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JACC. Advances Feb 2024Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the...
BACKGROUND
Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM)-1 are renal biomarkers increasingly appreciated for their role in the risk stratification and prognostication of heart failure (HF) patients. However, very few have been adopted clinically, owing to the lack of consistency.
OBJECTIVES
The authors aimed to study the association between cystatin C, NGAL, and KIM-1 and outcomes, mortality, hospitalizations, and worsening renal function (WRF) in patients with acute and chronic HF.
METHODS
We included peer-reviewed English-language articles from PubMed and EMBASE published up to December 2021. We analyzed the above associations using random-effects meta-analysis. Publication bias was assessed using funnel plots.
RESULTS
Among 2,631 articles, 100 articles, including 45,428 patients, met the inclusion criteria. Top-tertile of serum cystatin C, when compared to the bottom-tertile, carried a higher pooled hazard ratio (pHR) for mortality (pHR: 1.59, 95% CI: 1.42-1.77) and for the composite outcome of mortality and HF hospitalizations (pHR: 1.49, 95% CI: 1.23-1.75). Top-tertile of serum NGAL had a higher hazard for mortality (pHR: 2.91, 95% CI: 1.49-5.67) and composite outcome (HR: 4.11, 95% CI: 2.69-6.30). Serum and urine NGAL were significantly associated with WRF, with pHRs of 2.40 (95% CI: 1.48-3.90) and 2.01 (95% CI: 1.21-3.35). Urine KIM-1 was significantly associated with WRF (pHR: 1.60, 95% CI: 1.24-2.07) but not with other outcomes. High heterogeneity was noted between studies without an obvious explanation based on meta-regression.
CONCLUSIONS
Serum cystatin C and serum NGAL are independent predictors of adverse outcomes in HF. Serum and urine NGAL are important predictors of WRF in HF.
PubMed: 38939376
DOI: 10.1016/j.jacadv.2023.100765 -
Antioxidants (Basel, Switzerland) May 2024The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative... (Review)
Review
The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included ( = 41 MP; = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.
PubMed: 38929081
DOI: 10.3390/antiox13060642 -
European Journal of Pediatrics Jun 2024This study aimed to evaluate the current evidence on various aspects of fluid therapy such as type, volume, and timing of fluid bolus administration in children with...
UNLABELLED
This study aimed to evaluate the current evidence on various aspects of fluid therapy such as type, volume, and timing of fluid bolus administration in children with septic shock. Systematic review and meta-analysis of clinical trials including children less than 18 years of age admitted to the pediatric emergency and intensive care unit with severe infection and shock requiring fluid resuscitation. The intervention included balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The primary outcome was mortality rate. Of the 219 citations retrieved, 12 trials (3526 children with severe infection with or without malaria and shock) were included. The pooled results found no significant difference in the mortality rate between groups comparing balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The risk of acute kidney injury (AKI) was significantly less in the BC group compared to the NS group. The certainty of evidence for mortality was of "moderate certainty" in the BC vs NS group, and was of "very low certainty" for the other two groups.
CONCLUSIONS
The current meta-analysis found no significant difference in the mortality rate between the types of resuscitation fluid, and their speed or volume of administration. However, a significantly decreased risk of AKI was found in the BC group. More evidence is needed regarding the speed and volume of administration of fluid boluses in critically ill children.Prospero registration: CRD42020209066.
WHAT IS KNOWN
• Balanced crystalloids (BC) may be better than normal saline (NS) for fluid resuscitation in critically ill children.
WHAT IS NEW
• BC are better than NS for fluid resuscitation in critically ill children as they decrease AKI and hyperchloremia.
PubMed: 38916738
DOI: 10.1007/s00431-024-05653-w -
European Journal of Clinical... Jun 2024Atypical antipsychotics are associated with several adverse effects including metabolic syndrome, weight gain, QTc interval prolongation, and extrapyramidal effects.... (Review)
Review
PURPOSE
Atypical antipsychotics are associated with several adverse effects including metabolic syndrome, weight gain, QTc interval prolongation, and extrapyramidal effects. This study aims to investigate the risk of renal impairment in patients receiving atypical antipsychotics.
METHODS
A systematic literature search was conducted via PubMed and Ovid SP and Web of Science to retrieve studies reporting the risk of renal impairment in patients receiving atypical antipsychotic treatment. The pooled risk ratio (RR) of renal impairment and the subgroup analysis was calculated using the random-effects generic inverse variance method in Cochrane Review Manager.
