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Journal of Advanced Research Dec 2023Crush syndrome (CS) is a kind of traumatic and ischemic injury that seriously threatens life after prolonged compression. It is characterized by systemic inflammatory... (Review)
Review
BACKGROUND
Crush syndrome (CS) is a kind of traumatic and ischemic injury that seriously threatens life after prolonged compression. It is characterized by systemic inflammatory reaction, myoglobinuria, hyperkalemia and acute kidney injury (AKI). Especially AKI, it is the leading cause of death from CS. There are various cell death forms in AKI, among which ferroptosis is a typical form of cell death. However, the role of ferroptosis has not been fully revealed in CS-AKI.
AIM OF REVIEW
This review aimed to summarize the evidence of ferroptosis in CS-AKI and its related molecular mechanism, discuss the therapeutic significance of ferroptosis in CS-AKI, and open up new ideas for the treatment of CS-AKI.
KEY SCIENTIFIC CONCEPTS OF REVIEW
One of the main pathological manifestations of CS-AKI is renal tubular epithelial cell dysfunction and cell death, which has been attributed to massive deposition of myoglobin. Large amounts of myoglobin released from damaged muscle deposited in the renal tubules, impeding the normal renal tubules function and directly damaging the tubules with oxidative stress and elevated iron levels. Lipid peroxidation damage and iron overload are the distinguishing features of ferroptosis. Moreover, high levels of pro-inflammatory cytokines and damage-associated molecule pattern molecules (HMGB1, double-strand DNA, and macrophage extracellular trap) in renal tissue have been shown to promote ferroptosis. However, how ferroptosis occurs in CS-AKI and whether it can be a therapeutic target remains unclear. In our current work, we systematically reviewed the occurrence and underlying mechanism of ferroptosis in CS-AKI.
Topics: Humans; Acute Kidney Injury; Cell Death; Crush Syndrome; Ferroptosis; Myoglobin
PubMed: 36702249
DOI: 10.1016/j.jare.2023.01.016 -
Renal Failure Dec 2023Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE), but the efficacy of belimumab for lupus nephritis (LN) is not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE), but the efficacy of belimumab for lupus nephritis (LN) is not clear. We conducted this meta-analysis and systematic review to compare the efficacy and safety of belimumab with those of conventional therapy for LN.
METHODS
PubMed, EMBASE, Cochrane Library, Clinical Trials.gov were searched in 31 December 2022 to identify relevant adult human studies reporting effectiveness outcomes of belimumab in patients with LN. Review manager (RevMan 5.4) was used for data analysis with fixed effects model based on heterogeneities.
RESULTS
Six randomized controlled trials (RCTs) were included in the quantitative analysis. A total of 2960 participants were identified. Belimumab plus standard therapy significantly improved total renal response rates (RR, 1.31; 95% CI, 1.11-1.53; = 0.001) and complete renal RRs (1.47; 95% CI, 1.07-2.02; = 0.02) compared with the control plus standard therapy group. It significantly reduced the risk of renal flare (RR, 0.51; 95% CI, 0.37-0.69; < 0.001) and renal function worsening or progression to end-stage renal disease (ESRD) (RR, 0.56; 95% CI, 0.40-0.79; = 0.001). When assessed with the incidence of adverse events, no significant differences between the two groups were observed for the occurrence of treatment-related adverse events (RR, 1.04; 95% CI, 0.99-1.09; = 0.12).
CONCLUSIONS
This meta-analysis showed that belimumab plus standard therapy was more effective and had a favorable safety in patients with LN.
Topics: Adult; Humans; Lupus Nephritis; Lupus Erythematosus, Systemic; Antibodies, Monoclonal, Humanized; Kidney; Treatment Outcome; Immunosuppressive Agents
PubMed: 37194710
DOI: 10.1080/0886022X.2023.2207671 -
International Urology and Nephrology Jan 2024Sacubitril/valsartan, a new pharmacological class of angiotensin receptor neprilysin inhibitor, is beneficial to heart failure through blocking the degradation of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sacubitril/valsartan, a new pharmacological class of angiotensin receptor neprilysin inhibitor, is beneficial to heart failure through blocking the degradation of natriuretic peptides and inhibiting renin-angiotensin-aldosterone system (RAAS) activation which also relate to the pathophysiologic mechanisms of chronic kidney disease (CKD). However, its effects on CKD remain unclear. To assess the efficacy and safety of sacubitril/valsartan for patients with CKD, we performed this meta-analysis.
