Kidney Injury Research Articles

Urinary liver-type fatty acid-binding protein level as a prognostic indicator of acute kidney injury secondary to severe falciparum malaria.

Acute kidney injury (AKI) secondary to severe falciparum malaria possesses a high mortality rate; however, a prognostic marker of renal dysfunction has not yet been identified. Thus, we reported a case of a patient with AKI secondary to falciparum malaria who underwent hemodialysis and a renal biopsy due to prolonged renal dysfunction. The male patient, in his 50s, presented to our hospital with vomiting, diarrhea, fever, and decreased level of consciousness. The Giemsa-stained peripheral blood film revealed approximately 5% parasitemia, and a rapid diagnostic test was positive for Plasmodium falciparum. He was diagnosed with severe falciparum malaria and was started on quinine hydrochloride. Hemodialysis was initiated due to the decreased urine output and fluid retention. Subsequently, he was weaned off hemodialysis. The histopathological analysis of a renal biopsy revealed interstitial fibrosis, tubular atrophy, and chronic inflammatory cell infiltration; thus, malarial nephropathy was diagnosed. Thereafter, his renal function stabilized, and he was discharged from the hospital. The urinary liver-type fatty acid-binding protein (L-FABP) level decreased before renal function improved. Our report highlighted that long-term follow-up is essential for severe AKI secondary to malaria. The urinary L-FABP level may be a useful prognostic indicator of AKI secondary to severe falciparum malaria.

Neonatal somatic oxygenation and perfusion assessment using near-infrared spectroscopy : Part of the series on near-infrared spectroscopy by the European Society of Paediatric Research Special Interest Group "Near-Infrared Spectroscopy".

In this narrative review, we summarize the current knowledge and applications of somatic near-infrared spectroscopy (NIRS), with a focus on intestinal, renal, limb, and multi-site applications in neonates. Assessing somatic oxygenation at various body locations in neonates may aid in the understanding of underlying pathophysiology of organ injury. Considering cerebral autoregulation may be active to protect the brain during systemic circulatory failure, peripheral somatic oxygenation may potentially provide an early indication of neonatal cardiovascular failure and ultimate hypoxemic injury to vital organs including the brain. Certain intestinal oxygenation patterns appear to be associated with the onset and course of necrotizing enterocolitis, whereas impaired renal oxygenation may indicate the onset of acute kidney injury after various types of hypoxic events. Peripheral muscle oxygenation measured at a limb may be particularly effective in the early prediction of shock in neonates. Using multi-site NIRS may complement current approaches and clinical investigations to alert for neonatal tissue hypoxemia, and potentially even guide management. However, somatic NIRS has its inherent limitations in regard to accuracy. Interpretation of organ-specific values can also be challenging. Last, currently there are limited prospective intervention studies, and clinical benefits need to be examined further, after the clarification of critical threshold-values. IMPACT: The assessment of somatic oxygenation using NIRS may contribute to the prediction of specific diseases in hemodynamically challenged neonates. Furthermore, it may give early warning signs for impending cardiovascular failure, and impaired cerebral circulation and oxygenation. We present a comprehensive overview of the literature on applications of NIRS to various somatic areas, with a focus on its potential clinical applicability, including future research directions. This paper will enable prospective standardized studies, and multicenter collaboration to obtain statistical power, likely to advance the field.

Safety of Combined Statin and Fibrate Therapy: Risks of Liver Injury and Acute Kidney Injury in a Cohort Study from the Shizuoka Kokuho Database.

Statins and fibrates are important means of preventing cardiovascular diseases, particularly when administered in combination as part of various therapeutic strategies. In this study, we explored the risks associated with various combinations of these drugs. We aimed to evaluate the risk of 1-year hospitalization with acute kidney injury, liver injury, pancreatitis, or rhabdomyolysis related to the concurrent administration of statins and fibrates. We performed a retrospective cohort study using data from the Shizuoka Kokuho Database, focusing on patients prescribed statins, fibrates, or a combination. Four drug exposure patterns were evaluated: adding statins to fibrates (exposure 1), switching from fibrates to statins (exposure 2), adding fibrates to statins (exposure 3), and switching from statins to fibrates (exposure 4). Hospitalization for the specified conditions within 1year was the outcome. Propensity score matching was used to create balanced cohorts for comparison. We studied 269,226 statin users and 16,282 fibrate users. After propensity score matching, there were 498 participants in the group of exposure 1, matched with 2988 in the fibrate-only group; 1180 in the group of exposure 2, matched with 7080 in the fibrate-only group; 1183 in group of exposure 3, matched with 11,830 in the statin only group; and 1356 in group of exposure 4, matched with 13,560 in the statin only group. The 1-year hospitalization rate with liver injury was higher in the group of exposure 1 than in the fibrate-only group (1.2% vs 0.3%, p < 0.01), in the group of exposure 2 than in the fibrate-only group (0.9% vs 0.3%, p < 0.01), and in the group of exposure 4 than in the statin-only group (0.6% vs 0.2%, p = 0.02). There was also a higher risk of 1-year hospitalization with acute kidney injury in group of exposure 1 than in the fibrate-only group (1.3% vs 0.3%, p = 0.01) but not in evaluations of exposure 2, 3, and 4. However, there were no differences in the risks of 1-year hospitalization with pancreatitis or rhabdomyolysis among the matched groups. We have demonstrated higher risks of 1-year hospitalization with liver injury or acute kidney injury associated with the use of combinations of statins and fibrates. This underscores the need for a cautious approach to the prescribing of such drug combinations and the importance of monitoring patients for potential adverse events.

