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American Journal of Kidney Diseases :... Nov 2017Uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by... (Review)
Review
BACKGROUND
Uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by patients. The optimal treatments for uremic pruritus are not well defined.
STUDY DESIGN
Systematic review.
SETTING & POPULATION
Adult patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis.
SELECTION CRITERIA FOR STUDIES
PubMed, CINAHL, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and ClinicalTrials.gov from their inception to March 6, 2017, were systematically searched for randomized controlled trials (RCTs) of uremic pruritus treatments in patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis. 2 reviewers extracted data independently. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool.
INTERVENTION
Any intervention for the treatment of uremic pruritus was included.
OUTCOMES
A quantitative change in pruritus intensity on a visual analogue, verbal rating, or numerical rating scale.
RESULTS
44 RCTs examining 39 different treatments were included in the review. These treatments included gabapentin, pregabalin, mast cell stabilizers, phototherapy, hemodialysis modifications, and multiple other systemic and topical treatments. The largest body of evidence was found for the effectiveness of gabapentin. Due to the limited number of trials for the other treatments included, we are unable to comment on their efficacy. Risk of bias in most studies was high.
LIMITATIONS
Heterogeneity in design, treatments, and outcome measures rendered comparisons difficult and precluded meta-analysis.
CONCLUSIONS
Despite the acknowledged importance of uremic pruritus to patients, with the exception of gabapentin, the current evidence for treatments is weak. Large, simple, rigorous, multiarm RCTs of promising therapies are urgently needed.
Topics: Administration, Cutaneous; Amines; Analgesics; Anti-Asthmatic Agents; Antipruritics; Capsaicin; Cromolyn Sodium; Cyclohexanecarboxylic Acids; Gabapentin; Humans; Kidney Failure, Chronic; Phototherapy; Pregabalin; Pruritus; Renal Dialysis; Renal Insufficiency, Chronic; Uremia; gamma-Aminobutyric Acid
PubMed: 28720208
DOI: 10.1053/j.ajkd.2017.05.018 -
Blood Jan 2015Many patients with syndromes of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, have been reported to have... (Review)
Review
Many patients with syndromes of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, have been reported to have a drug-induced etiology, and many different drugs have been suspected as a cause of TMA. We established criteria to assess the strength of evidence for a causal association of a drug with TMA and systematically searched for all published reports of drug-induced TMA. We identified 1569 articles: 604 were retrieved for review, 344 reported evaluable data for 586 individual patients, 43 reported evaluable data on 46 patient groups. Seventy-eight drugs were described; 22 had evidence supporting a definite causal association with TMA. Three drugs accounted for 61 of the 104 patient reports with definite evidence (quinine, 34; cyclosporine, 15; tacrolimus, 12). Twenty additional drugs had evidence supporting a probable association with TMA. These criteria and data can provide support for clinicians evaluating patients with suspected TMA.
Topics: Drug-Related Side Effects and Adverse Reactions; Female; Hemolytic-Uremic Syndrome; Humans; Male; Purpura, Thrombocytopenic, Idiopathic
PubMed: 25414441
DOI: 10.1182/blood-2014-11-611335 -
Journal of Cachexia, Sarcopenia and... Apr 2018Recent data pose the question whether conservative management of chronic kidney disease (CKD) by means of a low-protein diet can be a safe and effective means to avoid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent data pose the question whether conservative management of chronic kidney disease (CKD) by means of a low-protein diet can be a safe and effective means to avoid or defer transition to dialysis therapy without causing protein-energy wasting or cachexia. We aimed to systematically review and meta-analyse the controlled clinical trials with adequate participants in each trial, providing rigorous contemporary evidence of the impact of a low-protein diet in the management of uraemia and its complications in patients with CKD.
METHODS
We searched MEDLINE (PubMed) and other sources for controlled trials on CKD to compare clinical management of CKD patients under various levels of dietary protein intake or to compare restricted protein intake with other interventions. Studies with similar patients, interventions, and outcomes were included in the meta-analyses.
RESULTS
We identified 16 controlled trials of low-protein diet in CKD that met the stringent qualification criteria including having 30 or more participants. Compared with diets with protein intake of >0.8 g/kg/day, diets with restricted protein intake (<0.8 g/kg/day) were associated with higher serum bicarbonate levels, lower phosphorus levels, lower azotemia, lower rates of progression to end-stage renal disease, and a trend towards lower rates of all-cause death. In addition, very-low-protein diets (protein intake <0.4 g/kg/day) were associated with greater preservation of kidney function and reduction in the rate of progression to end-stage renal disease. Safety and adherence to a low-protein diet was not inferior to a normal protein diet, and there was no difference in the rate of malnutrition or protein-energy wasting.
CONCLUSIONS
In this pooled analysis of moderate-size controlled trials, a low-protein diet appears to enhance the conservative management of non-dialysis-dependent CKD and may be considered as a potential option for CKD patients who wish to avoid or defer dialysis initiation and to slow down the progression of CKD, while the risk of protein-energy wasting and cachexia remains minimal.
Topics: Diet, Protein-Restricted; Disease Progression; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic
PubMed: 29094800
DOI: 10.1002/jcsm.12264 -
Iranian Journal of Kidney Diseases Mar 2018Uremic pruritus is characterized by an uncomfortable and unlimited sensation which leads to scratch, which strongly reduces the quality of life. Pruritus is a common... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Uremic pruritus is characterized by an uncomfortable and unlimited sensation which leads to scratch, which strongly reduces the quality of life. Pruritus is a common symptom in patients with end-stage renal disease. Various clinical trial studies have examined the effects of acupuncture and acupressure on treatment of uremic pruritus. This systematic review meta-analysis aimed to evaluate the effectiveness based on published studies.
MATERIALS AND METHODS
An electronic literature search was conducted to identify appropriate trial studies. The results for continuous outcomes were presented as weighted mean difference, with 95% confidence intervals.
RESULTS
A total of 5 articles, including 6 trials, were enrolled in this systematic review. Only 3 of the six trial studies used a visual analogue scale score for assessing pruritus and acupressure for intervention regime, which were considered for meta-analysis. The combined results showed that acupuncture or acupressure was effective in treatment of uremic pruritus (pooled mean difference, -1.994; 95% confidence interval, -2.544 to -1.445).
CONCLUSIONS
This study confirms that using acupuncture and acupressure is effective in treatment of uremic pruritus. However, further vigorous studies are needed to verify these findings.
Topics: Acupressure; Acupuncture Points; Acupuncture Therapy; Adult; Chi-Square Distribution; Female; Humans; Male; Middle Aged; Pruritus; Quality of Life; Risk Factors; Treatment Outcome; Uremia
PubMed: 29507269
DOI: No ID Found -
Frontiers in Medicine 2021Many putative uremic toxins-like indoxyl sulfate, p-cresol sulfate, kynurenic acid, uric acid, and CMPF-are organic anions. Both inter-organ and inter-organismal...
Many putative uremic toxins-like indoxyl sulfate, p-cresol sulfate, kynurenic acid, uric acid, and CMPF-are organic anions. Both inter-organ and inter-organismal communication are involved. For example, the gut microbiome is the main source of indole, which, after modification by liver drug metabolizing enzymes (DMEs), becomes indoxyl sulfate. Various organic anion transporters (organic anion transporters, OATs; organic anion-transporting polypeptides, OATPs; multidrug resistance-associated proteins, MRPs, and other ABC transporters like ABCG2)-often termed "drug transporters"-mediate movement of uremic toxins through cells and organs. In the kidney proximal tubule, critical roles for OAT1 and OAT3 in regulating levels of protein-bound uremic toxins have been established using knock-out mice. OATs are important in maintaining residual tubular function in chronic kidney disease (CKD); as CKD progresses, intestinal transporters like ABCG2, which extrude urate and other organic anions into the gut lumen, seem to help restore homeostasis. Uremic toxins like indoxyl sulfate also regulate signaling and metabolism, potentially affecting gene expression in extra-renal tissues as well as the kidney. Focusing on the history and evolving story of indoxyl sulfate, we discuss how uremic toxins appear to be part of an extensive "remote sensing and signaling" network-involving so-called drug transporters and drug metabolizing enzymes which modulate metabolism and signaling. This systems biology view of uremic toxins is leading to a new appreciation of uremia as partly due to disordered remote sensing and signaling mechanisms-resulting from, and causing, aberrant inter-organ (e.g., gut-liver- kidney-CNS) and inter-organismal (e.g., gut microbiome-host) communication.
PubMed: 33937275
DOI: 10.3389/fmed.2021.592602 -
Annals of Palliative Medicine Apr 2022Uremia is a clinical syndrome caused by the development of chronic renal failure to the end-stage. Corbrin Capsule has the effect of tonifying the lungs and kidneys and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Uremia is a clinical syndrome caused by the development of chronic renal failure to the end-stage. Corbrin Capsule has the effect of tonifying the lungs and kidneys and improving the essence and qi, which can improve the metabolic disorders of the body. However, there is currently no systematic evaluation of the efficacy of Corbrin Capsule in the treatment of uremia malnutrition, inflammation, and atherosclerosis (MIA) syndrome. This paper aiming to provide a reference for improving the prognosis of uremic MIA patients.
METHODS
According to the PICOS principle, the literature inclusion and exclusion criteria were formulated. The databases such as PubMed, Web of Science, Embase, and Cochrane Library were searched by computer using "Corbrin Capsule", "uremia", "MIA syndrome", and "kidney function" as search items. The outcome indicators were body mass index (BMI), C-reactive protein (CRP), blood urea nitrogen (BUN), and serum creatinine (sCr). Subsequently, the Cochrane Reviewer's Handbook 4.2.5 was adopted to assess the literature quality. The conventional treatment combined with Corbrin Capsule was defined as MIA/treatment group, and the conventional treatment was defined as the control group. The Review Manager (RevMan) 5.3 software was used to conduct a meta-analysis of the experimental data.
RESULTS
A total of 6 suitable included articles were selected, including 894 patients. The included literature was analyzed and found that there was no obvious publication bias. According to the results of meta-analysis, the total BMI score was mean difference (MD) [95% confidence interval (CI)]: -0.10 (-3.44 to 3.24) with Z=0.06 and P=0.95. The CRP total score was MD (95% CI): 1.40 (0.34 to 2.46) with Z=2.58 and P=0.010. The BUN index was MD (95% CI): -1.15 (-3.05 to 0.75) with Z=1.18, P=0.24. Analysis result of sCr index data was MD (95% CI): -72.82 (-202.16 to 56.52) with Z=1.10 and P=0.27.
DISCUSSION
Corbrin Capsule can effectively improve the relevant physiological indicators of patients with uremic MIA syndrome. However, the outcome indicators included in this study were insufficient, and it is necessary to further expand the sample size and outcome indicators in the future.
Topics: Atherosclerosis; Cordyceps; Female; Humans; Inflammation; Male; Malnutrition; Syndrome; Uremia
PubMed: 35523751
DOI: 10.21037/apm-22-291 -
The Cochrane Database of Systematic... Mar 2021Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The condition is primarily caused by inherited or acquired dysregulation of complement regulatory proteins with ~40% of those affected aged < 18 years. Historically, kidney failure and death were common outcomes, however, improved understanding of the condition has led to discovery of novel therapies.
OBJECTIVES
To evaluate the benefits and harms of interventions for aHUS.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies for randomised controlled studies (RCTs) up to 3 September 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. MEDLINE(OVID) 1946 to 27 July 2020 and EMBASE (OVID) 1974 to 27 July 2020 were searched for non-RCTs.
SELECTION CRITERIA
All randomised and non-randomised clinical trials comparing an intervention with placebo, an intervention with supportive therapy, or two or more interventions for aHUS were included. Given the rare nature of the condition in question, prospective single-arm studies of any intervention for aHUS were also included.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted pre-specified data from eligible studies and evaluated risk of bias using a newly developed tool based on existing Cochrane criteria. As statistical meta-analysis was not appropriate, qualitative analysis of data was then performed.
MAIN RESULTS
We included five single-arm studies, all of which evaluated terminal complement inhibition for the treatment of aHUS. Four studies evaluated the short-acting C5 inhibitor eculizumab and one study evaluated the longer-acting C5 inhibitor ravulizumab. All included studies within the review were of non-randomised, single-arm design. Thus, risk of bias is high, and it is challenging to draw firm conclusions from this low-quality evidence. One hundred patients were included within three primary studies evaluating eculizumab, with further data reported from 37 patients in a secondary study. Fifty-eight patients were included in the ravulizumab study. After 26 weeks of eculizumab therapy there were no deaths and a 70% reduction in the number of patients requiring dialysis. Complete thrombotic microangiopathic (TMA) response was observed in 60% of patients at 26 weeks and 65% at two years. After 26 weeks of ravulizumab therapy four patients had died (7%) and complete TMA response was observed in 54% of patients. Substantial improvements were seen in estimated glomerular filtration rate and health-related quality of life in both eculizumab and ravulizumab studies. Serious adverse events occurred in 42% of patients, and meningococcal infection occurred in two patients, both treated with eculizumab.
AUTHORS' CONCLUSIONS
When compared with historical data, terminal complement inhibition appears to offer favourable outcomes in patients with aHUS, based upon very low-quality evidence drawn from five single-arm studies. It is unlikely that an RCT will be conducted in aHUS and therefore careful consideration of future single-arm data as well as longer term follow-up data will be required to better understand treatment duration, adverse outcomes and risk of disease recurrence associated with terminal complement inhibition.
Topics: Antibodies, Monoclonal, Humanized; Atypical Hemolytic Uremic Syndrome; Bias; Complement Inactivating Agents; Glomerular Filtration Rate; Humans; Non-Randomized Controlled Trials as Topic; Quality of Life; Thrombotic Microangiopathies
PubMed: 33783815
DOI: 10.1002/14651858.CD012862.pub2 -
The Journal of Rheumatology Dec 2021The epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence, prevalence, risk factors, and treatments of peripheral neuropathy in SSc.
METHODS
A systematic review of MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for literature reporting peripheral neuropathy in SSc was performed. Studies evaluating incidence, prevalence, risk factors, and treatments were synthesized. A metaanalysis using a random effects model was used to evaluate the prevalence of peripheral neuropathy.
RESULTS
This systematic review identified 113 studies that reported 949 of 2143 subjects with at least 1 type of peripheral neuropathy. The mean age was 48.5 years. The mean time between SSc onset and detection of peripheral neuropathy was 8.85 years. The pooled prevalence of neuropathy was 27.37% (95% CI 22.35-32.70). Risk factors for peripheral neuropathy in SSc included advanced diffuse disease, anticentromere antibodies, calcinosis cutis, ischemia of the vasa nervorum, iron deficiency anemia, metoclopramide, pembrolizumab, silicosis, and uremia. There were 73 subjects with successful treatments (n = 36 restoring sensation, n = 37 restoring motor or sensorimotor function). Treatments included decompression surgery, prednisone, cyclophosphamide, carbamazepine, transcutaneous electrical nerve stimulation, tricyclic antidepressants, and intravenous Ig.
CONCLUSION
All-cause peripheral neuropathy is not uncommon in SSc. Compression neuropathies can be treated with decompression surgery. Observational data reporting immunosuppressives and anticonvulsants to treat peripheral neuropathy in SSc are limited and conflicting. Randomized controlled trials are needed to evaluate the efficacy of these interventions.
Topics: Humans; Incidence; Iron Deficiencies; Middle Aged; Peripheral Nervous System Diseases; Risk Factors; Scleroderma, Systemic
PubMed: 34210833
DOI: 10.3899/jrheum.201299 -
Journal of the American Society of... Sep 2014A growing number of publications supports a biologic effect of the protein-bound uremic retention solutes indoxyl sulfate and p-cresyl sulfate. However, the use of... (Review)
Review
A growing number of publications supports a biologic effect of the protein-bound uremic retention solutes indoxyl sulfate and p-cresyl sulfate. However, the use of unrealistically high free concentrations of these compounds and/or inappropriately low albumin concentrations may blur the interpretation of these results. Here, we performed a systematic review, selecting only studies in which, depending on the albumin concentration, real or extrapolated free concentrations of indoxyl sulfate and p-cresyl sulfate remained in the uremic range. The 27 studies retrieved comprised in vitro and animal studies. A quality score was developed, giving 1 point for each of the following criteria: six or more experiments, confirmation by more than one experimental approach, neutralization of the biologic effect by counteractive reagents or antibodies, use of a real-life model, and use of dose-response analyses in vitro and/or animal studies. The overall average score was 3 of 5 points, with five studies scoring 5 of 5 points and six studies scoring 4 of 5 points, highlighting the superior quality of a substantial number of the retrieved studies. In the 11 highest scoring studies, most functional deteriorations were related to uremic cardiovascular disease and kidney damage. We conclude that our systematic approach allowed the retrieval of methodologically correct studies unbiased by erroneous conditions related to albumin binding. Our data seem to confirm the toxicity of indoxyl sulfate and p-cresyl sulfate and support their roles in vascular and renal disease progression.
Topics: Animals; Cresols; Disease Models, Animal; Humans; Indican; Kidney; Models, Biological; Protein Binding; Renal Insufficiency, Chronic; Sulfuric Acid Esters; Toxins, Biological; Uremia
PubMed: 24812165
DOI: 10.1681/ASN.2013101062 -
Journal of Health, Population, and... Sep 2012Haemolytic-uraemic syndrome (HUS) is a serious sequela of diarrhoea and results in a high mortality rate. This systematic review aimed at estimating the proportion of... (Review)
Review
Haemolytic-uraemic syndrome (HUS) is a serious sequela of diarrhoea and results in a high mortality rate. This systematic review aimed at estimating the proportion of HUS cases that are linked to prior infection due to Shiga toxin-producing Escherichia coli (STEC) or Shigella dysenteriae type 1. A systematic review of the existing literature was done to identify cohort and case-control studies that examined the relationship between STEC and S. dysenteriae type 1 and HUS. After screening 2,516 articles, 11 studies were found that met the inclusion/exclusion criteria. Findings of case-control studies suggest that 60.8% of the HUS cases may be attributable to a previous infection with STEC. In cohort studies, 7.8% of participants with STEC and 8% of participants with S. dysenteriae type 1 developed HUS during follow-up. HUS is linked to diarrhoea due to both STEC and S. dysenteriae type 1. Thus, preventing infections caused by both pathogens is critical for the prevention and control of HUS, especially in areas where timely and effective treatment is not available.
Topics: Case-Control Studies; Cohort Studies; Diarrhea; Dysentery; Global Health; Hemolytic-Uremic Syndrome; Humans; Shiga-Toxigenic Escherichia coli; Shigella dysenteriae
PubMed: 23082627
DOI: 10.3329/jhpn.v30i3.12288