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Hypertension Research : Official... Jun 2024Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos....
Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos. They have been shown to be involved in maintaining homoeostasis as well as playing a role in the development of pathology including hypertension and cardiovascular disease. It is estimated that there is 10-10 circulating EVs/mL in the plasma of healthy individuals derived from various sources. While the effect of EVs on vascular haemodynamic parameters will be dependent on the details of the model studied, we systematically searched and summarized current literature to find patterns in how exogenously injected EVs affected vascular haemodynamics. Under homoeostatic conditions, evidence from wire and pressure myography data demonstrate that injecting isolated EVs derived from cell types found in blood and blood vessels resulted in the impairment of vasodilation in blood vessels ex vivo. Impaired vasodilation was also observed in rodents receiving intravenous injections of human plasma EVs from cardiovascular diseases including valvular heart disease, acute coronary syndrome, myocardial infarction and end stage renal disease. When EVs were derived from models of metabolic syndromes, such as diabetes, these EVs enhanced vasoconstriction responses in blood vessels ex vivo. There were fewer publications that assessed the effect of EVs in anaesthetised or conscious animals to confirm whether effects on the vasculature observed in ex vivo studies translated into alterations in vascular haemodynamics in vivo. In the available conscious animal studies, the in vivo data did not always align with the ex vivo data. This highlights the importance of in vivo work to determine the effects of EVs on the integrative vascular haemodynamics.
Topics: Animals; Humans; Cardiovascular Diseases; Extracellular Vesicles; Hemodynamics
PubMed: 38600279
DOI: 10.1038/s41440-024-01659-x -
World Journal of Nephrology Mar 2024Polycystic kidney disease (PKD) is the most common genetic cause of kidney disease. It is a progressive and irreversible condition that can lead to end-stage renal...
BACKGROUND
Polycystic kidney disease (PKD) is the most common genetic cause of kidney disease. It is a progressive and irreversible condition that can lead to end-stage renal disease and many other visceral complications. Current comprehensive data on PKD patterns in Africa is lacking.
AIM
To describe the prevalence and outcomes of PKD in the African population.
METHODS
A literature search of PubMed, African journal online, and Google Scholar databases between 2000 and 2023 was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed to design the study. Clinical presentations and outcomes of patients were extracted from the included studies.
RESULTS
Out of 106 articles, we included 13 studies from 7 African countries. Ten of them were retrospective descriptive studies concerning 943 PKD patients with a mean age of 47.9 years. The accurate prevalence and incidence of PKD were not known but it represented the third causal nephropathy among dialysis patients. In majority of patients, the diagnosis of the disease was often delayed. Kidney function impairment, abdominal mass, and hypertension were the leading symptoms at presentation with a pooled prevalence of 72.1% (69.1-75.1), 65.8% (62.2-69.4), and 57.4% (54.2-60.6) respectively. Hematuria and infections were the most frequent complications. Genotyping was performed in few studies that revealed a high proportion of new mutations mainly in the gene.
CONCLUSION
The prevalence of PKD in African populations is not clearly defined. Clinical symptoms were almost present with most patients who had kidney function impairment and abdominal mass at the diagnostic. Larger studies including genetic testing are needed to determine the burden of PKD in African populations.
