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Current Pharmaceutical Design 2023Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose cotransporter 2 inhibitors), a class of anti-diabetic medications, are shown to reduce cardiovascular and renal events. This systematic review and meta-analysis aimed to assess whether SGLT2i could become a new treatment strategy for CKD for its renal protection and safety.
METHODS
Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3.
RESULTS
Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group.
CONCLUSION
SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.
Topics: Humans; Acute Disease; Diabetes Mellitus, Type 2; Kidney; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37537933
DOI: 10.2174/1381612829666230804103643 -
European Journal of Haematology Jun 2022To conduct a systematic review of tranexamic acid (TXA) and the risk of renal failure from urinary clots in adult patients with hematuria.
OBJECTIVES
To conduct a systematic review of tranexamic acid (TXA) and the risk of renal failure from urinary clots in adult patients with hematuria.
METHODS
A systematic review of Medline, Embase, CENTRAL, www.
CLINICALTRIALS
gov, and Google Scholar were searched. Randomized control trials (RCTs) and observational studies that assessed the risk of renal failure with use of TXA among adults with hematuria were included. The primary outcome was renal failure due to urinary tract clots with TXA compared to no TXA (or placebo) or comparator.
RESULTS
We identified three RCTs (N = 466 patients) and three retrospective cohort studies (N=220 patients), and a total of 342 patients that had hematuria and received TXA. The patient population of the six studies included medical and surgical patients, with two of the three RCTs comprised patients undergoing percutaneous nephrolithotomy, and the third RCT comprised patients undergoing transurethral resection of the prostate. Documentation of renal function before and after TXA administration was documented in only two studies (N = 28 patients), and neither identified worsening renal function in those exposed to TXA.
CONCLUSIONS
There are limited studies evaluating the risk of renal failure in patients with hematuria who were exposed to TXA, and the available data does not suggest an increased risk.
Topics: Acute Kidney Injury; Adult; Antifibrinolytic Agents; Female; Hematuria; Humans; Male; Tranexamic Acid
PubMed: 35266205
DOI: 10.1111/ejh.13762 -
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 -
Journal of Clinical Pharmacy and... Mar 2022Acute kidney injury (AKI) is a complication following surgery and has been associated with worsened patient outcomes. Providers have used agents that may confer a degree... (Meta-Analysis)
Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Acute kidney injury (AKI) is a complication following surgery and has been associated with worsened patient outcomes. Providers have used agents that may confer a degree of renal protection in the perioperative stage. Such is the case of dexmedetomidine, a selective alpha-2 adrenergic agonist used in the intensive care unit (ICU) as a sedative agent. The primary objective of this meta-analysis was to characterize the use of dexmedetomidine and to evaluate its impact on renal markers and outcomes in patients after surgery.
METHODS
A systematic review of manuscripts was performed to identify patients who received dexmedetomidine after surgery by searching the PubMed, Embase, and Cochrane databases. The following parameters were captured: blood urea nitrogen (BUN), serum creatinine, creatinine clearance, neutrophil gelatinase-associated lipoprotein (NGAL), cystatin C, urine output, duration of mechanical ventilation, ICU length of stay, AKI, need for dialysis, and mortality.
RESULTS AND DISCUSSION
Nineteen studies with 3,395 patients were included in the analyses. The mean bolus and infusion dose of dexmedetomidine were 0.82 µg/kg and 0.54 mcg/kg/hr, respectively. There was a significant difference in creatinine clearance and NGAL in favour of the dexmedetomidine group. In addition, the dexmedetomidine group had a shorter ICU length of stay, and a lower risk of acute kidney injury and mortality compared to the control. There was no difference in the rest of the parameters.
WHAT IS NEW AND CONCLUSION
Dexmedetomidine appears to have postoperative renal protective effects. This is evidenced by lower NGAL levels and increased creatinine clearance in those who received dexmedetomidine. These effects are associated with decreases in ICU length of stay and risk of AKI and mortality.
