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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 -
Radiology Aug 2019Background Although nephrogenic systemic fibrosis (NSF) affects the use of gadolinium-based contrast agents (GBCAs) in MRI, there continues to be limited knowledge...
Background Although nephrogenic systemic fibrosis (NSF) affects the use of gadolinium-based contrast agents (GBCAs) in MRI, there continues to be limited knowledge because of the small number of patients with NSF. Purpose To perform a systematic review of NSF. Materials and Methods PubMed database was searched by using the term "Nephrogenic systemic fibrosis" from January 2000 to February 2019. Articles reporting details on individual patients with NSF diagnosis on the basis of both clinical presentations and biopsy confirmation were included. Data were pooled and authors were contacted for clarifications. Rates of NSF were compared through 2008 versus after 2008 and for group I versus group II GBCAs, assuming equal market share. Results Included were 639 patients from 173 articles. Data regarding sex were found for 295 men and 254 women. Age at NSF symptom onset was reported for 177 patients (mean, 49 years ± 16 [standard deviation]; age range, 6-87 years). There were 529 patients with documented exposure to GBCAs including gadodiamide ( = 307), gadopentetate dimeglumine ( = 49), gadoversetamide ( = 6), gadobutrol ( = 1), gadobenate dimeglumine ( = 1), multiple ( = 41), and unknown ( = 120). Among patients with previous exposure, only seven patients were administered GBCA after 2008, yielding a lower rate of NSF after 2008 ( < .001). There were motion limitations in 70.8% (296 of 418) of patients, indicating a more serious debilitation. Associated factors reported for NSF included exposure to GBCA group I ( < .001), dialysis, proinflammatory conditions, hyperphosphatemia, β-blockers, and epoetin. For 341 patients with follow-up, 12 patients were cured and 72 patients partially improved including one during pregnancy. Among those 84 patients reported as cured or improved, in 34 patients cure or improvement occurred after renal function restoration. Four deaths were attributed to NSF. Conclusion Although 639 patients with biopsy-confirmed nephrogenic systemic fibrosis were reported, only seven were after gadolinium-based contrast agent exposure after 2008, indicating that regulatory actions and practice changes have been effective preventive measures. Improvement and sometimes cure with renal function restoration are now possible. © RSNA, 2019 See also the editorial by Davenport in this issue.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Child; Contrast Media; Female; Gadolinium DTPA; Humans; Kidney; Male; Middle Aged; Nephrogenic Fibrosing Dermopathy; Organometallic Compounds; Young Adult
PubMed: 31264946
DOI: 10.1148/radiol.2019182916 -
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 -
Journal of Renal Nutrition : the... Mar 2024Internet search engines and social media websites are prominent and growing sources of dietary information for people with chronic kidney disease (CKD) and their...
OBJECTIVE
Internet search engines and social media websites are prominent and growing sources of dietary information for people with chronic kidney disease (CKD) and their healthcare providers. However, nutrition therapy for CKD is undergoing a paradigm shift, which may lead to inconsistent advice for managing hyperphosphatemia. The aim of this study was to summarize and evaluate online resources for phosphorus-specific nutrition therapy.
DESIGN AND METHODS
Patient-facing resources were collected from Google, Yahoo, and Facebook in June-July 2021. Using nine independent search terms, the first 100 hits were reviewed. Dietary advice for food types, food groups, food subgroups, and individual food items was categorized as "restricted," "recommended," "mixed," and "not mentioned." Information on publication date, source, and author(s), phosphorus bioavailability, and demineralization were also collected.
RESULTS
After removing duplicates, 199 resources from Google and Yahoo and 33 from Facebook were reviewed. Resources ranged from 2005 to 2021 and were primarily authored by registered dietitians and medical doctors (65% and 31%, respectively). Dietary advice mostly focuses on restricting high-phosphorus foods and phosphorus additive-based processed foods. Dietary restrictions were generally consistent with the traditional low-phosphorus diet, which targets whole grains, dairy, and plant-based protein foods, although major inconsistencies were noted. Phosphorus bioavailability and demineralization were rarely mentioned (16% and 8%, respectively). Similar findings were found on Facebook, but the limited number of resources limited meaningful comparisons.
CONCLUSION
Results showed that online resources for phosphorus-specific nutrition therapy are highly restrictive of heart-healthy food items and contain significant inconsistencies. Given the widespread and increasing use of online resources by people with CKD and health care professionals to inform dietary choices, efforts are urgently needed to establish consensus for phosphorus-specific nutrition therapy. Until then, the findings of this study provide a basis for increasing awareness of the potential for confusion arising from online resources.
PubMed: 38485068
DOI: 10.1053/j.jrn.2024.01.005 -
The Australasian Journal of Dermatology Aug 2019Calciphylaxis is a rare but life-threatening condition, most commonly affecting patients with stage 4 or 5 chronic kidney disease. No universally accepted therapy exists...
Calciphylaxis is a rare but life-threatening condition, most commonly affecting patients with stage 4 or 5 chronic kidney disease. No universally accepted therapy exists so far. In an attempt to avoid surgical intervention with parathyroidectomy, which is of questionable efficacy and carries several risks, a number of noninvasive treatments have been trialled with variable success. These treatments are aimed at modifying risk factors for calciphylaxis, in particular hypercalcaemia, hyperphosphataemia and hyperparathyroidism. The aim of this review was to summarise the available evidence to determine the potential role of cinacalcet in the treatment of calciphylaxis in patients with chronic kidney disease. Demographic, clinical and laboratory data were retrospectively collected from the available English and non-English literature. Overall, there was a very high response rate (partial or complete) of calciphylaxis lesions to both cinacalcet monotherapy and cinacalcet as part of a combination therapy (83.4% and 82.8%, respectively). When examining complete response to treatment specifically, combination therapy with cinacalcet proved more efficacious than monotherapy (62.1% versus 41.7%). There was also an associated rapid reduction of intact parathyroid hormone over a period of 2-33 months in both groups. While there are limitations as to how our data can be interpreted due to the heterogeneity of the methods and follow-up of the included case reports and case series, prompt and consistent therapy including cinacalcet may help improve the disease outcome. Additional research needs to be performed in this area, to further define the optimal use of cinacalcet for the treatment of calciphylaxis.
Topics: Calciphylaxis; Calcium-Regulating Hormones and Agents; Cinacalcet; Combined Modality Therapy; Humans; Renal Insufficiency, Chronic
PubMed: 30666627
DOI: 10.1111/ajd.12992 -
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