PubMed: 38596265
DOI: 10.5527/wjn.v13.i1.90402 -
Obesity Research & Clinical Practice 2024The BMI predicts mortality and cardiovascular disease (CVD) in the general population, while in patients with end-stage chronic kidney disease (CKD) a high BMI is... (Meta-Analysis)
Meta-Analysis Review
The BMI predicts mortality and cardiovascular disease (CVD) in the general population, while in patients with end-stage chronic kidney disease (CKD) a high BMI is associated with improved survival, a phenomenon referred to as the "obesity paradox". While BMI is easy to determine and helps to categorize patients, it does not differentiate between fat tissue, lean tissue and bone mass. As the BMI may be altered in CKD, e.g. by muscle wasting, we determined in this meta-analysis (i) the association of mortality with fat tissue quantity in CKD and (ii) the association of mortality with abdominal obesity (as measured by waist circumference (WC) or waist-to-hip ratio (WHR)) in CKD. We systematically reviewed databases for prospective or retrospective cohort studies. In eleven studies with 23,523 patients the association between mortality and high fat tissue quantity in CKD was calculated. The pooled hazard ratio (HR) for this association in the CKD group in the dialysis group 0.91 (CI 0.84- 0.98, p = 0.01) which is comparable to the HR for the association with BMI. The HR in patients without dialysis was 0.7 (95% CI 0.53- 0.93, p = 0.01), suggesting a better risk prediction of high fat tissue content with mortality as compared to higher BMI with mortality in patients with CKD without dialysis. Importantly, both BMI and fat tissue quantity in CKD are described by the "obesity paradox": the higher the fat tissue content or BMI, the lower the mortality risk. In thirteen studies with 55,175 patients the association between mortality and high WC or WHR in CKD (with or without dialysis) was calculated. We observed, that the HR in the WHR group was 1.31 (CI 1.08-1.58, p = 0.007), whereas the overall hazard ratio of both groups was 1.09 (CI 1.01-1.18, p = 0.03), indicating that a higher abdominal obesity as measured by WHR is associated with higher mortality in CKD. Our analysis suggests gender-specific differences, which need larger study numbers for validation. This meta-analysis confirms the obesity paradox in CKD using fat tissue quantity as measure and further shows that using abdominal obesity measurements in the routine in obese CKD patients might allow better risk assessment than using BMI or fat tissue quantity. Comparable to the overall population, here, the higher the WHR, the higher the mortality risk.
Topics: Humans; Adipose Tissue; Body Mass Index; Cardiovascular Diseases; Obesity; Obesity, Abdominal; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Waist Circumference; Waist-Hip Ratio
PubMed: 38582736
DOI: 10.1016/j.orcp.2024.03.007 -
Frontiers in Medicine 2024The introduction of antiretroviral therapy (ART) has significantly prolonged the lifespan of people living with human immunodeficiency virus (PLWH). However, the...
The introduction of antiretroviral therapy (ART) has significantly prolonged the lifespan of people living with human immunodeficiency virus (PLWH). However, the sustained use of this drug regimen has also been associated with a cluster of metabolic anomalies, including renal toxicity, which can lead to the development of kidney diseases. In this study, we reviewed studies examining kidney disease in PLWH sourced from electronic databases such as PubMed/MEDLINE, Scopus, and Google Scholar, as well as gray literature. The narrative synthesis of data from these clinical studies demonstrated that the serum levels of cystatin C remained unchanged or were not affected in PLWH on ART, while the creatinine-based glomerular filtration rate (GFR) fluctuated. In fact, some of the included studies showed that the creatinine-based GFR was increased in PLWH taking tenofovir disoproxil fumarate-containing ART, perhaps indicating that the use of both cystatin C- and creatinine-based GFRs is vital to monitor the development of kidney disease in PLWH. Clinical data summarized within this study indicate the potential detrimental effects of tenofovir-based ART regimens in causing renal tubular injury, while highlighting the possible beneficial effects of dolutegravir-based ART on improving the kidney function in PLWH. However, the summarized literature remains limited, while further clinical studies are required to provide insights into the potential use of cystatin C as a biomarker for kidney disease in PLWH.
PubMed: 38566923
DOI: 10.3389/fmed.2024.1295217 -
Journal of Clinical Medicine Mar 2024: Sacubitril/valsartan improves heart failure (HF) outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, randomized controlled trials... (Review)
Review
The Efficacy and Safety of Sacubitril/Valsartan Compared to Valsartan in Patients with Heart Failure and Mildly Reduced and Preserved Ejection Fractions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
: Sacubitril/valsartan improves heart failure (HF) outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, randomized controlled trials (RCTs) in patients with heart failure and mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) have shown inconsistent results. We conducted this meta-analysis to comprehensively evaluate the efficacy and safety of sacubitril/valsartan compared to valsartan within this specific patient population. : We searched the MEDLINE database and ClinicalTrials.gov and identified four RCTs that could be included in our analysis, with 3375 patients in the sacubitril/valsartan group and 3362 in the valsartan group. : Our study shows that, in patients with HFmrEF and HFpEF, sacubitril/valsartan was superior to valsartan in some of the key HF outcomes, such as the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), with a small but significant mean difference of 1.13 (95% confidence interval or CI of 0.15 to 2.11, -value 0.024), an improvement in the New York Heart Association (NYHA) class (odds ratio or OR of 1.32, 95% CI 1.11 to 1.58, -value 0.002), and the composite outcome of hospitalizations for HF and cardiovascular death, with a relative risk (RR) of 0.86 (95% CI 0.75 to 0.99, -value 0.04). However, there was no additional benefit with sacubitril/valsartan compared to valsartan for the outcomes of cardiovascular death and all-cause mortality. In terms of side effects, sacubitril/valsartan was associated with a higher risk of hypotension when compared to valsartan (OR 1.67, 95% CI 1.27 to 2.19, -value < 0.0001), but did not show an increased risk of hyperkalemia or worsening renal function. : In individuals with HFmrEF or HFpEF, sacubitril/valsartan can result in improvements in the HF outcomes of the KCCQ CSS, the NYHA class, and the composite outcome of hospitalization for HF and cardiovascular death when compared to valsartan. While there was a higher risk of hypotension with sacubitril/valsartan compared to valsartan, there was no corresponding increase in the risk of hyperkalemia or worsening renal function.
