Pleural Effusion and Invasive Hemodynamic Measurements in Advanced Heart Failure.

BACKGROUND: Pleural effusion is present in 50% to 80% of patients with acute heart failure, depending on image modality. We aim to describe the association between the presence and size of pleural effusion and central hemodynamics, including pulmonary capillary wedge pressure (PCWP) in an advanced heart failure population. METHODS: An observational, cross-sectional study in a cohort of patients with advanced heart failure (left ventricular ejection fraction ≤45%) who underwent right heart catheterization at The Department of Cardiology at Copenhagen University Hospital, Rigshospitalet, Denmark, between January 1, 2002 and October 31, 2020. The presence and size of pleural effusion were determined by a semiquantitative score of chest x-rays or computed tomography scans performed within 2 days of right heart catheterization. RESULTS: In 346 patients (50±13 years; 78% males) with median left ventricular ejection fraction of 20% (15-25), we identified 162 (47%) with pleural effusion. The pleural effusion size was medium in 38 (24%) and large in 30 (19%). Patients with pleural effusion had a 4.3 mm Hg (2.5-6.1) higher PCWP and 2.4 mm Hg (1.2-3.6) higher central venous pressure (P<0.001 for both). Patients with a medium/large pleural effusion had statistically significantly higher filling pressures than patients with a small effusion. Higher PCWP (odds ratio [OR], 1.06 [1.03-1.10]) and central venous pressure (OR, 1.09 [1.05-1.15]) were associated with pleural effusion in multivariable logistic regression adjusted for age, sex, and heart failure medications (P<0.001 for both). In a subgroup of 204 (63%) patients with serum albumin data, PCWP (OR, 1.06 [1.01-1.11]; P=0.032), central venous pressure (OR, 1.14 [1.06-1.23]; P<0.001) and serum albumin level (OR, 0.89 [0.83-0.95]; P<0.001) were independently associated with the presence of a medium/large-sized pleural effusion. CONCLUSIONS: In patients with left ventricular ejection fraction ≤45% undergoing right heart catheterization as part of advanced heart failure work-up, pleural effusion was associated with higher PCWP and central venous pressure and lower serum albumin.

Hypochlorous Acid-Modified Serum Albumin Causes NETosis in the Whole Blood Ex Vivo and in Isolated Neutrophils.

Type 2 diabetes mellitus (T2DM) is accompanied by halogenative stress resulting from the excessive activation of neutrophils and neutrophilic myeloperoxidase (MPO) generating highly reactive hypochlorous acid (HOCl). HOCl in blood plasma modifies serum albumin (Cl-HSA). We studied the formation of neutrophil extracellular traps (NETs) in the whole blood and by isolated neutrophils under the action of Cl-HSA. It was found that Cl-HSA induces neutrophil priming and NETosis. MPO-containing as well as MPO-free NETs were found. These NETs with different composition can be a product of NETosis of one and the same neutrophil. NET formation in neutrophils with vacuolated cytoplasm was detected. In the presence of Cl-HSA, acceleration of NET degradation was observed. Accelerated NET degradation and neutrophil priming can be the factors contributing to the development of complications in T2DM.

Separation and purification of bovine nasal cartilage-derived chondroitin sulfate and evaluation of its binding to bovine serum albumin.

This study employs an optimized and environmentally friendly method to extract and purify chondroitin sulfate (CS) from bovine nasal cartilage using enzymatic hydrolysis, ethanol precipitation, and DEAE Sepharose Fast Flow column chromatography. The extracted CS, representing 44.67 % ± 0.0016 of the cartilage, has a molecular weight of 7.62 kDa. Characterization through UV, FT-IR, NMR spectroscopy, and 2-aminoacridone derivatization HPLC revealed a high content of sulfated disaccharides, particularly ΔDi4S (73.59 %) and ΔDi6S (20.61 %). Interaction studies with bovine serum albumin (BSA) using fluorescence spectroscopy and molecular docking confirmed a high-affinity, static quenching interaction with a single binding site, primarily mediated by van der Waals forces and hydrogen bonding. The interaction did not significantly alter the polarity or hydrophobicity of BSA aromatic amino acids. These findings provide a strong foundation for exploring the application of CS in tissue engineering and drug delivery systems, leveraging its unique interaction with BSA for targeted delivery and enhanced efficacy.

Impact of nanosilver surface electronic distributions on serum protein interaction and hemocompatibility.