Machine learning derived serum creatinine trajectories in acute kidney injury in critically ill patients with sepsis

BackgroundCurrent classification for acute kidney injury (AKI) in critically ill patients with sepsis relies only on its severity-measured by maximum creatinine which overlooks inherent complexities and longitudinal evaluation of this heterogenous syndrome. The role of classification of AKI based on early creatinine trajectories is unclear.MethodsThis retrospective study identified patients with Sepsis-3 who developed AKI within 48-h of intensive care unit admission using Medical Information Mart for Intensive Care-IV database. We used latent class mixed modelling to identify early creatinine trajectory-based classes of AKI in critically ill patients with sepsis. Our primary outcome was development of acute kidney disease (AKD). Secondary outcomes were composite of AKD or all-cause in-hospital mortality by day 7, and AKD or all-cause in-hospital mortality by hospital discharge. We used multivariable regression to assess impact of creatinine trajectory-based classification on outcomes, and eICU database for external validation.ResultsAmong 4197 patients with AKI in critically ill patients with sepsis, we identified eight creatinine trajectory-based classes with distinct characteristics. Compared to the class with transient AKI, the class that showed severe AKI with mild improvement but persistence had highest adjusted risks for developing AKD (OR 5.16; 95% CI 2.87–9.24) and composite 7-day outcome (HR 4.51; 95% CI 2.69–7.56). The class that demonstrated late mild AKI with persistence and worsening had highest risks for developing composite hospital discharge outcome (HR 2.04; 95% CI 1.41–2.94). These associations were similar on external validation.ConclusionsThese 8 classes of AKI in critically ill patients with sepsis, stratified by early creatinine trajectories, were good predictors for key outcomes in patients with AKI in critically ill patients with sepsis independent of their AKI staging.

The Gut Microbial Metabolite Trimethylamine N -oxide, Incident CKD, and Kidney Function Decline.

Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Experimentally, TMAO causes kidney injury and tubulointerstitial fibrosis. Little is known about prospective associations between TMAO and kidney outcomes, especially incident CKD. We hypothesized that higher plasma TMAO levels would be associated with higher risk of incident CKD and greater rate of kidney function decline. We included 10,564 participants from two community-based, prospective cohorts with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 to assess incident CKD. TMAO was measured using targeted mass spectrometry at baseline and one follow-up visit. Creatinine and Cystatin C were measured up to 4 times during follow-up and used to compute eGFR. Incident CKD was defined as an eGFR decline ≥ 30% from baseline and a resulting eGFR<60 ml/min/1.73 m2. Time-varying Cox models assessed the association of serial TMAO measures with incident CKD, adjusting for sociodemographic, lifestyle, diet, and cardiovascular disease risk factors. Linear mixed models assessed the association with annualized eGFR change in 10,009 participants with at least one follow-up eGFR measure without exclusions for baseline eGFR levels. During a median follow-up of 9.4 years (interquartile range: 9.1-11.6 years), 979 incident CKD events occurred. Higher TMAO levels associated with higher risk of incident CKD (2nd to 5th vs. 1st quintile HR[95%CI]= 1.65 [1.22-2.23], 1.68 [1.26-2.25], 2.28 [1.72-3.02], and 2.24[1.68-2.98], respectively) and greater annualized eGFR decline ( 2nd to 5th vs. 1st quintile annualized eGFR change= -0.21 [-0.32, -0.09], -0.17 [-0.29, -0.05], -0.35 [-0.47, -0.22], and -0.43[-0.56, -0.30], respectively) with monotonic dose-response relationships. These associations were consistent across different racial/ethnic groups examined. The association with eGFR decline was similar to or larger than that seen for established CKD risk factors including diabetes, per 10 mmHg of higher systolic blood pressure, per 10 years of older age, and Black race. In community-based US adults, higher serial measures of plasma TMAO were associated with higher risk of incident CKD and greater annualized kidney function decline.

Cardiac Surgery-Associated Acute Kidney Injury in Children after Cardiopulmonary Bypass

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a complication of cardiopulmonary bypass surgery that frequently occurs in children. The increased availability of pediatric cardiac surgery leads to yearly increases in congenital heart disease (CHD) procedures performed worldwide. The number of complications, including pediatric CSA-AKI, has also increased. Children with CSA-AKI have worse postoperative periods and require more complex post-op intensive care. Thus, the timely commencement of interventions to prevent and to treat kidney injury in CHD children are one of a leading goals of pediatric cardiac intensive care.

The Expression of Markers of Acute Kidney Injury Kim1 and NGAL after Administration of High Doses of Lithium Carbonate in Mice with Engrafted Skin Melanoma B16.

