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Frontiers in Pharmacology 2023The efficacy of cuttlebone for treating hyperphosphatemia in patients with end-stage renal disease and its safety remained unclear. Randomized controlled trials...
The efficacy of cuttlebone for treating hyperphosphatemia in patients with end-stage renal disease and its safety remained unclear. Randomized controlled trials comparing the efficacy of cuttlebone with conventional interventions were retrieved from MEDLINE, EMBASE, Cochrane Library, Airiti Library, and other major Chinese databases until 1 February 2023. The primary outcome was circulating phosphate concentration, while secondary outcomes included circulating calcium and intact parathyroid hormone levels, calcium-phosphorus product, and treatment-related side-effects. Analysis of nine studies published between 2000 and 2019 including 726 participants showed a lower circulating phosphate concentration in the cuttlebone group than in controls [mean difference (MD) = -0.23, 95% CI: -0.39 to -0.06, = 0.006, I = 94%, 726 patients] and a dose-dependent effect of cuttlebone against hyperphosphatemia. Therapeutic benefits were noted after both short-term (1-2 months) and long-term (3-6 months) treatments. Besides, patients receiving hemodialysis showed a better response to cuttlebone than those receiving peritoneal dialysis. There was no difference in circulating calcium level (mean difference = 0.03, 95% CI: -0.01 to 0.07, = 0.17, I = 34%, 654 patients), while patients receiving cuttlebone showed lower circulating iPTH level and calcium-phosphorus product (MD = -43.63, 95% CI: -74.1 to -13.16, = 0.005, I = 76%, 654 patients), (MD = -0.38, 95% CI: -0.38 to -0.01, = 0.04, I = 83%, 520 patients). No difference in the risks of constipation, gastrointestinal discomfort, and elevated blood calcium was noted between the two groups. Compared with conventional phosphate-binding agents, cuttlebone more efficiently suppressed hyperphosphatemia with a dose-dependent effect. The limited number of included studies warrants further clinical investigations to verify our findings. https://www.crd.york.ac.uk/prospero/, identifier CRD42023396300.
PubMed: 37554990
DOI: 10.3389/fphar.2023.1206366 -
Frontiers in Oncology 2022This review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors.
OBJECTIVE
This review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors.
METHODS
PubMed, Embase, and ClinicalTrials.gov were searched until 10 February 2022. The safety outcome as adverse events and efficacy outcomes, including objective response rate, stable disease rates, and progressive disease rates, were selected and analyzed by comprehensive meta-analysis version 3.0 and STATA 15.0.
RESULTS
The most common all-grade adverse events were hyperphosphatemia, dry mouth, stomatitis, diarrhea, and dysgeusia. The occurrence of ≥3 adverse events was relatively low, and stomatitis and hyponatremia were the most common. Moreover, eye disorders could not be ignored. Efficacy in urothelial carcinoma patients was obviously better than in other solid tumor patients, with a higher objective response rate (0.38 versus 0.10) and lower progressive disease rate (0.26 versus 0.68). All responses occurred in patients with fibroblast growth factor receptor (FGFR) alteration. In those patients, a specific FGFR alteration () was observed to have a maximum response.
CONCLUSION
Erdafitinib has satisfactory clinical activity for metastatic urothelial carcinoma and other solid tumors, while the toxicity is acceptable. With more RCTs and combination therapy trials published, erdafitinib will be applied widely.
PubMed: 36776367
DOI: 10.3389/fonc.2022.907377 -
The European Journal of Health... Jun 2021Uncontrolled hyperphosphatemia in chronic kidney disease (CKD) patients commonly results in vascular calcification leading to increased risk of cardiovascular disease.... (Meta-Analysis)
Meta-Analysis
Evaluation of the cost-utility of phosphate binders as a treatment option for hyperphosphatemia in chronic kidney disease patients: a systematic review and meta-analysis of the economic evaluations.
BACKGROUND
Uncontrolled hyperphosphatemia in chronic kidney disease (CKD) patients commonly results in vascular calcification leading to increased risk of cardiovascular disease. Phosphate binders (PBs) are used for hyperphosphatemia and can be calcium-based (CBPBs) or non-calcium-based (NCBPBs), the latter being more expensive than CBPBs. In this study, we used meta-analysis approaches to assess the cost-utility of PBs for hyperphosphatemia in CKD patients.
METHODS
Relevant studies published prior to June 2019 were identified from PubMed, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database, and the Cost-Effectiveness Analysis Registry. Studies were eligible if they included CKD patients with hyperphosphatemia, compared any PBs and reported economic outcomes. Meta-analysis was applied to pool incremental net benefit (INB) across studies stratified by country income.
