-
Current Opinion in Chemical Biology Aug 2021The field of nuclear imaging and therapy is rapidly progressing with the development of targeted radiopharmaceuticals that show rapid targeting and rapid clearance with... (Review)
Review
The field of nuclear imaging and therapy is rapidly progressing with the development of targeted radiopharmaceuticals that show rapid targeting and rapid clearance with minimal background. Unfortunately, they are often reabsorbed in the kidneys, leading to possible nephrotoxicity, limiting the therapeutic dose, and/or reducing imaging quality. The blocking of endocytic receptors has been extensively used as a strategy to reduce kidney radiation. Alternatively, the physicochemical properties of radiotracers can be modulated to either prevent their reuptake or promote the excretion of radiometabolites. Other interesting strategies focus on the insertion of a cleavable linker between the radiolabel and the targeting moiety or pretargeting approaches in which the targeting moiety and radiolabel are administered separately. In the context of this review, we will discuss the latest advances and insights on strategies used to reduce renal retention of low- to moderate-molecular-weight radiopharmaceuticals.
Topics: Albumins; Animals; Contrast Media; Dose-Response Relationship, Radiation; Humans; Kidney; Molecular Weight; Radioisotopes; Radiopharmaceuticals; Single Photon Emission Computed Tomography Computed Tomography; Structure-Activity Relationship
PubMed: 34325089
DOI: 10.1016/j.cbpa.2021.06.008 -
Giornale Italiano Di Nefrologia :... Aug 2022The evaluation of renal function is computed using the estimated glomerular filtration rate methods or the measured glomerular filtration rate. Cystatin C has been well...
The evaluation of renal function is computed using the estimated glomerular filtration rate methods or the measured glomerular filtration rate. Cystatin C has been well studied as marker of renal function compared to serum creatinine, but only few studies compare Glomerular Filtration Rates estimated including both creatinine and cystatin (eGFRcyst-crea) to creatinine clearance (CrCl). This cross-sectional study compares CrCl and eGFRcyst-crea with eGFRcrea and searches for correlation with comorbidities. This cross-sectional study consists of 78 patients hospitalized for acute and/or chronic renal disease. We performed the concordance correlation coefficient analysis between the eGFRcrea and the CrCl and eGFRcyst-crea in the whole sample and in the various subgroups. Steiger's comparison of correlations from dependent samples showed a correlation coefficient between C-reactive protein and eGFRcyst-crea stronger than between C-reactive protein and CrCl (Z: 2.51, p=0.012). Similar results were showed with the association with procalcitonin (Z: 5.24, p<0.001), serum potassium (Z: -3.13, p=0.002), and severe CKD (Z: -2.54, p=0.011). The concordance correlation coefficient test showed major differences between diagnostic methods compared to eGFR-crea in diabetic subgroup, severe CKD, and in procalcitonin higher than 0.5ng/ml. The demonstration of a strong concordance between the eGFRcrea and the eGFRcyst-crea allows us to diagnose and to stage CKD better than creatinine clearance in patients with high inflammatory status. Furthermore, this information opens new research scenarios, and further, larger studies are needed to confirm these hypotheses.
Topics: C-Reactive Protein; Creatinine; Cross-Sectional Studies; Humans; Procalcitonin; Renal Insufficiency, Chronic
PubMed: 36073332
DOI: No ID Found -
Scientific Reports Jul 2022The aim of this study was to evaluate the prognostic value of the Lactate to Albumin (L/A) ratio compared to that of lactate and lactate clearance in predicting outcomes... (Comparative Study)
Comparative Study Observational Study
Comparison of lactate/albumin ratio to lactate and lactate clearance for predicting outcomes in patients with septic shock admitted to intensive care unit: an observational study.
The aim of this study was to evaluate the prognostic value of the Lactate to Albumin (L/A) ratio compared to that of lactate and lactate clearance in predicting outcomes in patients with septic shock. This was a multi-center observational study of adult patients with septic shock, who admitted to intensive care units (ICUs) at Shohada and Imam Reza Hospitals, Tabriz, Iran, between Sept 2018 and Jan 2021. The area under the curve (AUC) of receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were used to explore associations of the L/A ratio, lactate and lactate clearance on the primary (mortality) and secondary outcomes [ICU length of stay (LOS), duration of mechanical ventilation (MV), need of renal replacement therapy (RRT) and duration of using vasopressors] at baseline, 6 h and 24 h of septic shock recognition. Best performing predictive value for mortality were related to lactate clearance at 24 h, L/A ratio at 6 h and lactate levels at 24 h with (AUC 0.963, 95% CI 0.918-0.987, P < 0.001), (AUC 0.917, 95% CI 0.861-0.956, P < 0.001), and (AUC 0.904, 95% CI 0.845-0.946, P < 0.001), respectively. Generally, the lactate clearance at 24 h had better prognostic performance for mortality and duration of using vasopressor. However, the L/A ratio had better prognostic performance than serum lactate and lactate clearance for RRT, ICU LOS and MV duration.
