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Kidney Diseases (Basel, Switzerland) Mar 2020Nephropathy problems in the Udhanam region of Andhra Pradesh in India have motivated researchers to investigate the various factors related to chronic kidney disease... (Review)
Review
BACKGROUND
Nephropathy problems in the Udhanam region of Andhra Pradesh in India have motivated researchers to investigate the various factors related to chronic kidney disease (CKD). Initially, studies came across the markers of identification of CKD, i.e., glomerular filtration rate (GFR) and albumin creatinine rate, as global markers of identification. Cystatin C (Cys C) and its reciprocal (1/Cys C) are used to calculate GFR. This is a very easy method compared to the more accurate methods such as radiolabelled tracer clearances, which are invasive, may involve radiation, and require several hours to perform, e.g., 99-diethylene triamine penta-acetic acid (Tc-DTPA) and Cr-EDTA. This article provides the causes (or risk factors), symptoms, and complications of CKD in a clear manner such that even common people can easily understand. Once a patient is detected and proved to be affected by CKD then the patient as well as the caretakers, including doctors, must follow some constraints. Thereby it is possible to prevent CKD progression in the patient. Modern methods are needed to prevent the pathogens which are responsible for CKD.
SUMMARY
With the help of various engineering techniques one can easily design controllers to assess as well as to prevent CKD permanently. The easiest procedure for identifying CKD is to screen people. Current recommendations suggest screening of individuals with diabetes, hypertension, cardiovascular disease, and family history of kidney diseases in the course of routine health check-ups. Much work has been done in medical sciences in the area of CKD, but there is still scope for further research. From the recent studies, advanced tools such as data mining, etc., are considered to be the current trend in the area of CKD.
KEY MESSAGE
From this article, the authors propose that patients who are already affected by urinary tract infection, acute kidney injury, and a family history of CKD should be examined via some basic tests for the presence of CKD.
PubMed: 32309290
DOI: 10.1159/000504622 -
Journal of Clinical and Experimental... 2022The liver comprises both parenchymal and non-parenchymal cells with varying functions. Cirrhosis is often complicated by the development of portal hypertension and its... (Review)
Review
The liver comprises both parenchymal and non-parenchymal cells with varying functions. Cirrhosis is often complicated by the development of portal hypertension and its associated complications. Hence, assessment of liver in cirrhosis should include assessment of its structural, function of both hepatic and non-hepatic tissue and haemodynamic assessment of portal hypertension. There is no single test that can evaluate all functions of liver and assess prevalence and severity of portal hypertension. Commonly available tests like serum bilirubin, liver enzymes (alanine [ALT] and aspartate aminotransferase [AST], serum alkaline phosphatase [ALP], gamma glutamyl transpeptidase [GGT]), serum albumin and prothrombin time for assessment of liver functions partly assess liver functions. quantitative liver functions like indocyanine clearance tests [ICG-K], methacetin breath test [MBT] were developed to assess dynamic status of liver but has its own limitation and availability. Imaging based assessment of liver by transient elastography, MRI based 99 mTc-coupled asialoglycoprotein mebrofenin scan help the clinician to assess liver function, functional volume of liver left after surgery and portal hypertension [PH]. Hepatic venous pressure gradient still remains the gold standard for the assessment of portal hypertension but is invasive and not available in all centres. Combinations of blood parameters in form of various indices like fibrosis score of 4 [FIB-4], Lok index, scores like model for end stage liver disease (MELD) and Child-Turcotte Pugh score are commonly used for assessing liver function in clinical practice.
PubMed: 35677506
DOI: 10.1016/j.jceh.2021.11.004 -
ACS Omega May 2024Therapeutic proteins, pivotal for treating diverse human diseases due to their biocompatibility and high selectivity, often face challenges such as rapid serum...