METHODS
The Embase, PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) that compared sacubitril/valsartan with ACEI/ARBs in patients with CKD whose estimated glomerular filtration rate (eGFR) was below 60 mL/min/1.73 m. We adopted the Cochrane Collaboration tool for assessing the risk of bias. The effect size was estimated using the odds ratio (OR) with 95% confidence interval (CI).
RESULTS
Six trials with a total of 6217 patients with CKD were included. In terms of cardiovascular events, sacubitril/valsartan attenuated the risk of cardiovascular death or heart failure hospitalization (OR: 0.68, 95% CI 0.61-0.76, P < 0.00001, I = 43%). With respect to renal function, sacubitril/valsartan prevented the incidence of serum creatinine (Scr) elevation among patients with CKD (OR: 0.79, 95% CI 0.67-0.95, P = 0.01, I = 0%). Subgroup analysis about eGFR demonstrated that with long follow-up, sacubitril/valsartan significantly decreased the number of patients with more than 50% reduction in eGFR compared with ACEI/ARBs (OR: 0.52, 95% CI 0.32-0.84, P = 0.008, I = 9%). In patients with CKD, the incidence of end-stage renal disease (ESRD) was reduced with sacubitril/valsartan treatment, despite no statistically significant difference between the two groups (OR: 0.59, 95% CI 0.29-1.20, P = 0.14, I = 0%). As for the safety, we found that sacubitril/valsartan was associated with the occurrence of hypotension (OR: 1.71, 95% CI 1.15-2.56, P = 0.008, I = 51%). However, there was no trend towards increasing the risk of hyperkalemia in patients who received sacubitril/valsartan (OR: 1.09, 95% CI 0.75-1.60, P = 0.64, I = 64%).
CONCLUSION
This meta-analysis indicated that sacubitril/valsartan improved renal function and conferred effective cardiovascular benefits in patients with CKD, without serious safety issues being observed. Thus, sacubitril/valsartan may be a promising option for patients with CKD. Certainly, further large-scale randomized controlled trials are needed to confirm these conclusions.
SYSTEMATIC REVIEW REGISTRATION
[ https://inplasy.com/inplasy-2022-4-0045/ ], identifier [INPLASY202240045].
Topics: Humans; Angiotensin Receptor Antagonists; Drug Combinations; Heart Failure; Renal Insufficiency, Chronic; Stroke Volume; Tetrazoles; Valsartan; Aminobutyrates; Biphenyl Compounds
PubMed: 37195574
DOI: 10.1007/s11255-023-03599-w -
Frontiers in Immunology 2023Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2... (Review)
Review
Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Kidney
PubMed: 37809091
DOI: 10.3389/fimmu.2023.1213473 -
Pharmacology & Therapeutics Sep 2023We have performed a systematic review of studies reporting on the renal effects of SGLT2 inhibitors in rodent models of diabetes. In 105 studies, SGLT2 inhibitors... (Review)
Review
We have performed a systematic review of studies reporting on the renal effects of SGLT2 inhibitors in rodent models of diabetes. In 105 studies, SGLT2 inhibitors improved not only the glycemic control but also various aspects of renal function in most cases. These nephroprotective effects were similarly reported whether treatment with the SGLT2 inhibitor started concomitant with the onset of diabetes (within 1 week), early after onset (1-4 weeks) or after nephropathy had developed (>4 weeks after onset) with the latter probably having the greatest translational value. They were observed across various animal models of type 1 and type 2 diabetes/obesity (4 and 23 models, respectively), although studies in the type 2 diabetes model of db/db mice more often had negative data than in other models. Among possibly underlying pathophysiological mechanisms of nephroprotection, treatment with SGLT2 inhibitors had beneficial effects on lipid metabolism, blood pressure, glomerulosclerosis as well as renal tubular fibrosis, apoptosis, oxidative stress, and inflammation. These pathomechanisms highly influence atherosclerosis and renal health, which are two major factors that lead to an enhanced mortality in patients with diabetes and/or chronic kidney disease. Interestingly, renal SGLT2 inhibitor effects did not always correlate with those on glucose homeostasis, particularly in a limited number of direct comparative studies with other anti-diabetic treatments, indicating that nephroprotection may at least partly occur by mechanisms other than improving glycemic control. Our analyses did not provide evidence for different nephroprotective efficacy between SGLT2 inhibitors. Importantly, only four of 105 studies reported on female animals, and none provided direct comparative data between sexes. We conclude that more data on female animals and more direct comparative studies with other anti-diabetic compounds and combinations of treatments are needed.