Topics: Acute Kidney Injury; Adrenergic alpha-2 Receptor Agonists; Dexmedetomidine; Humans; Hypnotics and Sedatives; Kidney
PubMed: 34510502
DOI: 10.1111/jcpt.13527 -
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 -
Pharmaceutics Feb 2022Kidney function assessment in the critically ill overlooks the possibility for hyperfunctioning kidneys, known as augmented renal clearance (ARC), which could contribute... (Review)
Review
Kidney function assessment in the critically ill overlooks the possibility for hyperfunctioning kidneys, known as augmented renal clearance (ARC), which could contribute to therapeutic failures in the intensive care unit (ICU). The aim of this research is to conduct a systematic review and meta-analysis of prevalence and risk factors of ARC in the critically ill. MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, ProQuest Dissertations and Theses Global databases were searched on 27 October 2020. We included studies conducted in critically ill adults who reported the prevalence and/or risk factors of ARC. We evaluated study quality using the Joanna Briggs Institute appraisal tool. Case reports, reviews, editorials and commentaries were excluded. We generated a random-effects meta-analytic model using the inverse variance method and visualized the pooled estimates using forest plots. Seventy studies were included. The pooled prevalence (95% CI) was 39% (34.9-43.3). Prevalence for neuro, trauma, mixed and sepsis ICUs were 74 (55-87), 58 (48-67), 36 (31-41) and 33 (21-48), respectively. Age, male sex and trauma were associated with ARC with pooled OR (95% CI) of 0.95 (0.93-0.96), 2.36 (1.28-4.36), 2.60 (1.21-5.58), respectively. Limitations included variations in ARC definition, inclusion and exclusion criteria and studies design. In conclusion, ARC is prevalent in critically ill patients, especially those in the neurocritical care and trauma ICU population. Young age, male sex and trauma are risk factors for ARC in those with apparently normal renal function. Further research on optimal dosing of drugs in the setting of ARC is warranted. (Prospero registration: CRD42021246417).
PubMed: 35214177
DOI: 10.3390/pharmaceutics14020445 -
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 -
Disease Models & Mechanisms Jun 2023As kidney diseases affect ∼10% of the world population, understanding the underlying mechanisms and developing therapeutic interventions are of high importance....
As kidney diseases affect ∼10% of the world population, understanding the underlying mechanisms and developing therapeutic interventions are of high importance. Although animal models have enhanced knowledge of disease mechanisms, human (patho-)physiology may not be adequately represented in animals. Developments in microfluidics and renal cell biology have enabled the development of dynamic models to study renal (patho-)physiology in vitro. Allowing inclusion of human cells and combining different organ models, such as kidney-on-a-chip (KoC) models, enable the refinement and reduction of animal experiments. We systematically reviewed the methodological quality, applicability and effectiveness of kidney-based (multi-)organ-on-a-chip models, and describe the state-of-the-art, strengths and limitations, and opportunities regarding basic research and implementation of these models. We conclude that KoC models have evolved to complex models capable of mimicking systemic (patho-)physiological processes. Commercial chips and human induced pluripotent stem cells and organoids are important for KoC models to study disease mechanisms and assess drug effects, even in a personalized manner. This contributes to the Reduction, Refinement and Replacement of animal models for kidney research. A lack of reporting of intra- and inter-laboratory reproducibility and translational capacity currently hampers implementation of these models.
Topics: Animals; Humans; Reproducibility of Results; Induced Pluripotent Stem Cells; Kidney; Kidney Diseases; Lab-On-A-Chip Devices
PubMed: 37334839
DOI: 10.1242/dmm.050113 -
The Cochrane Database of Systematic... Nov 2021Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different... (Review)
Review
BACKGROUND
Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different approaches, including a more intensified antihypertensive therapy, lifestyle modifications or both, have largely failed to improve patients' outcomes and to reduce cardiovascular and renal risk. As renal sympathetic hyperactivity is a major driver of resistant hypertension, in the last decade renal sympathetic ablation (renal denervation) has been proposed as a possible therapeutic alternative to treat this condition.
OBJECTIVES
We sought to evaluate the short- and long-term effects of renal denervation in individuals with resistant hypertension on clinical end points, including fatal and non-fatal cardiovascular events, all-cause mortality, hospital admissions, quality of life, blood pressure control, left ventricular hypertrophy, cardiovascular and metabolic profile and kidney function, as well as the potential adverse events related to the procedure.
SEARCH METHODS
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to 3 November 2020: Cochrane Hypertension's Specialised Register, CENTRAL (2020, Issue 11), Ovid MEDLINE, and Ovid Embase. The World Health Organization International Clinical Trials Registry Platform (via CENTRAL) and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov were searched for ongoing trials. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) that compared renal denervation to standard therapy or sham procedure to treat resistant hypertension, without language restriction.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed study risk of bias. We summarised treatment effects on available clinical outcomes and adverse events using random-effects meta-analyses. We assessed heterogeneity in estimated treatment effects using Chi² and I² statistics. We calculated summary treatment estimates as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, and a risk ratio (RR) for dichotomous outcomes, together with their 95% confidence intervals (CI). Certainty of evidence has been assessed using the GRADE approach.
