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Biomedicines Dec 2022Chronic kidney disease-mineral and bone disorder is one of the complications associated with chronic kidney disease. About 10-50% of patients following kidney... (Review)
Review
Chronic kidney disease-mineral and bone disorder is one of the complications associated with chronic kidney disease. About 10-50% of patients following kidney transplantation have persistent hyperparathyroidism. Hypercalcaemic hyperparathyroidism has a negative impact on the kidney transplant outcome; therefore, it requires treatment. The data regarding the treatment of persistent hyperparathyroidism provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of persistent hyperparathyroidism treatment in patients following kidney transplantation. The Cochrane, PubMed, and Scopus databases were browsed independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness of calcitriol, paricalcitol, cinacalcet, and parathyroidectomy was compared and analysed. The mean calcium and parathormone (PTH) concentrations per patient in the group of paricalcitol increased by 1.27% and decreased by 35.14% (n = 248); in the group of cinacalcet decreased by 12.09% and 32.16% (n = 368); and in the group of parathyroidectomy decreased by 19.06% and 86.49% (n = 15) at the end of the study compared to the baseline (n = 244, n = 342 and n = 15), respectively. Paricalcitol, cinacalcet, and parathyroidectomy decreased the intact PTH level. Cinacalcet and parathyroidectomy lowered calcium levels in renal transplant patients with hypercalcaemia. Conversely, paricalcitol increased the serum calcium concentration. Cinacalcet seems to be a good candidate in the treatment of post-transplant hyperparathyroidism.
PubMed: 36672533
DOI: 10.3390/biomedicines11010025 -
The Journal of Clinical Endocrinology... Oct 2023Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid... (Meta-Analysis)
Meta-Analysis
CONTEXT
Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia.
OBJECTIVE
The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD).
METHODS
A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting.
RESULTS
Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed.
CONCLUSION
This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.
Topics: Humans; Calcifediol; Calcium; Ergocalciferols; Hyperparathyroidism, Secondary; Network Meta-Analysis; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic
PubMed: 37235771
DOI: 10.1210/clinem/dgad289 -
International Urology and Nephrology Apr 2016The goal of this systematic review is to evaluate the efficacy and safety of paricalcitol versus active non-selective vitamin D receptor activators (VDRAs) for secondary... (Meta-Analysis)
Meta-Analysis Review
Comparison between paricalcitol and active non-selective vitamin D receptor activator for secondary hyperparathyroidism in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.
PURPOSE
The goal of this systematic review is to evaluate the efficacy and safety of paricalcitol versus active non-selective vitamin D receptor activators (VDRAs) for secondary hyperparathyroidism (SHPT) management in chronic kidney disease (CKD) patients.
METHODS
PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), clinicaltrials.gov (inception to September 2015), and ASN Web site were searched for relevant studies. A meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs that assessed the effects and adverse events of paricalcitol and active non-selective VDRA in adult CKD patients with SHPT was performed using Review Manager 5.2.
RESULTS
A total of 10 trials involving 734 patients were identified for this review. The quality of included trials was limited, and very few trials reported all-cause mortality or cardiovascular calcification without any differences between two groups. Compared with active non-selective VDRAs, paricalcitol showed no significant difference in both PTH reduction (MD -7.78, 95% CI -28.59-13.03, P = 0.46) and the proportion of patients who achieved the target reduction of PTH (OR 1.27, 95% CI 0.87-1.85, P = 0.22). In addition, no statistical differences were found in terms of serum calcium, episodes of hypercalcemia, serum phosphorus, calcium × phosphorus products, and bone metabolism index.
CONCLUSIONS
Current evidence is insufficient, showing paricalcitol is superior to active non-selective VDRAs in lowering PTH or reducing the burden of mineral loading. Further trials are required to prove the tissue-selective effect of paricalcitol and to overcome the limitation of current research.
Topics: Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Parathyroid Hormone; Randomized Controlled Trials as Topic; Receptors, Calcitriol; Renal Insufficiency, Chronic
PubMed: 26748501
DOI: 10.1007/s11255-015-1195-6 -
PloS One 2016Vitamin D receptor activators (VDRAs) can protect against mineral bone disease, but they are reported to elevate serum creatinine (SCr) and may also reduce glomerular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin D receptor activators (VDRAs) can protect against mineral bone disease, but they are reported to elevate serum creatinine (SCr) and may also reduce glomerular filtration rate (GFR).
