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BMC Nephrology May 2024Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD.... (Comparative Study)
Comparative Study
BACKGROUND
Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies.
METHODS
Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker.
RESULTS
Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics.
CONCLUSIONS
C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.
Topics: Humans; Female; Citrulline; Male; Protein Carbamylation; Biomarkers; Middle Aged; Renal Insufficiency, Chronic; Aged; Prospective Studies; Risk Assessment; Kidney Failure, Chronic; Prognosis; Proportional Hazards Models; Serum Albumin
PubMed: 38816682
DOI: 10.1186/s12882-024-03619-6 -
BMJ Open Diabetes Research & Care May 2024ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing...
INTRODUCTION
ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.
RESEARCH DESIGN AND METHODS
Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.
RESULTS
The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.
CONCLUSIONS
Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.
TRIAL REGISTRATION NUMBER
UMIN000011525.
Topics: Humans; Male; Female; Diabetic Nephropathies; Angiotensin-Converting Enzyme 2; Biomarkers; Middle Aged; Glomerular Filtration Rate; Peptidyl-Dipeptidase A; Aged; Prognosis; Disease Progression; Follow-Up Studies
PubMed: 38816205
DOI: 10.1136/bmjdrc-2024-004237 -
BMJ Open May 2024This study aimed to describe the clinical characteristics of adults with suspected acute community-acquired pneumonia (CAP) on hospitalisation, evaluate their prediction...
Community-acquired pneumonia: use of clinical characteristics of acutely admitted patients for the development of a diagnostic model - a cross-sectional multicentre study.
OBJECTIVES
This study aimed to describe the clinical characteristics of adults with suspected acute community-acquired pneumonia (CAP) on hospitalisation, evaluate their prediction performance for CAP and compare the performance of the model to the initial assessment of the physician.
DESIGN
Cross-sectional, multicentre study.
SETTING
The data originated from the INfectious DisEases in Emergency Departments study and were collected prospectively from patient interviews and medical records. The study included four Danish medical emergency departments (EDs) and was conducted between 1 March 2021 and 28 February 2022.
PARTICIPANTS
A total of 954 patients admitted with suspected infection were included in the study.
PRIMARY AND SECONDARY OUTCOME
The primary outcome was CAP diagnosis assessed by an expert panel.
RESULTS
According to expert evaluation, CAP had a 28% prevalence. 13 diagnostic predictors were identified using least absolute shrinkage and selection operator regression to build the prediction model: dyspnoea, expectoration, cough, common cold, malaise, chest pain, respiratory rate (>20 breaths/min), oxygen saturation (<96%), abnormal chest auscultation, leucocytes (<3.5×10/L or >8.8×10/L) and neutrophils (>7.5×10/L). C reactive protein (<20 mg/L) and having no previous event of CAP contributed negatively to the final model. The predictors yielded good prediction performance for CAP with an area under the receiver-operator characteristic curve (AUC) of 0.85 (CI 0.77 to 0.92). However, the initial diagnosis made by the ED physician performed better, with an AUC of 0.86 (CI 84% to 89%).
CONCLUSION
Typical respiratory symptoms combined with abnormal vital signs and elevated infection biomarkers were predictors for CAP on admission to an ED. The clinical value of the prediction model is questionable in our setting as it does not outperform the clinician's assessment. Further studies that add novel diagnostic tools and use imaging or serological markers are needed to improve a model that would help diagnose CAP in an ED setting more accurately.
TRIAL REGISTRATION NUMBER
NCT04681963.
Topics: Humans; Community-Acquired Infections; Cross-Sectional Studies; Male; Female; Middle Aged; Aged; Pneumonia; Emergency Service, Hospital; Hospitalization; Denmark; Adult; ROC Curve; Prospective Studies; C-Reactive Protein
PubMed: 38816044
DOI: 10.1136/bmjopen-2023-079123 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising...