RESULTS
A total of 4 studies involving 514,710 patients (221, 873 patients on atypical antipsychotics/CKD and 292, 837 controls) were included in this meta-analysis. Patients on atypical antipsychotics exhibited an increased risk of renal impairment, with a pooled risk ratio of 1.34 (95%CI 1.23-1.47). Subgroup analysis demonstrated that atypical antipsychotic use was associated with an increased risk of both acute kidney injury (AKI) (RR 1.51, 95%CI 1.34-1.71) and chronic kidney disease (CKD) (RR: 1.23, 95%CI 1.12-1.35).
CONCLUSION
Patients receiving atypical antipsychotics have an increased risk of renal impairment. Quetiapine carries the highest risk of renal impairment encompassing both AKI and CKD.
PubMed: 38916726
DOI: 10.1007/s00228-024-03714-5 -
The American Journal of Gastroenterology Jun 2024Diagnostic paracentesis is recommended for patients with cirrhosis admitted to the hospital, but adherence is suboptimal with unclear impact on clinical outcomes. This...
INTRODUCTION
Diagnostic paracentesis is recommended for patients with cirrhosis admitted to the hospital, but adherence is suboptimal with unclear impact on clinical outcomes. This meta-analysis aimed to assess the outcomes of early vs. delayed diagnostic paracentesis among hospitalized patients with cirrhosis and ascites.
METHODS
We searched multiple databases for studies comparing early vs. delayed diagnostic paracentesis among hospitalized patients with cirrhosis and ascites. The pooled odds ratio (OR) and mean difference (MD) with confidence intervals (CI) for proportional and continuous variables were calculated using the random-effects model. Early diagnostic paracentesis was defined as receiving diagnostic paracentesis within 12-24 hours of admission. The primary outcome was in-hospital mortality. Secondary outcomes were length-of-hospital-stay (LOS), acute kidney injury (AKI), and 30-day readmission.
RESULTS
Seven studies (n=78,744) (n=45,533 early vs. n=33,211 delayed diagnostic paracentesis) were included. Early diagnostic paracentesis was associated with lower in-hospital mortality (OR 0.61, 95% CI 0.46-0.82, P=0.001), LOS (MD -4.85 days; 95% CI -6.45, -3.20; P<0.001), and AKI (OR 0.62, 95% CI 0.42-0.92, P=0.02) compared to delayed diagnostic paracentesis, with similar 30-day readmission (OR 1.11, 95% CI 0.52-2.39, P=0.79). Subgroup analysis revealed consistent results for in-hospital mortality whether early diagnostic paracentesis performed within 12 hours (OR 0.51, 95% CI 0.32-0.79, P=0.003, I2=0%) or within 24 hours of admission (OR 0.67, 95% CI 0.45-0.98, P=0.04, I2=82%). Notably, the mortality OR was numerically lower when diagnostic paracentesis was performed within 12 hours, and the results were precise and homogenous (I2=0%).
CONCLUSIONS
Findings from this meta-analysis suggest that early diagnostic paracentesis is associated with better patient outcomes. Early diagnostic paracentesis within 12 hours of admission may be associated with the greatest mortality benefit. Data from large-scale randomized trials are needed to validate our findings, especially if there is a greater mortality benefit for early diagnostic paracentesis within 12 hours.
PubMed: 38916217
DOI: 10.14309/ajg.0000000000002906 -
BMC Cardiovascular Disorders Jun 2024Transcatheter aortic valve implantation (TAVI) is a well-established treatment for high and intermediate-risk patients with severe aortic stenosis (AS). Recent studies...
BACKGROUND
Transcatheter aortic valve implantation (TAVI) is a well-established treatment for high and intermediate-risk patients with severe aortic stenosis (AS). Recent studies have demonstrated non-inferiority of TAVI compared to surgery in low-risk patients. In the past decade, numerous literature reviews (SLRs) have assessed the use of TAVI in different risk groups. This is the first attempt to provide an overview of SRs (OoSRs) focusing on secondary studies reporting clinical outcomes/process indicators. This research aims to summarize the findings of extant literature on the performance of TAVI over time.
METHODS
A literature search took place from inception to April 2024. We searched MEDLINE and the Cochrane Library for SLRs. SLRs reporting at least one review of clinical indicators were included. Subsequently, a two-step inclusion process was conducted: [1] screening based on title and abstracts and [2] screening based on full-text papers. Relevant data were extracted and the quality of the reviews was assessed.
