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Clinical Toxicology (Philadelphia, Pa.) Jun 2022Enemas containing phosphate are widely prescribed and may cause important adverse effects. A systemic review published in 2007 reported the literature on the adverse...
INTRODUCTION
Enemas containing phosphate are widely prescribed and may cause important adverse effects. A systemic review published in 2007 reported the literature on the adverse effects of phosphate enemas from January 1957 to March 2007 and identified 12 deaths. These were thought due to electrolyte disturbances, heart failure and kidney injury. These data raised concerns about the use of phosphate enemas in routine practice. Newer osmotic-based enema alternatives are now available that do not contain absorbable ions. We sought to review the literature since this review and evaluate the latest data on the toxicity of phosphate-containing enemas. To gain a fuller picture we included case series and larger studies as well as case reports.
OBJECTIVES
To review the toxicity of phosphate enemas, particularly with respect to acute metabolic consequences and their associated clinical features. To identify risk factors for metabolic toxicity and consider whether phosphate enemas should be relatively contra-indicated in specific patient groups.
METHODS
A systematic literature review was conducted in PubMed, Google Scholar, and Cochrane Reviews (2005-2021) using the search terms 'phosphate enema or sodium phosphate enema' or 'phosphate-based enema' or (phosphate AND enema) or (Fleet AND enema) or 'sodium phosphate laxatives' or 'sodium phosphate catharsis' or 'sodium phosphate cathartic'. Relevant papers were read, and data were extracted.
RESULTS
The searches identified 489 papers of which 25 were relevant: seven papers were case reports or small case series of metabolic abnormalities from the use of phosphate enemas in nine children, six were case reports on 16 adults. Nine papers were large case series or clinical studies that included data on systemic metabolic effects, of varying size from 24 healthy volunteers to a cohort of 70,499 patients. Case reports identified seven adult deaths but none in children. Children most often presented with decreased consciousness (6/9), and tetany (4/9). In adults overall only five cases had clinical features reported, hypotension was seen in four and QT prolongation in two. Treatment was generally symptomatic, with intravenous fluid and calcium salts for electrolyte changes and hypocalcaemia, and vasopressors for severe hypotension. Haemodialysis was used in three children and peritoneal dialysis in one, all of whom survived. In adults, haemodialysis did not prevent death in two of four cases in whom it was used. Common factors underlying toxicity were inappropriately high phosphate dose, or enema retention, both resulting in greater absorption of phosphate. Associated pre-disposing conditions included Hirschsprung disease in children and co-morbidity and renal impairment (2/5) in older adults. Absolute reported changes in serum phosphate or calcium were not accurate indicators of outcome. Larger case series and clinical trials confirm an acute effect of phosphate enemas on serum phosphate, which was related to both dose and retention time. These effects were not seen with non-phosphate preparations. In these cases series, adverse events were rarely reported.
CONCLUSION
Phosphate enemas are potentially toxic, particularly in young children with Hirschsprung disease and in the elderly with co-morbidity. Raised awareness of the risk of phosphate enemas is still required. Other less toxic enema preparations are available and should be considered in patients at extremes of age. If phosphate enemas are the only clinical option careful monitoring of biochemical sequelae should be undertaken.
Topics: Aged; Calcium; Child; Child, Preschool; Enema; Hirschsprung Disease; Humans; Hypotension; Laxatives; Phosphates
PubMed: 35510830
DOI: 10.1080/15563650.2022.2054424 -
European Journal of Endocrinology Nov 2023Pseudohypoparathyroidism type 1a (PHP1a) is a rare endocrine disease caused by partial defects of the α subunit of the stimulatory Guanosin triphosphate (GTP) binding...
BACKGROUND
Pseudohypoparathyroidism type 1a (PHP1a) is a rare endocrine disease caused by partial defects of the α subunit of the stimulatory Guanosin triphosphate (GTP) binding protein (Gsα) resulting from maternal GNAS gene variation. The clinical manifestations are related to PTH resistance (hypocalcemia, hyperphosphatemia, and elevated serum intact PTH) in the presence or absence of multihormone resistance, and Albright's hereditary osteodystrophy (AHO).
OBJECTIVES
To summarize the molecular genetics results and clinical characteristics as well as to explore the correlations between them.
METHODS
Articles pertaining to PHP1a until May, 31, 2021 were reviewed and 527 patients with genetic diagnosis were included in the data analysis. The clinical characteristics and molecular genetics results of these patients were analyzed and compared to explore the correlations between them.