Translation of silver-based nanotechnology "from bench to bedside" requires a deep understanding of the molecular aspects of its biological action, which remains controversial at low concentrations and non-spherical morphologies. Here, we present a hemocompatibility approach based on the effect of the distinctive electronic charge distribution in silver nanoparticles (nanosilver) on blood components. On basis of spectroscopic, volumetric, microscopic, dynamic light scattering measurements, pro-coagulant activity tests and cellular inspection we determine that, at extremely low nanosilver concentrations (0.125 - 2.5 µg mL-1) there is a relevant interaction effect on serum albumin and on red blood cells. The explanation has its origin in the surface charge distribution of nanosilver and their electron-mediated energy transfer mechanism. Prism-shaped nanoparticles, with anisotropic charge distributions, act at the surface level generating a compaction of the native protein molecule, while the spherical nanosilver, by exhibiting isotropic surface charge, generates a polar environment comparable to the solvent. Both morphologies induce aggregation at NPs / BSA ≅ 0.044 molar ratio values without altering the coagulation cascade tests, although the spherical-shaped nanosilver has a negative impact on red blood cells. Overall, our results suggest that the electron distributions of nanosilver, even at extremely low concentrations, are a critical factor influencing the molecular structure of blood proteins and red blood cells' membranes. Isotropic forms of nanosilver should be considered with caution, as they are not always the least harmful.

New molecular mechanism of nanoplastics affecting cadmium protein toxicity: Conformational response and differential binding of human serum albumin.

The significant health risks of nanoplastics (NPs) and cadmium (Cd) are currently attracting a great deal of attention and research. At present, the effects and mechanisms of NPs and Cd on human serum albumin (HSA), a key functional protein in the organism on transportation, remain unknown. Here, the differences in the effects and mechanisms of action of Cd alone and composite systems (NPsCd) were explored by enzyme activity assay, multi-spectroscopy analysis and molecular docking. The results showed that HSA activity was inhibited and decreased to 80 % and 69.55 % (Cd = 30 mg/L) by Cd alone and NPs-Cd exposure, respectively. Exposure to Cd induced backbone disruption and protein defolding of HSA, and secondary structure disruption was manifested by the reduction of α-helix. Cd exposure also induces fluorescence sensitization of HSA. Notably, the addition of NPs further exacerbated the effects associated with Cd exposure, which was consistent with the changes in HSA activity. Thus, the above conformational changes may be responsible for inducing the loss of enzyme activity. Moreover, it was determined by RLS spectroscopy that NPs-Cd bound to HSA in the form of protein crowns. Molecular docking has further shown that Cd binds to the surface of Sudlow site II of HSA, suggesting that Cd impairs the function of HSA by affecting the protein structure. More importantly, the addition of NPs further exacerbated the disruption of the protein structure by the adherent binding of HSA on the surface of the plastic particles, which induced a greater change in the enzyme activity. This study provides useful perspectives for investigating the impact of composite pollution on HSA of human functional proteins.

Introduction to the concept of effective albumin concentration.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The purpose of this article is to discuss how the structural and presumably functional integrity of albumin, as described by the concept of effective albumin concentration (eAlb), has potentially important clinical implications beyond the total albumin concentration (tAlb) routinely reported by clinical laboratories. SUMMARY: Albumin has several functions beyond its oncotic effects, including molecule binding, substance transport, detoxification actions, and serving as an antioxidant. However, there are conformational changes that occur during or following the manufacture of albumin and during its administration to patients with various disease states, such as decompensated liver disease, that often impair these functions. Such impairments are not reflected in tAlb values reported by clinical laboratories and might explain the disconnect often seen between albumin's proposed beneficial mechanistic functions and its less-than-predicted clinical effectiveness as noted in published studies. The concept of eAlb has been introduced to describe albumin with structural and functional integrity. Limited studies have found associations between eAlb values and patient prognostic indicators, but the techniques used to decide these effective concentrations to date are complicated and require specialized equipment and experienced researchers for proper interpretation. CONCLUSION: Estimation of eAlb may provide valuable information on the functional ability of albumin beyond the tAlb reported by clinical laboratories, but more research is needed to decide how this information is best used in the clinical setting.

Novel Dissymmetric Formal Quinoidal Molecules End-capped by Dicyanomethylene and Triphenylphosphonium.