PubMed: 38541798
DOI: 10.3390/jcm13061572 -
Cancers Mar 2024Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding... (Review)
Review
Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding ablative techniques compared both laparoscopic and PCA with PN. That is why we decided to perform a meta-analysis that focused solely on PCA. The aim of this study was to compare the complications and functional and oncological outcomes between PCA and PN. A systematic literature search was performed in January 2024. Data for dichotomous and continuous variables were expressed as pooled odds ratios (ORs) and mean differences (MDs), both with 95% confidence intervals (CIs). Effect measures for the local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were expressed as pooled hazard ratios with 95% CIs. Among 6487 patients included in the 14 selected papers, 1554 (23.9%) and 4924 (76.1%) underwent PCA and PN, respectively. Compared with the PN group, patients undergoing PCA had significantly lower overall and major postoperative complication rates. There was no difference in renal function between PCA and PN groups. When analysing collective data for cT1 renal carcinoma, PCA was associated with worse LRFS compared with PN. However, subgroup analysis revealed that in the case of PCA, LRFS was not decreased in patients with cT1a tumours. Moreover, patients undergoing robotic-assisted PN had improved LRFS compared with those undergoing PCA. No significant differences were observed between PCA and PN in terms of MFS and CSS. Finally, PCA was associated with worse OS than PN in both collective and subgroup analyses. In conclusion, PCA is associated with favourable postoperative complication rates relative to PN. Regarding LRFS, PCA is not worse than PN in cT1a tumours but has a substantially relevant disadvantage in cT1b tumours. Also, RAPN might be the only surgical modality that provides better LRFS than PCA. In cT1 tumours, PCA shows MFS and CSS comparable to PN. Lastly, PCA is associated with a shorter OS than PN.
PubMed: 38539509
DOI: 10.3390/cancers16061175 -
Anatolian Journal of Cardiology Mar 2024AngioJet rheolytic thrombectomy (ART) system has been widely used as a catheter-directed treatment (CDT) method in acute pulmonary embolism (PE), however, there has been...
BACKGROUND
AngioJet rheolytic thrombectomy (ART) system has been widely used as a catheter-directed treatment (CDT) method in acute pulmonary embolism (PE), however, there has been a controversy regarding the safety of its use. In this systematic review and meta-analysis, we evaluated the efficacy and safety outcomes of ART in patients with PE.
METHODS
Our meta-analysis have been based on search in the MEDLINE, EMBASE, and Cochrane Library for studies published up to August 2022. The primary outcomes were overall pooled rates of major bleeding (MB) and minor bleeding (mB), worsening renal function (WRF), bradycardia/conduction disturbance (BCD), and PE-related and all-cause mortality in patients who underwent ART.
RESULTS
Among the 233 studies documented at initial search, 24 studies were eligible for meta-analysis, and a total of 427 PE patients who underwent ART were evaluated. Overall pooled rates of MB and mB were 9.6% (95% CI 5.9%-15.2%) and 9.2% (95% CI 6.1%-13.6%), transient BCD and WRF were 18.2% (95% CI 12.4%-26%) and 15% (95% CI 10%-21.8%), and PE-related death and all-cause death were 12.7% (95% CI 9.1%-17.3%) and 15% (95% CI 11%-20%), respectively. However, significant heterogeneity and some evidence of funnel plot asymmetry and publication bias were noted for MB, BCD and WRF, but not for PE-related death and all-cause death.
CONCLUSION
Overall pooled rates of bleeding events, BCD and WRF episodes, PE-related death and all-cause death may be considered as encouraging results for efficacy and safety issues of ART utilization in specific scenarios of acute PE, and a reappraisal for black-box warning on ART seems to be necessary.