Topics: Adult; Albumins; Humans; Intensive Care Units; Lactic Acid; Prognosis; ROC Curve; Retrospective Studies; Shock, Septic
PubMed: 35906231
DOI: 10.1038/s41598-022-14764-z -
Mediators of Inflammation 2019Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections... (Review)
Review
Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world's most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports-and is supported by-uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as "leaky gut." Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.
Topics: Albumins; Animals; Humans; Inflammation; Liver Cirrhosis; Macrophages; Reactive Oxygen Species
PubMed: 30930689
DOI: 10.1155/2019/7537649 -
Frontiers in Cellular and Infection... 2022This study aimed to investigate the clinical and biochemical profiles of patients with imported malaria infection between 1 January 2011 and 30 April 2022 and admitted...
OBJECTIVES
This study aimed to investigate the clinical and biochemical profiles of patients with imported malaria infection between 1 January 2011 and 30 April 2022 and admitted to the Fourth People's Hospital of Nanning.
METHODS
This cohort study enrolled 170 patients with conformed imported malaria infection. The clinical and biochemical profiles of these participants were analyzed with malaria parasite clearance, and signs and symptoms related to malaria disappearance were defined as the primary outcome. A multivariable logistic regression model was used to evaluate the odds ratios (ORs) with 95% confidence intervals (CIs) for cerebral malaria. The Cox model was used to estimate the hazard ratios (HRs) with 95% CIs for parasite clearance.
RESULTS
Adenosine deaminase and parasitemia were found to be independent risk factors for severe malaria in patients with imported malaria (OR = 1.0088, 95% CI: 1.0010-1.0167, = 0.0272 and OR = 2.0700, 95% CI: 1.2584-3.4050, = 0.0042, respectively). A 0.5-standard deviation (SD) increase of variation for urea (HR = 0.6714, 95% CI: 0.4911-0.9180), a 0.5-SD increase of variation for creatinine (HR = 0.4566, 95% CI: 0.2762-0.7548), a 0.25-SD increase of variation for albumin (HR = 0.4947, 95% CI: 0.3197-0.7653), a 0.25-SD increase of variation for hydroxybutyrate dehydrogenase (HR = 0.6129, 95% CI: 0.3995-0.9402), and a 1.0-SD increase of variation for ferritin (HR = 0.5887, 95% CI: 0.3799-0.9125) were associated with a higher risk for increased parasite clearance duration than a low-level change.
CONCLUSIONS
Aspartate aminotransferase, urea, creatinine, albumin, hydroxybutyrate dehydrogenase, and ferritin are useful biochemical indicators in routine clinical practice to evaluate prognosis for imported malaria.
Topics: Humans; Cohort Studies; Creatinine; Hydroxybutyrate Dehydrogenase; Retrospective Studies; Communicable Diseases, Imported; Malaria, Cerebral; Ferritins; Albumins; Urea
PubMed: 36439238
DOI: 10.3389/fcimb.2022.1008430 -
Clinical Pharmacokinetics Jan 2018Paclitaxel is an anticancer agent efficacious in the treatment of ovarian, breast, and lung cancer. Due to a strong link between the pharmacokinetics and therapeutic... (Comparative Study)
Comparative Study Review
Paclitaxel is an anticancer agent efficacious in the treatment of ovarian, breast, and lung cancer. Due to a strong link between the pharmacokinetics and therapeutic efficacy of paclitaxel, we reviewed the literature on paclitaxel pharmacokinetics. Systematic data mining was performed to extract the maximum concentration (C ), clearance (CL), and time of paclitaxel plasma concentration above 0.05 µmol/L (T > 0.05 µmol/L) following monotherapy of both the widely used cremophor-diluted paclitaxel and nanoparticle albumin-bound (nab-)paclitaxel. We identified a total of 53 studies yielding 121 aggregated pharmacokinetic profiles for paclitaxel monotherapy and extracted reported mean and median estimates of pharmacokinetic parameters. Paclitaxel has been studied formally at doses of 15-825 mg/m and infused over 0.5-96 h; included studies examined both weekly and every 3-weeks dosing cycles. The most widely used dose of cremophor-diluted paclitaxel, 175 mg/m given as a 3-h infusion, leads to an interstudy median C of 5.1 µmol/L [interquartile range (IQR) 4.5-5.7], CL of 12.0 L/h/m (IQR 10.9-12.9), and T > 0.05 µmol/L of 23.8 h (IQR 21.5-26.8). Importantly, the significant interindividual variation widely reported in the literature is not reflected in these interstudy estimates of pharmacokinetic parameters. Cremophor-diluted paclitaxel pharmacokinetics are non-linear following short (<6 h) but not long (>24 h) infusions. A similar pattern of non-linearity was observed for nab-paclitaxel, although the number of studies was limited. The pharmacokinetics of paclitaxel monotherapy have been widely studied at numerous dose levels of the Cremophor EL formulation, but are less well-characterized for the newer nab-paclitaxel formulation. In conclusion, paclitaxel pharmacokinetics are non-linear for short infusion times but not for longer infusions. Whether a similar conclusion can be drawn for nab-paclitaxel formulations requires further study.