METHODS
We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the effect of VDRAs on kidney function and adverse events. MEDLINE, EMBASE, the Cochrane Controlled Trials Register were searched for RCTs that evaluate vitamin D receptor activators (alfacalcidol, calcitriol, doxercalciferol, falecalcitriol, maxacalcitol and paricalcitol) up to March 2015.
RESULTS
We included 31 studies, all of which were performed between 1976 and 2015, which enrolled 2621 patients. Patients receiving VDRAs had lower eGFR (weighted mean difference WMD -1.29 mL/min /1.73 m2, 95% CI -2.42 to -0.17) and elevated serum creatinine (WMD 7.03 μmol/L, 95% CI 0.61 to 13.46) in sensitivity analysis excluding studies with dropout rate more than 30%. Subgroup analysis of the 5 studies that not use SCr-based measures did not indicated lower GFR in the VDRAs group(WMD -0.97 mL/min/1.73 m2, 95% CI -4.85 to 2.92). Compared with control groups, there was no difference in all-cause mortality (relative risk RR 1.41, 95% CI 0.58 to 3.80), cardiovascular disease (RR 0.84, 95% CI 0.42 to 1.71), and severe adverse events (RR 1.15, 95% CI 0.75 to 1.77) for the VDRAs groups. Episodes of hypercalcemia (RR 3.29, 95% CI 2.02 to 5.38) were more common in the VDRAs group than in the control group.
CONCLUSIONS
Administration of VDRAs increased serum creatinine levels. Subgroup analysis of studies that did not use SCr-based measures did not indicate a lower GFR in the VDRA group. Future studies with non-SCr-based measures are needed to assess whether the mild elevations of serum creatinine are of clinical significance.
Topics: Bone Density Conservation Agents; Bone Diseases; Cardiovascular Diseases; Creatinine; Databases, Factual; Glomerular Filtration Rate; Humans; Hypercalcemia; Receptors, Calcitriol
PubMed: 26812502
DOI: 10.1371/journal.pone.0147347 -
European Review For Medical and... Jan 2022The data on the treatment of secondary hyperparathyroidism (SHPT) provided in scientific publications are divergent and contradictory. Therefore, the aim of our...
OBJECTIVE
The data on the treatment of secondary hyperparathyroidism (SHPT) provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of SHPT treatment in (chronic kidney disease) CKD.
MATERIALS AND METHODS
The Cochrane, PubMed, and Scopus databases were searched independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness and side effects of calcifediol, ergocaliferol, calcitriol, paricalcitol, and cinacalcet were compared and analyzed.
RESULTS
Extended-release (ER) calcifediol raised the total serum 25-hydroxyvitamin D level over the threshold of 30 ng/mL in 80% of the patients analyzed in the study. It is the level required for intact PTH (iPTH) suppression. ER calcifediol reduced the iPTH level by 30% in about 30% of the patients, whereas only 2.1% of them had hypercalcemia. Calcitriol significantly decreased the iPTH values. It was the cause of hypercalcemia in 1.7% of the patients. The reduction of the iPTH level by more than 30% was observed in 85.7% of the patients in the paracalcitol group after 48-week supplementation. Paricalcitol was the cause of hypercalcemia in 1.9% of the patients. The cinacalcet therapy resulted in the highest percentage of patients with the iPTH level within the limits recommended by the KDOQI (70-110 ng/L for stage 4 CKD and 150-300 ng/L for stage 5 CKD). 92% of the patients met the KDOQI guidelines and the mean decrease in the serum iPTH level was 68%.
CONCLUSIONS
Calcifediol ER, paricalcitol, and cinacalcet significantly decreased the iPTH level in the patients under study. Paricalcitol increased the serum calcium concentration the most of all the drugs under analysis. It is noteworthy that only cinacalcet does not carry the risk of hypercalcemia.
Topics: Calcitriol; Calcium; Cinacalcet; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Parathyroid Hormone; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 35049000
DOI: 10.26355/eurrev_202201_27773 -
PloS One 2020Paricalcitol, a new vitamin D receptor activator (VDRA), is reported to be more effective than other VDRAs in reducing calcium and phosphorus levels in patients... (Comparative Study)
Comparative Study Meta-Analysis
A comparative analysis of the efficacy and safety of paricalcitol versus other vitamin D receptor activators in patients undergoing hemodialysis: A systematic review and meta-analysis of 15 randomized controlled trials.
