on laboratory results for PTH, calcium, and Ca x P. The primary end point was the greater than 50% reduction in baseline PTH. Secondary end points were the occurrence of hypercalcemia and elevated Ca x P product. RESULTS: Paricalcitol-treated patients achieved a > or =50% reduction from baseline PTH significantly faster than did the calcitriol-treated patients (P = 0.025) and achieved a mean reduction of PTH into a desired therapeutic range (100 to 300 pg/mL) at approximately week 18, whereas the calcitriol-treated patients, as a group, were unable to achieve this range. Moreover, Paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and/or increased Ca x P product than calcitriol patients (P = 0.008). CONCLUSION: Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca x P product than calcitriol therapy.

  • suppression of parathyroid hormone secretion in hemodialysis patients comparison of Paricalcitol with calcitriol
    American Journal of Kidney Diseases, 2001
    Co-Authors: Stuart M Sprague, Edgar V Lerma, Daniel Mccormmick, Mohan Abraham, Daniel Batlle
    Abstract:

    Abstract Paricalcitol was introduced recently as an effective alternative to calcitriol for the suppression of parathyroid hormone (PTH) in patients with end-stage renal disease. An international, multicenter, double-blinded, randomized, comparative study of intravenous Paricalcitol and calcitriol was performed. Results from 38 patients at dialysis units affiliated with the Northwestern University Medical School (Chicago and Evanston, IL) are reported here while a report of the full clinical trial is being completed. Results were evaluated in terms of obtaining the following end points: decrease of at least 50% in baseline PTH concentration and the occurrence of hypercalcemia and hyperphosphatemia. Paricalcitol therapy was started at a dose of 0.04 μg/kg and increased by 0.04-μg/kg increments every 4 weeks to a maximum allowable dose of 0.24 μg/kg or until there was at least a 50% decrease in serum PTH concentration. Calcitriol therapy was started at a dose of 0.01 μg/kg and increased by 0.01-μg/kg increments every 4 weeks to a maximum allowable dose of 0.06 μg/kg or until there was at least a 50% decrease in serum PTH concentration. Mean baseline serum PTH, calcium, and phosphorus concentrations were similar. Reductions in PTH occurred more rapidly in subjects administered Paricalcitol compared with calcitriol, with no difference in serum calcium levels throughout the study between groups. The percentage of subjects experiencing severe hyperphosphatemia (serum phosphorus >8.0 mg/dL) was greater in those administered calcitriol compared with Paricalcitol. In conclusion, our data suggest that Paricalcitol reduces PTH levels more rapidly, with fewer episodes of hyperphosphatemia, than intravenous calcitriol.

Miklos Z Molnar - One of the best experts on this subject based on the ideXlab platform.

  • administered Paricalcitol dose and survival in hemodialysis patients a marginal structural model analysis
    Pharmacoepidemiology and Drug Safety, 2012
    Co-Authors: Jessica E Miller, Miklos Z Molnar, Csaba P Kovesdy, Joshua J Zaritsky, Elani Streja, Isidro B Salusky, Onyebuchi A Arah, Kamyar Kalantarzadeh
    Abstract:

    Several observational studies have indicated that vitamin D receptor activators (VDRA), including Paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients. However, patients with higher serum parathyroid hormone, a surrogate of higher death risk, are usually given higher VDRA doses, which can lead to confounding by indication and attenuate the expected survival advantage of high VDRA doses.We examined mortality-predictability of low (>1 but <10 µg/week) versus high (≥10 µg/week) dose of administered Paricalcitol over time in a contemporary cohort of 15 442 MHD patients (age 64 ± 15 years, 55% men, 44% diabetes, 35% African-Americans) from all DaVita dialysis clinics across the USA (7/2001-6/2006 with survival follow-ups until 6/2007) using conventional Cox regression, propensity score (PS) matching, and marginal structural model (MSM) analyses.In our conventional Cox models and PS matching models, low dose of Paricalcitol was not associated with mortality either in baseline (hazard ratio (HR): 1.03, 95% confidence interval (CI): (0.97-1.09)) and (HR: 0.99, 95%CI:(0.86-1.14)) or time-dependent (HR: 1.04, 95%CI: (0.98-1.10)) and (HR: 1.12, 95%CI: (0.98-1.28)) models, respectively. In contrast, compared to high dose of Paricalcitol, low dose was associated with a 26% higher risk of mortality (HR: 1.26, 95%CI: (1.19-1.35)) in MSM. The association between dose of Paricalcitol and mortality was robust in almost all subgroups of patients using MSMs.Higher dose of Paricalcitol appears causally associated with greater survival in MHD patients. Randomized controlled trials need to verify the survival effect of Paricalcitol dose in MHD patients are indicated.