A number of quinoidal molecules with symmetric end-capping groups, particularly dicyanomethylene units, have been synthesized for organic optoelectronic materials. In comparison, dissymmetric quinoidal molecules, characterized by end-capping with different groups, are less explored. In this paper, we present the unexpected formation of new formal quinoidal molecules, which are end-capped with both dicyanomethylene and triphenylphosphonium moieties. The structures of these dissymmetric quinoidal molecules were firmly verified by single crystal structural analyses. On the basis of the control experiments and DFT calculations, we proposed the reaction mechanism for the formation of these dissymmetric quinoidal molecules. The respective zwitterionic forms should make contributions to the ground state structures of these quinoidal molecules based on the analysis of their bond lengths and aromaticity and Mayer Bond Orbital (MBO) calculation. This agrees well with the fact that negative solvatochromism was observed for these quinoidal molecules. Although these new quinoidal molecules are non-emissive both in solutions and crystalline states, they become emissive with quantum yields up to 51.4% after elevating the solvent viscosity or dispersing them in a PMMA matrix. Interestingly, their emissions can also be switched on upon binding with certain proteins, in particular with human serum albumin.

Elucidating the effect of levothyroxine and triiodothyronine on methylglyoxal derived stress.

PURPOSE: Methylglyoxal (MG) is the most potent precursor during the formation of the advanced glycation end products (AGEs). MG-dependent glycative stress contributes to pathogenesis of diabetes, age-related disorders, and cancer. There is a great need to study the reduction process of glycative stress for effective management of metabolic disorders. From natural compounds to synthetic drugs, each element contributes to the reduction of glycative stress. Previously, it was established that the lowering of uric acid, low-density lipoprotein cholesterol, and urine albumin excretion rate, as well as reducing total oxidative stress, were all achieved more effectively with a levothyroxine regimen. Still, there is no such study found that supports the MG-dependent glycative stress reduction with thyroid hormone compound. Our study aims to investigate the effects of T3 and T4 on MG-dependent glycative stress. METHODS: The antiglycation effect was assayed through NBT assay, DNPH assay, ELISA, and fluorescence spectrophotometer. The intracellular reduction in reactive oxygen species (ROS) has been estimated through confocal microscopy. RESULTS: The results revealed an effective reduction in the formation of AGEs adducts and intracellular ROS formation. CONCLUSION: The investigation concludes AGEs formation was suppressed using these compounds, although in vivo and rigorous clinical trials are required in order to verify these findings.

Association between serum albumin and body water using a bioelectrical impedance analyzer: a case report of longitudinal variation in a child with initial idiopathic nephrotic syndrome.

Background: Bioelectrical impedance analysis (BIA) is a commonly used noninvasive technique for body composition assessment with recently expanded indications. This reproducible measurement method uses electrical conductivity to evaluate body composition, including fluid status. In pediatric idiopathic nephrotic syndrome (INS), albumin leaks into the urine, resulting in dysregulated colloid-osmotic pressure in the blood vessels. This results in decreased circulating blood volume and edema. Blood tests are a useful evaluation method; however, it cannot be performed frequently in children because of their invasive nature. Herein, we present a case of a child with INS demonstrating a longitudinal correlation between serum albumin (S-Alb) levels and extracellular water (ECW)/total body water (TBW) ratio. Case Description: A 6-year-old boy was admitted to the hospital for INS treatment after informed consent was obtained. He presented with severe proteinuria symptoms and an increased weight of 3 kg before the onset of INS. Standard treatment with prednisolone (PSL) for 28 days was initiated, and his proteinuria resolved on day 7. During the acute course, albumin replacement was conducted thrice for fluid management purposes and did not cause severe intravascular dehydration. The fluid composition was assessed over time; each measurement lasted for approximately 10 minutes and was performed on the same day as the blood tests. Nine measurements were taken, and S-Alb levels and the ECW/TBW ratio (r=-0.72, P<0.04) exhibited a significant negative correlation. Conclusions: BIA can potentially predict S-Alb levels objectively and noninvasively within a short period. Although further validation is needed, this measurement can reduce the invasiveness of testing in children with INS.

The Effectiveness of Albumin-to-Globulin Ratio as a Prognostic Biomarker in Primary Gastrointestinal Cancer: A Systematic Review and Meta-Analysis.

