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Biomedicine & Pharmacotherapy =... Jul 2024The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives... (Review)
Review
The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives on the pathogenesis and treatment of kidney diseases. lncRNAs, a class of transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized as key regulatory molecules influencing gene expression through diverse mechanisms. They modulate the epigenetic modifications by recruiting or blocking enzymes responsible for adding or removing methyl or acetyl groups, such as DNA, N6-methyladenosine (m6A) and histone methylation and acetylation, subsequently altering chromatin structure and accessibility. In kidney diseases such as acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), and renal cell carcinoma (RCC), aberrant patterns of DNA/RNA/histone methylation and acetylation have been associated with disease onset and progression, revealing a complex interplay with lncRNA dynamics. Recent studies have highlighted how lncRNAs can impact renal pathology by affecting the expression and function of key genes involved in cell cycle control, fibrosis, and inflammatory responses. This review will separately address the roles of lncRNAs and epigenetic modifications in renal diseases, with a particular emphasis on elucidating the bidirectional regulatory effects and underlying mechanisms of lncRNAs in conjunction with DNA/RNA/histone methylation and acetylation, in addition to the potential exacerbating or renoprotective effects in renal pathologies. Understanding the reciprocal relationships between lncRNAs and epigenetic modifications will not only shed light on the molecular underpinnings of renal pathologies but also present new avenues for therapeutic interventions and biomarker development, advancing precision medicine in nephrology.
Topics: RNA, Long Noncoding; Humans; Epigenesis, Genetic; Histones; Acetylation; DNA Methylation; Kidney Diseases; Chromatin; Animals
PubMed: 38870627
DOI: 10.1016/j.biopha.2024.116922 -
World Journal of Urology Jun 2024Graft stones in renal transplant recipients pose a unique challenge, finding effective interventions to ensure optimal graft function and patient well-being. Various...
INTRODUCTION/OBJECTIVE
Graft stones in renal transplant recipients pose a unique challenge, finding effective interventions to ensure optimal graft function and patient well-being. Various methods of stone clearance have been described for graft stones, including percutaneous nephrolithotomy (PCNL). While PCNL is a promising approach for managing graft stones, specific outcomes and associated characteristics for this approach have not been comprehensively evaluated before. This study aims to evaluate the safety and efficacy of the use of PCNL as the primary intervention of graft stones by assessing stone-free rates (SFR), treatment impact on graft function, and perioperative complications.
METHODS
A retrospective clinical audit was performed for all transplants performed in a single center from 2007 to 2022, which included all graft lithiasis patients who were treated with PCNL. Both perioperative parameters and post-operative outcomes were collected. In addition, a systematic review including articles from MEDLINE, Embase, Web of Science yielded 18 full-text articles published between 1/1/2000 and 15/11/2023. The results pertaining to patients who underwent PCNLs for graft stones were cross-referenced and thoroughly evaluated. The review encompassed a comprehensive analysis of clinical data, postoperative outcomes, and procedural details. The protocol for the systematic review was prospectively registered on PROSPERO (CRD42023486825).
RESULTS
In our center, 6 graft lithiasis patients were treated with PCNL. The initial SFR was 83.3%. SFR at 3 months and 1 year were both 100.0%. SFR at 3 years was 66.7%. Other centers reported initial SFR of 82.6-100.0% (interquartile range). SFR at 3 months, 1 year, 3 years was not well reported across the included studies. Incidence of graft lithiasis ranged from 0.44%-2.41%. Most common presentations at diagnosis were oliguria/anuria/acute kidney injury and asymptomatic. Reported complications included blood loss, transient hematuria, high urine output, sepsis, and damage to surrounding structures. The most commonly reported metabolic abnormalities in transplant lithiasis patients included hyperuricemia and hyperparathyroidism.
CONCLUSION
PCNL is a practical and efficient choice for addressing graft lithiasis, demonstrating excellent stone clearance and minimal perioperative complications. These findings show the importance of PCNL as a primary intervention in this complex patient population.
Topics: Humans; Nephrolithotomy, Percutaneous; Kidney Transplantation; Retrospective Studies; Adult; Kidney Calculi; Male; Female; Postoperative Complications; Middle Aged
PubMed: 38869666
DOI: 10.1007/s00345-024-05079-x -
Renal Failure Dec 2024This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m) patients combined with heart... (Meta-Analysis)
Meta-Analysis Review
AIMS
This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies.
