BACKGROUND Parathyroid hormone(PTH)levels may fluctuate in patients undergoing hemodialysis because of changes in calcium,phosphorus,and vitamin D levels.For these patients,the“Kidney Disease:Improving Global Outcome...BACKGROUND Parathyroid hormone(PTH)levels may fluctuate in patients undergoing hemodialysis because of changes in calcium,phosphorus,and vitamin D levels.For these patients,the“Kidney Disease:Improving Global Outcomes”clinical practice guidelines recommend PTH levels be maintained in the range of two to nine times of the upper normal limit.Maintaining this balance is critical to prevent renal osteodystrophy.When the severity of hyperparathyroidism exceeds the recommended limits,vitamin D receptor agonists may be used for lowering PTH levels.Paricalcitol,as a biologically active vitamin D analog,is a selective activator of vitamin D responsive pathways.Both calcitriol and paricalcitol can be used as PTHlowering agents.There is conflicting data about their comparative effectiveness for controlling hyperparathyroidism in patients undergoing hemodialysis and a meta-analysis revealed no differences between the two.AIM To give real world data comparing paricalcitol and calcitriol as PTH-lowering agents in patients undergoing hemodialysis.METHODS Patients undergoing hemodialysis whose PTH levels exceeded nine times of the upper normal limit were enrolled in the study.Depending on patient preferences,they were either given calcitriol or paricalcitol.Intravenous calcitriol was given 2μg at the end of each dialysis sessions,and intravenous paricalcitol was administered as 5μg twice per week.Demographic data,calcium-phosphorus levels,change in PTH levels in 6 months,and ratios of 25%and 50%reductions in PTH levels were compared between the two groups.RESULTS A total of 21 patients were enrolled in this comparative study,eight patients received paricalcitol and 13 were prescribed calcitriol.A 50%reduction in PTH levels could be achieved in five patients in the paricalcitol group(62.5%);only one patient in the calcitriol group achieved the same reduction(7.6%).The difference was statistically significant(P=0.014).However,there was no difference in the ratio of patients who had a 25%reduction in PTH levels(87.5%vs 38.4%;P=0.067).PTH levels could be maintained in the targeted range in 87.5%of the patients in the paricalcitol group and in 69.2%of the patients in the calcitriol group(P=0.36).However,PTH could be better suppressed under paricalcitol.Clinically important hyperphosphatemia or hypercalcemia was not observed in either the paricalcitol or the calcitriol groups.CONCLUSION Although the PTH lowering effect of paricalcitol is stronger than calcitriol,both may help maintain PTH levels in the targeted range.Paricalcitol may be preferred for patients who have very high levels of PTH because it seems to cause a faster decline.Calcitriol may be preferred for a slower and limited decline.Prospective further studies with larger samples may be needed for a better comparison.展开更多
BACKGROUND Diabetic nephropathy(DN)is frequently seen in the development of diabetes mellitus,and its pathogenic factors are complicated.Its current treatment is controversial,and there is a lack of a relevant efficac...BACKGROUND Diabetic nephropathy(DN)is frequently seen in the development of diabetes mellitus,and its pathogenic factors are complicated.Its current treatment is controversial,and there is a lack of a relevant efficacy prediction model.AIM To determine the effects of paricalcitol combined with hemodiafiltration on bonemetabolism-related indexes in patients with DN and chronic renal failure(CRF),and to construct an efficacy prediction model.METHODS We retrospectively analyzed 422 patients with DN and CRF treated in Cangzhou Central Hospital between May 2020 and May 2022.We selected 94 patients who met the inclusion and exclusion criteria.Patients were assigned to a dialysis group(n=45)and a joint group(n=49)in relation to therapeutic regimen.The clinical efficacy of the two groups was compared after treatment.The changes in laboratory indexes after treatment were evaluated,and the two groups were compared for the incidence of adverse reactions.The predictive value of laboratory indexes on the clinical efficacy on patients was analyzed.RESULTS The dialysis group showed a notably worse improvement in clinical efficacy than the joint group(P=0.017).After treatment,the joint group showed notably lower serum levels of serum creatinine,uric acid(UA)and blood urea nitrogen(BUN)than the dialysis group(P<0.05).After treatment,the joint group had lower serum levels of phosphorus,procollagen type I amino-terminal propeptide(PINP)and intact parathyroid hormone than the dialysis group,but a higher calcium level(P<0.001).Both groups had a similar incidence of adverse reactions(P>0.05).According to least absolute shrinkage and selection operator regression analysis,UA,BUN,phosphorus and PINP were related to treatment efficacy.According to further comparison,the non-improvement group had higher risk scores than the improvement group(P<0.0001),and the area under the curve of the risk score in efficacy prediction was 0.945.CONCLUSION For treatment of CRF and DN,combined paricalcitol and hemodiafiltration can deliver higher clinical efficacy and improve the bone metabolism of patients,with good safety.展开更多