Topics: Animals; Female; Mice; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Kidney; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37495021
DOI: 10.1016/j.pharmthera.2023.108503 -
Clinica Chimica Acta; International... Jun 2024High serum galectin-3 has been associated with adverse outcomes among dialysis patients, although its prognostic role remains unclear among individuals with... (Review)
Review
BACKGROUND AND AIMS
High serum galectin-3 has been associated with adverse outcomes among dialysis patients, although its prognostic role remains unclear among individuals with earlier-stage chronic kidney disease. The present systematic review aims to evaluate the association of serum galectin-3 with survival, cardiovascular disease and kidney disease progression among non-dialysis chronic kidney disease patients.
METHODS
PubMed, Scopus, Web of Science, CENTRAL and Google Scholar were systematically searched till November 10, 2023. All observational studies assessing the prognostic role of serum galectin-3 in patients with non-dialysis chronic kidney disease were included.
RESULTS
Overall, 12 studies (10 cohort, 2 cross-sectional) were included, comprising 9,349 patients. The endpoint of survival was assessed in 5 studies, indicating a significant association between increasing serum galectin-3 levels and higher all-cause mortality risk (Hazard ratio per unit: 1.22, 95 % confidence intervals-CI: 1.05-1.41, ≥6 ng/mL: 2.66, 95 % CI: 1.68-4.23). Current evidence coming from 4 studies was inconclusive regarding the potential link of galectin-3 and kidney function decline, yielding conflicting results. No significant associations between serum galectin-3 and heart failure, cardiovascular events or death were consistently reported.
CONCLUSIONS
This systematic review supports the prognostic role of galectin-3 in chronic kidney disease, as its increased serum values may be associated with higher all-cause mortality risk. No clear role could be supported for serum galectin-3 regarding the prediction of cardiovascular disease or kidney disease progression.
Topics: Humans; Renal Insufficiency, Chronic; Galectin 3; Cardiovascular Diseases; Galectins; Blood Proteins; Disease Progression; Prognosis
PubMed: 38750780
DOI: 10.1016/j.cca.2024.119727 -
Clinical Nutrition ESPEN Aug 2023The aim of the study was to map evidence on the association between phase angle (PhA) and body composition in populations healthy and clinical populations). A systematic... (Review)
Review
The aim of the study was to map evidence on the association between phase angle (PhA) and body composition in populations healthy and clinical populations). A systematic search for information regarding the topic was conducted in nine electronic databases (CINAHL, LILACS, PubMed, SciELO, Scopus, SPORTDiscus, Science Direct, MEDLINE and Web of Science) between October and November 2021. Studies with different designs, which allowed extracting information about the relationship between PhA and body composition (body cell mass [BCM], muscle tissue, bone mineral content, lean mass, total fat mass, visceral fat, and lean soft tissue mass [LSTM]) were included. Of the total of 11,913 initially identified studies, 59 were included after reading titles, abstracts, full texts and references. Most studies (40.67%; n = 24) presented data from Brazilian samples. With regard to the design of studies, 15 (25.42%) had longitudinal design. The age group of studies was wide, with studies involved 3-year-old children and 88-year-old adults. Body fat mass was evaluated by 31 studies (52.54%) in which 11 observed inverse relationships, nine studies showed direct relationships and 11 observed no relationship. Regarding lean mass, muscle mass, and fat-free mass components, most studies observed direct relationship with PhA (n = 37; 86.04%). It could be concluded that the phase angle was directly associated with lean mass and muscle mass in different age groups (children, adolescents, adults and older adults) and in people with different health diagnoses (HIV, cancer, hemodialysis, sarcopenia and without the diagnosis of diseases). Regarding body fat and the other investigated components, there is not enough evidence to establish the direction of associations.
Topics: Adolescent; Child, Preschool; Humans; Adipose Tissue; Body Composition; Bone Density; Muscle, Skeletal; Renal Dialysis; Adult; Aged, 80 and over
PubMed: 37344079
DOI: 10.1016/j.clnesp.2023.05.015 -
Scientific Reports Sep 2023The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney... (Meta-Analysis)
Meta-Analysis
The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79-0.95) and of heart failure (RR 0.67; 95% CI 0.61-0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75-1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68-0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72-0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Kidney; Acute Kidney Injury; Renal Insufficiency, Chronic
PubMed: 37741858
DOI: 10.1038/s41598-023-42989-z -
European Review For Medical and... Sep 2023Hyperhomocysteinemia is a well-known marker that is associated with an increased risk of atherosclerosis due to its toxic effect on endothelial cells. This, in turn,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hyperhomocysteinemia is a well-known marker that is associated with an increased risk of atherosclerosis due to its toxic effect on endothelial cells. This, in turn, leads to cardiovascular injury and increases morbidity. Different studies have shown alterations in the levels of homocysteine with respect to multiple disease states. Whether this non-traditional marker is associated with cardiovascular injury or not is subject to conflicting results. The purpose of this systematic review is to evaluate the role of homocysteine in the formation of atherosclerotic cardiovascular disease in young adults and children.