RESULTS
We included 33 SLRs with different risks assessed via the Society of Thoracic Surgeons (STS) score. Mortality rates were comparable between TAVI and Surgical Aortic Valve Replacement (SAVR) groups. TAVI is associated with lower rates of major bleeding, acute kidney injury (AKI) incidence, and new-onset atrial fibrillation. Vascular complications, pacemaker implantation, and residual aortic regurgitation were more frequent in TAVI patients.
CONCLUSION
This study summarizes TAVI performance findings over a decade, revealing a shift to include both high and low-risk patients since 2020. Overall, TAVI continues to evolve, emphasizing improved outcomes, broader indications, and addressing challenges.
Topics: Humans; Transcatheter Aortic Valve Replacement; Aortic Valve Stenosis; Risk Factors; Treatment Outcome; Risk Assessment; Aortic Valve; Postoperative Complications; Time Factors; Systematic Reviews as Topic
PubMed: 38907344
DOI: 10.1186/s12872-024-03980-2 -
Clinical Kidney Journal Jun 2024Acute kidney injury (AKI) is associated with increased morbidity/mortality. With artificial intelligence (AI), more dynamic models for mortality prediction in AKI...
BACKGROUND
Acute kidney injury (AKI) is associated with increased morbidity/mortality. With artificial intelligence (AI), more dynamic models for mortality prediction in AKI patients have been developed using machine learning (ML) algorithms. The performance of various ML models was reviewed in terms of their ability to predict in-hospital mortality for AKI patients.
METHODS
A literature search was conducted through PubMed, Embase and Web of Science databases. Included studies contained variables regarding the efficacy of the AI model [the AUC, accuracy, sensitivity, specificity, negative predictive value and positive predictive value]. Only original studies that consisted of cross-sectional studies, prospective and retrospective studies were included, while reviews and self-reported outcomes were excluded. There was no restriction on time and geographic location.
RESULTS
Eight studies with 37 032 AKI patients were included, with a mean age of 65.3 years. The in-hospital mortality was 18.0% in the derivation and 15.8% in the validation cohorts. The pooled [95% confidence interval (CI)] AUC was observed to be highest for the broad learning system (BLS) model [0.852 (0.820-0.883)] and elastic net final (ENF) model [0.852 (0.813-0.891)], and lowest for proposed clinical model (PCM) [0.765 (0.716-0.814)]. The pooled (95% CI) AUC of BLS and ENF did not differ significantly from other models except PCM [Delong's test = .022]. PCM exhibited the highest negative predictive value, which supports this model's use as a possible rule-out tool.
CONCLUSION
Our results show that BLS and ENF models are equally effective as other ML models in predicting in-hospital mortality, with variability across all models. Additional studies are needed.
PubMed: 38903953
DOI: 10.1093/ckj/sfae150 -
The Cochrane Database of Systematic... Jun 2024Peritoneal dialysis (PD) and haemodialysis (HD) are two possible modalities for people with kidney failure commencing dialysis. Only a few randomised controlled trials... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peritoneal dialysis (PD) and haemodialysis (HD) are two possible modalities for people with kidney failure commencing dialysis. Only a few randomised controlled trials (RCTs) have evaluated PD versus HD. The benefits and harms of the two modalities remain uncertain. This review includes both RCTs and non-randomised studies of interventions (NRSIs).
OBJECTIVES
To evaluate the benefits and harms of PD, compared to HD, in people with kidney failure initiating dialysis.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies from 2000 to June 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. MEDLINE and EMBASE were searched for NRSIs from 2000 until 28 March 2023.
SELECTION CRITERIA
RCTs and NRSIs evaluating PD compared to HD in people initiating dialysis were eligible.
DATA COLLECTION AND ANALYSIS
Two investigators independently assessed if the studies were eligible and then extracted data. Risk of bias was assessed using standard Cochrane methods, and relevant outcomes were extracted for each report. The primary outcome was residual kidney function (RKF). Secondary outcomes included all-cause, cardiovascular and infection-related death, infection, cardiovascular disease, hospitalisation, technique survival, life participation and fatigue.