BACKGROUND Secondary hyperparathyroidism(SHPT)is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients.SHPT can increase bone fragility and calcification of bloo...BACKGROUND Secondary hyperparathyroidism(SHPT)is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients.SHPT can increase bone fragility and calcification of blood vessels and soft tissues,which greatly increases the risk of death.AIM To discuss the outcome,safety and other potential benefits of paricalcitol injection in hemodialysis patients with SHPT.METHODS We recruited 40 patients who received hemodialysis at our hospital for chronic renal failure with SHPT between March and December 2019.They received paricalcitol injection for 24 wk(starting dose,0.06–0.08μg/kg),three times per week.They were followed up at the baseline(week 0),week 4,week 12 and week 24.The primary outcome indicator was the percentage of patients with a>30%decrease in intact parathyroid hormone(iPTH)levels at week 24 compared with the baseline.The secondary outcome indicators included percentage decrease in iPTH levels at week 24,standard-reaching rate of iPTH(percentage of patients with iPTH down to 130–585 pg/mL),changes in serum levels of calcium(Ca),phosphate(P),Ca×P product,alkaline phosphatase(ALP),creatinine(Cre),hemoglobin(Hb),and C-reactive protein(CRP),and incidence of adverse events(AEs).RESULTS After 24 wk of treatment,iPTH levels decreased significantly(598.88±381.29 pg/mL vs 888.84±376.88 pg/mL,P<0.05).More than 30%decrease of iPTH was found in 21 of 36(58.33%)patients.The average decrease in iPTH levels was 32.16±4.33%;the standard-reaching rate of iPTH levels was 66.67%(24/36);and ALP levels decreased significantly compared with the baseline(113.72±41.73 IU/L vs 133.45±56.86 IU/L)(t=2.798,P<0.05).There were no significant differences in the serum levels of calcium,Hb,Cre and CRP compared with the baseline(P>0.05).After 24 wk of treatment,serum P levels decreased compared with the baseline(1.91±0.40 mmol/L vs 2.16±0.66 mmol/L)(t=2.830,P<0.05).Ca×P product decreased significantly compared with the baseline(56.38±13.22 mg2/dL2 vs 63.97±20.30 mg2/dL2)(t=2.717,P<0.05).No serious adverse events occurred.CONCLUSION Paricalcitol was a safe and effective treatment for hemodialysis patients with SHPT.It decreased serum levels of iPTH,ALP and P and maintained stability of serum Ca levels.展开更多
AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in Apo E-knock out mice. METHODS: Animals treated for 4 mo as group(1) Apo E-knock out plus vehicle, g...AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in Apo E-knock out mice. METHODS: Animals treated for 4 mo as group(1) Apo E-knock out plus vehicle, group(2) Apo E-knock out plus paricalcitol(200 ng thrice a week),(3) Apo Eknock out plus enalapril(30 mg/L),(4) Apo E-knock out plus paricalcitol plus enalapril and(5) normal. Blood pressure(BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses. RESULTS: Apo E-deficient mice developed high BP(127 ± 3 mm Hg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22 phox, manganese-superoxide dismutase, inducible nitric oxide synthase(NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, Cu Zn-SOD and e NOS levels significantly depleted in Apo E-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in Apo E-knock out animals. CONCLUSION: Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.展开更多
Active vitamin D (1,25D) is a fat-soluble vitamin that is mainly produced in the skin by the conversion of 7-dehydrocholesterol under ultraviolet light stimulation.Its role in calcium homeostasis,bone growth, and prev...Active vitamin D (1,25D) is a fat-soluble vitamin that is mainly produced in the skin by the conversion of 7-dehydrocholesterol under ultraviolet light stimulation.Its role in calcium homeostasis,bone growth, and prevention of rickets and osteomalacia has been known for over two hundred years.Its展开更多
Paricalcitol,an analog of vitamin D,is used as a drug for the prevention and treatment of secondary hyperparathyroidism.In this paper,a new strategy for the synthesis of paricalcitol is described.This approach include...Paricalcitol,an analog of vitamin D,is used as a drug for the prevention and treatment of secondary hyperparathyroidism.In this paper,a new strategy for the synthesis of paricalcitol is described.This approach includes three main improvements:one-pot regioselective ozonization cleavage of the side-chain and methylene at C-19,free-radical reduction removal of the OH group formed at C-19,and side-chain assembly using a Wittig reaction.These are all new strategies for the synthesis of 19-nor-vitamin D2 compounds.展开更多