Albumin-to-globulin ratio (AGR) is a cheap, widely accessible component of common blood work that has been implicated in the prognosis of various cancers. This effect is attributed to the cooperative relationship between albumin reflecting the body's nutritional status and globulin serving as an indicator of immune status. With the high morbidity and mortality associated with gastrointestinal cancer and the increasing necessity for cost-effective health care, research into AGR's potential as an indicator of prognosis is warranted. A database search, including key terms between AGR and gastrointestinal cancer, was performed. Random-effects meta-analysis was completed on extracted hazard ratios with two-sided p-values <0.05 being deemed significant. A total of 8,384 patients with gastrointestinal cancer were included. A low AGR was found to be associated with increased risk for reduced overall survival in cancer of the primary GI tract (HR: 1.82, 1.35-2.45, p < 0.001), esophageal cancer (HR: 1.57, 1.19-2.06, p < 0.001), colon cancer (HR: 3.36, 2.02-5.58, p < 0.001), and colorectal cancer (HR: 2.27, 1.15-4.48, p = 0.02) populations. A low AGR is significantly associated with increased risk for reduced overall survival in primary gastrointestinal cancer. Due to the ease of access and low cost to physicians and patients, incorporation of AGR into clinical evaluation of prognosis in these cancers should prove beneficial to patient outcomes.

The relationship between Glasgow Prognostic Score and hospital duration in patients with inflammatory bowel diseases.

BACKGROUND AND OBJECTIVES: Both hypoalbuminemia and inflammation were common in patients with inflammatory bowel diseases (IBD), however, the combination of the two parameters on hospital duration re-mained unknown. METHODS AND STUDY DESIGN: This is a retrospective two-centre study performed in two tertiary hospitals in Shanghai, China. Serum levels of C-Reactive Protein (CRP) and albumin (ALB) were measured within 2 days of admission. Glasgow prognostic score (GPS), based on CRP and ALB, was calculated as follows: point "0" as CRP <10 mg/L and ALB ≥35 g/L; point "1" as either CRP ≥10 mg/L or ALB <35 g/L; point "2" as CRP ≥10 mg/L and ALB <35 g/L. Patients with point "0" were classified as low-risk while point "2" as high-risk. Length of hospital stay (LOS) was defined as the interval between admission and discharge. RESULTS: The proportion of low-risk and high-risk was 69.3% and 10.5% respectively among 3,009 patients (65% men). GPS was associated with LOS [ß=6.2 d; 95% CI (confidence interval): 4.0 d, 8.4 d] after adjustment of potential co-variates. Each point of GPS was associated with 2.9 days (95% CI: 1.9 d, 3.9 d; ptrend<0.001) longer in fully adjusted model. The association was stronger in patients with low prealbumin levels, hypocalcaemia, and hypokalaemia relative to their counterparts. CONCLUSIONS: GPS was associated with LOS in IBD patients. Our results highlighted that GPS could serve as a convenient prognostic tool associated with nutritional status and clinical outcome.

Interaction mechanism of oseltamivir phosphate with bovine serum albumin: multispectroscopic and molecular docking study.

Oseltamivir phosphate (OP) is an antiviral drug with potential risks to human health due to overuse, leading to serious consequences such as gastrointestinal disturbances, abnormal neuropsychiatric symptoms, and sudden death. Therefore, gaining an in-depth understanding of its interaction with proteins is crucial. We investigated the interaction between OP and bovine serum albumin (BSA) utilizing multispectral methods (i.e., fluorescence, ultraviolet absorption, circular dichroism) combined with molecular docking techniques. Fluorescence spectroscopy indicated that OP quenched BSA fluorescence by forming the OP-BSA complex. The Stern-Volmer constants (KSV) between OP and BSA were determined to be 3.06 × 103 L/mol, 2.36 × 103 L/mol, and 1.86 × 103 L/mol at 293 K, 298 K, and 303 K, respectively. OP occupies exclusively one binding site on BSA, and the fluorescent probe displacement measurements revealed that this is BSA site I. Thermodynamic data (∆H, ∆S, and ∆G) obtained by fitting the van't Hoff equation were - 77.49 kJ/mol, -176.54 J/(mol∙K), and - 24.88 kJ/mol, respectively, suggesting that hydrogen bonding and van der Waals forces mainly participate in OP-BSA complex stabilization. Moreover, the reaction occurs spontaneously at room temperature. Synchronous fluorescence spectra indicated that OP interacts with tryptophan residue of BSA. The results of ultraviolet (UV) and 3D fluorescence spectroscopy indicated that the OP-BSA complex formation altered the microenvironment around amino acid residues. Circular dichroism spectra revealed that the addition of OP decreased the α-helix content of BSA by 7.13%. Docking analysis confirmed that OP binds to BSA site I through hydrogen bonding with amino acids VAL342, SER453, and ASP450. Finally, ADMET studies were conducted to explore the pharmacokinetics of OP as an antiviral drug.