Paricalcitol, a new vitamin D receptor activator (VDRA), is reported to be more effective than other VDRAs in reducing calcium and phosphorus levels in patients undergoing hemodialysis. However, the efficacy and safety of paricalcitol remain controversial. This analysis compares paricalcitol with other VDRAs in patients undergoing hemodialysis. We searched the Cochrane Library, PubMed, EMBASE, Web of Science, and CNKI up to April 22, 2019. Standardized mean difference (SMD), risk ratio (RR) and 95% confidence interval (CI) values were estimated to compare the outcomes of the groups. Two reviewers extracted data and assessed trial quality independently. All statistical analyses were performed using the standard statistical procedures of RevMan 5.2 and Stata 12.0. Fifteen studies (N = 110,544) were included in this meta-analysis. Of these studies, 11 were randomized controlled trials (RCTs) and 4 were non-randomized studies of interventions (NRSIs). Patients receiving paricalcitol experienced better overall survival (OS) than patients receiving other VDRAs, with a pooled hazard ratio of 0.86 (95% CI 0.80-0.91; P < 0.00001). Intact parathyroid hormone (iPTH) levels were significantly reduced in the paricalcitol group compared to the group receiving other VDRAs, with a pooled SMD of -0.53 (95% CI -0.89- -0.16; P = 0.004). There was a significant increase in serum calcium levels from baseline in the paricalcitol group compared to the other VDRAs group when limiting the analysis to RCTs, with a pooled SMD of 2.14 (95% CI 0.90-3.38; P = 0.0007). Changes in serum calcium levels were significantly lower in the paricalcitol group when the analysis was limited to NRSIs, with a pooled SMD of -0.85 (95% CI -1.34--0.35; P = 0.0008). The NSRI analysis also showed a significant reduction in serum phosphorus levels in the paricalcitol group, with a pooled SMD of -0.57 (95% CI -1.00--0.13; P = 0.01). No significant differences were observed in the incidence of hypercalcemia, hyperphosphatemia, or adverse events. Generally, paricalcitol seems superior to other VDRAs in reducing mortality and iPTH levels in patients undergoing hemodialysis. However, the comparative effectiveness of paricalcitol in reducing serum calcium and phosphorus levels needs further exploration. No significant difference was found in the rate of adverse events.
Topics: Calcium; Disease-Free Survival; Ergocalciferols; Female; Humans; Male; Parathyroid Hormone; Phosphorus; Randomized Controlled Trials as Topic; Receptors, Calcitriol; Renal Dialysis; Survival Rate
PubMed: 32470067
DOI: 10.1371/journal.pone.0233705 -
BMC Pharmacology & Toxicology Feb 2024Previous studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported... (Meta-Analysis)
Meta-Analysis
The effect of oral supplementation of Paricalcitol on C-reactive protein levels in chronic kidney disease patients: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials.
BACKGROUND
Previous studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported inconsistent findings. In this systematic review and meta-analysis, we have analyzed and interpreted the results obtained from previous randomized clinical trials on the effect of paricalcitol on C-reactive protein in CKD patients in the literature.
METHODS
MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched until January 2023 and related articles were obtained through a careful screening process allowing extraction of required data from selected articles. The effect size was calculated using a random effect model and weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using Cochran's Q test and I.
RESULTS
Amongst the 182 articles obtained from the initial search, 4 studies (6 arms) were finally included in the meta-analysis. Pooled analysis shows that C-reactive protein levels significantly decrease after oral supplementation with paricalcitol (WMD: -2.55 mg/L, 95% CI (-4.99 to -0.11; P = 0.04). The studies used in this meta-analysis showed significant heterogeneity (I = 66.3% and P = 0.01).
CONCLUSION
Oral paricalcitol supplementation in CKD patients can significantly reduce C-reactive protein levels, which may prevent CKD progression.
