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Kidney360 Aug 2023HDF and MCO have shown greater clearance of middle-size uremic solutes in comparison with HF dialyzers; MCO has never been studied in HDF. MCO in HDF does not increase...
KEY POINTS
HDF and MCO have shown greater clearance of middle-size uremic solutes in comparison with HF dialyzers; MCO has never been studied in HDF. MCO in HDF does not increase the clearance of B2M and results in a higher loss of albumin.
BACKGROUND
Middle molecule removal and albumin loss have been studied in medium cutoff (MCO) membranes on hemodialysis (HD). It is unknown whether hemodiafiltration (HDF) with MCO membranes provides additional benefit. We aimed to compare the removal of small solutes and 2-microglobulin (B2M), albumin, and total proteins between MCO and high-flux (HFX) membranes with both HD and HDF, respectively.
METHODS
The cross-over study comprised 4 weeks, one each with postdilutional HDF using HFX (HFX-HDF), MCO (MCO-HDF), HD with HFX (HFX-HD), and MCO (MCO-HD). MCO and HFX differ with respect to several characteristics, including membrane composition, pore size distribution, and surface area (HFX, 2.5 m; MCO, 1.7 m). There were two study treatments per week, one after the long interdialytic interval and another midweek. Reduction ratios of vitamin B12, B2M, phosphate, uric acid, and urea corrected for hemoconcentration were computed. Dialysis albumin and total protein loss during the treatment were quantified from dialysate samples.
RESULTS
Twelve anuric patients were studied (six female patients; 44±19 years; dialysis vintage 35.2±28 months). The blood flow was 369±23 ml/min, dialysate flow was 495±61 ml/min, and ultrafiltration volume was 2.8±0.74 L. No significant differences were found regarding the removal of B2M, vitamin B12, and water-soluble solutes between dialytic modalities and dialyzers. Albumin and total protein loss were significantly higher in MCO groups than HFX groups when compared with the same modality. HDF groups had significantly higher albumin and total protein loss than HD groups when compared with the same dialyzer. MCO-HDF showed the highest protein loss among all groups.
CONCLUSIONS
MCO-HD is not superior to HFX-HD and HFX-HDF for both middle molecule and water-soluble solute removal. Protein loss was more pronounced with MCO when compared with HFX on both HD and HDF modalities. MCO-HDF has no additional benefits regarding better removal of B2M but resulted in greater protein loss than MCO-HD.
Topics: Cross-Over Studies; Hemodiafiltration; Renal Dialysis; Humans; Albumins
PubMed: 37651666
DOI: 10.34067/KID.0000000000000185 -
Clinical Pharmacology and Therapeutics May 2022For a number of years, our laboratory has been investigating the underlying reasons for the published poor in vitro-in vivo extrapolation (IVIVE) predictability of human... (Review)
Review
For a number of years, our laboratory has been investigating the underlying reasons for the published poor in vitro-in vivo extrapolation (IVIVE) predictability of human clearance both from a theoretical and from an experimental perspective. Here, we critically examine clearance concepts and commonly employed IVIVE approaches, concluding that there is no theoretical reason that IVIVE should work, just as it does not. Our analysis, however, has identified 10 misconceptions and/or poorly understood aspects of clearance that are listed in the Conclusion section of this manuscript. Chief among these are that all published human drug clearance values are arterial clearances-clearance calculated as organ blood flow multiplied by the extraction ratio is the arterial clearance of the organ of elimination (and not the published drug clearance value)-and that the well-stirred model equation taught in all pharmacokinetic courses that relates organ blood flow, fraction unbound in blood, and intrinsic clearance has no validity. We further list 10 conclusions relating to the IVIVE process. The primary IVIVE-related conclusions are that the intrinsic clearance value determined from an in vitro incubation is an arterial intrinsic clearance, there is no theoretical basis upon which an arterial intrinsic clearance can be related to a whole-body arterial clearance to accomplish IVIVE, there are no published data demonstrating that in vitro intrinsic metabolic clearance can predict in vivo organ clearance as IVIVE assumes, and the scientific basis for the hypothesized albumin-mediated hepatic uptake phenomenon is invalid. We further propose three IVIVE process recommendations.