Topics: Albumins; Antineoplastic Agents, Phytogenic; Dose-Response Relationship, Drug; Glycerol; Humans; Infusions, Intravenous; Neoplasms; Nonlinear Dynamics; Paclitaxel; Surface-Active Agents; Time Factors
PubMed: 28612269
DOI: 10.1007/s40262-017-0563-z -
Journal of Nuclear Medicine : Official... May 2023Fibroblast activation protein (FAP) has received increasing attention as an oncologic target because of its prominent expression in solid tumors but virtual absence from...
Fibroblast activation protein (FAP) has received increasing attention as an oncologic target because of its prominent expression in solid tumors but virtual absence from healthy tissues. Most radioligand therapies (RLTs) targeting FAP, however, suffer from inadequate tumor retention or clearance from healthy tissues. Herein we report a FAP-targeted RLT comprising an FAP6 ligand conjugated to DOTA and an albumin binder (4--iodophenylbutyric acid, or IP) for enhanced pharmacokinetics. We evaluated the performance of the resulting FAP6-IP-DOTA conjugate in 4 tumor models, 3 of which express FAP only on cancer-associated fibroblasts, that is, analogously to human tumors. Single-cell RNA-sequencing data were analyzed from 34 human breast, ovarian, colorectal, and lung cancers to quantify FAP-overexpressing cells. FAP6-DOTA conjugates were synthesized with or without an albumin binder (IP) and investigated for binding to human FAP-expressing cells. Accumulation of In- or Lu-labeled conjugates in KB, HT29, U87MG, and 4T1 murine tumors was also assessed by radioimaging or biodistribution analyses. Radiotherapeutic potency was quantitated by measuring tumor volumes versus time. Approximately 5% of all cells in human tumors overexpressed FAP (cancer-associated fibroblasts comprised ∼77% of this FAP-positive subpopulation, whereas ∼2% were cancer cells). FAP6 conjugates bound to FAP-expressing cells with high affinity (dissociation constant, ∼1 nM). Lu-FAP6-IP-DOTA achieved an 88-fold higher tumor dose than Lu-FAP6-DOTA and improved all tumor-to-healthy-organ ratios. Single doses of Lu-FAP6-IP-DOTA suppressed tumor growth by about 45% in all tested tumor models without causing reproducible toxicities. We conclude that Lu-FAP6-IP-DOTA constitutes a promising candidate for FAP-targeted RLT of solid tumors.
Topics: Humans; Animals; Mice; Tissue Distribution; Cell Line, Tumor; Albumins; Fibroblasts
PubMed: 37116911
DOI: 10.2967/jnumed.122.264494 -
Kidney360 Jun 2023Albumin kinetics not only reflected the pathophysiology of minimal change nephrotic syndrome but was also a predictor of relapse. The high estimated 24-hour albumin...
KEY POINTS
Albumin kinetics not only reflected the pathophysiology of minimal change nephrotic syndrome but was also a predictor of relapse. The high estimated 24-hour albumin clearance predicts the minimal change nephrotic syndrome relapse. The 24-hour albumin clearance can easily be calculated from only serum albumin and urinary protein excretion, which are routine laboratory measurements.
BACKGROUND
Although albuminuria leakage that occurs in minimal change nephrotic syndrome (MCNS) may be related to the disease state, albumin kinetics in MCNS has never been evaluated. In this study, we investigated albumin kinetics in adult Japanese patients with MCNS by the estimated 24-hour albumin clearance (eC) and examined the association between eC and relapse.
METHODS
We retrospectively identified 103 adult patients with a histological diagnosis of MCNS from four hospitals in Japan (2010–2020). The primary outcome is the first relapse in 2 years after complete remission after corticosteroid therapy. The eC [l/min] was defined as (2.71828 [g/24 hours])/(serum albumin [g/dl]×1440 [min/24 hours]) for women and (2.71828 [g/24 hours])/(serum albumin [g/dl]×1440 [min/24 hours]) for men.