Topics: Humans; C-Reactive Protein; Dietary Supplements; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Ergocalciferols
PubMed: 38395972
DOI: 10.1186/s40360-024-00740-y -
Calcified Tissue International Aug 2021A large proportion of patients with chronic kidney disease (CKD) are vitamin D deficient (plasma 25-hydroxyvitamin D (25(OH)D) < 25 or 30 nmol/L per UK and US... (Meta-Analysis)
Meta-Analysis
Vitamin D Supplementation for Patients with Chronic Kidney Disease: A Systematic Review and Meta-analyses of Trials Investigating the Response to Supplementation and an Overview of Guidelines.
A large proportion of patients with chronic kidney disease (CKD) are vitamin D deficient (plasma 25-hydroxyvitamin D (25(OH)D) < 25 or 30 nmol/L per UK and US population guidelines) and this contributes to the development of CKD-mineral bone disease (CKD-MBD). Gaps in the evidence-base for the management of vitamin D status in relation to CKD-MBD are hindering the formulation of comprehensive guidelines. We conducted a systemic review of 22 RCTs with different forms of vitamin D or analogues with CKD-MBD related outcomes and meta-analyses for parathyroid hormone (PTH). We provide a comprehensive overview of current guidelines for the management of vitamin D status for pre-dialysis CKD patients. Vitamin D supplementation had an inconsistent effect on PTH concentrations and meta-analysis showed non- significant reduction (P = 0.08) whereas calcifediol, calcitriol and paricalcitol consistently reduced PTH. An increase in Fibroblast Growth Factor 23 (FGF23) with analogue administration was found in all 3 studies reporting FGF23, but was unaltered in 4 studies with vitamin D or calcifediol. Few RCTS reported markers of bone metabolism and variations in the range of markers prevented direct comparisons. Guidelines for CKD stages G1-G3a follow general population recommendations. For the correction of deficiency general or CKD-specific patient guidelines provide recommendations. Calcitriol or analogues administration is restricted to stages G3b-G5 and depends on patient characteristics. In conclusion, the effect of vitamin D supplementation in CKD patients was inconsistent between studies. Calcifediol and analogues consistently suppressed PTH, but the increase in FGF23 with calcitriol analogues warrants caution.
Topics: Dietary Supplements; Fibroblast Growth Factor-23; Humans; Parathyroid Hormone; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency
PubMed: 33895867
DOI: 10.1007/s00223-021-00844-1 -
The Cochrane Database of Systematic... Nov 2015Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates. This is an update of a review first published in 2010.
OBJECTIVES
This review aimed to examine the benefits (improved growth rates, reduced risk of bone fractures and deformities, reduction in PTH levels) and harms (hypercalcaemia, blood vessel calcification, deterioration in kidney function) of interventions (including vitamin D preparations and phosphate binders) for the prevention and treatment of metabolic bone disease in children with CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 8 September 2015 through contact with the Trial's Search Co-ordinator using search terms relevant for this review.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2 to 5D.
DATA COLLECTION AND ANALYSIS
Data were assessed for study eligibility, risk of bias and extracted independently by two authors. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model.
MAIN RESULTS
This review included 18 studies (576 children); three new studies were added for this update. Adequate sequence generation and allocation concealment were reported in 12 and 11 studies respectively. Only four studies reported blinding of children, investigators or outcome assessors. Nine studies were at low risk of attrition bias and 12 studies were at low risk of selective reporting bias.Eight different interventions were compared. Two studies compared intraperitoneal (IP) with oral calcitriol. PTH levels were significantly lower with IP compared with oral calcitriol (1 study: MD -501.00 pg/mL, 95% CI -721.54 to -280.46) but the number of children with abnormal bone histology did not differ between treatments. Three studies compared intermittent with daily oral calcitriol. The change in mean height SDS (1 study: MD 0.13, 95% CI -0.22 to 0.48) and the percentage fall in parathyroid hormone (PTH) levels at eight weeks (1 study: MD -5.50%, 95% CI -32.37 to 21.37) and 12 months (1 study: MD -6.00% 95% CI -25.27 to 13.27) did not differ between treatments.Four studies compared active vitamin D preparations (calcitriol, paricalcitol, 1α-hydroxyvitamin D) with placebo or no specific treatment. One study reported vitamin D preparations significantly reduced PTH levels (-55.00 pmol/L, 95% CI -83.03 to -26.97). There was no significant difference in hypercalcaemia risk with vitamin D preparations compared with placebo or no specific treatment (4 studies, 103 children: RD 0.08 mg/dL, 95% CI -0.08 to 0.24). However, there was heterogeneity (I(2) = 55%) with one study showing a significantly greater risk of hypercalcaemia with intravenous (IV) calcitriol administration. Two studies (97 children) compared calcitriol with other vitamin D preparations and both found no significant differences in growth between preparations.Two studies compared ergocalciferol in patients with CKD and vitamin D deficiency. Elevated PTH levels developed significantly later in ergocalciferol treated children (1 study: hazard ratio 0.30, 95% CI 0.09 to 0.93) though the number with elevated PTH levels did not differ between groups (1 study, 40 children: RR 0.33, 95% CI 0.11 to 1.05).Two studies compared calcium carbonate with aluminium hydroxide as phosphate binders. One study (17 children: MD -0.86 SDS, 95% CI -2.24 to 0.52) reported no significant difference in mean final height SDS between treatments. Three studies compared sevelamer with calcium-containing phosphate binders. There were no significant differences in the final calcium, phosphorus or PTH levels between binders. More episodes of hypercalcaemia occurred with calcium-containing binders. One study reported no significant differences between calcitriol and doxercalciferol in bone histology or biochemical parameters.