Topics: Hepatocytes; Humans; Kinetics; Liver; Metabolic Clearance Rate; Models, Biological
PubMed: 34731496
DOI: 10.1002/cpt.2482 -
Frontiers in Immunology 2020Pentraxins are soluble innate immunity receptors involved in sensing danger molecules. They are classified as short (CRP, SAP) and long pentraxin subfamilies, including... (Review)
Review
Pentraxins are soluble innate immunity receptors involved in sensing danger molecules. They are classified as short (CRP, SAP) and long pentraxin subfamilies, including the prototypic long pentraxin PTX3. Pentraxins act mainly as bridging molecules favoring the clearance of microbes and dead cells. They are also involved in many other biological processes, such as regulation of complement activation, inflammation and tissue homeostasis. Autoantibodies directed against pentraxins have been reported in various autoimmune diseases, especially in systemic lupus erythematosus and ANCA-associated vasculitis. In this review, we review the main biological characteristics and functions of pentraxins and summarize data concerning autoantibodies directed against pentraxins in the context of autoimmune diseases and discuss their potential pathological role.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Autoantibodies; Bystander Effect; C-Reactive Protein; Humans; Lupus Erythematosus, Systemic; Serum Amyloid P-Component
PubMed: 33664737
DOI: 10.3389/fimmu.2020.626343 -
Annals of Hepatology 2024Hepatorenal syndrome (HRS) is a serious complication of cirrhosis treated with various medications. We aim to evaluate terlipressin and albumin's effectiveness and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND OBJECTIVES
Hepatorenal syndrome (HRS) is a serious complication of cirrhosis treated with various medications. We aim to evaluate terlipressin and albumin's effectiveness and safety compared to albumin and noradrenaline in adult hepatorenal disease patients.
MATERIALS AND METHODS
Clinical trials from four databases were included. Cochrane's approach for calculating bias risk was utilized. We rated the quality evaluation by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included the following outcomes: serum creatinine (mg/dl), urine output (ml/24 h), mean arterial pressure (mmHg), reversal rate of HRS, mortality rate, blood plasma renin activity (ng/ml/h), plasma aldosterone concentration (pg/ml), urine sodium (mEq/l), and creatinine clearance (ml/min).
RESULTS
Our analysis of nine clinical studies revealed that the noradrenaline group was associated with higher creatinine clearance (MD = 4.22 [0.40, 8.05]), (P = 0.03). There were no significant differences in serum creatinine levels (MD = 0.03 [-0.07, 0.13]), urinary sodium (MD = -1.02 [-5.15, 3.11]), urine output (MD = 32.75 [-93.94, 159.44]), mean arterial pressure (MD = 1.40 [-1.17, 3.96]), plasma renin activity (MD = 1.35 [-0.17, 2.87]), plasma aldosterone concentration (MD = 55.35 [-24.59, 135.29]), reversal rate of HRS (RR = 1.15 [0.96, 1.37]), or mortality rate (RR = 0.87 [0.74, 1.01]) between the two groups (p-values > 0.05).
CONCLUSIONS
Noradrenaline is a safe alternative medical therapy for HRS.
Topics: Humans; Terlipressin; Hepatorenal Syndrome; Norepinephrine; Albumins; Treatment Outcome; Vasoconstrictor Agents; Adult; Creatinine; Lypressin
PubMed: 38460713
DOI: 10.1016/j.aohep.2024.101495 -
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 -
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 -
Critical Care (London, England) Dec 2021The measurement of circulating substrate concentrations does not provide information about substrate kinetics. It, therefore, remains unclear if a decrease in plasma... (Observational Study)
Observational Study
BACKGROUND
The measurement of circulating substrate concentrations does not provide information about substrate kinetics. It, therefore, remains unclear if a decrease in plasma concentration of albumin, as seen during critical illness, is a consequence of suppressed production in the liver or increased peripheral clearance. In this study, using stable isotope tracer infusions, we measured albumin and fibrinogen kinetics in septic patients and in a control group of non-septic subjects.