The expression of marker proteins of acute kidney injury after administration of high doses of lithium carbonate was assessed to evaluate the possibility of lithium use in neutron capture therapy. In mice with implanted skin melanoma B16, the expression of Kim1 (kidney injury molecule 1) and NGAL (neutrophil gelatinase-associated lipocalin) proteins in the kidneys was evaluated immunohistochemically 15, 30, 90, 180 min, and 7 days after peroral administration of lithium carbonate at single doses of 300 and 400 mg/kg. An increase in the expression of the studied proteins was found in 30 and 90 min after administration of 400 mg/kg lithium carbonate, however, 7 days after the drug administration, the expression returned to the level observed in the control group. It can be suggested that single administration of lithium carbonate in the studied doses effective for lithium neutron capture therapy will not significantly affect the renal function.

Megalin‐related mechanism of hemolysis‐induced acute kidney injury and the therapeutic strategy

AbstractHemolysis‐induced acute kidney injury (AKI) is attributed to heme‐mediated proximal tubule epithelial cell (PTEC) injury and tubular cast formation due to intratubular protein condensation. Megalin is a multiligand endocytic receptor for proteins, peptides, and drugs in PTECs and mediates the uptake of free hemoglobin and the heme‐scavenging protein α1‐microglobulin. However, understanding of how megalin is involved in the development of hemolysis‐induced AKI remains elusive. Here, we investigated the megalin‐related pathogenesis of hemolysis‐induced AKI and a therapeutic strategy using cilastatin, a megalin blocker. A phenylhydrazine‐induced hemolysis model developed in kidney‐specific mosaic megalin knockout (MegKO) mice confirmed megalin‐dependent PTEC injury revealed by the co‐expression of kidney injury molecule‐1 (KIM‐1). In the hemolysis model in kidney‐specific conditional MegKO mice, the uptake of hemoglobin and α1‐microglobulin as well as KIM‐1 expression in PTECs was suppressed, but tubular cast formation was augmented, likely due to the nonselective inhibition of protein reabsorption in PTECs. Quartz crystal microbalance analysis revealed that cilastatin suppressed the binding of megalin with hemoglobin and α1‐microglobulin. Cilastatin also inhibited the specific uptake of fluorescent hemoglobin by megalin‐expressing rat yolk sac tumor‐derived L2 cells. In a mouse model of hemolysis‐induced AKI, repeated cilastatin administration suppressed PTEC injury by inhibiting the uptake of hemoglobin and α1‐microglobulin and also prevented cast formation. Hemopexin, another heme‐scavenging protein, was also found to be a novel ligand of megalin, and its binding to megalin and uptake by PTECs in the hemolysis model were suppressed by cilastatin. Mass spectrometry‐based semiquantitative analysis of urinary proteins in cilastatin‐treated C57BL/6J mice indicated that cilastatin suppressed the reabsorption of a limited number of megalin ligands in PTECs, including α1‐microglobulin and hemopexin. Collectively, cilastatin‐mediated selective megalin blockade is an effective therapeutic strategy to prevent both heme‐mediated PTEC injury and cast formation in hemolysis‐induced AKI. © 2024 The Pathological Society of Great Britain and Ireland.

Geriatric nutritional risk index is associated with the occurrence of acute kidney injury in critically ill patients with acute heart failure

Background: During the acute heart failure (AHF), acute kidney injury (AKI) is highly prevalent in critically ill patients. The occurrence of the latter condition increases the risk of mortality in patients with acute heart failure. The current research on the relationship between nutritional risk and the occurrence of acute kidney injury in patients with acute heart failure is very limited. Methods: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.1) database. We included adult patients with AHF who were admitted to the intensive care unit in the study. Results: A total of 1310 critically ill patients with acute heart failure were included. The AUC of geriatric nutritional risk index (GNRI) (0.694) is slightly superior to that of controlling nutritional status (CONUT) (0.656) and prognostic nutritional index (PNI) (0.669). The Log-rank test revealed a higher risk of acute kidney injury in patients with high nutritional risk (p < 0.001). Multivariate COX regression analysis indicated that a high GNRI (adjusted HR 0.62, p < 0.001) was associated with a reduced risk of AKI during hospitalization in AHF patients. The final subgroup analysis demonstrated no significant interaction of GNRI in all subgroups except for diabetes subgroup and ventilation subgroup (P for interaction: 0.057-0.785). Conclusion: Our study findings suggest a correlation between GNRI and the occurrence of acute kidney injury in patients hospitalized with acute heart failure.