At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising the development of patient-specific delivery systems and thus the provision of efficient and sustainable drugs. Protein drugs for subcutaneous administration, by allowing less frequent application, represent one of the most important parts of the pharmaceutical field, but their development is inevitably faced with obstacles in providing protein stability and suitable formulation viscosity. To gain further knowledge and fill the gaps in the already constructed data platform for the development of monoclonal antibody formulations, we designed a study that examines small model proteins, bovine serum albumin. The main aim of the presented work is to evaluate the effect of protein concentrations on critical quality attributes of both, pre-lyophilised liquid formulations, and lyophilised products. Through the study, the hypothesis that increasing protein concentration leads to higher viscosity and higher reconstitution time without affecting the stability of the protein was confirmed. The most important finding is that sucrose plays a key role in the lyophilisation of investigated protein, nevertheless, it can be predicted that, to ensure the beneficial effect of mannitol, its amount has to prevail over the amount of sucrose.
Topics: Freeze Drying; Serum Albumin, Bovine; Viscosity; Drug Compounding; Humans; Sucrose; Drug Stability; Chemistry, Pharmaceutical; Excipients; Mannitol; Protein Stability
PubMed: 38815206
DOI: 10.2478/acph-2024-0013 -
Environmental Health Perspectives May 2024The anticaking agent, used in a wide variety of powdered food products, interfered with immune tolerance of ovalbumin, a model antigen; and it worsened gut inflammation...
The anticaking agent, used in a wide variety of powdered food products, interfered with immune tolerance of ovalbumin, a model antigen; and it worsened gut inflammation in a mouse model of celiac disease.
Topics: Animals; Mice; Food Hypersensitivity; Silicon Dioxide; Ovalbumin; Food Additives; Celiac Disease; Disease Models, Animal; Nanoparticles
PubMed: 38814861
DOI: 10.1289/EHP14923 -
Heliyon May 2024No markers have been used to diagnose historical peritoneal dialysis (PD)-related peritonitis. Cyclophilin A (CypA) is associated with glucose toxicity and inflammation....
INTRODUCTION
No markers have been used to diagnose historical peritoneal dialysis (PD)-related peritonitis. Cyclophilin A (CypA) is associated with glucose toxicity and inflammation. We hypothesize that dialysate CypA can be a marker for historical peritonitis (at least 3 months free from peritonitis).
METHOD
An enzyme-linked immunosorbent assay kit was used to measure the concentration of dialysate CypA. Clinical and laboratory data were collected to correlate with historical peritonitis. Mann-Whitney test and -square test were used for analysis. Receiver operating characteristic (ROC) analysis was used to evaluate predictive power.
RESULTS
Out of a total of 31 patients who had undergone PD for at least 2 years, 18 had no history of PD-related peritonitis, while 13 had experienced PD-related peritonitis at least once. Overall, the patients in this population were in good health (normal white blood cell count, no anemia, normal electrolyte and serum albumin levels). There were no significant differences between patients with and without a history of peritonitis, except for blood white blood cell count (5650.6 ± 1848.4 vs. 7154.6 ± 2056.8, p = 0.032) and dialysate CypA value (24.27 ± 22.715 vs. 54.41 ± 45.63, p = 0.020). In the univariate analysis, only the dialysate CypA level showed a statistically significant association with historical peritonitis (HR = 1.030, 95 % CI = 1.010-1.062, p = 0.046). The AUC for dialysate CypA (>34.83 ng/mL) was 0.748, with a sensitivity of 0.615 and specificity of 0.833.
CONCLUSION
PD peritonitis poses a significant threat to the long-term use of peritoneal dialysis. Based on our study, even in the absence of concurrent infection, dialysate CypA can serve as a predictive marker for historical peritonitis, demonstrating high predictive power along with fair sensitivity and good specificity.
PubMed: 38813216
DOI: 10.1016/j.heliyon.2024.e31021 -
Turkish Journal of Medical Sciences 2023Immunosuppressive and immunomodulatory treatments developed in recent years as a result of a better understanding of the pathophysiology of systemic rheumatic diseases...