Therapeutic proteins, pivotal for treating diverse human diseases due to their biocompatibility and high selectivity, often face challenges such as rapid serum clearance, enzymatic degradation, and immune responses. To address these issues and enable prolonged therapeutic efficacy, techniques to extend the serum half-life of therapeutic proteins are crucial. The AlbuCatcher, a conjugate of human serum albumin (HSA) and SpyCatcher, was proposed as a general technique to extend the serum half-life of diverse therapeutic proteins. HSA, the most abundant blood protein, exhibits a long intrinsic half-life through Fc receptor (FcRn)-mediated recycling. The SpyTag/SpyCatcher (ST/SC) system, known for forming irreversible isopeptide bonds, was employed to conjugate HSA and therapeutic proteins. Site-specific HSA conjugation to SC was achieved using an inverse electron-demand Diels-Alder (IEDDA) reaction, minimizing activity loss. Using urate oxidase (Uox) as a model protein with a short half-life, the small ST was fused to generate Uox-ST. Then, HSA-conjugated Uox (Uox-HSA) was successfully prepared via the Uox-ST/AlbuCatcher reaction. In vitro enzyme assays demonstrated that the impact of ST fusion and HSA conjugation on Uox enzymatic activity is negligible. Pharmacokinetics studies in mice revealed that Uox-HSA exhibits a significantly longer serum half-life (about 18 h) compared to Uox-WT (about 2 h). This extended half-life is attributed to FcRn-mediated recycling of HSA-conjugated Uox, demonstrating the effectiveness of the AlbuCatcher strategy in enhancing the pharmacokinetics of therapeutic proteins.
PubMed: 38826564
DOI: 10.1021/acsomega.4c02303 -
Pharmaceutics Dec 2022Cefiderocol is a siderophore cephalosporin antibiotic active against Gram-negative bacteria, including extended-spectrum beta-lactamase and carbapenemase-producing...
BACKGROUND
Cefiderocol is a siderophore cephalosporin antibiotic active against Gram-negative bacteria, including extended-spectrum beta-lactamase and carbapenemase-producing strains. The pharmacokinetics of cefiderocol has been studied in healthy subjects and particularly in phase II and III studies. This retrospective study investigated intravenous cefiderocol population pharmacokinetics in adult patients treated by cefiderocol.
METHODS
We studied 55 consecutive patients hospitalized in an intensive care unit. Cefiderocol plasma samples were obtained on different occasions during treatment. Plasma concentration was assayed using mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2020R1.
RESULTS
A total of 205 plasma samples were obtained from 55 patients. Eighty percent of patients received cefiderocol for ventilator-associated pneumonia due to carbapenem-resistant infection. Cefiderocol concentration time-courses were best fit to a two-compartment open model with first-order elimination. Elimination clearance was positively related to renal function (estimated by the CKD formula). Adding albumin plasma binding in the model significantly improved the model assuming a ~40% unbound drug fraction given a ~40 g/L albuminemia. The final model included CKD plus cefiderocol plasma binding effects. Fat-free mass was better than total body weight to influence, via the allometric rule, clearance and volume terms, but this effect was negligible. The final clearance based on free circulating drug (CL) for a typical patient, CKD = 90, was 7.38 L/h [relative standard error, RSE, 22%] with a between-subject variability of 0.47 [RSE 10%] (exponential distribution).
CONCLUSION
This study showed that albumin binding and CKD effects were significant predictors of unbound and total plasma cefiderocol concentrations. Our results indicate that individual adjustment of cefiderocol can be used to reach high minimum inhibitory concentrations based on an estimation of unbound drug concentration and optimize therapeutic efficacy.
PubMed: 36559279
DOI: 10.3390/pharmaceutics14122786 -
Frontiers in Immunology 2019The functions of pentraxins, like C-reactive protein (CRP), serum amyloid protein P (SAP) and pentraxin-3 (PTX3), are to coordinate spatially and temporally targeted... (Review)
Review
The functions of pentraxins, like C-reactive protein (CRP), serum amyloid protein P (SAP) and pentraxin-3 (PTX3), are to coordinate spatially and temporally targeted clearance of injured tissue components, to protect against infections and to regulate related inflammation together with the complement system. For this, pentraxins have a dual relationship with the complement system. Initially, after a focused binding to their targets, e.g., exposed phospholipids or cholesterol in the injured tissue area, or microbial components, the pentraxins activate complement by binding its first component C1q. However, the emerging inflammation needs to be limited to the target area. Therefore, pentraxins inhibit complement at the C3b stage to prevent excessive damage. The complement inhibitory functions of pentraxins are based on their ability to interact with complement inhibitors C4bp or factor H (FH). C4bp binds to SAP, while FH binds to both CRP and PTX3. FH promotes opsonophagocytosis through inactivation of C3b to iC3b, and inhibits AP activity thus preventing formation of the C5a anaphylatoxin and the complement membrane attack complex (MAC). Monitoring CRP levels gives important clinical information about the extent of tissue damage and severity of infections. CRP is a valuable marker for distinguishing bacterial infections from viral infections. Disturbances in the functions and interactions of pentraxins and complement are also involved in a number of human diseases. This review will summarize what is currently known about the FH family proteins and pentraxins that interact with FH. Furthermore, we will discuss diseases, where interactions between these molecules may play a role.