Multi-spectral and docking assessments to explore the combination of an antiviral drug, entecavir with bovine serum albumin.

Molecular interaction of entecavir (ETV) with the transport protein, albumin from bovine serum (BSA) was explored through multispectral and molecular docking approaches. The BSA fluorescence was appreciably quenched upon ETV binding and the quenching nature was static. The ETV-BSA complexation and the static quenching process were further reiterated using UV-visible absorption spectra. The binding constant (Ka) values of the complex were found as 1.47 × 104-4.0 × 103 M-1, which depicting a modarate binding strength in the ETV-BSA complexation. The experimental outcomes verified that the stable complexation was primarily influenced by hydrophobic interactions, hydrogen bonds and van der Waals forces. Synchronous and 3-D fluorescence spectral results demonstrated that ETV had significant impact on the hydrophobicity and polarity of the molecular environment near Tyr and Trp residues. Competitive site-markers displacement (with warfarin and ketoprofen) results discovered the suitable binding locus of ETV at site I in BSA. The molecular docking assessments also revealed that ETV formed hydrogen bonds and hydrophobic interactions with BSA, predominantly binding to site I (sub-domain IIA) of BSA.

Glycation and drug binding by serum albumin.

Accumulation of glycation products in patients with hyperglycaemic conditions can lead to their reaction with the proteins in the human system such as serum albumin, haemoglobin, insulin, plasma lipoproteins, lens proteins and collagen among others which have important biological functions. Therefore, it is important to understand if glycation of these proteins affects their normal action not only qualitatively, but also importantly quantitatively. Glycation of human serum albumin can easily be carried out over period of weeks and its drug transportability may be examined, in addition to characterisation of the amadori products. A combination of ultrasensitive isothermal titration calorimetry, differential scanning calorimetry, spectroscopy and chromatography provides structure-property-energetics correlations which are important to obtain mechanistic aspects of drug recognition, conformation of the protein, and role of amadori products under conditions of glycation. The role of advance glycation end products is important in recognition of antidiabetic drugs. Further, the extent of glycation of the protein and its implication on drug transportability investigated by direct calorimetric methods enables unravelling mechanistic insights into role of functionality on drug molecules in the binding process, and hinderance in the recognition process, if any, as a result of glycation. It is possible that the drug binding ability of the protein under glycation conditions may not be adversely affected, or may even lead to strengthened ability. Rigorous studies on such systems with diverse functionality on the drug molecules is required which is essential in deriving guidelines for improvements in the existing drugs or in the synthesis of new molecular entities directed towards addressing diabetic conditions.

Peptide-Carrier Conjugation.

To produce antibodies against synthetic peptides, it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined.

Prevalence and associated factors of infection in children with nephrotic syndrome aged 2-18 years in the northwest and east Amhara region, Ethiopia: a multi-center cross-sectional retrospective study.

BACKGROUND: Infection is the most common complication of pediatric patients with nephrotic syndrome. The factors associated with infection in nephrotic syndrome are lacking. The objective of the study was to identify the prevalence and associated factors among children with nephrotic syndrome aged 2 to 18 years. METHODS: We conducted a hospital-based retrospective cross-sectional study. The data collector installed an Epi5 collector electronic data-collecting tool from Google Play. Then, we exported the data to Stata version 15.1 for analysis. The mean, standard deviation, frequency, and percentage were used for descriptive statistics. The logistic regression model was used to identify the factors associated with infection. RESULTS: In this study, the prevalence of infection among nephrotic syndrome children is 39.8% (95%CI: 30.7, 49.7). The types of infection identified were pneumonia, urinary tract infection, diarrheal disease, cutaneous fungal infection, intestinal parasitic infection, and sepsis. The presence of hematuria increased the odds of infection by 5-times. On the other hand, low level of serum albumin increased the odds of infection by 7%. Being a rural resident increased the odds of infection by 3.3-times as compared to urban. CONCLUSIONS: Serum albumin level, presence of hematuria, and rural residence were significantly associated with infection. We recommended a longitudinal incidence study on large sample size at multicenter to strengthen this finding.

Association between blood urea nitrogen to serum albumin ratio and in-hospital mortality in critical patients with diabetic ketoacidosis: a retrospective analysis of the eICU database.

