Individualizing Therapy in Patients With Chronic Kidney Disease

2008 ◽  
Vol 21 (3) ◽  
pp. 225-236
Author(s):  
Melanie S. Joy ◽  
Mary La ◽  
Bo Xiao
Keyword(s):  
Drug Disposition ◽  
Kidney Diseases ◽  
Therapeutic Interventions ◽  
Patient Specific ◽  
Patient Centered ◽  
Glomerular Diseases ◽  
Metabolizing Enzymes ◽  
Chronic Kidney Diseases ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme

Patients with chronic kidney diseases have multiple clinical abnormalities that may affect disposition of drugs, including alterations in glomerular filtration rate, excretion of plasma proteins, reductions in serum albumin, and reductions in drug metabolizing enzyme activity. Inflammation may also influence the previous factors. Concomitant drug therapies can lead to drug— drug interactions that may affect the pharmacokinetics of administered drugs. Pharmacogenomics has begun to be evaluated for effects of genotype and haplotype of drug metabolizing enzymes and transporters on drug disposition. Because of the multiple potential etiologies for alterations in drug disposition in patients with chronic kidney diseases, they require appropriate evaluation for implementation of individualized strategies in therapies to enhance efficacy and reduce toxicities. This review will highlight the disease- and patient-specific variables that are targets for patient-centered approaches to therapeutic interventions. The field of pharmacogenomics will be reviewed with reference to common therapies for transplantation and glomerular diseases.

scholarly journals Post PCI Vascular and Bleeding Complications in Patients with or Without CKD

2016 ◽  
Vol 01 (01) ◽  
pp. 022-027
Author(s):  
Harish Oruganti ◽  
Jyotsna Maddury
Keyword(s):  
Renal Failure ◽  
Kidney Diseases ◽  
Vascular Complications ◽  
Therapeutic Interventions ◽  
Bleeding Complications ◽  
Access Site ◽  
Chronic Kidney Diseases ◽  
Artery Disease ◽  
General Populations ◽  
Distal Embolisation

AbstractBACKGROUND: There is increasing trend of both Cardiovascular disease (CVD) and chronic kidney diseases (CKD) in general populations. The individuals with CKD are more likely to die of CVD than of kidney failure. Both diagnostic and therapeutic interventions are crucial in management of CKD patients with coronary artery disease. As CKD itself is associated with more bleeding complications we aim to study the incidence of vascular complications (vessel thrombosis, distal embolisation, dissection, poorly controlled bleeding at puncture site, pseudoaneurysm, arteriovenous fistula, retroperitoneal hematoma, and development of femoral neuropathy) in Percutaneous intervention (PCI) patients with renal failure.METHODS: 950 patients who underwent PCI procedures were classified into CKD (GFR<60ml/min/m2) (n=380, 40%) and non-CKD (n=570, 60%) groups. Two groups were analyzed for the occurrence of vascular complications post PCI.RESULTS: Vascular complications were seen in 28 out of 380 patients with CKD (7.37%) and 17 out of 570 patients without CKD (2.98%). Patients with renal failure (GFR<60ml/min/m2) were found to have higher risk of vascular complications post PCI. [p = 0.03, OR = 2.588 (1.344-5.017)]. Non access site complications were more common in patients with CKD compared to non CKD. 16 patients with CKD developed non access site complications compared to 9 in patients without CKD.[p=0.001, odds ratio 2.793(1.15-6.916)CONCLUSIONS: This study demonstrates higher risk of vascular complications post-PCI in patients with CKD compared to non CKD patients. Higher incidence of non access site complications was also observed in CKD patients.

scholarly journals The effects of benzopyrene and safrole on biphenyl 2-hydroxylase and other drug-metabolizing enzymes

1976 ◽  
Vol 154 (3) ◽  
pp. 773-780 ◽  
Author(s):  
F J. McPherson ◽  
J W. Bridges ◽  
D V. Parke
Keyword(s):  
Intraperitoneal Administration ◽  
Albino Rats ◽  
Hydroxylase Activity ◽  
Metabolizing Enzymes ◽  
Enzyme Systems ◽  
Drug Metabolizing Enzyme ◽  
In Vitro Investigation ◽  
Wistar Albino Rats ◽  
Metabolizing Enzyme