The role of pre-existing renal dysfunction on in-hospital morbidity and mortality in patients with acute coronary syndrome

Abstract Funding Acknowledgements None. Introduction The baseline renal function is an important predictor for the prognosis of patients with acute coronary syndrome (ACS). The aim of our study was to analyse the impact of pre-existing renal failure (RF) and the risk profile of patients with ACS on the development of in-hospital morbidity and mortality. Materials and methods This was a single-center cross-sectional cohort study on 2702 patients with ACS. The main exclusion criterion was pre-existing left ventricular (LV) dysfunction. Demographical and clinical characteristics, biochemical parameters, the anatomical distribution of coronary artery disease, and the final outcomes were analysed according to presence of RF at the moment of the index event. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease Study Group Equation (MDRD), where patients with eGFR&amp;lt;60 ml/min/1.73 m2 had moderate to severe renal dysfunction. Results 777 (22.3%) out of 2702 patients had eGFR &amp;lt;60 ml/min at the moment of the index event. These patients were predominantly female, 34.1% (333) vs.17.7% (444), p=0.0004,OR 1.921(95%CI 1.701-2.168);older (70.0±9.7vs.60.5±10.7;p &amp;lt;0.000). They had significantly higher values of cardiac troponin (p=0.007), stress glycemia (p=0.000019), glycated hemoglobin (p=0.000012), and WBC (p=0.00001), meaning the extent of myocardial injury was bigger, with a more activated neuro-hormonal and inflammatory response in the conditions of the notably widespread anatomical distribution of CAD. However, patients with significantly reduced eGFR were less likely to be offered coronary angiography and PCI treatment, OR 0.524 (95%CI 0.434–0.632),p &amp;lt;0.000. As expected, anemia predominated in these patients (RBC 4.88±0.75 vs 4.53±0.58, p=0.000001; OR 1.27 (95% CI 1.09-1.48), and Hgb 143.81±16.69 vs 132.03±21.34, p=0.00001). They had a significantly lower level of sodium (p=0.008) and a higher level of potassium (p=0.00003). Interestingly, patients with eGFR &amp;lt;60 ml/min had lower lipoprotein levels. In-hospital mortality rate was 4.2%, however, significantly higher in reduced eGFR group (12% vs 1.9%, OR 6.9 (95% CI 4.9–9.8), p &amp;lt;0.00004). These patients were more likely to develop acute kidney injury [25.7% vs. 1.3%, OR 1.6 (95% CI 1.3-1.9, p = 0.000021)], pulmonary oedema [8% vs. 1.8%, OR 1.12 (95% CI 1.02-1.23, p = 0.000021), and cardiogenic shock [19.5% vs. 2.6%, OR 1.22 (95% CI 1.2-1.4), p = 0.00023]. Independent variables associated with RF were: advanced age, female gender, extracardiac ASCVD, previous CVI, previous RAAS treatment, stress glycemia, triglyceride, cholesterol, LDL-C, Hgb, WBC, and potassium level. Conclusion Patients with reduced eGFR (&amp;lt;60 ml/min) have a very specific risk profile, as identified in our study, and reduced eGFR is a major contributor to the prognosis of ACS, highly responsible for in-hospital morbidity and mortality.Multivariate logistic regression analysis

Delineation of renal protein profiles in aristolochic acid I-induced nephrotoxicity in mice by label-free quantitative proteomics

Introduction: Aristolochic acid nephropathy (AAN) is a kidney injury syndrome caused by aristolochic acids exposure. Our study used label-free quantitative proteomics to delineate renal protein profiles and identify key proteins after exposure to different doses of aristolochic acid I (AAI).Methods: Male C57BL/6 mice received AAI (1.25 mg/kg/d, 2.5 mg/kg/d, or 5 mg/kg/d) or vehicle for 5 days.Results and discussion: The results showed that AAI induced dose-dependent nephrotoxicity. Differences in renal protein profiles between the control and AAI groups increased with AAI dose. Comparing the control with the low-, medium-, and high-dose AAI groups, we found 58, 210, and 271 differentially expressed proteins, respectively. Furthermore, protein-protein interaction network analysis identified acyl-CoA synthetase medium-chain family member 3 (Acsm3), cytochrome P450 family 2 subfamily E member 1 (Cyp2e1), microsomal glutathione S-transferase 1 (Mgst1), and fetuin B (Fetub) as the key proteins. Proteomics revealed that AAI decreased Acsm3 and Cyp2e1 while increasing Mgst1 and Fetub expression in mice kidneys, which was further confirmed by Western blotting. Collectively, in AAI-induced nephrotoxicity, renal protein profiles were dysregulated and exacerbated with increasing AAI dose. Acsm3, Cyp2e1, Mgst1, and Fetub may be the potential therapeutic targets for AAN.

Urgent transcatheter aortic valve implantation (TAVI) is associated with increased in-hospital mortality: a systematic review and meta-analysis