PubMed: 38530216
DOI: 10.14744/AnatolJCardiol.2024.4081 -
Journal of Clinical Laboratory Analysis Apr 2024Kidney disease is fairly unique due to the lack of symptoms associated with disease activity, and it is therefore dependent on biological monitoring. Dried biofluids,... (Review)
Review
BACKGROUND
Kidney disease is fairly unique due to the lack of symptoms associated with disease activity, and it is therefore dependent on biological monitoring. Dried biofluids, particularly dried capillary blood spots, are an accessible, easy-to-use technology that have seen increased utility in basic science research over the past decade. However, their use is yet to reach the kidney patient population clinically or in large-scale discovery science initiatives. The aim of this study was to systematically evaluate the existing literature surrounding the use of dried biofluids in kidney research.
METHODS
A systematic literature review was conducted using three search engines and a predefined search term strategy. Results were summarised according to the collection method, type of biofluid, application to kidney disease, cost, sample stability and patient acceptability.
RESULTS
In total, 404 studies were identified and 67 were eligible. In total, 34,739 patients were recruited to these studies with a skew towards male participants (> 73%). The majority of samples were blood, which was used either for monitoring anti-rejection immunosuppressive drug concentrations or for kidney function. Dried biofluids offered significant cost savings to the patient and healthcare service. The majority of patients preferred home microsampling when compared to conventional monitoring.
CONCLUSION
There is an unmet need in bringing dried microsampling technology to advance kidney disease despite its advantages. This technology provides an opportunity to upscale patient recruitment and longitudinal sampling, enhance vein preservation and overcome participation bias in research.
Topics: Humans; Dried Blood Spot Testing; Kidney Diseases
PubMed: 38525922
DOI: 10.1002/jcla.25032 -
International Journal of... 2024The impact of interleukin-10 (IL-10) gene promoter polymorphisms (SNPs) on treatment response in HCV patients was dissimilarly estimated. Hence, the aim of this... (Meta-Analysis)
Meta-Analysis
The impact of interleukin-10 (IL-10) gene promoter polymorphisms (SNPs) on treatment response in HCV patients was dissimilarly estimated. Hence, the aim of this meta-analysis was to robustly assess the effect of IL-10 SNPs on treatment response in HCV patients. An electronic literature search was carried out through PubMed, EMBASE, Web of science, and Scopus databases. Studies assessing the association between IL-10 polymorphisms and treatment response in HCV patients were included. Studies were excluded if genotype frequencies are not consistent with the Hardy-Weinberg Equilibrium (HWE) or in case of including patients with hepatitis B virus coinfection. Risk of bias in included studies was assessed using the Newcastle-Ottawa Scale. Meta-analyses were performed for the influence of IL-10 gene promoter SNPs (rs1800896 (-1082 A/G), rs1800871 (-819 C/T), and rs1800872 (-592 C/T)) and haplotypes on treatment response in HCV patients. Subgroup analyses, meta-regressions, publication bias assessment, and sensitivity analyses were also conducted. Overall, 32 studies with a total of 5943 HCV cases and 2697 controls were included in the present study. The -1082*G allele was significantly associated with increased risk of non-response (NR) to treatment, OR [95% CI] = 1.29 [1.1-1.51], = .002. Besides, the rs1800872 -592*C allele was significantly associated with increased NR risk, OR [95% CI] = 1.22 [1.02-1.46], = .03. Subgroup analysis showed that this association remained significant only in patients treated with PEG-IFN alone, = .01. The -1082*G/-819*C/-592*C (GCC) haplotype was significantly associated with increased NR risk, OR [95% CI] = 1.62 [1.13-2.23], = .009. Our results suggest that the IL-10 rs1800896 was associated with NR risk especially in North-African and Asian populations. Moreover, the IL-10 gene promoter -1082*G/-819*C/-592*C (GCC) haplotype which has been associated with higher production of IL-10, was significantly associated with increased NR risk.
Topics: Humans; Genetic Predisposition to Disease; Genotype; Hepatitis C; Interleukin-10; Polymorphism, Single Nucleotide; Promoter Regions, Genetic
PubMed: 38520313
DOI: 10.1177/03946320241240705 -
Cureus Feb 2024The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs)... (Review)
Review
The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizing outcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.
PubMed: 38516472
DOI: 10.7759/cureus.54487