Topics: Animals; C-Reactive Protein; Complement Activation; Complement Factor H; Complement Membrane Attack Complex; Complement System Proteins; Humans; Serum Amyloid P-Component
PubMed: 31428091
DOI: 10.3389/fimmu.2019.01750 -
Clinical and Experimental Medicine Mar 2024Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is... (Review)
Review
Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is characterised by scar tissue formation, portal hypertension, and ascites (accumulation of fluid in the abdominal cavity) in decompensated cirrhosis. This review evaluates how albumin infusion ameliorates cirrhosis-associated complications. Since albumin is an oncotic plasma protein, albumin infusion allows movement of water into the intravascular space, aids with fluid resuscitation, and thereby contributes to resolving cirrhosis-induced hypovolemia (loss of extracellular fluid) seen in ascites. Thus, albumin infusion helps prevent paracentesis-induced circulatory dysfunction, a complication that occurs when treating ascites. When cirrhosis advances, other complications such as spontaneous bacterial peritonitis and hepatorenal syndrome can manifest. Infused albumin helps mitigate these by exhibiting plasma expansion, antioxidant, and anti-inflammatory functions. In hepatic encephalopathy, albumin infusion is thought to improve cognitive function by reducing ammonia concentration in blood and thereby tackle cirrhosis-induced hepatocyte malfunction in ammonia clearance. Infused albumin can also exhibit protective effects by binding to the cirrhosis-induced proinflammatory cytokines TNFα and IL6. While albumin administration has shown to prolong overall survival of cirrhotic patients with ascites in the ANSWER trial, the ATTIRE and MACHT trials have shown either no effect or limitations such as development of pulmonary oedema and multiorgan failure. Thus, albumin infusion is not a generic treatment option for all cirrhosis patients. Interestingly, cirrhosis-induced structural alterations in native albumin (which lead to formation of different albumin isoforms) can be used as prognostic biomarkers because specific albumin isoforms indicate certain complications of decompensated cirrhosis.
Topics: Humans; Ascites; Ammonia; Liver Cirrhosis; Albumins; Protein Isoforms
PubMed: 38551716
DOI: 10.1007/s10238-024-01315-1 -
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 -
International Journal of Nephrology and... 2021Hypoalbuminemia results when compensatory mechanisms are unable to keep pace with derangements in catabolism/loss and/or decreased synthesis of albumin. Across many... (Review)
Review
Hypoalbuminemia results when compensatory mechanisms are unable to keep pace with derangements in catabolism/loss and/or decreased synthesis of albumin. Across many disease states, including chronic kidney disease (CKD), hypoalbuminemia is a well-established, independent risk factor for adverse outcomes, including mortality. In the setting of CKD, reduced serum albumin concentrations are often a manifestation of protein-energy wasting, a state of metabolic and nutritional alterations resulting in reduced protein and energy stores. The progression of CKD to kidney failure and the initiation of maintenance hemodialysis (HD) further predisposes an already at-risk population toward hypoalbuminemia such that approximately 60% of HD patients have albumin concentrations <4.0 g/dl. Albumin loss into the dialysate through the dialyzer appears to be a potentially modifiable cause of hypoalbuminemia in some patients. A group of newer dialyzers for maintenance HD-sometimes termed protein-leaking or medium cut-off membranes-aim to improve clearance of middle molecules (vs high flux dialyzers) but are associated with increased albumin losses. In this article, we will examine the impact of dialyzer selection on albumin losses during conventional HD, including the clinical relevance of such losses on serum albumin levels. Data on the clinical relevance of albumin losses during dialysis and current gaps in the evidence base are also discussed.
PubMed: 33505168
DOI: 10.2147/IJNRD.S291348 -
Annals of Surgery Oct 2023Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an...
OBJECTIVE AND BACKGROUND
Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE).
METHODS
12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC).
RESULTS
A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed.
CONCLUSION
Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.
PubMed: 37860868
DOI: 10.1097/SLA.0000000000006127 -
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