文摘BACKGROUND Parathyroid hormone(PTH)levels may fluctuate in patients undergoing hemodialysis because of changes in calcium,phosphorus,and vitamin D levels.For these patients,the“Kidney Disease:Improving Global Outcomes”clinical practice guidelines recommend PTH levels be maintained in the range of two to nine times of the upper normal limit.Maintaining this balance is critical to prevent renal osteodystrophy.When the severity of hyperparathyroidism exceeds the recommended limits,vitamin D receptor agonists may be used for lowering PTH levels.Paricalcitol,as a biologically active vitamin D analog,is a selective activator of vitamin D responsive pathways.Both calcitriol and paricalcitol can be used as PTHlowering agents.There is conflicting data about their comparative effectiveness for controlling hyperparathyroidism in patients undergoing hemodialysis and a meta-analysis revealed no differences between the two.AIM To give real world data comparing paricalcitol and calcitriol as PTH-lowering agents in patients undergoing hemodialysis.METHODS Patients undergoing hemodialysis whose PTH levels exceeded nine times of the upper normal limit were enrolled in the study.Depending on patient preferences,they were either given calcitriol or paricalcitol.Intravenous calcitriol was given 2μg at the end of each dialysis sessions,and intravenous paricalcitol was administered as 5μg twice per week.Demographic data,calcium-phosphorus levels,change in PTH levels in 6 months,and ratios of 25%and 50%reductions in PTH levels were compared between the two groups.RESULTS A total of 21 patients were enrolled in this comparative study,eight patients received paricalcitol and 13 were prescribed calcitriol.A 50%reduction in PTH levels could be achieved in five patients in the paricalcitol group(62.5%);only one patient in the calcitriol group achieved the same reduction(7.6%).The difference was statistically significant(P=0.014).However,there was no difference in the ratio of patients who had a 25%reduction in PTH levels(87.5%vs 38.4%;P=0.067).PTH levels could be maintained in the targeted range in 87.5%of the patients in the paricalcitol group and in 69.2%of the patients in the calcitriol group(P=0.36).However,PTH could be better suppressed under paricalcitol.Clinically important hyperphosphatemia or hypercalcemia was not observed in either the paricalcitol or the calcitriol groups.CONCLUSION Although the PTH lowering effect of paricalcitol is stronger than calcitriol,both may help maintain PTH levels in the targeted range.Paricalcitol may be preferred for patients who have very high levels of PTH because it seems to cause a faster decline.Calcitriol may be preferred for a slower and limited decline.Prospective further studies with larger samples may be needed for a better comparison.
文摘BACKGROUND Diabetic nephropathy(DN)is frequently seen in the development of diabetes mellitus,and its pathogenic factors are complicated.Its current treatment is controversial,and there is a lack of a relevant efficacy prediction model.AIM To determine the effects of paricalcitol combined with hemodiafiltration on bonemetabolism-related indexes in patients with DN and chronic renal failure(CRF),and to construct an efficacy prediction model.METHODS We retrospectively analyzed 422 patients with DN and CRF treated in Cangzhou Central Hospital between May 2020 and May 2022.We selected 94 patients who met the inclusion and exclusion criteria.Patients were assigned to a dialysis group(n=45)and a joint group(n=49)in relation to therapeutic regimen.The clinical efficacy of the two groups was compared after treatment.The changes in laboratory indexes after treatment were evaluated,and the two groups were compared for the incidence of adverse reactions.The predictive value of laboratory indexes on the clinical efficacy on patients was analyzed.RESULTS The dialysis group showed a notably worse improvement in clinical efficacy than the joint group(P=0.017).After treatment,the joint group showed notably lower serum levels of serum creatinine,uric acid(UA)and blood urea nitrogen(BUN)than the dialysis group(P<0.05).After treatment,the joint group had lower serum levels of phosphorus,procollagen type I amino-terminal propeptide(PINP)and intact parathyroid hormone than the dialysis group,but a higher calcium level(P<0.001).Both groups had a similar incidence of adverse reactions(P>0.05).According to least absolute shrinkage and selection operator regression analysis,UA,BUN,phosphorus and PINP were related to treatment efficacy.According to further comparison,the non-improvement group had higher risk scores than the improvement group(P<0.0001),and the area under the curve of the risk score in efficacy prediction was 0.945.CONCLUSION For treatment of CRF and DN,combined paricalcitol and hemodiafiltration can deliver higher clinical efficacy and improve the bone metabolism of patients,with good safety.