MAIN RESULTS
A total of 153 reports of 84 studies (2 RCTs, 82 NRSIs) were included. Studies varied widely in design (small single-centre studies to international registry analyses) and in the included populations (broad inclusion criteria versus restricted to more specific participants). Additionally, treatment delivery (e.g. automated versus continuous ambulatory PD, HD with catheter versus arteriovenous fistula or graft, in-centre versus home HD) and duration of follow-up varied widely. The two included RCTs were deemed to be at high risk of bias in terms of blinding participants and personnel and blinding outcome assessment for outcomes pertaining to quality of life. However, most other criteria were assessed as low risk of bias for both studies. Although the risk of bias (Newcastle-Ottawa Scale) was generally low for most NRSIs, studies were at risk of selection bias and residual confounding due to the constraints of the observational study design. In children, there may be little or no difference between HD and PD on all-cause death (6 studies, 5752 participants: RR 0.81, 95% CI 0.62 to 1.07; I = 28%; low certainty) and cardiovascular death (3 studies, 7073 participants: RR 1.23, 95% CI 0.58 to 2.59; I = 29%; low certainty), and was unclear for infection-related death (4 studies, 7451 participants: RR 0.98, 95% CI 0.39 to 2.46; I = 56%; very low certainty). In adults, compared with HD, PD had an uncertain effect on RKF (mL/min/1.73 m) at six months (2 studies, 146 participants: MD 0.90, 95% CI 0.23 to 3.60; I = 82%; very low certainty), 12 months (3 studies, 606 participants: MD 1.21, 95% CI -0.01 to 2.43; I = 81%; very low certainty) and 24 months (3 studies, 334 participants: MD 0.71, 95% CI -0.02 to 1.48; I = 72%; very low certainty). PD had uncertain effects on residual urine volume at 12 months (3 studies, 253 participants: MD 344.10 mL/day, 95% CI 168.70 to 519.49; I = 69%; very low certainty). PD may reduce the risk of RKF loss (3 studies, 2834 participants: RR 0.55, 95% CI 0.44 to 0.68; I = 17%; low certainty). Compared with HD, PD had uncertain effects on all-cause death (42 studies, 700,093 participants: RR 0.87, 95% CI 0.77 to 0.98; I = 99%; very low certainty). In an analysis restricted to RCTs, PD may reduce the risk of all-cause death (2 studies, 1120 participants: RR 0.53, 95% CI 0.32 to 0.86; I = 0%; moderate certainty). PD had uncertain effects on both cardiovascular (21 studies, 68,492 participants: RR 0.96, 95% CI 0.78 to 1.19; I = 92%) and infection-related death (17 studies, 116,333 participants: RR 0.90, 95% CI 0.57 to 1.42; I = 98%) (both very low certainty). Compared with HD, PD had uncertain effects on the number of patients experiencing bacteraemia/bloodstream infection (2 studies, 2582 participants: RR 0.34, 95% CI 0.10 to 1.18; I = 68%) and the number of patients experiencing infection episodes (3 studies, 277 participants: RR 1.23, 95% CI 0.93 to 1.62; I = 20%) (both very low certainty). PD may reduce the number of bacteraemia/bloodstream infection episodes (2 studies, 2637 participants: RR 0.44, 95% CI 0.27 to 0.71; I = 24%; low certainty). Compared with HD; It is uncertain whether PD reduces the risk of acute myocardial infarction (4 studies, 110,850 participants: RR 0.90, 95% CI 0.74 to 1.10; I = 55%), coronary artery disease (3 studies, 5826 participants: RR 0.95, 95% CI 0.46 to 1.97; I = 62%); ischaemic heart disease (2 studies, 58,374 participants: RR 0.86, 95% CI 0.57 to 1.28; I = 95%), congestive heart failure (3 studies, 49,511 participants: RR 1.10, 95% CI 0.54 to 2.21; I = 89%) and stroke (4 studies, 102,542 participants: RR 0.94, 95% CI 0.90 to 0.99; I = 0%) because of low to very low certainty evidence. Compared with HD, PD had uncertain effects on the number of patients experiencing hospitalisation (4 studies, 3282 participants: RR 0.90, 95% CI 0.62 to 1.30; I = 97%) and all-cause hospitalisation events (4 studies, 42,582 participants: RR 1.02, 95% CI 0.81 to 1.29; I = 91%) (very low certainty). None of the included studies reported specifically on life participation or fatigue. However, two studies evaluated employment. Compared with HD, PD had uncertain effects on employment at one year (2 studies, 593 participants: RR 0.83, 95% CI 0.20 to 3.43; I = 97%; very low certainty).