MATERIALS AND METHODS
This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). A search was done using specific keywords, including "homocysteine", "coronary artery disease", and "atherosclerosis", amongst several others, from the databases of PubMed, COCHRANE, and EBSCO. The data items included the diseased sample population along with the intervention used, or investigations carried out and the findings of the studies. Finally, 35 eligible studies were included.
RESULTS
Young patients with atherosclerotic cardiovascular disease were more likely to have elevated levels of homocysteine compared to elderly patients. Elevated levels of homocysteine have been observed with several genetic, nutritional deficiencies, and autoimmune states such as rheumatoid arthritis. On the other hand, decreased levels of homocysteine have been observed after certain intervention treatments, such as oral contraceptive pills, L-thyroxine, and even the adoption of certain diets. In the majority of studies, whenever homocysteine levels were higher than normal, this was reflected by an increased carotid intima-media thickness.
CONCLUSIONS
Homocysteine has a high correlation with atherosclerotic cardiovascular disease in young and overweight patients. In addition, the relationship of homocysteine with smoking, genetic polymorphism, specific hormonal and renal disorders, nutritional deficiencies (vitamin B12 and folic acid), and the use of specific medicines are among the other recurring findings. Given that many of these studies focus only on women, the relationship between homocysteine and atherosclerotic cardiovascular diseases in males is still unclear. Whether males are more prone to hyperhomocysteinemia needs to be assessed. Still, precise processes underlying variations in homocysteine in relation to all influencing factors are unclear and need further studies.
Topics: Male; Child; Humans; Female; Aged; Cardiovascular Diseases; Carotid Intima-Media Thickness; Prognosis; Hyperhomocysteinemia; Homocysteine; Endothelial Cells; Atherosclerosis; Folic Acid; Vitamin B 12; Risk Factors
PubMed: 37782175
DOI: 10.26355/eurrev_202309_33784 -
Journal of Nephrology Dec 2023Kidney involvement is common in hospitalized coronavirus disease 2019 (COVID-19) patients during the acute phase, little is known about the long-term impact of COVID-19... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kidney involvement is common in hospitalized coronavirus disease 2019 (COVID-19) patients during the acute phase, little is known about the long-term impact of COVID-19 on the kidney.
METHODS
This is a systematic review and meta-analysis on long-term renal outcomes among COVID-19 patients. We carried out a systematic literature search in PUBMED, EMBASE, SCOPUS, and Cochrane COVID-19 study register and performed the random-effects meta-analysis of rates. The search was last updated on November 23, 2022.
RESULTS
The study included 12 moderate to high-quality cohort studies involving 6976 patients with COVID-19-associated acute kidney injury and 5223 COVID-19 patients without acute kidney injury. The summarized long-term renal non-recovery rate, dialysis-dependent rate, and complete recovery rate among patients with COVID-19-associated AKI was 22% (12-33%), 6% (2-12%), and 63% (44-81%) during a follow-up of 90-326.5 days. Heterogeneity could be explained by differences in the prevalence of chronic kidney disease and proportion of acute kidney injury requiring renal replacement therapy using meta-regression; patients with more comorbidities or higher renal replacement therapy rate had higher non-recovery rates. The summarized long-term kidney function decrease rate among patients without acute kidney injury was 22% (3-51%) in 90-199 days, with heterogeneity partially explained by severity of infection.
CONCLUSION
Patients with more comorbidities tend to have a higher renal non recovery rate after COVID-19-associated acute kidney injury; for COVID-19 patients without acute kidney injury, decrease in kidney function may occur during long-term follow-up. Regular evaluation of kidney function during the post-COVID-19 follow-up among high-risk patients may be necessary.
Topics: Humans; COVID-19; Renal Dialysis; Renal Replacement Therapy; Acute Kidney Injury; Kidney
PubMed: 37787893
DOI: 10.1007/s40620-023-01731-8