基金Supported by 2019 Anhui University Natural Science Research Project,No.KJ2019A0094,No.KJ2019A0095Huainan City"50 Science and Technology Stars"Innovation Team Projectand Scientific Research Platform of Huainan Science and Technology Bureau,No.2017G32.
文摘BACKGROUND Secondary hyperparathyroidism(SHPT)is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients.SHPT can increase bone fragility and calcification of blood vessels and soft tissues,which greatly increases the risk of death.AIM To discuss the outcome,safety and other potential benefits of paricalcitol injection in hemodialysis patients with SHPT.METHODS We recruited 40 patients who received hemodialysis at our hospital for chronic renal failure with SHPT between March and December 2019.They received paricalcitol injection for 24 wk(starting dose,0.06–0.08μg/kg),three times per week.They were followed up at the baseline(week 0),week 4,week 12 and week 24.The primary outcome indicator was the percentage of patients with a>30%decrease in intact parathyroid hormone(iPTH)levels at week 24 compared with the baseline.The secondary outcome indicators included percentage decrease in iPTH levels at week 24,standard-reaching rate of iPTH(percentage of patients with iPTH down to 130–585 pg/mL),changes in serum levels of calcium(Ca),phosphate(P),Ca×P product,alkaline phosphatase(ALP),creatinine(Cre),hemoglobin(Hb),and C-reactive protein(CRP),and incidence of adverse events(AEs).RESULTS After 24 wk of treatment,iPTH levels decreased significantly(598.88±381.29 pg/mL vs 888.84±376.88 pg/mL,P<0.05).More than 30%decrease of iPTH was found in 21 of 36(58.33%)patients.The average decrease in iPTH levels was 32.16±4.33%;the standard-reaching rate of iPTH levels was 66.67%(24/36);and ALP levels decreased significantly compared with the baseline(113.72±41.73 IU/L vs 133.45±56.86 IU/L)(t=2.798,P<0.05).There were no significant differences in the serum levels of calcium,Hb,Cre and CRP compared with the baseline(P>0.05).After 24 wk of treatment,serum P levels decreased compared with the baseline(1.91±0.40 mmol/L vs 2.16±0.66 mmol/L)(t=2.830,P<0.05).Ca×P product decreased significantly compared with the baseline(56.38±13.22 mg2/dL2 vs 63.97±20.30 mg2/dL2)(t=2.717,P<0.05).No serious adverse events occurred.CONCLUSION Paricalcitol was a safe and effective treatment for hemodialysis patients with SHPT.It decreased serum levels of iPTH,ALP and P and maintained stability of serum Ca levels.
基金Supported by A research grant from Abbott Pharmaceutical,United States
文摘AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in Apo E-knock out mice. METHODS: Animals treated for 4 mo as group(1) Apo E-knock out plus vehicle, group(2) Apo E-knock out plus paricalcitol(200 ng thrice a week),(3) Apo Eknock out plus enalapril(30 mg/L),(4) Apo E-knock out plus paricalcitol plus enalapril and(5) normal. Blood pressure(BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses. RESULTS: Apo E-deficient mice developed high BP(127 ± 3 mm Hg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22 phox, manganese-superoxide dismutase, inducible nitric oxide synthase(NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, Cu Zn-SOD and e NOS levels significantly depleted in Apo E-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in Apo E-knock out animals. CONCLUSION: Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.
基金Sao Paulo Research Foundation(FAPESP),[Grant No.2013/26257-8]
文摘Active vitamin D (1,25D) is a fat-soluble vitamin that is mainly produced in the skin by the conversion of 7-dehydrocholesterol under ultraviolet light stimulation.Its role in calcium homeostasis,bone growth, and prevention of rickets and osteomalacia has been known for over two hundred years.Its
基金supported by the National Natural Science Foundation of China (20802028 and 21072084)
文摘Paricalcitol,an analog of vitamin D,is used as a drug for the prevention and treatment of secondary hyperparathyroidism.In this paper,a new strategy for the synthesis of paricalcitol is described.This approach includes three main improvements:one-pot regioselective ozonization cleavage of the side-chain and methylene at C-19,free-radical reduction removal of the OH group formed at C-19,and side-chain assembly using a Wittig reaction.These are all new strategies for the synthesis of 19-nor-vitamin D2 compounds.