BACKGROUND/AIM
Immunosuppressive and immunomodulatory treatments developed in recent years as a result of a better understanding of the pathophysiology of systemic rheumatic diseases (SRDs) improve the prognosis. Despite medical advances, individuals with SRDs at any stage may require intensive care and have a high mortality rate. The aim of this study was to investigate the demographic and clinical characteristics of patients with rheumatic diseases admitted to the intensive care unit (ICU), and the factors associated with the risk of mortality.
MATERIALS AND METHODS
This was a retrospective, cross-sectional study that included patients with rheumatic diseases in the medical ICU. Factors of ICU 28-day mortality were identified by multiple-variable logistic analysis.
RESULTS
A total of 127 patients with SRDs admitted to the medical ICU were enrolled. Systemic lupus erythematosus (SLE) (32.3%) was the most common diagnosis of SRDs in patients admitted to the ICU. The reasons for admission to the ICU were combined infection and primary SRD flare-up (35.4%), primary SRD flare-up (22%), SRD-unrelated reasons (22%), infection (17.3%), drug side effects (3.9%), and SRD-related complications (0.8%). The most common organ dysfunctions before (49.6%) and during (77.2%) admission to ICU were in the respiratory system. The 28-day mortality was 78 (61.4%). While the maximum procalcitonin, serum lactate, and blood urea nitrogen (BUN) levels were higher in the nonsurvivor group, the platelet and serum albumin levels were statistically significantly lower than those in the survivor group (p < 0.05). Acute respiratory failure (ARF), the presence of septic shock, the need for invasive mechanical ventilation (IMV), BUN level, and low platelet-lymphocyte ratio (PLR) were significant in the final multiple-variable model.
CONCLUSION
Significant predictors of mortality in patients with rheumatic diseases may include ARF, septic shock, the need for IMV, and high BUN and low PLR levels.
Topics: Humans; Male; Female; Retrospective Studies; Intensive Care Units; Middle Aged; Cross-Sectional Studies; Rheumatic Diseases; Adult; Aged; Hospital Mortality; Lupus Erythematosus, Systemic
PubMed: 38813000
DOI: 10.55730/1300-0144.5673 -
Frontiers in Neuroscience 2024The relationship between routine cerebrospinal fluid (CSF) testing and the disease phenotype of amyotrophic lateral sclerosis (ALS) is unclear, and there are some...
BACKGROUND
The relationship between routine cerebrospinal fluid (CSF) testing and the disease phenotype of amyotrophic lateral sclerosis (ALS) is unclear, and there are some contradictions in current studies.
METHODS
This study aimed to analyze the relationship between CSF profiles and disease phenotype in ALS patients. We collected 870 ALS patients and 96 control subjects admitted to West China Hospital of Sichuan University. CSF microprotein, albumin, IgG, index of IgG (IgG), albumin quotient (Q), and serum IgG were examined.
RESULTS
In ALS patients, CSF IgG, and Q were significantly increased, while CSF IgG was decreased, compared with control subjects. Approximately one-third of ALS patients had higher CSF IgG levels. The multiple linear regression analysis identified that CSF IgG was weakly negatively associated with ALS functional rating scale revised (ALSFRS-R) scores ( = -0.062, = 0.041). This significance was found in male ALS but not in female ALS. The Cox survival analyses found that upregulated CSF IgG was significantly associated with the increased mortality risk in ALS [HR = 1.219 (1.010-1.470), = 0.039].
CONCLUSION
In the current study, the higher CFS IgG was associated with increased mortality risk of ALS. CSF IgG may be associated with the severity of ALS. These findings may be sex-specific.
PubMed: 38812975
DOI: 10.3389/fnins.2024.1375892 -
Frontiers in Genetics 2024Genome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors...
Genetic association and transferability for urinary albumin-creatinine ratio as a marker of kidney disease in four Sub-Saharan African populations and non-continental individuals of African ancestry.