RESULTS
A total of 25 studies encompassing 32 comparisons were eligible. Lanthanum carbonate, a NCBPB, was a more cost-effective option than CBPBs in high-income countries (HICs), with a pooled INB of $3984.4 (599.5-7369.4), especially in pre-dialysis patients and used as a second-line option with INBs of $4860.2 (641.5-9078.8), $4011.0 (533.7-7488.3), respectively. Sevelamer, also a NCBPB, was not more cost-effective as a first-line option compared to CBPBs with a pooled INB of $6045.8 (- 23,453.0 to 35,522.6) and $34,168.9 (- 638.0 to 68,975.7) in HICs and upper middle-income countries, respectively.
CONCLUSIONS
Lanthanum carbonate was significantly more cost-effective than CBPBs as a second-line option for hyperphosphatemia in pre-dialysis patients in HICs. However, the use of sevelamer is not more cost-effective as a first-line option compared to CBPBs.
Topics: Cost-Benefit Analysis; Humans; Hyperphosphatemia; Phosphates; Renal Dialysis; Renal Insufficiency, Chronic; State Medicine
PubMed: 33677736
DOI: 10.1007/s10198-021-01275-3 -
Clinical Journal of the American... Dec 2020Hyperphosphatemia is a persistent problem in individuals undergoing maintenance hemodialysis, which may contribute to vascular and bone complications. In some dialysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Hyperphosphatemia is a persistent problem in individuals undergoing maintenance hemodialysis, which may contribute to vascular and bone complications. In some dialysis centers, dietitians work with patients to help them manage serum phosphate. Given the regularity of hyperphosphatemia in this population and constraints on kidney dietitian time, the authors aimed to evaluate the evidence for this practice.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
There was a systematic review and meta-analysis of clinical trials. MEDLINE, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, and other databases were searched for controlled trials published from January 2000 until November 2019 in the English language. Included studies were required to examine the effect of phosphate-specific diet therapy provided by a dietitian on serum phosphate in individuals on hemodialysis. Risk of bias and certainty of evidence were assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method.
RESULTS
Of the 8054 titles/abstracts identified, 168 articles were reviewed, and 12 clinical trials (11 randomized, one nonrandomized) were included. Diet therapy reduced serum phosphate compared with controls in all studies, reaching statistical significance in eight studies, although overall certainty of evidence was low, primarily due to randomization issues and deviations from protocol. Monthly diet therapy (20-30 minutes) significantly lowered serum phosphate in patients with persistent hyperphosphatemia for 4-6 months, without compromising nutrition status (mean difference, -0.87 mg/dl; 95% confidence interval, -1.40 to -0.33 mg/dl), but appeared unlikely to maintain these effects if discontinued. Unfortunately, trials were too varied in design, setting, and approach to appropriately pool in meta-analysis, and were too limited in number to evaluate the timing, dose, and strategy of phosphate-specific diet therapy.
CONCLUSIONS
There is low-quality evidence that monthly diet therapy by a dietitian appears to be a safe and efficacious treatment for persistent hyperphosphatemia in patients on HD.
Topics: Humans; Hyperphosphatemia; Nutritional Status; Phosphates; Phosphorus, Dietary; Quality of Life; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 33380474
DOI: 10.2215/CJN.09360620 -
Journal of Pharmacy & Pharmaceutical... 2022This narrative review explores the currently published studies that have evaluated tenapanor for the treatment of hyperphosphatemia in end-stage kidney disease (ESKD)...
PURPOSE
This narrative review explores the currently published studies that have evaluated tenapanor for the treatment of hyperphosphatemia in end-stage kidney disease (ESKD) patients on hemodialysis. This medication's new phosphate lowering mechanism of action reduces intestinal phosphate absorption predominantly through reduction of passive paracellular phosphate flux by inhibition of the sodium/hydrogen exporter isoform 3 (NHE3). Tenapanor additionally prevents active transcellular phosphate absorption compensation by decreasing the expression of sodium phosphorus 2b transport protein (NaPi2b).
METHODS
A comprehensive search of the literature was conducted using PubMed and ClinicalTrials.gov search engines. The search term "tenapanor hyperphosphatemia" was used for study retrieval. Results were limited to studies published in the English language and excluded review articles. Human, animal, and in vitro studies were included. No date range was specified.
RESULTS
A total of 11 primary studies were identified and included in this review, the largest human study of which enrolled 236 patients. Each study is presented in table format along with measured end points.