Abstract Funding Acknowledgements None. Introduction Transcatheter Aortic Valve Implantation (TAVI) is recommended for patients suffering from severe aortic stenosis (AoS) as an elective procedure. Taking into consideration that AoS is associated with acute heart failure and cardiogenic stroke resistant to pharmacotherapy, urgent TAVI might be a therapeutic option. However, a few data exist regarding its safety and efficacy against this background. Purpose Aim of our systematic review and meta-analysis is to compare in-hospital mortality among patients undergoing urgent and elective TAVI. Methods We systematically screened three major databases (Medline, Cochrane Central Register of Controlled Trials and Scopus) searching for studies comparing urgent versus elective TAVI. Primary endpoint of our systematic review and meta-analysis is the in-hospital mortality. Only studies provided data about in-hospital mortality were considered for our analysis. Secondary endpoints included acute kidney injury (AKI), permanent pacemaker implantation (PPM) and ischemic stroke. All the secondary endpoints were evaluated during the first 30-days after TAVI. Risk ratio (RR) was calculated with 95% confidence intervals (CIs) and a random-effects model (Mantel-Haenzel) was used to estimate the pooled RR. Results Twelve studies, all retrospective except one, published between 2014 and 2023 were included in our analysis. A total of 133,348 patients undergoing TAVI were included in our analysis; 110,606 had elective procedure and the 22,742 urgent intervention. Mortality rate was 5.1% in urgent and 2.2% in elective group. The risk of mortality is 2.38 times higher in the urgent TAVI group compared to the elective TAVI group (RR: 2.38, 95% CI: 1.80, 3.15). Data about AKI, PPM and stroke during the first 30-days were available for 12, 11 and 11 studies, respectively. The risk for AKI is significantly higher in patients having undergone urgent TAVI (RR: 2.10, 95% CI:1.62, 2.73). No significant differences were observed in stroke incidence (RR: 1.07, 95% CI: 0.97, 1.18) and PPM (RR: 1.05, 95%CI: 0.99, 1.11) during 30-days follow-up. Conclusion To the best of our knowledge, this is the first systematic review and meta-analysis showing that urgent TAVI is associated with significantly higher in-hospital mortality rates, compared to elective TAVI. Given these results, it is advisable to prefer an elective procedure, prior disease's worsening, in order to prevent the increased risk of in-hospital mortality associated with urgent TAVI.In-hospital mortality

Admission plasma concentration of neutrophil gelatinase-associated lipocalin and -C-reactive protein have additive prognostic value in patients with STEMI

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by Righospitalets Forskningsfond (07IO) Lundbeck Foundation (R186-2015-2132). Background Inflammation plays an apparent critical role in patients with acute coronary syndrome (ACS) and is associated with mortality. However, the complex process is poorly understood. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker originating from mature neutrophils and renal tubular cells. It has previously been shown to be associated with mortality and acute kidney injury in ACS patients. In this study we sought to assess the potential additive prognostic value of NGAL and its relation to other markers of inflammation. Methods In 1556 consecutive ST-elevation myocardial infarction (STEMI) patients, NGAL and C-reactive protein (CRP) plasma concentration were measured at hospital admission, before acute coronary angiography. Patients were stratified to plasma concentration of both biomarkers &amp;gt;/&amp;lt; the median concentration into 4 groups (low NGAL/ low CRP (group 1), low NGAL/high CRP (2), high NGAL/low CRP (3), high NGAL/high CRP(4)). Primary outcome was 30-day all-cause mortality. Results In total, 477 (31%), 324 (21%), 316 (20%), and 439 (28%) patients were stratified in group 1-4, respectively. With 0, 1, or 2 biomarker plasma concentration above the median (group 1 – 4), patients were older (61 – 67 years old, p&amp;lt;0.0001), had more comorbidity (hypertension (40 – 53%), p=0.002; previous stroke (4.0 – 9.9%), p=0.007; peripheral arterial disease (PAD) (2.6 – 10%), p&amp;lt;0.0001; chronic kidney dysfunction (CKD) (0.6 – 11%), p&amp;lt;0.0001) and more critical per-infarction circumstances (time from symptom debut to angiography (170 – 229 minutes), p&amp;lt;0.0001; cardiogenic shock (1.3 – 14%), p&amp;lt;0.0001, cardiac arrest (0.8 – 3.4%), p=0.0002) and lower left ventricular ejection fraction (LVEF) (48 – 43%, p&amp;lt;0.0001). Increased NGAL and CRP was associated with 30-day all-cause mortality (Figure A). Only high NGAL/high CRP was independently associated with 30-day mortality in a cox proportional hazard model when adjusting for age, hypertension, previous stroke, CKD, LVEF, and cardiogenic shock (HR (95% CI) 5.19 (1.20 – 22.52), p=0.03). Both CRP and NGAL had significant predictive value of 30-day mortality (AUC ROC 0.67, p&amp;lt;0.0001 and 0.78, p&amp;lt;0.0001, respectively). Combining NGAL and CRP did, however, not increase the predictive value of NGAL alone (AUC ROC 0.77, p=0.86) (Figure B). Conclusion Combined admission NGAL and CRP plasma concentration was independently associated with 30-day all-cause mortality in STEMI patients. Adding CRP to NGAL did, however, not increase the predictive value.Figure AFigure B

Combined biomarker testing for the assessment of cardio-renal interactions among myocardial infarction patients