RESULTS
Relapse was observed in 44 patients (103 kidney biopsy samples; 42.7%). The mean patient age was 41.0 years. Patients had an eGFR of 71.0 ml/min per 1.73 m, urinary protein excretion of 6.8 g/d, serum albumin of 1.4 g/dl, and eC of 2.27 l/min. eC was strongly associated with hypoalbuminemia, severe proteinuria, lipid abnormalities, and coagulopathy. In the multivariable analysis, a high eC was significantly associated with relapse after adjusting for age, eGFR, time to complete remission, and urinary protein excretion (adjusted hazard ratio, 5.027; 95% confidence interval, 1.88 to 13.47; = 0.001).
CONCLUSIONS
This study revealed that eC, which could substitute albumin kinetics, reflected the severity of MCNS, and a high eC was associated with recurrence.
Topics: Humans; Nephrosis, Lipoid; Kidney Function Tests; Nephrotic Syndrome; Chronic Disease; Albumins; Recurrence
PubMed: 37166949
DOI: 10.34067/KID.0000000000000143 -
World Journal of Gastroenterology Oct 2022Estimation of the functional reserve of the remnant liver is important to reduce morbidity and mortality. (Review)
Review
BACKGROUND
Estimation of the functional reserve of the remnant liver is important to reduce morbidity and mortality.
AIM
To estimate the functional reserve of the remnant liver in patients with hepatocellular carcinoma (HCC).
METHODS
We reviewed the medical records of 199 patients who underwent resection of HCC. Hepatic clearance of the remnant liver was calculated using fusion images of Tc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography. Posthepatectomy liver failure (PHLF) was classified according to the International Study Group of Liver Surgery. Complications was classified according to Clavien-Dindo classification. We analyzed by the risk factors for PHLF, morbidity and mortality with multivariate analysis.
RESULTS
Twenty-seven (30%) patients had major complications and 23 (12%) developed PHLF. The incidence of major complications increased with increasing albumin-bilirubin (ALBI) grade. The area under the curve values for hepatic clearance of the remnant liver, liver to heart-plus-liver radioactivity at 15 min (LHL15), and ALBI score predicting PHLF were 0.868, 0.629, and 0.655, respectively. The area under the curve for hepatic clearance of the remnant liver, LHL15, and ALBI score predicting major complications were 0.758, 0.594, and 0.647, respectively. The risk factors for PHLF and major complications were hepatic clearance of the remnant liver and intraoperative bleeding.
CONCLUSION
The measurement of hepatic clearance may predict PHLF and major complications for patients undergoing resection of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Hepatectomy; Liver Neoplasms; Retrospective Studies; Liver Failure; Bilirubin; Albumins; Postoperative Complications
PubMed: 36304091
DOI: 10.3748/wjg.v28.i38.5614 -
Journal of Clinical Pharmacology Feb 2021Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced treatment efficacy, and increased risk of infusion-related reactions. The aim of this study was to identify predictors of baseline infliximab clearance and early antidrug antibody formation. Pharmacokinetic and pharmacokinetic/pharmacodynamic models for infliximab were developed using 21 178 observations from 859 patients from the PLANETRA (ClinicalTrials.gov identifier: NCT01217086) and PLANETAS (NCT01220518) studies in rheumatoid arthritis and ankylosing spondylitis, respectively, to address the specified aims. Infliximab pharmacokinetics were well described by a 2-compartment model with linear mean estimated baseline clearance of 0.26 L/day. Alongside increased body weight, serum C-reactive protein, and antidrug antibody concentrations and decreased serum albumin, elevated serum glucose levels predicted higher clearance. In patients with rheumatoid arthritis, baseline infliximab clearance and body weight were the only identified predictors of early antidrug antibody detection. The odds ratio for antidrug antibody detection for each 0.1 L/day increase in baseline infliximab clearance was 1.78 (95% confidence interval, 1.50-2.12); for each 10-kg increase in body weight, this was 1.19 (1.06-1.33). Here we describe increased serum glucose levels as a novel independent predictor of baseline infliximab clearance. Estimates of baseline infliximab clearance should be incorporated to guide dosing modifications and/or antidrug antibody prophylaxis in clinical practice.
Topics: Adolescent; Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Blood Glucose; Body Weight; C-Reactive Protein; Double-Blind Method; Female; Humans; Infliximab; Male; Metabolic Clearance Rate; Middle Aged; Serum Albumin; Spondylitis, Ankylosing; Young Adult
PubMed: 32905628
DOI: 10.1002/jcph.1732