MAIN RESULTS
We found 15 eligible studies (1416 participants). In four studies, renal denervation was compared to sham procedure; in the remaining studies, renal denervation was tested against standard or intensified antihypertensive therapy. Most studies had unclear or high risk of bias for allocation concealment and blinding. When compared to control, there was low-certainty evidence that renal denervation had little or no effect on the risk of myocardial infarction (4 studies, 742 participants; RR 1.31, 95% CI 0.45 to 3.84), ischaemic stroke (5 studies, 892 participants; RR 0.98, 95% CI 0.33 to 2.95), unstable angina (3 studies, 270 participants; RR 0.51, 95% CI 0.09 to 2.89) or hospitalisation (3 studies, 743 participants; RR 1.24, 95% CI 0.50 to 3.11). Based on moderate-certainty evidence, renal denervation may reduce 24-hour ambulatory blood pressure monitoring (ABPM) systolic BP (9 studies, 1045 participants; MD -5.29 mmHg, 95% CI -10.46 to -0.13), ABPM diastolic BP (8 studies, 1004 participants; MD -3.75 mmHg, 95% CI -7.10 to -0.39) and office diastolic BP (8 studies, 1049 participants; MD -4.61 mmHg, 95% CI -8.23 to -0.99). Conversely, this procedure had little or no effect on office systolic BP (10 studies, 1090 participants; MD -5.92 mmHg, 95% CI -12.94 to 1.10). Moderate-certainty evidence suggested that renal denervation may not reduce serum creatinine (5 studies, 721 participants, MD 0.03 mg/dL, 95% CI -0.06 to 0.13) and may not increase the estimated glomerular filtration rate (eGFR) or creatinine clearance (6 studies, 822 participants; MD -2.56 mL/min, 95% CI -7.53 to 2.42). AUTHORS' CONCLUSIONS: In patients with resistant hypertension, there is low-certainty evidence that renal denervation does not improve major cardiovascular outomes and renal function. Conversely, moderate-certainty evidence exists that it may improve 24h ABPM and diastolic office-measured BP. Future trials measuring patient-centred instead of surrogate outcomes, with longer follow-up periods, larger sample size and more standardised procedural methods are necessary to clarify the utility of this procedure in this population.
Topics: Antihypertensive Agents; Blood Pressure; Denervation; Humans; Hypertension; Kidney
PubMed: 34806762
DOI: 10.1002/14651858.CD011499.pub3 -
ESC Heart Failure Dec 2020A worsening renal function is prevalent among patients with cardiovascular disease, especially heart failure (HF). Sacubitril/valsartan appears to prevent worsening of... (Review)
Review
A worsening renal function is prevalent among patients with cardiovascular disease, especially heart failure (HF). Sacubitril/valsartan appears to prevent worsening of renal function and progression of chronic kidney disease (CKD) as compared with renin-angiotensin system (RAS) inhibitors alone in HF patients. It is unclear whether these advantages are present in HF patients only, or can be extended to other categories of patients, in which this drug was studied. We performed a systematic review and meta-analysis to assess the consistency of effect size regarding renal outcome across randomized controlled trials (RCTs) that compared sacubitril/valsartan with RAS inhibitors in patients with or without HF. We searched Medline (PubMed), Scopus, and Thomson Reuters Web of Science databases until June 2020. We took into account RCTs that compared sacubitril/valsartan with a RAS inhibitor and reported data regarding renal function. We used random-effects models to obtain summary odds ratio (OR) with 95% confidence interval (CI). We extracted hazard ratios for renal outcomes, glomerular filtration rate slopes or rates of renal adverse events. Sensitivity analyses were performed by moderator analysis and random-effects meta-regression. The search revealed 10 RCTs (published between 2012 and 2019) on 16 456 subjects. Sacubitril/valsartan resulted in a lower risk of renal dysfunction as compared with RAS inhibitors alone [k = 10; pooled OR = 0.70 (95% CI 0.57-0.85); P < 0.001], with a moderate inconsistency between studies [Q(9) = 15.18; P = 0.086; I = 40.73%]. A stronger association was found in studies including older patients (k = 10; β = -0.047730; P = 0.020) or HF patients with preserved ejection fraction [pooled OR = 0.53 (0.41-0.68) vs. 0.76 (0.57-1.01) for studies on HF patients with reduced ejection fraction; P for comparison = 0.065]. The effect size did not change with different comparators (angiotensin-converting enzyme inhibitors vs. angiotensin II type 1 receptor blockers, P = 0.279). No significant association was found when the analysis was restricted to studies on non-HF patients [k = 3; pooled OR = 0.86 (0.61-1.22); P = 0.403] and studies with high risk of bias [k = 3; pooled OR = 0.34 (0.08-1.44); P = 0.143]. Our findings support the role of sacubitril/valsartan on preservation of renal function, especially in older patients and HF patients with preserved ejection fraction. However, evidence is currently limited to HF patients, while the renal outcome of sacubitril/valsartan therapy outside the HF setting needs to be further investigated.
PubMed: 32960491
DOI: 10.1002/ehf2.13002