METHODS
The Embase, PubMed and the Cochrane Library were searched for relevant studies from inception to December 2023. Dichotomous variables were described as event counts with the odds ratio (OR) and 95% confidence interval (CI) values. Continuous variables were expressed as mean standard deviation (SD) with 95% CIs.
RESULTS
A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m patients combined with heart failure. In terms of efficacy, we analyzed the incidence of cardiovascular events and found that sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization in chronic kidney disease (CKD) stages 3-5 patients with heart failure (OR: 0.65, 95%CI: 0.54-0.78). Moreover, sacubitril/valsartan prevented the serum creatinine elevation (OR: 0.81, 95%CI: 0.68-0.95), the eGFR decline (OR: 0.83, 95% CI: 0.73-0.95) and the development of end-stage renal disease in this population (OR:0.73, 95%CI:0.60-0.89). As for safety outcomes, we did not find that the rate of hyperkalemia (OR:1.31, 95%CI:0.79-2.17) and hypotension (OR:1.57, 95%CI:0.94-2.62) were increased in sacubitril/valsartan group among CKD stages 3-5 patients with heart failure.
CONCLUSIONS
Our meta-analysis proves that sacubitril/valsartan has a favorable effect on cardiac function without obvious risk of adverse events in abnormal renal function patients combined with heart failure, indicating that sacubitril/valsartan has the potential to become perspective treatment for these patients.
Topics: Valsartan; Humans; Biphenyl Compounds; Aminobutyrates; Drug Combinations; Heart Failure; Tetrazoles; Angiotensin Receptor Antagonists; Glomerular Filtration Rate; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic; Creatinine
PubMed: 38869007
DOI: 10.1080/0886022X.2024.2349135 -
Cureus May 2024Chronic kidney disease (CKD) is a progressive condition characterized by gradual loss of kidney function, necessitating timely monitoring and interventions. This... (Review)
Review
Chronic kidney disease (CKD) is a progressive condition characterized by gradual loss of kidney function, necessitating timely monitoring and interventions. This systematic review comprehensively evaluates the application of artificial intelligence (AI) and machine learning (ML) techniques for predicting CKD progression. A rigorous literature search identified 13 relevant studies employing diverse AI/ML algorithms, including logistic regression, support vector machines, random forests, neural networks, and deep learning approaches. These studies primarily aimed to predict CKD progression to end-stage renal disease (ESRD) or the need for renal replacement therapy, with some focusing on diabetic kidney disease progression, proteinuria, or estimated glomerular filtration rate (GFR) decline. The findings highlight the promising predictive performance of AI/ML models, with several achieving high accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve scores. Key factors contributing to enhanced prediction included incorporating longitudinal data, baseline characteristics, and specific biomarkers such as estimated GFR, proteinuria, serum albumin, and hemoglobin levels. Integration of these predictive models with electronic health records and clinical decision support systems offers opportunities for timely risk identification, early interventions, and personalized management strategies. While challenges related to data quality, bias, and ethical considerations exist, the reviewed studies underscore the potential of AI/ML techniques to facilitate early detection, risk stratification, and targeted interventions for CKD patients. Ongoing research, external validation, and careful implementation are crucial to leveraging these advanced analytical approaches in clinical practice, ultimately improving outcomes and reducing the burden of CKD.
PubMed: 38864072
DOI: 10.7759/cureus.60145 -
Frontiers in Pharmacology 2024Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure...
Effect of sacubitril-valsartan on left ventricular remodeling in patients with acute myocardial infarction after primary percutaneous coronary intervention: a systematic review and meta-analysis.
BACKGROUND
Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure (HF). However, the effect of sacubitril-valsartan in patients with acute myocardial infarction (AMI) remains controversial. Therefore, we conducted this meta-analysis to investigate whether sacubitril-valsartan could reverse left ventricular remodeling and reduce cardiovascular adverse events in AMI patients after primary percutaneous coronary intervention (PPCI).
MATERIALS AND METHODS
Two researchers independently retrieved the relevant literature from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database. The retrieval time was limited from inception to 1 June 2023. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analyzed.