BACKGROUND
Genome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors influencing kidney disease in Sub-Saharan African (SSA) populations. This study presents the largest GWAS for urinary albumin-to-creatinine ratio (UACR) in SSA individuals, including 8,970 participants living in different African regions and an additional 9,705 non-resident individuals of African ancestry from the UK Biobank and African American cohorts.
METHODS
Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations.
RESULTS
Two genome-wide significant (P < 5 × 10) UACR-associated loci were identified, one in the on chromosome 6 in the meta-analysis of resident African individuals, and another in the region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including , and . PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained.
CONCLUSION
This study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes.
PubMed: 38812969
DOI: 10.3389/fgene.2024.1372042 -
Frontiers in Endocrinology 2024Although lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (Hs-CRP) are closely associated with the mortality of acute myocardial infarction (AMI), their...
Synergistic effect of lipoprotein(a) and high-sensitivity C-reactive protein on the risk of all-cause and cardiovascular death in patients with acute myocardial infarction: a large prospective cohort study.
OBJECTIVE
Although lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (Hs-CRP) are closely associated with the mortality of acute myocardial infarction (AMI), their synergistic effect on the risk of death remains unknown. Therefore, this study aimed to explore the combined effect of Lp(a) and Hs-CRP on the incidence of all-cause and cardiovascular death in AMI patients.
METHODS
A comprehensive cohort study enrolled 912 AMI patients, categorizing them into four groups based on Lp(a) and Hs-CRP levels: Group 1 [Lp(a) < 30 mg/dL & Hs-CRP < 2 mg/L], Group 2 [Lp(a) < 30 mg/dL & Hs-CRP ≥ 2 mg/L], Group 3 [Lp(a) ≥ 30 mg/dL & Hs-CRP < 2 mg/L], and Group 4 [Lp(a) ≥ 30 mg/dL & Hs-CRP ≥ 2 mg/L]. Cox regression analysis, Kaplan-Meier survival analysis and sensitivity analysis were employed to determine the combined effects of Lp(a) and Hs-CRP on the risk of all-cause and cardiovascular death.
RESULTS
Over a median observation period of 38.98 months, 217 patients passed away, with 137 deaths attributed to cardiovascular causes. The multivariate Cox regression analysis revealed that in the comprehensively adjusted Model 3, only Lp(a) and the combination of Lp(a) and Hs-CRP exhibited a strong association with cardiovascular death risk. Specifically, for Lp(a) levels ≥ 30 mg/dL compared to < 30 mg/dL, the hazard ratio (HR) was 2.434 with a 95% confidence interval (CI) of 1.653-3.583 (P < 0.001); for log(Lp(a)), the HR was 2.630 with a 95% CI of 1.530-4.523 (P < 0.001); for Group 4 versus Group 1, the HR was 2.346 with a 95% CI of 1.054-5.220 (P = 0.037); and for Group 4 versus Groups 1 + 2 + 3, the HR was 1.878 with a 95% CI of 1.284-2.748 (P = 0.001). Sensitivity analysis indicated that the synergy between Lp(a) and Hs-CRP continued to be independently associated with the risk of cardiovascular death. For Group 3 versus Group 1, the HR was 3.353 with a 95% CI of 1.133-9.917 (P = 0.029); for Group 4 versus Group 1, the HR was 3.710 with a 95% CI of 1.466-9.392 (P = 0.006); and for Group 4 versus Groups 1 + 2 + 3, the HR was 2.433 with a 95% CI of 1.620-3.656 (P < 0.001).
CONCLUSIONS
Compared to elevated levels of either Lp(a) or Hs-CRP alone, the concurrent high levels of both significantly increased the risk of cardiovascular death in patients with AMI, underscoring the importance of considering their combined effects in the prognostic management of AMI patients.
Topics: Humans; C-Reactive Protein; Male; Myocardial Infarction; Female; Middle Aged; Lipoprotein(a); Prospective Studies; Aged; Cardiovascular Diseases; Risk Factors; Biomarkers; Prognosis; Cause of Death; Cohort Studies
PubMed: 38812817
DOI: 10.3389/fendo.2024.1392859