Background: This study aimed to investigate the association between blood urea nitrogen to serum albumin ratio (BAR) and the risk of in-hospital mortality in patients with diabetic ketoacidosis. Methods: A total of 3,962 diabetic ketoacidosis patients from the eICU Collaborative Research Database were included in this analysis. The primary outcome was in-hospital death. Results: Over a median length of hospital stay of 3.1 days, 86 in-hospital deaths were identified. One unit increase in LnBAR was positively associated with the risk of in-hospital death (hazard ratio [HR], 1.82 [95% CI, 1.42-2.34]). Furthermore, a nonlinear, consistently increasing correlation between elevated BAR and in-hospital mortality was observed (P for trend =0.005 after multiple-adjusted). When BAR was categorized into quartiles, the higher risk of in-hospital death (multiple-adjusted HR, 1.99 [95% CI, (1.1-3.6)]) was found in participants in quartiles 3 to 4 (BAR≥6.28) compared with those in quartiles 1 to 2 (BAR<6.28). In the subgroup analysis, the LnBAR-hospital death association was significantly stronger in participants without kidney insufficiency (yes versus no, P-interaction=0.023). Conclusion: There was a significant and positive association between BAR and the risk of in-hospital death in patients with diabetic ketoacidosis. Notably, the strength of this association was intensified among those without kidney insufficiency.

Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites.

In the present work, we study different physicochemical properties related to LADME processes of volasertib, a Polo-like kinase 1 inhibitor in advanced clinical trials. Firstly, the protonation equilibria, the extent of ionization at the physiological pH and pKa values of this drug are studied combining spectroscopic techniques and computational calculations. Secondly, the binding process of volasertib to the human serum albumin (HSA) protein is analyzed by fluorescence spectroscopy. We report a high binding constant to HSA (Ka = 4.10 × 106 M-1) and their pharmacokinetic implications are discussed accordingly. The negative enthalpy and entropy (ΔH0 = -54.49 kJ/mol; ΔS0 = -58.90 J K-1 mol-1) determined for the binding process suggests the implication of hydrogen bonds and van der Waals interactions in the formation of the HSA-volasertib complex. Additionally, volasertib is encapsulated in an alginate/montmorillonite bionanocomposite as a proof of concept for an oral delivery nanocarrier. The physical properties of that nanocomposite as well as volasertib delivery kinetics are analyzed.

Association between serum albumin creatinine ratio and all-cause mortality in intensive care unit patients with heart failure.

Background: The serum albumin creatinine ratio (sACR) has been established as a potential indicator for heart disease, however, its relationship with prognosis in intensive care unit (ICU) patients with heart failure remains uncertain. This study aimed to investigate the association between sACR levels and all-cause mortality ICU patients with heart failure. Methods: Clinical data from MIMIC-Ⅳ database was utilized for the analysis of ICU patients with heart failure. Patients were categorized into quartiles (Q1-Q4) based on sACR levels. Kaplan-Meier survival analysis and multivariate adjusted Cox regression models were employed to assess the association between sACR levels and mortality outcomes within 365 days. Subgroup analysis was used to evaluate the prognostic impact of sACR across diverse populations. Restricted cubic spline curves and threshold effect analysis were utilized to quantify the dose-response relationship between sACR levels and risk of all-cause mortality. Mediating effects analysis was conducted to present the involvement of albumin and creatinine in the association between sACR and outcomes. Results: The analysis encompassed a cohort of 4,506 patients, with Kaplan-Meier curves indicating that individuals with lower sACR levels exhibited an elevated risk of all-cause mortality (log-rank p < 0.001). Multivariate adjusted Cox regression and subgroup analysis demonstrated that individuals in Q2 [hazard ratio (HR) 0.82, 95%CI 0.71∼0.96], Q3 (HR 0.76, 95%CI 0.64∼0.91) and Q4 (HR 0.62, 95%CI 0.50∼0.76) had a decreased risk of mortality compared to individuals in Q1 (lower levels of sACR) (p for trend < 0.001), and this inverse relationship was consistently observed across various subgroups. Subsequent restricted cubic spline analysis revealed a negative yet nonlinear relationship between sACR and all-cause mortality (p for nonlinear < 0.001), and threshold effect analysis indicated an effect threshold of 3.75. Additionally, mediating effects analysis emphasized that sACR influenced the outcome not only through serum albumin and creatinine pathways, but also through direct mechanisms. Conclusion: The study found that low levels of sACR were independently associated with an increased risk of one-year all-cause mortality in ICU patients with heart failure, with a threshold effect, which could potentially serve as an early warning indicator for high-risk populations.