RESULTS
In total, 21 RCTs involving 2442 AMI patients who underwent PPCI for revascularization were included in this meta-analysis. The meta-analysis showed that compared with the angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril-valsartan treatment in AMI patients after PPCI significantly reduced left ventricular end-diastolic dimension (LVEDD) (weighted mean difference (WMD) -3.11, 95%CI: -4.05∼-2.16, < 0.001), left ventricular end-diastolic volume (LVEDV) (WMD -7.76, 95%CI: -12.24∼-3.27, = 0.001), left ventricular end-systolic volume (LVESV) (WMD -6.80, 95%CI: -9.45∼-4.15, < 0.001) and left ventricular end-systolic dimension (LVESD) (WMD -2.53, 95%CI: -5.30-0.24, < 0.001). Subgroup analysis according to the dose of sacubitril-valsartan yielded a similar result. Meanwhile, PPCI patients using sacubitril-valsartan therapy showed lower risk of major adverse cardiac events (MACE) (OR = 0.36, 95%CI: 0.28-0.46, < 0.001), myocardial reinfarction (OR = 0.54, 95%CI: 0.30-0.98, = 0.041) and HF (OR = 0.35, 95%CI: 0.26-0.47, < 0.001) without increasing the risk of renal insufficiency, hyperkalemia, or symptomatic hypotension. At the same time, the change of LV ejection fraction (LVEF) (WMD 3.91, 95%CI: 3.41-4.41, < 0.001), 6 min walk test (6MWT) (WMD 43.56, 95%CI: 29.37-57.76, < 0.001) and NT-proBNP level (WMD -130.27, 95%CI: -159.14∼-101.40, < 0.001) were statistically significant.
CONCLUSION
In conclusion, our meta-analysis indicates that compared with ACEI/ARB, sacubitril-valsartan may be superior to reverse left ventricular remodeling, improve cardiac function, and effectively reduce the risk of MACE, myocardial reinfarction, and HF in AMI patients after PPCI during follow-up without increasing the risk of adverse reactions including renal insufficiency, hyperkalemia, and symptomatic hypotension.
PubMed: 38863978
DOI: 10.3389/fphar.2024.1366035 -
Korean Circulation Journal Apr 2024The efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) may depend on renal function, and this raises theoretical concern over its effects on cardiovascular...
Cardiovascular Outcomes of Sodium-Glucose Cotransporter-2 Inhibitors Therapy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Updated Meta-Analysis.
BACKGROUND AND OBJECTIVES
The efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) may depend on renal function, and this raises theoretical concern over its effects on cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).
METHODS
This systematic review and updated meta-analysis of randomized controlled trials (RCTs) compared cardiovascular outcomes of patients with T2DM and CKD treated with SGLT2i to placebo. PubMed, Embase, and Cochrane were systematically searched. Prespecified subgroup analyses were performed in strata of estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m² and 45 to 59 mL/min/1.73 m².
RESULTS
Nine RCTs comprising 29,146 patients were selected. Average follow-up ranged from 0.75 to 4.2 years. SGLT2i were shown to reduce the risk of all-cause mortality (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.97; p=0.01), the composite of cardiovascular mortality or hospitalizations for heart failure (HHF: HR, 0.71; 95% CI, 0.65-0.78; p<0.001), cardiovascular mortality (HR, 0.86; 95% CI, 0.76-0.98; p=0.02), HHF (HR, 0.62; 95% CI, 0.55-0.71; p<0.001), major adverse cardiovascular events (HR, 0.85; 95% CI, 0.77-0.94; p=0.002), stroke (HR, 0.76; 95% CI, 0.59-0.97; p=0.03), and myocardial infarction (HR, 0.78; 95% CI, 0.67-0.91; p=0.001). These findings were consistent over strata of eGFR, albeit with a lower incidence of stroke in patients treated with SGLT2i with eGFR <45 mL/min/1.73 m² (p-value for interaction=0.04).
CONCLUSIONS
Compared with a placebo, patients with T2DM and CKD treated with SGLT2i experience a reduction in all-cause mortality, cardiovascular mortality, and HHF.