METHODS
With the approval from the institutional Research Ethics Board and after obtaining written informed consent from patients or their substitute decision maker, mechanically ventilated patients with sepsis and patients scheduled for elective coronary artery bypass grafting were enrolled. Patients in the non-sepsis group were studied on the day before surgery. The stable isotope L-[ring-H]phenylalanine was used to measure absolute synthesis rates (ASR) of albumin and fibrinogen. A priming dose of L-[ring-H]phenylalanine (4 µmol/kg) was given followed by a six-hour infusion at a rate of 0.15 µmol/kg/min. At baseline and hourly thereafter, blood was drawn to measure isotope enrichments by gas chromatography/mass spectrometry. Very low density lipoprotein apolipoprotein-B 100 isotopic enrichment was used to represent the isotopic enrichment of the phenylalanine precursor pool from which the liver synthesizes proteins. Plasma albumin and fibrinogen concentrations were also measured.
RESULTS
Mean plasma albumin in septic patients was decreased when compared to non-septic patients, while synthesis rates were comparable. Mean plasma fibrinogen and ASR in septic patients was increased when compared to non-septic patients. In non-septic patients, no statistically significant correlation between plasma albumin and ASR was observed but plasma fibrinogen significantly correlated with ASR. In septic patients, plasma albumin and fibrinogen significantly correlated with ASR.
CONCLUSIONS
While septic patients showed lower plasma albumin levels than non-septic patients, albumin synthesis was similar in the two groups suggesting that hypoalbuminemia during sepsis was not caused by suppressed hepatic production but a result of enhanced clearance from the circulation. Hyperfibrinogenemia in septic patients was a consequence of increased fibrinogen production.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02865408 (registered on August 12, 2016) and ClinicalTrials.gov: NCT02549443 (registered on September 15, 2015).
Topics: Fibrinogen; Humans; Hypoalbuminemia; Kinetics; Sepsis; Serum Albumin
PubMed: 34920728
DOI: 10.1186/s13054-021-03860-7 -
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 -
Mathematical Biosciences and... Oct 2023Human immunodeficiency virus (HIV) infection is a major public health concern with 1.2 million people living with HIV in the United States. The role of nutrition in...
Human immunodeficiency virus (HIV) infection is a major public health concern with 1.2 million people living with HIV in the United States. The role of nutrition in general, and albumin/globulin in particular in HIV progression has long been recognized. However, no mathematical models exist to describe the interplay between HIV and albumin/globulin. In this paper, we present a family of models of HIV and the two protein components albumin and globulin. We use albumin, globulin, viral load and target cell data from simian immunodeficiency virus (SIV)-infected monkeys to perform model selection on the family of models. We discover that the simplest model accurately and uniquely describes the data. The selection of the simplest model leads to the observation that albumin and globulin do not impact the infection rate of target cells by the virus and the clearance of the infected target cells by the immune system. Moreover, the recruitment of target cells and immune cells are modeled independently of globulin in the selected model. Mathematical analysis of the selected model reveals that the model has an infection-free equilibrium and a unique infected equilibrium when the immunological reproduction number is above one. The infection-free equilibrium is locally stable when the immunological reproduction number is below one, and unstable when the immunological reproduction number is greater than one. The infection equilibrium is locally stable whenever it exists. To determine the parameters of the best fitted model we perform structural and practical identifiability analysis. The structural identifiability analysis reveals that the model is identifiable when the immune cell infection rate is fixed at a value obtained from the literature. Practical identifiability reveals that only seven of the sixteen parameters are practically identifiable with the given data. Practical identifiability of parameters performed with synthetic data sampled a lot more frequently reveals that only two parameters are practically unidentifiable. We conclude that experiments that will improve the quality of the data can help improve the parameter estimates and lead to better understanding of the interplay of HIV and albumin-globulin metabolism.
Topics: Animals; Humans; HIV Infections; Models, Theoretical; Simian Immunodeficiency Virus; Albumins
PubMed: 38052613
DOI: 10.3934/mbe.2023865 -
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