Abstract Funding Acknowledgements None. Background The utility of different biomarkers for the prediction of either renal or cardiovascular outcomes following ST-elevation myocardial infarction (STEMI) has been evaluated in several studies however, very few data exist on the prognostic value of combining biomarkers. Among numerous biomarkers examined, C-reactive protein (CRP) and Neutrophil gelatinase associated Lipocalin (NGAL) stand high in their utility to assess the cardiorenal crosstalk. The aim of this study was to assess the prognostic value of combined CRP and NGAL measurement for the assessment of renal and cardiovascular outcomes in reperfused STEMI patients. Methods Blood samples for plasma NGAL and CRP were drawn 24 hours after admission. High NGAL and CRP were defined as values within the 4th quartile (&amp;gt;75percentile). Patients were stratified into 4 study groups: Low NGAL/Low CRP, LOW NGAL/high CRO, High NGAL /low CRP and high NGAL/high CRP. Patients were assessed for the occurrence of in-hospital adverse clinical events (MACE). These included occurrence of acute kidney injury , 30-day mortality and their combination. Results A total of 311 patients were included (mean age 66 ± 14 years, 81% males). According to the 4 study groups, there was a stepwise increase in the proportion of in hospital MACE ( 9% vs. 21% vs. 40% vs. 68% ;p,0.001,figure 1). In a multivariate regression model , compared to patients having low NGAL/low CRP we observed a graded, independent increase in the risk for MACE for low NGAL/high CRP , high NGAL/low CRP and high NGAL/high CRP levels( OR 2.89, p=0.02 vs. OR 3.29,p&amp;lt;0.001 vs. OR 17.6,p&amp;lt;0.001 respectively). Peak concentrations showed significant areas under the curves (AUCs) for the prediction of MACE for both CRP AUC (0.692,95% CI 0.62-0.76) and NGAL ( AUC 0.778,95% CI 0.72-0.84). The combination of NGAL and CRP yielded a significant increase in AUC to 0.822 (95% CI 0.77 to 0.88) (combined biomarkers vs CRP: p&amp;lt;0.001 and combined vs. NGAL :p=0.02,figure 2). Conclusions In patients with reperfused STEMI, the combined assessment of NGAL and CRP provided incremental prognostic information for the prediction of in hospital MACE when compared with single-biomarker measurement.Proportion of in-hospital MACEAUC CR NGAL

3-Year Outcomes for Degenerative Mitral Regurgitation Repair in a Medicare Population.

Mitral valve repair (MVr) has become the standard therapy for degenerative mitral regurgitation (DMR), but real-world late mortality, reintervention, and readmission data are lacking. This study estimates MVr outcomes for DMR to 3 years in the Medicare fee-for-service population. There were 4,219 DMR patients older than 65 years undergoing MVr within the Medicare 100% standard analytic file from October 2015 to December 2018 who were evaluated. Outcomes were analyzed for isolated MVr patients (n = 2,433) and patients undergoing MVr with certain concomitant procedures: MVr + tricuspid valve surgery (TVS; n = 619), MVr + cardiac ablation (CA; n = 540), and MVr + left atrial appendage closure (n = 627). Outcomes over a 3-year period included all-cause mortality, reintervention, rehospitalization, and common complications. All outcomes were modeled with adjustments for patient demographics and comorbid conditions. The average age for all patients was 71.9 ± 5.2 years. Adjusted all-cause mortality and MV reintervention (surgery or transcatheter) at 3 years for the primary cohort of isolated MVr was 3.5% and 1.6%, respectively. Directionally higher mortality at 3 years was observed in patients with concomitant TVS or CA. All-cause readmission and cardiac readmission for isolated MVr was 37.0% and 14.1%, with the highest rates for those with concomitant TVS or CA. Acute kidney injury and stroke/transient ischemic attack were the most common adverse events over 3 years for all patients. The 3-year mortality and reintervention rates in Medicare patients undergoing degenerative MVr are low. Those undergoing concomitant TVS or CA had directionally higher mortality and cardiac readmission rates. These results help refine outcome benchmarks as new transcatheter MVr procedures continue to emerge.

Risk factors and early prediction of cardiorenal syndrome type 3 among acute kidney injury patients: a cohort study

Background Type 3 cardiorenal syndrome (CRS type 3) triggers acute cardiac injury from acute kidney injury (AKI), raising mortality in AKI patients. We aimed to identify risk factors for CRS type 3 and develop a predictive nomogram. Methods In this retrospective study, 805 AKI patients admitted at the Department of Nephrology, Second Hospital of Shanxi Medical University from 1 January 2017, to 31 December 2021, were categorized into a study cohort (406 patients from 2017.1.1-2021.6.30, with 63 CRS type 3 cases) and a validation cohort (126 patients from 1 July 2021 to 31 Dec 2021, with 22 CRS type 3 cases). Risk factors for CRS type 3, identified by logistic regression, informed the construction of a predictive nomogram. Its performance and accuracy were evaluated by the area under the curve (AUC), calibration curve and decision curve analysis, with further validation through a validation cohort. Results The nomogram included 6 risk factors: age (OR = 1.03; 95%CI = 1.009–1.052; p = 0.006), cardiovascular disease (CVD) history (OR = 2.802; 95%CI = 1.193–6.582; p = 0.018), mean artery pressure (MAP) (OR = 1.033; 95%CI = 1.012–1.054; p = 0.002), hemoglobin (OR = 0.973; 95%CI = 0.96-–0.987; p < 0.001), homocysteine (OR = 1.05; 95%CI = 1.03–1.069; p < 0.001), AKI stage [(stage 1: reference), (stage 2: OR = 5.427; 95%CI = 1.781–16.534; p = 0.003), (stage 3: OR = 5.554; 95%CI = 2.234–13.805; p < 0.001)]. The nomogram exhibited excellent predictive performance with an AUC of 0.907 in the study cohort and 0.892 in the validation cohort. Calibration and decision curve analyses upheld its accuracy and clinical utility. Conclusions We developed a nomogram predicting CRS type 3 in AKI patients, incorporating 6 risk factors: age, CVD history, MAP, hemoglobin, homocysteine, and AKI stage, enhancing early risk identification and patient management.