TRIAL REGISTRATION
PROSPERO Identifier: CRD42023401081.
PubMed: 38859642
DOI: 10.4070/kcj.2023.0241 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2024Malnutrition, a significant problem in patients with chronic kidney disease (CKD), is linked to lower health-related quality of life, longer and more frequent hospital... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Malnutrition, a significant problem in patients with chronic kidney disease (CKD), is linked to lower health-related quality of life, longer and more frequent hospital admissions, worse functional capacity, and higher levels of morbidity. However, the extent of its impact on mortality is poorly elucidated. This systematic review and meta-analysis aimed to investigate the impact of malnutrition on mortality among CKD patients on dialysis.
METHODS
This meta-analysis was designed and performed in accordance with the PRISMA guidelines (CRD42023394584). A systematic electronic literature search was conducted in PubMed, ScienceDirect, and Embase to identify relevant cohort studies. The studies that reported nutritional status and its impact on mortality in patients were considered for analysis. The generic inverse variance method was used to pool the hazard ratio effect estimates by employing a random effects model. The Newcastle-Ottawa scale was used for the quality assessment. The statistical analysis was performed by utilizing RevMan and CMA 2.0.
RESULTS
A total of 29 studies that comprised 11,063 patients on dialysis whose nutritional status was evaluated were eligible for quantitative analysis. Based on a comparison between the "malnutrition" category and the reference "normal nutrition status" category, the results showed that the overall pooled hazard risk (HR) for mortality was (HR 1.49, 95% CI: 1.36-1.64, p < 0.0001). According to the subgroup analysis, the hemodialysis subgroup had greater mortality hazards (HR 1.53; 95% CI 1.38-1.70, p < 0.0001), compared to the peritoneal dialysis subgroup (HR 1.26; 95% CI 1.15-1.37, p < 0.00001). Additionally, the overall incidence of mortality was explored but the authors were unable to combine the results due to limitations with the data.
CONCLUSION
The findings conclude that malnutrition is a strong predictor of mortality among patients on dialysis, with the hemodialysis subgroup having a higher mortality hazard compared to the peritoneal dialysis subgroup. The results of this study will advocate for early nutritional evaluation and timely dietary interventions to halt the progression of CKD and death.
Topics: Humans; Malnutrition; Renal Dialysis; Renal Insufficiency, Chronic; Nutritional Status
PubMed: 38852509
DOI: 10.1016/j.clnu.2024.05.037 -
Drugs - Real World Outcomes Jun 2024Multimorbidity is common in hospitalised adults who are at increased risk of inappropriate prescribing including drug-disease interactions. These interactions occur when...
BACKGROUND AND OBJECTIVE
Multimorbidity is common in hospitalised adults who are at increased risk of inappropriate prescribing including drug-disease interactions. These interactions occur when a medicine being used to treat one condition exacerbates a concurrent medical condition and may lead to adverse health outcomes. The aim of this review was to examine the association between drug-disease interactions and the risk of mortality and readmission in hospitalised middle-aged and older adults.
METHODS
A systematic review was conducted on drug-disease interactions in hospitalised middle-aged (45-64 years) and older adults (≥65 years). The study protocol was prospectively registered with PROSPERO (Registration Number: CRD42022341998). Drug-disease interactions were defined as a medicine being used to treat one condition with the potential to exacerbate a concurrent medical condition or that were inappropriate based on a comorbid medical condition. Both observational and interventional studies were included. The outcomes of interest were mortality and readmissions. The databases searched included MEDLINE, CINAHL, EMBASE, Web of Science, SCOPUS and the Cochrane Library from inception to 12 July, 2022. A meta-analysis was performed to pool risk estimates using the random-effects model.
RESULTS
A total of 563 studies were identified and four met the inclusion criteria. All were observational studies in older adults, with no studies identified in middle-aged adults. Most of the studies were at risk of bias because of an inadequate adjustment for covariates and a lack of clarity around individuals lost to follow-up. There were various definitions of drug-disease interactions within these four studies. Two studies assessed drugs that were contraindicated based on renal function, one assessed an individual drug-disease combination, and one was based on the clinical judgement of a pharmacist. There were two studies that showed an association between drug-disease interactions and the outcomes of interest. One reported that the use of diltiazem in patients with heart failure was associated with an increased risk of readmissions. The second reported that the use of medicines contraindicated according to renal function were associated with increased risk of all-cause mortality and a composite of mortality and readmission. Three of the studies (total study population = 5705) were amenable to a meta-analysis, which showed no significant association between drug-disease interactions and readmissions (odds ratio = 1.0, 95% confidence interval 0.80-1.38).