CONCLUSIONS
Tenapanor is the first drug in its class that lowers hyperphosphatemia in ESKD patients through a novel mechanism of action involving paracellular inactive transport. Although more studies are needed, early results indicate that tenapanor may have a place in managing hyperphosphatemia in ESKD patients both as monotherapy and as an adjunct to existing phosphate binder therapy.
Topics: Animals; Biological Transport, Active; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Humans; Hyperphosphatemia; Intestinal Absorption; Isoquinolines; Kidney Failure, Chronic; Phosphates; Rats; Sodium-Hydrogen Exchanger 3; Sulfonamides
PubMed: 35041802
DOI: 10.18433/jpps32284 -
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 -
British Journal of Clinical Pharmacology Feb 2021Phosphate-lowering effects of ferric citrate were reported in several clinical trials, but mostly in small-scale studies. The aim of this meta-analysis was to... (Meta-Analysis)
Meta-Analysis
AIMS
Phosphate-lowering effects of ferric citrate were reported in several clinical trials, but mostly in small-scale studies. The aim of this meta-analysis was to investigate the efficacy and safety of ferric citrate in controlling hyperphosphataemia and iron-deficiency anaemia in chronic kidney disease (CKD) patients.
METHODS
PubMed, Embase and Cochrane Library were searched for clinical trials that enrolled CKD patients receiving ferric citrate for hyperphosphataemia. Two investigators performed systematic literature search to identify eligible studies, evaluated risk of bias and extracted relevant data.
RESULTS
Sixteen studies were included in the meta-analysis. Phosphate-lowering effects of ferric citrate were greater compared to no active treatment (standardized mean difference [SMD] = -1.15; P < 0.001) and comparable to other phosphate binders (SMD = 0.03; P = 0.61). Calcium concentrations post ferric citrate treatment did not differ compared to no active treatment (SMD = 0.15; P = 0.21) but were significantly lower compared to other phosphate binders (SMD = -0.14; P = 0.01). These led to significant reductions in calcium-phosphorus product with ferric citrate versus no active control (SMD = -1.02; P < 0.001) but no difference versus active control (SMD = -0.01; P = 0.93). Intact parathyroid hormone showed no substantial between-group difference in both comparison against no active and active controls. Ferric citrate improved iron stores and anaemia parameters, but increased risk of diarrhoea, abdominal pain and discoloured faeces.
CONCLUSION
Ferric citrate was effective in lowering phosphorus and phosphorus-calcium product versus no active treatment and had comparable effects versus other phosphate binders. Calcium levels were significantly lower with ferric citrate than with other phosphate-lowering treatment. Ferric citrate had additive effects on iron repletion and anaemia control and was associated with mostly gastrointestinal side effects.
Topics: Anemia, Iron-Deficiency; Ferric Compounds; Humans; Hyperphosphatemia; Phosphates; Renal Insufficiency, Chronic
PubMed: 32470149
DOI: 10.1111/bcp.14396 -
The Cochrane Database of Systematic... Dec 2020Vitamin D is a secosteroid hormone that is important for its role in calcium homeostasis to maintain skeletal health. Linear growth faltering and stunting remain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin D is a secosteroid hormone that is important for its role in calcium homeostasis to maintain skeletal health. Linear growth faltering and stunting remain pervasive indicators of poor nutrition status among infants and children under five years of age around the world, and low vitamin D status has been linked to poor growth. However, existing evidence on the effects of vitamin D supplementation on linear growth and other health outcomes among infants and children under five years of age has not been systematically reviewed.
OBJECTIVES
To assess effects of oral vitamin D supplementation on linear growth and other health outcomes among infants and children under five years of age.