AUTHORS' CONCLUSIONS
The comparative effectiveness of PD and HD on the preservation of RKF, all-cause and cause-specific death risk, the incidence of bacteraemia, other vascular complications (e.g. stroke, cardiovascular events) and patient-reported outcomes (e.g. life participation and fatigue) are uncertain, based on data obtained mostly from NRSIs, as only two RCTs were included.
Topics: Humans; Peritoneal Dialysis; Renal Dialysis; Randomized Controlled Trials as Topic; Bias; Kidney Failure, Chronic; Quality of Life; Adult; Cause of Death; Middle Aged; Observational Studies as Topic
PubMed: 38899545
DOI: 10.1002/14651858.CD013800.pub2 -
International Journal of Molecular... Jun 2024Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in... (Meta-Analysis)
Meta-Analysis Review
Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in clinical practice. This meta-analysis aims to assess the effect of IL-10 immunotherapy on renal ischemia-reperfusion injury. Medline, Embase, Cochrane-library, Google Scholar and clinicaltrials.gov were searched up to 31 March 2023. Preclinical and clinical interventional studies investigating IL-10 immunotherapy for renal ischemia-reperfusion were eligible for inclusion. The primary endpoint was renal function (serum creatinine) following ischemia-reperfusion. The secondary endpoints included mitochondrial integrity, cellular proliferation, regulated cell death (TUNEL assay), expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β), M1/M2 macrophage polarization, tissue integrity (tubular injury score), long-term kidney fibrosis (fibrotic area %) and adverse events (pulmonary toxicity, cardiotoxicity hepatotoxicity). The search returned 861 records. From these, 16 full texts were screened and subsequently, seven animal studies, corresponding to a population of 268 mice/rats, were included. Compared to the control treatment, IL-10 immunotherapy reduced serum creatinine more effectively within 24 h of administration (95% CI: -9.177, -5.601, I = 22.42%). IL-10 immunotherapy promoted mitochondrial integrity and cellular proliferation and reduced regulated cell death (95% CI: -11.000, -4.184, I = 74.94%). It decreased the expression of TNF-α, IL-6 and IL-1β, led to M2 polarization of the local macrophages, reduced tubular injury score (95% CI: -8.917, -5.755, I = 22.71%), and long-term kidney fibrosis (95% CI: -6.963, -3.438, I = 0%). No adverse outcomes were captured. In Conclusion, IL-10 immunotherapy safely improves outcomes in animal models of renal ischemia-reperfusion; the translational potential of IL-10 immunotherapy needs to be further investigated in clinical trials.
Topics: Reperfusion Injury; Animals; Interleukin-10; Humans; Immunotherapy; Kidney; Acute Kidney Injury; Mice
PubMed: 38892418
DOI: 10.3390/ijms25116231 -
Journal of Cardiothoracic and Vascular... Apr 2024To evaluate the impact of acute kidney injury on transition to chronic kidney disease (CKD) after cardiac surgery and to determine frequency of incident CKD in these... (Review)
Review
OBJECTIVES
To evaluate the impact of acute kidney injury on transition to chronic kidney disease (CKD) after cardiac surgery and to determine frequency of incident CKD in these patients.
DESIGN
A systematic review and meta-analysis of observational studies.
SETTING
Electronic databases Medline and Embase were systematically searched from 1974 to February 6, 2023.
PARTICIPANTS
Eligible studies were original observational studies on adult cardiac surgery patients, written in the English language, and with clear kidney disease definitions. Exclusion criteria were studies with previously transplanted populations, populations with preoperative kidney impairment, ventricular assist device procedures, endovascular procedures, a kidney follow-up period of <90 days, and studies not presenting necessary data for effect size calculations.
INTERVENTIONS
Patients developing postoperative acute kidney injury after cardiac surgery were compared with patients who did not develop acute kidney injury.
MEASUREMENTS AND MAIN RESULTS
The search identified 4,329 unique studies, 87 underwent full-text review, and 12 were included for analysis. Mean acute kidney injury occurrence across studies was 16% (minimum-maximum: 8-50), while mean occurrence of CKD was 24% (minimum-maximum: 3-35), with high variability depending on definitions and follow-up time. Acute kidney injury was associated with increased odds of CKD in all individual studies. The pooled odds ratio across studies was 5.67 (95% confidence interval, 3.34-9.64; p < 0.0001).
CONCLUSIONS
Acute kidney injury after cardiac surgery was associated with a more than 5-fold increased odds of developing CKD. New-onset CKD occurred in almost 1 in 4 patients in the years after surgery.
PubMed: 38879369
DOI: 10.1053/j.jvca.2024.03.044