CONCLUSIONS
Few studies were identified examining the risk of drug-disease interactions and mortality and readmission in hospitalised adults. Most of the identified studies were at risk of bias. There is no universal accepted definition of drug-disease interactions in the literature. Further studies are needed to develop a standardised and accepted definition of these interactions to guide further research in this area.
PubMed: 38852118
DOI: 10.1007/s40801-024-00432-3 -
Journal of Pharmaceutical Health Care... Jun 2024Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor...
BACKGROUND
Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, and suppression of thyroid function. In this systematic review and meta-analysis (PROSPERO: CRD42023471516), we aimed to evaluate the relationship between roxadustat use and suppression of thyroid function.
METHODS
We conducted a comprehensive search of MEDLINE via PubMed, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases using the search term "roxadustat" to identify all relevant studies. The study population comprised adults with renal anemia who participated in a randomized controlled trial or observational study, with roxadustat as the intervention and a placebo or erythropoiesis-stimulating agent (ESA) as the comparator. The primary outcome was suppression of thyroid function and the secondary outcome was hypothyroidism. A meta-analysis was conducted using the DerSimonian-Laird random effects model based on the size of the intention-to-treat population, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Two reviewers independently screened the articles, extracted data, and assessed studies using the ROBINS-I tool.
RESULTS
Of the six studies eligible for inclusion, a meta-analysis was performed using data from two observational studies comparing roxadustat and ESA. The meta-analysis showed that the incidence of suppression of thyroid function was significantly higher with roxadustat use than with ESA use (OR: 6.45; 95% CI: 3.39-12.27; I = 12%). Compared with ESA, roxadustat seemed to potentially increase the risk for suppression of thyroid function in patients with renal anemia.
CONCLUSIONS
Our findings highlighted the importance of monitoring thyroid function in patients treated with roxadustat. The results of this review may enhance the safety of using roxadustat to treat renal anemia through advance recognition of the risk for suppression of thyroid function.
PubMed: 38851711
DOI: 10.1186/s40780-024-00351-z -
Research in Veterinary Science Aug 2024Chronic kidney disease (CKD) and acute kidney injury (AKI) are diseases which affect the urinary tract characterized by the loss of renal function. Their therapy... (Meta-Analysis)
Meta-Analysis Review
Chronic kidney disease (CKD) and acute kidney injury (AKI) are diseases which affect the urinary tract characterized by the loss of renal function. Their therapy requires different therapeutic goals. Mesenchymal stem cells (MSC) transplantation has spread over the years as a treatment for many diseases. In the urinary tract, studies report anti-inflammatory, antiapoptotic, antifibrotic, antioxidant and angiogenic effects. This work reports the results of a meta-analysis about the effects of the MSC application in serum levels of creatinine in dogs and cats with AKI and CKD. The work followed PRISMA guidelines. Data were screened, selected, and extracted with characteristics about the studies. The kinds of injury were classified according to their identification and the risk of bias was calculated by the system SYRCLE. The results of each group were combined by the inverse variance method. The heterogeneity was evaluated by the I test. For the mean of creatinine, a meta-analysis was performed according to the study group and number of applications and separately for the control and treatment groups according to the kind of injury, dose, application route, and moment. At all, 4742 articles were found. Of these, 40 were selected for eligibility, 16 underwent qualitative analysis and 9 to the quantitative. The results denote advantage to the group treated with MSC over placebo. A statistical difference was observed both in combined analysis and in the subgroups division. However, a high heterogeneity was found, which indicates considerable variation between the studies, which indicates caution in generalize the results.
Topics: Animals; Dogs; Mesenchymal Stem Cell Transplantation; Acute Kidney Injury; Cat Diseases; Cats; Dog Diseases; Renal Insufficiency, Chronic; Creatinine
PubMed: 38851051
DOI: 10.1016/j.rvsc.2024.105313