SEARCH METHODS
In December 2019, we searched CENTRAL, PubMed, Embase, 14 other electronic databases, and two trials registries. We also searched the reference lists of relevant publications for any relevant trials, and we contacted key organisations and authors to obtain information on relevant ongoing and unpublished trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of oral vitamin D supplementation, with or without other micronutrients, compared to no intervention, placebo, a lower dose of vitamin D, or the same micronutrients alone (and not vitamin D) in infants and children under five years of age who lived in any country.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
Out of 75 studies (187 reports; 12,122 participants) included in the qualitative analysis, 64 studies (169 reports; 10,854 participants) contributed data on our outcomes of interest for meta-analysis. A majority of included studies were conducted in India, USA, and Canada. Two studies reported for-profit funding, two were categorised as receiving mixed funding (non-profit and for-profit), five reported that they received no funding, 26 did not disclose funding sources, and the remaining studies were funded by non-profit funding. Certainty of evidence varied between high and very low across outcomes (all measured at endpoint) for each comparison. Vitamin D supplementation versus placebo or no intervention (31 studies) Compared to placebo or no intervention, vitamin D supplementation (at doses 200 to 2000 IU daily; or up to 300,000 IU bolus at enrolment) may make little to no difference in linear growth (measured length/height in cm) among children under five years of age (mean difference (MD) 0.66, 95% confidence interval (CI) -0.37 to 1.68; 3 studies, 240 participants; low-certainty evidence); probably improves length/height-for-age z-score (L/HAZ) (MD 0.11, 95% CI 0.001 to 0.22; 1 study, 1258 participants; moderate-certainty evidence); and probably makes little to no difference in stunting (risk ratio (RR) 0.90, 95% CI 0.80 to 1.01; 1 study, 1247 participants; moderate-certainty evidence). In terms of adverse events, vitamin D supplementation results in little to no difference in developing hypercalciuria compared to placebo (RR 2.03, 95% CI 0.28 to 14.67; 2 studies, 68 participants; high-certainty evidence). It is uncertain whether vitamin D supplementation impacts the development of hypercalcaemia as the certainty of evidence was very low (RR 0.82, 95% CI 0.35 to 1.90; 2 studies, 367 participants). Vitamin D supplementation (higher dose) versus vitamin D (lower dose) (34 studies) Compared to a lower dose of vitamin D (100 to 1000 IU daily; or up to 300,000 IU bolus at enrolment), higher-dose vitamin D supplementation (200 to 6000 IU daily; or up to 600,000 IU bolus at enrolment) may have little to no effect on linear growth, but we are uncertain about this result (MD 1.00, 95% CI -2.22 to 0.21; 5 studies, 283 participants), and it may make little to no difference in L/HAZ (MD 0.40, 95% CI -0.06 to 0.86; 2 studies, 105 participants; low-certainty evidence). No studies evaluated stunting. As regards adverse events, higher-dose vitamin D supplementation may make little to no difference in developing hypercalciuria (RR 1.16, 95% CI 1.00 to 1.35; 6 studies, 554 participants; low-certainty evidence) or in hypercalcaemia (RR 1.39, 95% CI 0.89 to 2.18; 5 studies, 986 participants; low-certainty evidence) compared to lower-dose vitamin D supplementation. Vitamin D supplementation (higher dose) + micronutrient(s) versus vitamin D (lower dose) + micronutrient(s) (9 studies) Supplementation with a higher dose of vitamin D (400 to 2000 IU daily, or up to 300,000 IU bolus at enrolment) plus micronutrients, compared to a lower dose (200 to 2000 IU daily, or up to 90,000 IU bolus at enrolment) of vitamin D with the same micronutrients, probably makes little to no difference in linear growth (MD 0.60, 95% CI -3.33 to 4.53; 1 study, 25 participants; moderate-certainty evidence). No studies evaluated L/HAZ or stunting. In terms of adverse events, higher-dose vitamin D supplementation with micronutrients, compared to lower-dose vitamin D with the same micronutrients, may make little to no difference in developing hypercalciuria (RR 1.00, 95% CI 0.06 to 15.48; 1 study, 86 participants; low-certainty evidence) and probably makes little to no difference in developing hypercalcaemia (RR 1.00, 95% CI 0.90, 1.11; 2 studies, 126 participants; moderate-certainty evidence). Four studies measured hyperphosphataemia and three studies measured kidney stones, but they reported no occurrences and therefore were not included in the comparison for these outcomes.
AUTHORS' CONCLUSIONS
Evidence suggests that oral vitamin D supplementation may result in little to no difference in linear growth, stunting, hypercalciuria, or hypercalcaemia, compared to placebo or no intervention, but may result in a slight increase in length/height-for-age z-score (L/HAZ). Additionally, evidence suggests that compared to lower doses of vitamin D, with or without micronutrients, vitamin D supplementation may result in little to no difference in linear growth, L/HAZ, stunting, hypercalciuria, or hypercalcaemia. Small sample sizes, substantial heterogeneity in terms of population and intervention parameters, and high risk of bias across many of the included studies limit our ability to confirm with any certainty the effects of vitamin D on our outcomes. Larger, well-designed studies of long duration (several months to years) are recommended to confirm whether or not oral vitamin D supplementation may impact linear growth in children under five years of age, among both those who are healthy and those with underlying infectious or non-communicable health conditions.
Topics: Administration, Oral; Body Height; Child, Preschool; Confidence Intervals; Growth; Growth Disorders; Humans; Hypercalcemia; Hypercalciuria; Infant; Infant, Newborn; Micronutrients; Placebos; Randomized Controlled Trials as Topic; Vitamin D; Vitamins
PubMed: 33305842
DOI: 10.1002/14651858.CD012875.pub2