RESULTS
A total of 258 GNAS rare variants (RVs) were identified in 527 patients. The RVs were most commonly found in exons 1 and 7 (17.6% each), with frameshift (36.8%), and missense (31.3%) being the main types of RVs. The median age of onset was 5.0 years old. The most common clinical manifestations were elevation of PTH (86.7%) and AHO (87.5%). Thyroid stimulating hormone resistance was the most common hormone resistance (75.5%) other than PTH resistance. Patients with missense and in-frame RVs had lower incidence rates of the round face (P = .001) and subcutaneous ossifications (P < .001) than those with loss-of-function (non-sense, frameshift, splicing site variants, and large deletions) variants.
CONCLUSIONS
This study revealed the correlation between loss-of-function RVs with round faces and subcutaneous ossifications in PHP 1a patients. Further exploration of genotype-phenotype correlations through more standardized and prospective studies with long-term follow-up is necessary.
Topics: Humans; Child, Preschool; Prospective Studies; Chromogranins; Pseudohypoparathyroidism; GTP-Binding Protein alpha Subunits, Gs; Genetic Association Studies
PubMed: 37837607
DOI: 10.1093/ejendo/lvad142 -
International Urology and Nephrology Apr 2018To evaluate the efficacy and safety of the restricted protein diet supplemented with keto analogues when applied in end-stage renal disease (ESRD). (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the efficacy and safety of the restricted protein diet supplemented with keto analogues when applied in end-stage renal disease (ESRD).
METHODS
The Cochrane Library, PubMed, Embase, CBM and CENTRAL databases were searched and reviewed up to January 2017. Clinical trials were analyzed using RevMan 5.3 software.
RESULTS
Five randomized controlled trials were selected and included in this study according to our inclusion and exclusion criteria. Changes in serum albumin, PTH, triglyceride, cholesterol, calcium, phosphorus, hemoglobin, Kt/v and CRP before and after treatment were analyzed. Meta-analysis results indicated that, compared with normal protein diet, low-protein diet (LPD) supplemented with keto analogues (sLPD) could improve serum albumin (P < 0.00001), hyperparathyroidism (P < 0.00001) and hyperphosphatemia (P = 0.008). No differences in triglyceride, cholesterol, hemoglobin, Kt/v and CRP were observed between different protein intake groups.
CONCLUSION
Restricted protein diet supplemented with keto analogues (sLPD) may improve nutritional status and prevent hyperparathyroidism in ESRD patients. The current data were mainly obtained from short-term, single-center trails with small sample sizes and limited nutritional status indexes, indicating a need for further study.
Topics: Diet, Protein-Restricted; Dietary Supplements; Humans; Hyperparathyroidism; Hyperphosphatemia; Keto Acids; Kidney Failure, Chronic; Nutritional Status; Randomized Controlled Trials as Topic; Serum Albumin
PubMed: 28975468
DOI: 10.1007/s11255-017-1713-9 -
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 -
Cureus Apr 2024Rhabdomyolysis, a medical condition caused by the destruction of striated muscle fibers, can have many etiologies, with the most common one being traumatic etiologies,... (Review)
Review
Rhabdomyolysis, a medical condition caused by the destruction of striated muscle fibers, can have many etiologies, with the most common one being traumatic etiologies, that is, crushing injuries, heavy exertion, and being trapped under rubbles, and so forth. Rhabdomyolysis causes many complications, including acute kidney injury and different electrolyte imbalances, which later can cause cardiac dysrhythmia and even death as a result. This systematic review and meta-analysis investigate the incidence of imbalances of four important electrolytes among patients diagnosed with traumatic rhabdomyolysis. PubMed, Scopus, Web of Science, and Embase databases were searched for any article related to traumatic rhabdomyolysis using keywords related to the topic of our study, excluding case studies and case series. Relevant data were extracted from the included articles, and finally, a meta-analysis was performed on them to calculate the pooled incidence of each electrolyte imbalance. Collectively, 32 articles were included in our study (through the database and citation checking). The following were the pooled incidence of each electrolyte imbalance: hyperkalemia, 31% (95%CI 22%-41%); hypokalemia, 10% (95%CI 4%-17%); hypernatremia, 3% (95%CI 0%-8%); hyponatremia, 23% (95%CI 7%-44%); hypercalcemia, 0% (95%CI 0%-1%); hypocalcemia, 57% (95%CI: 22%-88%); hyperphosphatemia, 33% (95%CI 11%-59%); hypophosphatemia, 4% (95%CI 0%-16%). According to the meta-analyses, the rate of hyperkalemia, hyponatremia, hypocalcemia, and hyperphosphatemia is higher than their counterpart in patients diagnosed with traumatic rhabdomyolysis.