  • administered Paricalcitol dose and survival in hemodialysis patients a marginal structural model analysis
    Pharmacoepidemiology and Drug Safety, 2012
    Co-Authors: Jessica E Miller, Miklos Z Molnar, Csaba P Kovesdy, Joshua J Zaritsky, Elani Streja, Isidro B Salusky, Onyebuchi A Arah
    Abstract:

    Author(s): Miller, Jessica E; Molnar, Miklos Z; Kovesdy, Csaba P; Zaritsky, Joshua J; Streja, Elani; Salusky, Isidro; Arah, Onyebuchi A; Kalantar-Zadeh, Kamyar | Abstract: PurposeSeveral observational studies have indicated that vitamin D receptor activators (VDRA), including Paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients. However, patients with higher serum parathyroid hormone, a surrogate of higher death risk, are usually given higher VDRA doses, which can lead to confounding by indication and attenuate the expected survival advantage of high VDRA doses.MethodsWe examined mortality-predictability of low (g1 but l10 µg/week) versus high (≥10 µg/week) dose of administered Paricalcitol over time in a contemporary cohort of 15 442 MHD patients (age 64 ± 15 years, 55% men, 44% diabetes, 35% African-Americans) from all DaVita dialysis clinics across the USA (7/2001-6/2006 with survival follow-ups until 6/2007) using conventional Cox regression, propensity score (PS) matching, and marginal structural model (MSM) analyses.ResultsIn our conventional Cox models and PS matching models, low dose of Paricalcitol was not associated with mortality either in baseline (hazard ratio (HR): 1.03, 95% confidence interval (CI): (0.97-1.09)) and (HR: 0.99, 95%CI:(0.86-1.14)) or time-dependent (HR: 1.04, 95%CI: (0.98-1.10)) and (HR: 1.12, 95%CI: (0.98-1.28)) models, respectively. In contrast, compared to high dose of Paricalcitol, low dose was associated with a 26% higher risk of mortality (HR: 1.26, 95%CI: (1.19-1.35)) in MSM. The association between dose of Paricalcitol and mortality was robust in almost all subgroups of patients using MSMs.ConclusionsHigher dose of Paricalcitol appears causally associated with greater survival in MHD patients. Randomized controlled trials need to verify the survival effect of Paricalcitol dose in MHD patients are indicated.

Michael Amdahl - One of the best experts on this subject based on the ideXlab platform.

  • study design and baseline characteristics of the
    2016
    Co-Authors: Markus Ketteler, Kevin J Martin, Michael Amdahl, Mario Cozzolino, David Goldsmith, Amit Sharma, Samina Khan, Emily Dumas, Steven Marx, Paul Audhya
    Abstract:

    Paricalcitol versus cinacalcet plus low-dose vitamin D for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis

  • 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
    Co-Authors: Markus Ketteler, Kevin J Martin, Michael Amdahl, Mario Cozzolino, David Goldsmith, Amit Sharma, Steven E Marx, Myles Wolf, Samina Khan
    Abstract:

    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 ¼ 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 ¼ 0.260). Cochran–Mantel–Haenszel analysis, controlling for stratum, revealed overall superiority of Paricalcitol (56.0%) over cinacalcet (38.2%; P ¼ 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.