AUTHORS' CONCLUSIONS
Bone disease, assessed by changes in PTH levels, is improved by all vitamin D preparations. However, no consistent differences between routes of administration, frequencies of dosing or vitamin D preparations were demonstrated. Although fewer episodes of high calcium levels occurred with the non-calcium-containing phosphate binder, sevelamer, compared with calcium-containing binders, there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents. All studies were small with few data available on patient-centred outcomes (growth, bone deformities) and limited data on biochemical parameters or bone histology resulting in considerable imprecision of results thus limiting the applicability to the care of children with CKD.
Topics: Aluminum Hydroxide; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcitriol; Calcium; Calcium Carbonate; Child; Chronic Disease; Ergocalciferols; Humans; Kidney Diseases; Parathyroid Hormone; Phosphorus; Polyamines; Randomized Controlled Trials as Topic; Sevelamer; Vitamin D
PubMed: 26561037
DOI: 10.1002/14651858.CD008327.pub2 -
Giornale Italiano Di Nefrologia :... Feb 2023Secondary hyperparathyroidism (SHPT) is a common and major complication of chronic kidney disease (CKD) among patients on dialysis and in patients with CKD stage G3 to... (Meta-Analysis)
Meta-Analysis
Secondary hyperparathyroidism (SHPT) is a common and major complication of chronic kidney disease (CKD) among patients on dialysis and in patients with CKD stage G3 to G5. SHPT in CKD is caused by disturbances in metabolic parameters. Paricalcitol (PCT), other active vitamin D analogous (doxercalciferol and alfacalcidol), and active vitamin D (calcitriol) have been commonly used to treat SHPT in non-dialysis CKD (ND-CKD) for several years. However, recent studies indicate that these therapies adversely increase serum calcium, phosphate, and fibroblast growth factor 23 (FGF-23) levels. Extended release calcifediol (ERC) has been developed as an alternative treatment for SHPT in ND-CKD. The present meta-analysis compares the effect of ERC against PCT in the control of PTH and calcium levels. A systematic literature review was conducted, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to identify studies for inclusion in the Network Meta-Analysis (NMA). 18 publications were eligible for inclusion in the network meta-analysis and 9 articles were included in the final NMA. The estimated PTH reduction from PCT (-59.5 pg/ml) was larger than the PTH reduction from ERC (-45.3 pg/ml), but the difference in treatment effects did not show statistical significance. Treatment with PCT caused statistically significant increases in calcium vs. placebo (increase: 0.31 mg/dl), while the marginal increase in calcium from treatment with ERC (increase: 0.10 mg/dl) did not reach statistical significance. The evidence suggests that both PCT and ERC are effective in reducing levels of PTH, whereas calcium levels tended to increase from treatment with PCT. Therefore, ERC may be an equally effective, but more tolerable treatment alternative to PCT.
Topics: Humans; Calcifediol; Calcium; Network Meta-Analysis; Vitamin D; Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic; Parathyroid Hormone
PubMed: 36883925
DOI: No ID Found