PubMed: 38817473
DOI: 10.7759/cureus.59333 -
Journal of Nephrology Mar 2022Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory... (Meta-Analysis)
Meta-Analysis
The impact of phosphate lowering agents on clinical and laboratory outcomes in chronic kidney disease patients: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory parameters. This meta-analysis was conducted to comprehensively examine the impact of all phosphate lowering agents on various aspects of clinical and laboratory outcomes in CKD patients.
METHOD
A systematic literature search was performed in MEDLINE, Scopus, and the Cochrane Register of Controlled Trials until July 2020 to identify randomized controlled trials (RCTs) which compared the effects of each phosphate lowering agent with controls, comprising placebo and all other phosphate lowering agents. Various clinical and laboratory outcomes were analyzed. Random effects model was used to compute the standardized mean difference for continuous variables and the risk ratio (RR) for binary variables.
RESULTS
This meta-analysis included 127 RCTs with 20,215 patients. Sevelamer and lanthanum significantly reduced all-cause mortality (RR 0.610, 95% CI 0.401-0.929 and 0.467, 95% CI 0.337-0.647, respectively) but not cardiovascular (CV) mortality or CV events. Hospitalization rates were significantly diminished by sevelamer (RR 0.527; 95% CI 0.308-0.902). Certain phosphate lowering agents improved biochemical parameters including serum phosphate, calcium, coronary artery calcium scores, fibroblast growth factor-23, bone biomarkers, and lipid profiles. Intact parathyroid hormone and bone mineral density were not significantly changed.
CONCLUSIONS
In addition to decreasing serum phosphate levels, various beneficial effects on clinical and laboratory parameters of phosphate lowering agents might play potential roles in diminishing morbidity and mortality in CKD patients.
Topics: Humans; Hyperphosphatemia; Phosphates; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sevelamer
PubMed: 34061337
DOI: 10.1007/s40620-021-01065-3 -
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 -
American Journal of Kidney Diseases :... Aug 2017Owing to its longer treatment duration-up to 8 hours per dialysis treatment-in-center thrice-weekly nocturnal hemodialysis (HD) is receiving greater attention. To better... (Comparative Study)
Comparative Study Review
BACKGROUND
Owing to its longer treatment duration-up to 8 hours per dialysis treatment-in-center thrice-weekly nocturnal hemodialysis (HD) is receiving greater attention. To better understand the evidence for in-center nocturnal HD, we sought to systematically review the literature to determine the effects of in-center nocturnal HD versus conventional HD on clinically relevant outcomes.
STUDY DESIGN
We searched MEDLINE, Embase, Evidence-Based Medicine Reviews (EBMR), Web of Science, and Scopus from the earliest date in the database to November 2016.
SETTING & POPULATION
Adults receiving in-center nocturnal HD compared with those receiving conventional HD.
SELECTION CRITERIA FOR STUDIES
All quasi-experimental and observational studies were considered; randomized trials were sought but not found.
PREDICTOR
Nocturnal vs conventional in-center HD.
OUTCOMES
Indexes of blood pressure and left ventricular hypertrophy, markers of anemia, measures of bone mineral metabolism, nutrition, quality of life, sleep quality, episodes of intradialytic hypotension, hospitalization, and mortality.
RESULTS
Of 2,086 identified citations, 21 met the inclusion criteria, comprising a total of 1,165 in-center nocturnal HD patients and 15,865 conventional HD patients. Although there was substantial heterogeneity in reporting of outcomes, we pooled data for measures of blood pressure, anemia, and mineral metabolism. Though heterogeneity was generally high, in-center nocturnal HD was associated with improved systolic blood pressure (-3.18 [95% CI, -5.58 to -0.78) mm Hg, increased hemoglobin levels (0.53 [95% CI, 0.11-0.94] g/dL), and lower serum phosphate levels (-0.97 [95% CI, -1.48 to -0.46] mg/dL).
LIMITATIONS
No randomized trials have been conducted to address the clinical effects of in-center nocturnal HD. The quality of the observational literature contributing to the results of this review was generally poor to moderate. Confounded outcomes are a significant concern. Publication bias and outcome reporting bias remain possibilities.
CONCLUSIONS
Relative to conventional HD, in-center nocturnal HD was associated with improvements in several clinically relevant outcomes. Other benefits may not have been detected due to small sample sizes of included studies; no prespecified outcome was worse with in-center nocturnal HD.
Topics: Ambulatory Care Facilities; Hemodialysis, Home; Humans; Renal Dialysis; Treatment Outcome
PubMed: 28359656
DOI: 10.1053/j.ajkd.2017.01.047 -
International Urology and Nephrology Mar 2016To evaluate the efficacy and safety of the restricted protein diet (low or very low protein diet) supplemented with keto analogues in the treatment of chronic kidney... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To evaluate the efficacy and safety of the restricted protein diet (low or very low protein diet) supplemented with keto analogues in the treatment of chronic kidney disease (CKD).
METHODS
The Cochrane library, PubMed, Embase, CBM and CENTRAL databases were searched and reviewed up to April 2015. Clinical trials were analyzed using RevMan 5.3 software.
RESULTS
Seven random control trials, one cross-over trial and one non-randomized concurrent control trial were selected and included in this study according to our inclusion and exclusion criteria. The changes of eGFR, BUN, Scr, albumin, PTH, triglyceride, cholesterol, calcium, phosphorus and nutrition indexes (BMI, lean body mass and mid-arm muscular circumference) before and after treatment were analyzed. The meta-analysis results indicated that, comparing with normal protein diet, low protein diet (LPD) or very low protein diet (vLPD) supplemented with keto analogues (s(v)LPD) could significantly prevent the deterioration of eGFR (P < 0.001), hyperparathyroidism (P = 0.04), hypertension (P < 0.01) and hyperphosphatemia (P < 0.001). No differences in BUN, Scr, Albumin, triglyceride, cholesterol, hemoglobin, calcium and nutrition indexes were observed between different protein intake groups.
CONCLUSION
Restricted protein diet supplemented with keto analogues (s(v)LPD) could delay the progression of CKD effectively without causing malnutrition.
Topics: Diet, Protein-Restricted; Dietary Supplements; Disease Progression; Humans; Ketoses; Renal Insufficiency, Chronic
PubMed: 26620578
DOI: 10.1007/s11255-015-1170-2 -
American Journal of Kidney Diseases :... Jan 2018Understanding phosphate kinetics in dialysis patients is important for the prevention of hyperphosphatemia and related complications. One approach to gain new insights...
BACKGROUND
Understanding phosphate kinetics in dialysis patients is important for the prevention of hyperphosphatemia and related complications. One approach to gain new insights into phosphate behavior is physiologic modeling. Various models that describe and quantify intra- and/or interdialytic phosphate kinetics have been proposed, but there is a dearth of comprehensive comparisons of the available models. The objective of this analysis was to provide a systematic review of existing published models of phosphate metabolism in the setting of maintenance hemodialysis therapy.
STUDY DESIGN
Systematic review.
SETTING & POPULATION
Hemodialysis patients.
SELECTION CRITERIA FOR STUDIES
Studies published in peer-reviewed journals in English about phosphate kinetic modeling in the setting of hemodialysis therapy.
PREDICTOR
Modeling equations from specific reviewed studies.
OUTCOMES
Changes in plasma phosphate or serum phosphate concentrations.
RESULTS
Of 1,964 nonduplicate studies evaluated, 11 were included, comprising 9 different phosphate models with 1-, 2-, 3-, or 4-compartment assumptions. Between 2 and 11 model parameters were included in the models studied. Quality scores of the studies using the Newcastle-Ottawa Scale ranged from 2 to 11 (scale, 0-14). 2 studies were considered low quality, 6 were considered medium quality, and 3 were considered high quality.
LIMITATIONS
Only English-language studies were included.
CONCLUSIONS
Many parameters known to influence phosphate balance are not included in existing phosphate models that do not fully reflect the physiology of phosphate metabolism in the setting of hemodialysis. Moreover, models have not been sufficiently validated for their use as a tool to simulate phosphate kinetics in hemodialysis therapy.
Topics: Humans; Hyperphosphatemia; Kidney Failure, Chronic; Kinetics; Latent Class Analysis; Phosphates; Renal Dialysis
PubMed: 29191624
DOI: 10.1053/j.ajkd.2017.07.016