Clinical significance of the lactate-to-albumin ratio on prognosis in critically ill patients with acute kidney injury

Objective To explore the relationship between lactate-to-albumin ratio (LAR) at ICU admission and prognosis in critically ill patients with acute kidney injury (AKI). Methods A retrospective analysis was conducted. Patients were divided into low (<0.659) LAR and high LAR (≥0.659) groups. Least absolute shrinkage and selection operator regression analysis was conducted to select variables associated with the 30-day prognosis. Cox regression analyses were performed to assess the association between LAR and mortality. Kaplan-Meier curves were plotted to compare cumulative survival rates between high and low LAR groups. Subgroup analysis was employed to assess the stability of the results. ROC curve was used to determine the diagnostic efficacy of LAR on prognosis. Results A nonlinear relationship was observed between LAR and the risk of 30-day and 360-day all-cause mortality in AKI patients (p < 0.001). Cox regulation showed that high LAR (≥ 0.659) was an independent risk factor for 30-day and 360-day all-cause mortality in patients with AKI (p < 0.001). The Kaplan-Meier survival curves demonstrated a noteworthy decrease in cumulative survival rates at both 30 and 360 days for the high LAR group in comparison to the low LAR group (p < 0.001). Subgroup analyses demonstrated the stability of the results. ROC curves showed that LAR had a diagnostic advantage when compared with lactate or albumin alone (p < 0.001). Conclusion High LAR (≥0.659) at ICU admission was an independent risk factor for both short-term (30-day) and long-term (360-day) all-cause mortality in patients with AKI.

Association of urgent transcatheter aortic valve replacement (TAVR) with acute kidney injury 30-days post-TAVR: a systematic review and meta-analysis

Abstract Funding Acknowledgements None. Introduction Recent studies have proven that TAVR is a viable treatment option for symptomatic aortic stenosis (AS), regardless of surgical risk, even though, there are certain significant hazards associated with it. Even with the improvements in technique and experience, peri- and post-procedural complications like acute kidney injury (AKI) continue to occur frequently and are recognized for their serious clinical implications in the setting of TAVR. The vast majority of TAVR procedures conducted across the US are elective procedures on patients who are hemodynamically stable. Nonetheless, published data, imply that urgent TAVR, despite higher mortality rates is a feasible option to treat decompensated severe aortic valve stenosis. Purpose The aim of this systematic review and meta-analysis is to assess AKI in patients 30-days after an urgent TAVR and compare them with the elective TAVR population. Methods This meta-analysis adhered to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive database search was conducted using three major databases (Medline, Cochrane Central Register of Controlled Trials and Scopus) for studies comparing patients submitted to urgent versus elective TAVR. Primary endpoint of our systematic review and meta-analysis is the AKI 30-days after TAVR. Only studies provided data about our primary endpoint were considered in the analysis. Secondary endpoints included myocardial infarction (MI), permanent pacemaker implantation (PPM) and bleeding events during the first 30-days post-procedurally. Risk ratio (RR) was calculated with 95% confidence intervals (CIs) and a random-effects model (Mantel-Haenzel) was used to estimate the pooled RR. Results A total of 16 studies with 101,568 patients were added in our analysis. Among them, 16,349 patients underwent an urgent TAVR, while the rest 85,219 had an elective procedure. Our analysis showed that patients submitted to urgent TAVR have 258% higher risk for AKI during the first 30-days post-procedurally (RR: 2.58, 95%CI: 1.98, 3.37) (Figure). Data about the 30-days MI, PPM and bleeding events were available for 9, 15 and 11 studies, respectively. The risk for MI appeared to be significantly higher in patients undergone urgent TAVR (RR: 5.49, 95% CI: 1.76, 17.05), while the risk for bleeding events was slightly higher in the same group (RR: 1.39, 95% CI: 1.14, 1.70). No significant differences were observed in PPM incidence (RR: 1.05, 95%CI: 1.00, 1.11) during 30-days follow-up. Conclusion In this systematic review and meta-analysis, patients undergoing urgent TAVR procedures compared to elective procedures have increased risk for AKI during the first 30-days post-TAVR. Thus, when urgent TAVR is performed risk factors for AKI should be evaluated and proper renal protection measures, such as adequate hydration and minimal contrast agent administration, should be implemented. Further research in this area is warranted.