  • selective vitamin d receptor activation with Paricalcitol for reduction of albuminuria in patients with type 2 diabetes vital study a randomised controlled trial
    The Lancet, 2010
    Co-Authors: Dick De Zeeuw, Yili Pritchett, Rajiv Agarwal, Daniel W Coyne, Michael Amdahl, Paul Audhya, Tushar S Garimella, Hanshenrik Parving, Giuseppe Remuzzi, Eberhard Ritz
    Abstract:

    Summary Background Despite treatment with renin–angiotensin–aldosterone system (RAAS) inhibitors, patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria. We aimed to assess whether Paricalcitol could be used to reduce albuminuria in patients with diabetic nephropathy. Methods In this multinational, placebo-controlled, double-blind trial, we enrolled patients with type 2 diabetes and albuminuria who were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Patients were assigned (1:1:1) by computer-generated randomisation sequence to receive 24 weeks' treatment with placebo, 1 μg/day Paricalcitol, or 2 μg/day Paricalcitol. The primary endpoint was the percentage change in geometric mean urinary albumin-to-creatinine ratio (UACR) from baseline to last measurement during treatment for the combined Paricalcitol groups versus the placebo group. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00421733. Findings Between February, 2007, and October, 2008, 281 patients were enrolled and assigned to receive placebo (n=93), 1 μg Paricalcitol (n=93), or 2 μg Paricalcitol (n=95); 88 patients on placebo, 92 on 1 μg Paricalcitol, and 92 on 2 μg Paricalcitol received at least one dose of study drug, and had UACR data at baseline and at least one timepoint during treatment, and so were included in the primary analysis. Change in UACR was: −3% (from 61 to 60 mg/mmol; 95% CI −16 to 13) in the placebo group; −16% (from 62 to 51 mg/mmol; −24 to −9) in the combined Paricalcitol groups, with a between-group difference versus placebo of −15% (95% CI −28 to 1; p=0·071); −14% (from 63 to 54 mg/mmol; −24 to −1) in the 1 μg Paricalcitol group, with a between-group difference versus placebo of −11% (95% CI −27 to 8; p=0·23); and −20% (from 61 to 49 mg/mmol; −30 to −8) in the 2 μg Paricalcitol group, with a between-group difference versus placebo of −18% (95% CI −32 to 0; p=0·053). Patients on 2 μg Paricalcitol showed an early, sustained reduction in UACR, ranging from −18% to −28% (p=0·014 vs placebo). Incidence of hypercalcaemia, adverse events, and serious adverse events was similar between groups receiving Paricalcitol versus placebo. Interpretation Addition of 2 μg/day Paricalcitol to RAAS inhibition safely lowers residual albuminuria in patients with diabetic nephropathy, and could be a novel approach to lower residual renal risk in diabetes. Funding Abbott.

  • Paricalcitol treated patients experience improved hospitalization outcomes compared with calcitriol treated patients in real world clinical settings
    Nephrology Dialysis Transplantation, 2004
    Co-Authors: Deborah Dobrez, Michael Amdahl, Steven E Marx, Joel Z Melnick, Angelo Mathes, Stuart M Sprague
    Abstract:

    BACKGROUND: Abnormalities of serum calcium, phosphorous and intact parathyroid hormone (PTH) are associated with morbidity and mortality in haemodialysis patients. Pharmacologic parenteral vitamin D administration is used to correct these abnormalities; however, the relationship between vitamin D therapies and hospitalizations has never been addressed. METHODS: Healthcare data from January 1999 to November 2001 were analysed for 11,443 adult haemodialysis patients who received at least 10 doses of vitamin D therapy. Multivariate models were used to evaluate the effects of vitamin D therapy on: (i) total number of hospitalizations, (ii) total number of hospital days and (iii) risk of first hospitalization after initiation of vitamin D therapy. RESULTS: When compared with the calcitriol group, the Paricalcitol group had a lower risk of first all-cause hospitalization (14% less likely, P<0.0001), fewer hospitalizations per year (0.642 fewer, P<0.001) and fewer hospital days per year (6.84 fewer, P<0.001). In the Paricalcitol and calcitriol groups, respectively, 5.6 and 41.3% patients switched to another vitamin D compound. For those patients who started and remained on the same vitamin D product, Paricalcitol-treated patients experienced 0.846 fewer hospitalizations per year and 9.17 fewer hospital days per year, P<0.001 for both. The Paricalcitol group also had a lower risk of first PTH-related hospitalizations, fewer PTH-related annual hospitalizations and fewer days per year. CONCLUSION: Paricalcitol-treated patients experienced fewer hospitalizations and hospital days per year when compared with calcitriol-treated patients. Initiating vitamin D therapy with Paricalcitol may result in overall savings of approximately 7600-11,000 US dollars per patient per year. A randomized, controlled, blinded study would be valuable in confirming and understanding these results.

  • Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism
    Kidney International, 2003
    Co-Authors: Michael Amdahl, Francisco Llach, Daniel Batlle, Stuart M Sprague, Carol Taccetta
    Abstract:

    Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Background Management of secondary hyperparathyroidism has included the use of active vitamin D or vitamin D analogs for the suppression of parathyroid hormone (PTH) secretion. Although, these agents are effective, therapy is frequently limited by hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus (Ca × P) product. In clinical studies, Paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia as compared to placebo. A comparative study was undertaken in order to determine whether Paricalcitol provides a therapeutic advantage to calcitriol. Methods A double-blind, randomized, multicenter study comparing the safety and effectiveness of intravenous Paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients was performed. A total of 263 randomized patients were enrolled at domestic and international sites. Following the baseline period, patients with serum Ca × P Results Paricalcitol-treated patients achieved a ≥50% reduction from baseline PTH significantly faster than did the calcitriol-treated patients ( P = 0.025) and achieved a mean reduction of PTH into a desired therapeutic range (100 to 300 pg/mL) at approximately week 18, whereas the calcitriol-treated patients, as a group, were unable to achieve this range. Moreover, Paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and/or increased Ca × P product than calcitriol patients ( P = 0.008). Conclusion Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca × P product than calcitriol therapy.

Suk Young Kim - One of the best experts on this subject based on the ideXlab platform.

  • Paricalcitol pretreatment attenuates renal ischemia reperfusion injury via prostaglandin e2 receptor ep4 pathway
    Oxidative Medicine and Cellular Longevity, 2017
    Co-Authors: Yu Ah Hong, Keum Jin Yang, So Young Jung, Ki Cheol Park, Hyunsu Choi, Sang Ju Lee, Yoon Kyung Chang, Cheol Whee Park, Chul Woo Yang, Suk Young Kim
    Abstract:

    The protective mechanism of Paricalcitol remains unclear in renal ischemia-reperfusion (IR) injury. We investigated the renoprotective effects of Paricalcitol in IR injury through the prostaglandin E2 (PGE2) receptor EP4. Paricalcitol was injected into IR-exposed HK-2 cells and mice subjected to bilateral kidney ischemia for 23 min and reperfusion for 24 hr. Paricalcitol prevented IR-induced cell death and EP4 antagonist cotreatment offset these protective effects. Paricalcitol increased phosphorylation of Akt and cyclic AMP responsive element binding protein (CREB) and suppressed nuclear factor-κB (NF-κB) in IR-exposed cells and cotreatment of EP4 antagonist or EP4 small interfering RNA blunted these signals. In vivo studies showed that Paricalcitol improved renal dysfunction and tubular necrosis after IR injury and cotreatment with EP4 antagonist inhibited the protective effects of Paricalcitol. Phosphorylation of Akt was increased and nuclear translocation of p65 NF-κB was decreased in Paricalcitol-treated mice with IR injury, which was reversed by EP4 blockade. Paricalcitol decreased oxidative stress and apoptosis in renal IR injury. Paricalcitol also attenuated the infiltration of inflammatory cells and production of proinflammatory cytokines after IR injury. EP4 antagonist abolished these antioxidant, anti-inflammatory, and antiapoptotic effects. The EP4 plays a pivotal role in the protective effects of Paricalcitol in renal IR injury.

  • Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E₂ receptor EP4
    The Korean Society of Nephrology, 2017
    Co-Authors: Yu Ah Hong, Keum Jin Yang, So Young Jung, Yoon Kyung Chang, Cheol Whee Park, Chul Woo Yang, Suk Young Kim, Hyeon Seok Hwang
    Abstract:

    Background: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether Paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin E₂ (PGE₂) receptor EP4. Methods: Human renal tubular epithelial (HK-2) cells were pretreated with Paricalcitol (2 ng/mL) for 1 hour and exposed to LPS (1 μg/mL). The effects of Paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA) were investigated. Results: The expression of cyclooxygenase-2, PGE₂, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with Paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB (NF-κB) were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with Paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of Paricalcitol on p65 NF-κB nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by Paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. Conclusion: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after Paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury