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The Cochrane Database of Systematic... Aug 2023Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause... (Review)
Review
BACKGROUND
Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017.
OBJECTIVES
To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination.
SEARCH METHODS
We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE).
MAIN RESULTS
We included three RCTs with 385 participants. We rated the certainty of the evidence as low to very low across different outcomes according to GRADE methodology, downgrading for risk of bias concerns, indirectness, and imprecision. Hydroxyurea versus placebo One RCT published in 2011 compared hydroxyurea to placebo in 193 children aged nine to 18 months. We are unsure if hydroxyurea compared to placebo reduces or prevents progression of kidney disease assessed by change in glomerular filtration rate (mean difference (MD) 0.58 mL/min /1.73 m, 95% confidence interval (CI) -14.60 to 15.76; 142 participants; very low certainty). Hydroxyurea compared to placebo may improve the ability to concentrate urine (MD 42.23 mOsm/kg, 95% CI 12.14 to 72.32; 178 participants; low certainty), and may make little or no difference to SCD-related serious adverse events, including acute chest syndrome (risk ratio (RR) 0.39, 99% CI 0.13 to 1.16; 193 participants; low certainty), painful crisis (RR 0.68, 99% CI 0.45 to 1.02; 193 participants; low certainty); and hospitalisations (RR 0.83, 99% CI 0.68 to 1.01; 193 participants; low certainty). No deaths occurred in either trial arm and the RCT did not report quality of life. Angiotensin-converting enzyme inhibitors versus placebo One RCT published in 1998 compared an ACEI (captopril) to placebo in 22 adults with normal blood pressure and microalbuminuria. We are unsure if captopril compared to placebo reduces proteinuria (MD -49.00 mg/day, 95% CI -124.10 to 26.10; 22 participants; very low certainty). We are unsure if captopril reduces or prevents kidney disease as measured by creatinine clearance; the trial authors stated that creatinine clearance remained constant over six months in both groups, but provided no comparative data (very low certainty). The RCT did not report serious adverse events, all-cause mortality, or quality of life. Angiotensin-converting enzyme inhibitors versus vitamin C One RCT published in 2020 compared an ACEI (lisinopril) with vitamin C in 170 children aged one to 18 years with normal blood pressure and microalbuminuria. It reported no data we could analyse. We are unsure if lisinopril compared to vitamin C reduces proteinuria in this population: the large drop in microalbuminuria in both arms of the trial after only one month on treatment may have been due to an overestimation of microalbuminuria at baseline rather than a true effect. The RCT did not report serious adverse events, all-cause mortality, or quality of life.
AUTHORS' CONCLUSIONS
We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.
Topics: Child; Adult; Humans; Adolescent; Hydroxyurea; Antisickling Agents; Acute Chest Syndrome; Captopril; Lisinopril; Creatinine; Anemia, Sickle Cell; Kidney Failure, Chronic; Proteinuria; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid
PubMed: 37539955
DOI: 10.1002/14651858.CD012380.pub3 -
Reproductive Biomedicine Online Aug 2015The p53 tumour suppressor gene plays an important role in angiogenesis and apoptosis. The association between Arg72Pro polymorphism and recurrent pregnancy loss (RPL)... (Meta-Analysis)
Meta-Analysis Review
The p53 tumour suppressor gene plays an important role in angiogenesis and apoptosis. The association between Arg72Pro polymorphism and recurrent pregnancy loss (RPL) has been studied but with inconsistent results. A meta-analysis was conducted to examine whether p53 Arg72Pro polymorphism is a risk factor for RPL. Electronic searches of PubMed, Embase and Web of Knowledge were conducted to identify relevant studies. The final meta-analysis included six published articles with 730 RPL cases and 613 controls. The pooled results suggested that the variant genotype was associated with the RPL risk in additive model (Pro versus Arg; odds ratio [OR] = 1.28; 95% confidence interval [CI]: 1.06 to 1.54) and recessive model (Pro/Pro versus Arg/Pro + Arg/Arg; OR = 1.82; 95% CI: 1.21 to 2.73). In the stratified analysis by ethnicity, for white people the results were consistent. The Egger's regression asymmetry test suggested a lack of publication bias. Results of this meta-analysis suggest that p53 codon 72 polymorphism is associated with RPL, especially in white people. Identification of p53 codon 72 mutation would have some implication for primary prevention of RPL and screening of high-risk individuals. Large well-designed studies are needed to fully describe the association between this polymorphism and RPL.
Topics: Abortion, Habitual; Arginine; Codon; Female; Humans; Polymorphism, Single Nucleotide; Proline; Tumor Suppressor Protein p53
PubMed: 26099444
DOI: 10.1016/j.rbmo.2015.05.003 -
Clinics and Research in Hepatology and... Mar 2022Biofilm-producing bacteria are relatively resistant to antibiotics, as the penetration of antibiotics into the endopolysaccharide envelope is incomplete. N Acetyl... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Biofilm-producing bacteria are relatively resistant to antibiotics, as the penetration of antibiotics into the endopolysaccharide envelope is incomplete. N Acetyl cysteine (NAC) is known to destabilize the biofilms, as it cleaves the disulfide bonds of mucus glycoproteins, reducing the viscosity and thickness of mucus. This allows NAC to act synergistically with antibiotics for the eradication of H Pylori. The meta-analysis evaluates the evidence of the efficacy of adjuvant N acetyl cysteine (NAC) compared to standard therapies in the eradication of H. Pylori infections.
METHODS
We searched randomized clinical trials in MEDLINE, Cochrane Central Register of Clinical Trials (CENTRAL), EBSCO, Database of Abstracts of Reviews of Effects (DARE), and Google Scholar. We included trials comparing standard treatment protocols plus adjuvant NAC and the same regimen without NAC. These studies included adults with a diagnosis of Helicobacter pylori infection. Our primary outcome was the successful eradication of H. Pylori. The results were pooled using a random-effects model, and data were analyzed using RevMan 5.0 software. Cochrane collaboration's tool was used to assess the risk of bias. Publication bias and other inconsistencies were assessed. Sensitivity analyses and grading of evidence were performed.
FINDINGS
Eight studies, comprising 1167 patients, were included in the meta-analysis, the pooled outcomes of patients on adjuvant NAC+ standard eradication therapy noted an eradication rate of 76.1% (n=581) compared to the patients in standard eradication therapy with a rate of 72.18% (n=586), RR 1.17 [95% CI (0.99, 1.39); I2= 64%; p value=0.07]. Moderate to severe heterogeneity was noted. These pooled results show that adjuvant NAC plus standard treatment protocols are not superior to standard treatment protocols for H pylori eradication. Similar results were seen in the use of adjuvant NAC with 'currently used standard treatment protocols' (78.3% versus 76.3%, RR 1.08, [95% CI 0.94 to 1.25]; I2=55%; p=0.28; n= 829 patients], as well as in the treatment of naïve patients (79.8% versus 80.9%, RR 1.00[95% CI 0.87 to 1.15]; i2=27%; P=-0.98; n= 775 patients].
CONCLUSION
Adjuvant NAC plus standard treatment protocols are not superior to standard treatment protocols for H. pylori eradication. These findings are consistent with the use of adjuvant NAC with 'currently used standard treatment protocols' (clarithromycin-based triple therapies) and also with adjuvant NAC used in the treatment of naïve patients. We are moderately certain of these findings. Future studies could explore the use of NAC as a pretreatment before using the current standard therapies in the eradication of H. Pylori rather than NAC as adjuvant therapy.
FUNDING
None.
Topics: Adult; Anti-Bacterial Agents; Clarithromycin; Cysteine; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 34775122
DOI: 10.1016/j.clinre.2021.101832 -
Pharmacological Research May 2020The effect of roxadustat (FG-4592) on individuals with chronic kidney diseases (CKD) patients receiving or not receiving the dialysis was unclear. The aim of this study... (Meta-Analysis)
Meta-Analysis
Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: A systematic review and meta-analysis.
The effect of roxadustat (FG-4592) on individuals with chronic kidney diseases (CKD) patients receiving or not receiving the dialysis was unclear. The aim of this study was to evaluate the efficacy of roxadustat for the treatment of anemia in patients who are dialysis dependent (DD) or dialysis independent (NDD) CKD. We performed a systematic review of randomised controlled trials (RCTs) comparing treatment with roxadustat versus placebo or epoetin alfa up to November 2019. We investigated the efficacy of roxadustat in the levels of hemoglobin and other clinical parameters in renal anemia in patients with NDD and DD-CKD. We estimated weighted-mean difference (WMD) using random effect models. We included six RCTs comprising 1001 patients of whom 70.6 % were treated with roxadustat and 294 controls. The control group for studies of NDD-CKD patients was placebo whereas an active control of epoetin-alfa was used in studies of DD-CKD patients. Median follow-up time was 8 weeks. All trials were industry-sponsored. Overall, roxadustat increased hemoglobin levels by 1.20 g/dl (95 % CI:0.66, 1.75,P < 0.0001,I = 99.3 %). Hemoglobin levels increased by 1.99 g/dl in NDD-CKD patients versus placebo and 0.52 g/dl in DD-CKD patients versus epoetin-alfa. Roxadustat was associated with a decrease the levels of hepcidin by -49.3 ng/dl (-38.5 ng/dl in NDD patients versus placebo and -27.7 ng/dl in DD patients versus epoetin alfa), a decrease in ferritin of -49.7 μmol/l (-52.2 μmol/l in NDD patients versus placebo and -7.3 μmol/l in DD patients versus epoetin alfa), and increase in total iron-binding capacity of 32.2 μmol/l (14.1 μmol/l in NDD patients versus placebo and 13.6 μmol/l in DD patients versus epoetin alfa). The percentage change in the transferrin saturation levels was -2.07 % (-6%, NDD patients versus placebo, and +3.7 % in DD patients versus epoetin alfa) in anemia associated CKD patients. This review found roxadustast increases the levels of hemoglobin, serum transferrin, intestinal iron absorption, and reduces hepcidin in both NDD and DD-CKD patients. Safety data is still emerging.
Topics: Anemia; Glycine; Humans; Isoquinolines; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 32171893
DOI: 10.1016/j.phrs.2020.104747 -
The Cochrane Database of Systematic... Jul 2012Chronic kidney disease (CKD) is a major public health issue worldwide. Standard therapies to delay CKD progression include dietary protein restriction and administration... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic kidney disease (CKD) is a major public health issue worldwide. Standard therapies to delay CKD progression include dietary protein restriction and administration of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) to help control blood pressure and confer additional renoprotective effects. Despite such interventions, CKD incidence and mortality rates continue to increase. Rheum officinale (Da Huang) a medicinal herb used widely in China to treat CKD has been reported to offer a range of pharmacological properties that may delay disease progression.
OBJECTIVES
To assess the benefits and harms of Rheum officinale for preventing the progression of CKD.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register and CENTRAL (Issue 4, 2011), MEDLINE, EMBASE, the Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), VIP (Chongqing VIP Chinese Science and Technology Periodical Database), and Wanfang Data. We also handsearched reference lists of articles. We applied no restrictions on language of publication.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that assessed the benefits and harms of Rheum officinale for preventing the progression of CKD regardless of dosage, type, maturity, mode of administration, duration of treatment, or storage time before use.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We expressed results for dichotomous outcomes (need for renal replacement therapy, all-cause mortality, quality of life) as risk ratios (RR) with 95% confidence intervals (CI). Continuous outcomes (glomerular filtration rate (GFR), serum creatinine (SCr), creatinine clearance (CrCl), blood urea nitrogen (BUN)) were expressed as mean differences (MD) with 95% CIs.
MAIN RESULTS
We identified nine studies that enrolled 682 participants. None of the studies reported blinding or group allocation methods. Seven studies were judged to be at low risk of incomplete outcome reporting; three studies were judged to be a low risk of selective reporting (protocols were available and/or all outcomes relevant to the this review were reported); and two studies were judged free of other potential biases.Seven studies compared Rheum officinale with no treatment and two made comparisons with captopril, an angiotensin-converting enzyme inhibitor (ACEi). Compared with no treatment, Rheum officinale had a positive effect on SCr (MD -87.49 µmol/L, 95% CI -139.25 to -35.72) and BUN (MD -10.61 mmol/L, 95% CI -19.45 to -2.21). Compared with captopril, a statistically significant difference was not demonstrated in relation to Rheum officinale for any outcome (BUN, CrCl, or patients' capacity to undertake work). No data were available on all-cause mortality or cost of treatment. Only minor adverse events were reported in association with Rheum officinale.
AUTHORS' CONCLUSIONS
Currently available evidence concerning the efficacy of Rheum officinale to improve SCr and BUN levels in patients with CKD is both scant and low quality. Although Rheum officinale does not appear to be associated with serious adverse events among patients with CKD, there is no current evidence to support any recommendation for its use.
Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Disease Progression; Humans; Kidney Failure, Chronic; Medicine, Chinese Traditional; Phytotherapy; Rheum
PubMed: 22786510
DOI: 10.1002/14651858.CD008000.pub2 -
International Journal of Obesity (2005) Feb 2024Overweight and obesity are the consequence of a sustained positive energy balance. Twin studies show high heritability rates pointing to genetics as one of the principal... (Review)
Review
BACKGROUND
Overweight and obesity are the consequence of a sustained positive energy balance. Twin studies show high heritability rates pointing to genetics as one of the principal risk factors. By 2022, genomic studies led to the identification of almost 300 obesity-associated variants that could help to fill the gap of the high heritability rates. The endocannabinoid system is a critical regulator of metabolism for its effects on the central nervous system and peripheral tissues. Fatty acid amide hydrolase (FAAH) is a key enzyme in the inactivation of one of the two endocannabinoids, anandamide, and of its congeners. The rs324420 variant within the FAAH gene is a nucleotide missense change at position 385 from cytosine to adenine, resulting in a non-synonymous amino acid substitution from proline to threonine in the FAAH enzyme. This change increases sensitivity to proteolytic degradation, leading to reduced FAAH levels and increased levels of anandamide, associated with obesity-related traits. However, association studies of this variant with metabolic parameters have found conflicting results. This work aims to perform a systematic review of the existing literature on the association of the rs324420 variant in the FAAH gene with obesity and its related traits.
METHODS
A literature search was conducted in PubMed, Web of Science, and Scopus. A total of 645 eligible studies were identified for the review.
RESULTS/CONCLUSIONS
After the identification, duplicate elimination, title and abstract screening, and full-text evaluation, 28 studies were included, involving 28 183 individuals. We show some evidence of associations between the presence of the variant allele and higher body mass index, waist circumference, fat mass, and waist-to-hip ratio levels and alterations in glucose and lipid homeostasis. However, this evidence should be taken with caution, as many included studies did not report a significant difference between genotypes. These discordant results could be explained mainly by the pleiotropy of the endocannabinoid system, the increase of other anandamide-like mediators metabolized by FAAH, and the influence of gene-environment interactions. More research is necessary to study the endocannabinoidomic profiles and their association with metabolic diseases.
Topics: Humans; Endocannabinoids; Obesity; Phenotype; Amidohydrolases; Arachidonic Acids; Polyunsaturated Alkamides
PubMed: 38114812
DOI: 10.1038/s41366-023-01428-9 -
Caries Research 2022Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the...
Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the literature regarding the concentrations of salivary proteins in caries-free (CF) and caries-active (CA) subjects. Hence, this systematic review was conducted to update our previous systematic review published in 2013 that aimed to assess the association between caries and salivary proteins by comparing CF and CA individuals. Thereby, evaluating the possibility of whether salivary proteins can be regarded as biomarkers for caries. An extensive search of studies was conducted using PubMed, EMBASE, Clarivate Analytics' Web of Science, and Elsevier's Scopus between July 2012 and January 2022, without any language restriction. Manual searching in Google Scholar and evaluation of bibliographies of the included studies were also undertaken. The Newcastle-Ottawa Scale was used to assess the risk of bias (RoB) within the included studies. Of 22 included studies, 1,551 human subjects (range: 30-213 participants) were recruited, of which 848 individuals (54.7%) were CA and 703 (45.3%) were CF. Regarding the utilization of DMFT as the caries index, high variability was observed across different articles. A statistically significant increase in the salivary levels of alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, and mucin-1 was found in CA patients, while the salivary levels of carbonic anhydrase 6, proteinase-3, and statherin were observed to be significantly increased in CF subjects. Conflicting results were found regarding the salivary levels of immunoglobulin A and total proteins among CA and CF subjects. The included studies were categorized as low RoB (n = 15), medium RoB (n = 4), and high RoB (n = 3). Due to significant heterogeneity among the included studies, no meta-analysis could be performed. In conclusion, the salivary levels of protein(s) might be a useful biomarker for caries diagnosis, especially alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, mucin-1, carbonic anhydrase 6, proteinase-3, and statherin. However, their diagnostic value must be verified by large-scale prospective studies.
Topics: Humans; Mucin-1; Dental Caries; Histatins; Lactoperoxidase; Prospective Studies; Salivary Proteins and Peptides; Biomarkers; Proline; alpha-Amylases; Peptide Hydrolases
PubMed: 36116431
DOI: 10.1159/000526942 -
Clinical Drug Investigation May 2013Chronic hepatitis C represents an important health problem. The aim of our meta-analysis was to establish the role of reference single nucleotide (rs) 12979860 allele of... (Meta-Analysis)
Meta-Analysis Review
Role of interleukin-28B polymorphism as a predictor of sustained virological response in patients with chronic hepatitis C treated with triple therapy: a systematic review and meta-analysis.
BACKGROUND AND OBJECTIVE
Chronic hepatitis C represents an important health problem. The aim of our meta-analysis was to establish the role of reference single nucleotide (rs) 12979860 allele of interleukin-28B (IL28B) CC versus CT+TT genotype (the most researched allele of IL28B) as a predictor of sustained virological response (SVR) in patients with chronic hepatitis C treated with triple therapy.
METHODS
The PubMed, MEDLINE, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases as well as abstract books from important gastroenterology and hepatology meetings were searched for all studies published until 15 July 2012 that analysed the relationship between the polymorphism of IL28B and SVR in patients with chronic hepatitis C, genotype 1, treated with pegylated interferon + ribavirin + direct antiviral agents (telaprevir or boceprevir). The following keywords were used: IL28B polymorphism, chronic hepatitis C, sustained virological response, SVR, triple therapy, telaprevir, boceprevir.
RESULTS
Odds ratios (ORs) with 95 % confidence intervals were pooled from five study populations (1,641 cases) using a random-effects model. The SVR rate was significantly higher in patients with the CC genotype of IL28B than in those with non-CC genotypes (CT and TT): OR = 3.91 (95 % CI 2.11-7.28), p < 0.0001. Higher SVR rates were obtained in chronic hepatitis C patients with the CC genotype of IL28B, regardless of their therapeutic status (naïve patients: OR = 3.99 [95 % CI 1.67-9.51], p < 0.0001; and previously treated ones: OR = 2.15 [95 % CI 1.35-3.43], p = 0.001).
CONCLUSION
IL28B polymorphism seems to influence the SVR rate in patients with chronic hepatitis C treated with triple therapy, but further studies are needed to clarify the mechanism and the influence of other factors on the SVR rates.
Topics: Antiviral Agents; Drug Therapy, Combination; Gene Frequency; Genotype; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Interferons; Interleukins; Linear Models; Odds Ratio; Oligopeptides; Pharmacogenetics; Phenotype; Polyethylene Glycols; Polymorphism, Single Nucleotide; Proline; Recombinant Proteins; Ribavirin; Treatment Outcome
PubMed: 23532802
DOI: 10.1007/s40261-013-0074-0 -
Parasitology Jun 2019Although leucocytes are targets of renin-angiotensin system (RAS) effector molecules and RAS-modulating drugs exert immunomodulatory effects, their impact on Trypanosoma...
Although leucocytes are targets of renin-angiotensin system (RAS) effector molecules and RAS-modulating drugs exert immunomodulatory effects, their impact on Trypanosoma cruzi infection remains poorly understood. By using the framework of a systematic review, we integrated the preclinical and clinical evidence to investigate the relevance of angiotensin-inhibiting drugs on T. cruzi infections. From a comprehensive and structured search in biomedical databases, only original studies were analysed. In preclinical and clinical studies, captopril, enalapril and losartan were RAS-modulating drugs used. The main in vitro findings indicated that these drugs increased parasite uptake per host cells, IL-12 expression by infected dendritic cells and IFN-γ by T lymphocytes, in addition to attenuating IL-10 and IL-17 production by CD8 + T cells. In animal models, reduced parasitaemia, tissue parasitism, leucocytes infiltration and mortality were often observed in T. cruzi-infected animals receiving RAS-modulating drugs. In patients with Chagas' disease, these drugs exerted a controversial impact on cytokine and hormone levels, and a limited effect on cardiovascular function. Considering a detailed evaluation of reporting and methodological quality, the current preclinical and clinical evidence is at high risk of bias, and we hope that our critical analysis will be useful in mitigating the risk of bias in further studies.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; CD8-Positive T-Lymphocytes; Captopril; Chagas Cardiomyopathy; Chagas Disease; Clinical Studies as Topic; Cytokines; Drug Evaluation, Preclinical; Enalapril; Humans; Losartan; Mice; Trypanosoma cruzi
PubMed: 30782223
DOI: 10.1017/S003118201900009X -
The Cochrane Database of Systematic... Feb 2023IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis of childhood but may also occur in adults. This small vessel... (Review)
Review
BACKGROUND
IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis of childhood but may also occur in adults. This small vessel vasculitis is characterised by palpable purpura, abdominal pain, arthritis or arthralgia and kidney involvement. This is an update of a review first published in 2009 and updated in 2015.
OBJECTIVES
To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo, no treatment or any other agent for (1) the prevention of severe kidney disease in people with IgAV with or without kidney involvement at onset, (2) the treatment of established severe kidney disease (macroscopic haematuria, proteinuria, nephritic syndrome, nephrotic syndrome with or without acute kidney failure) in IgAV, and (3) the prevention of recurrent episodes of IgAV-associated kidney disease.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 2 February 2023 through contact with the Information Specialist 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.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing interventions used to prevent or treat kidney disease in IgAV compared with placebo, no treatment or other agents were included.
DATA COLLECTION AND ANALYSIS
Two authors independently determined study eligibility, assessed the risk of bias and extracted data from each study. Statistical analyses were performed using the random-effects model, and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Twenty studies (1963 enrolled participants) were identified; one three-arm study has been assessed as two studies. Nine studies were at low risk of bias for sequence generation (selection bias), and nine studies were at low risk of bias for allocation concealment (selection bias). Blinding of participants and personnel (performance bias) and outcome assessment (detection bias) was at low risk of bias in four and seven studies, respectively. Nine studies reported complete outcome data (attrition bias), while 10 studies reported expected outcomes, so were at low risk of reporting bias. Five studies were at low risk of other bias. Eleven studies evaluated therapy to prevent persistent kidney disease in IgAV with or without kidney involvement at presentation. There was probably no difference in the risk of persistent kidney disease any time after treatment (5 studies, 746 children: RR 0.74, 95% CI 0.42 to 1.32) or at one, three, six and 12 months in children given prednisone for 14 to 28 days at presentation of IgAV compared with placebo or supportive treatment (moderate certainty evidence). There may be no differences in the risk of any persistent kidney disease with antiplatelet therapy (three studies) or heparin (two studies) in children with or without any kidney disease at study entry, although heparin may reduce the risk of proteinuria by three months compared with placebo or no specific treatment (2 studies, 317 children: RR 0.47, 95% CI 0.31 to 0.73). One study comparing montelukast with placebo found no differences in outcomes as assessed by severity scale scores. Nine studies examined the treatment of severe IgAV-associated kidney disease. In two studies (one involving 56 children and the other involving 54 adults), there may be no differences in efficacy outcomes or adverse effects with cyclophosphamide compared with placebo or supportive treatment. In two studies, there may be no differences in the numbers achieving remission of proteinuria with intravenous (IV) cyclophosphamide compared with mycophenolate mofetil (MMF) (65 children evaluated) or tacrolimus (142 children evaluated). In three small studies comparing cyclosporin with methylprednisolone (15 children), MMF with azathioprine (26 children), or MMF with leflunomide (19 children), it is unclear whether the treatment had any effect on the numbers in remission or the degree of proteinuria between treatment groups because of small numbers of included participants. In one study comparing plasmapheresis, cyclophosphamide and methylprednisolone with cyclophosphamide and methylprednisolone, there may be no difference in the numbers achieving remission. One study compared fosinopril with no specific therapy and reported fosinopril reduced the number of participants with proteinuria. No studies were identified that evaluated the efficacy of therapy on kidney disease in participants with recurrent episodes of IgAV.
AUTHORS' CONCLUSIONS
There are no substantial changes in conclusions from this update compared with the initial review or the previous update despite the addition of five studies. From generally low to moderate certainty evidence, we found that there may be little or no benefit in the use of corticosteroids or antiplatelet agents to prevent persistent kidney disease in children with IgAV in participants with no or minimal kidney involvement at presentation. We did not find any studies which evaluated corticosteroids in children presenting with IgAV and nephritic and/or nephrotic syndrome, although corticosteroids are recommended in such children in guidelines. Though heparin may be effective in reducing proteinuria, this potentially dangerous therapy is not justified to prevent serious kidney disease when few children with IgAV develop severe kidney disease. There may be no benefit of cyclophosphamide compared with no specific treatment or corticosteroids. While there may be no benefit in the efficacy of MMF or tacrolimus compared with IV cyclophosphamide in children or adults with IgAV and severe kidney disease, adverse effects, particularly infections, may be lower in MMF or tacrolimus-treated children. Because of small patient numbers and events leading to imprecision in results, it remains unclear whether cyclosporin, MMF or leflunomide have any role in the treatment of children with IgAV and severe kidney disease. We did not identify any studies which evaluated corticosteroids.
Topics: Adult; Child; Humans; Fosinopril; IgA Vasculitis; Kidney Diseases; Leflunomide; Proteinuria; Tacrolimus; Vasculitis
PubMed: 36853224
DOI: 10.1002/14651858.CD005128.pub4