Acute kidney injury in acute decompensated heart failure related cardiogenic shock: data from the Alt-Shock2 registry

Abstract Funding Acknowledgements None. Background Acute kidney injury (AKI) is one of the most common complications in patients with cardiogenic shock (CS), proving the strict relationship between heart and kidney (the so-called cardio-renal syndrome). AKI is a marker of shock severity, but also independently associated with worse outcomes. Purpose Many data are available on the prevalence of AKI in acute heart failure, but very few studies assessed the role of AKI in CS and they were mainly focused on acute myocardial infarction (AMI)-related CS. Aim of our study was to analyze the impact of AKI on acute decompensated heart failure (ADHF)-CS. Methods Between March 2020 and August 2022, we prospectively enrolled 375 CS patients from a Cardiac Intensive Care Units Network of 12 centers. Among these patients 121 (33.9% of the whole cohort) with ADHF-CS were included for the present analysis. AKI was defined according to KDIGO 2012 criteria as serum creatinine increase ≥ 0.3 mg/dl or 1.5 times compared to admission value, or urinary output &amp;lt; 0.5 ml/kg/h. Results Table 1 shows the baseline characteristics of the cohort. Patients with AKI were older (70 years old [55.5; 76] vs 61 [54; 69], p&amp;lt;0.05), had more comorbidities and a worse CS profile on admission. On multivariable analysis, SCAI stage D-E on admission was independently associated with a higher risk of AKI 24 hours after admission (OR 5.54 and p = 0.01). Treatment with mechanical circulatory support did not prevent AKI (OR 0.84 and p = 0.8). Notably, patients with a greater reduction in central venous pressure (CVP) 24 hours after admission had a lower risk of AKI (deltaCVP in AKI group 0 [-3;0] versus deltaCVP in no-AKI group -3 [-6;0], p = 0.025). Kaplan-Meier curves showed significantly worse survival in patients with AKI (Figure 1A). Cox regression analysis confirmed an association between AKI and increased risk of death (HR 2.14, CI 95% 1.16-3.96, p = 0.01). Notably, this association was even more pronounced in patients with SCAI stages A-B-C (HR 2.81, CI 95% 1.30-6.09, p = 0.01). Finally, in patients treated with renal replacement therapy (RRT) there was no association with lower survival at 180-days follow up (Figure 1B). Conclusions Our study confirms that AKI is a predictor of adverse outcomes in patients with ADHF-CS. Effective decongestion 24 hours after admission was associated with a lower risk of AKI. Considering that AKI had a negative impact even at lower SCAI stages, our findings underscore the importance of early identification of renal injury to promptly target decongestion with pharmacologic therapy and, ultimately, early use of RRT.

Using continuous electronic urine output monitoring for the management of acute cardio-renal syndrome in patients with acute decompensated heart failure

Abstract Funding Acknowledgements None. Background Patients admitted for acute decompensated heart failure (ADHF) are at high risk for type I cardio-renal syndrome (CRS) related to venous congestion and diuretic resistance. Positive fluid balance has been associated with adverse outcomes including acute kidney injury (AKI) and mortality. In critically ill patients urine output (UO) is used both to assess deterioration of renal function as well as for management of fluid balance .We investigated the possible effect of real-time UO monitoring, fluid balance, renal outcomes and 30-day mortality of patients admitted to the cardiac intensive care unit (ICU) with ADHF. Methods We performed a case series of 50 patients admitted to the cardiac ICU from July 2021 and June 2023 with ADHF. Their standard foley catheter was connected to an electronic monitoring system that continuously monitors UO in real-time. Its technology is described elsewhere (1). The UO monitoring system displays UO trends on the consoles that are updated in real-time. UO trends were utilized to guide an individualized approach for the pharmacologic management of each patient, based on blood pressure, hourly UO and total fluid balance. Daily and accumulated fluid balance was registered at up to 72 hours following admission. Patient outcomes included change in fluid balance, incidence of AKI and 30-day mortality. The case series group was than compared to a historical group of 50 matched controlled patients admitted between 2019-2020. Patients were matched according to cause of admission, age and glomerular filtration rate. Results In the study cohort the median age was 71±12 years, and 36 (72%) were men. In the historical cohort the median age was 71±13 years, and 36 (72%) were men. Patients in the electronic urinary monitoring cohort demonstrated significantly more negative daily and cumulative fluid balance as compared to the historical cohort, (P&amp;lt;0.001 for all, Figure 1). Incidence of AKI and the combined endpoint of AKI and 30-day mortality was significantly lower in the electronic UO monitoring cohort (24% vs. 46%, p=0.0197 and 40% vs 78%, P&amp;lt;0.0001 respectively). These changes were more prominent in the subgroup of patients with chronic kidney disease (Figure 2). Conclusion We demonstrated that real time monitoring of UO was associated with better prevention of fluid overload and the management of type I CRS in patients with ADHF. Further studies on larger populations are required to validate the potential utility of UO trending in the management of critically ill patients with ADHF.Fluid balance renal senseAKI and 30-day mortality