A study was made of the nature and specificity of the increase in biphenyl 2-hydroxylase activity after preincubation of liver microsomal preparations with various carcinogens in vitro. This enhancement of enzyme activity in vitro was investigated in mouse, hamster and rat, and although the rat appears to be atypical in the variation of the pattern of 2- and 4-hydroxylation with age, similar enhancements were detectable in each species examined. An increase in biphenyl 2-hydroxylase activity was apparent 2h after intraperitoneal administration of safrole or benzopyrene to mature Wistar albino rats and appeared to be similar in nature to that observed after preincubation of liver microsomal preparations with the same chemical in vitro. Investigation of other drug-metabolizing enzyme systems suggests that the enhancing effects of carcinogens in vitro are specific for biphenyl 2-hydroxylase. No correlation between the enhancement of biphenyl 2-hydroxylase and inhibtion of biphenyl 4-hydroxylase was apparent.

Pharmacogenetic pathway analysis of irinotecan

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3073-3073
Author(s):  
G. L. Rosner ◽  
J. C. Panetta ◽  
L. Xiao ◽  
F. Innocenti ◽  
M. J. Ratain
Keyword(s):  
Enterohepatic Circulation ◽  
Parent Compound ◽  
Patient Specific ◽  
Model Parameters ◽  
Data Sets ◽  
Concentration Data ◽  
Linear Combinations ◽  
Functional Polymorphisms ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme

3073 Background: Irinotecan (IRN), a chemotherapeutic agent for various solid tumors, is the parent compound for SN-38, the active metabolite. The pharmacokinetics (PK) of IRN are complex and associated with variability in clinical outcomes. We sought to learn about the pharmacogenetics (PGx) of IRN by relating the drug’s PK to polymorphisms (SNPs) in drug-metabolizing enzyme and transporter genes potentially relevant to IRN. Methods: We measured concentrations of IRN and 3 metabolites in 86 patients. We fit a novel 7-compartment (15 parameter) model (including enterohepatic circulation) to the concentration data for IRN and metabolites. We applied principal components (PCs) analysis to the patient-specific PK model parameters to reduce the number of outcome variables and to identify appropriate linear combinations of the parameters that relate to IRN’s metabolic pathways. We then analyzed associations between SNPs and PCs to learn about functional polymorphisms. Associations are significant if p < 0.05. Results: We found that 8 PCs accounted for 90% of the total variation in the 15 fitted parameters. PC #1 corresponded to SN-38 in plasma and was associated with SNPs in the CYP3A4, MRP2, and ABCG2 genes. PC #2, the IRN compartments’ PC, was associated with a SNP in OATP-C*1b. The APC PC was associated with a CYP3A5 SNP. The SN-38 glucuronidation PC was associated with UGT1A1 and UGT1A9 polymorphisms. Conclusions: PC analysis is a useful way to reduce the dimension of multiple PK parameters and to produce pathway-specific and interpretable measures relating to PK. The use of PCs in PGx analysis allows identification of potential functional polymorphisms, which can be further evaluated in other data sets. [Table: see text]

scholarly journals Searching for Potential Markers of Glomerulopathy in Urine by HS-SPME-GC×GC TOFMS

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1817
Author(s):  
Tomasz Ligor ◽  
Joanna Zawadzka ◽  
Grzegorz Strączyński ◽  
Rosa M. González Paredes ◽  
Anna Wenda-Piesik ◽  
...  
Keyword(s):  
Metabolic Profile ◽  
Solid Phase Microextraction ◽  
Solid Phase ◽  
Kidney Diseases ◽  
Glomerular Diseases ◽  
Chronic Kidney Diseases ◽  
Volatile Metabolites ◽  
Flight Mass Spectrometry ◽  
Volatile Organic ◽  
And Control

Volatile organic compounds (VOCs) exiting in urine are potential biomarkers of chronic kidney diseases. Headspace solid phase microextraction (HS-SPME) was applied for extraction VOCs over the urine samples. Volatile metabolites were separated and identified by means of two-dimensional gas chromatography and time of flight mass spectrometry (GC × GC TOF MS). Patients with glomerular diseases (n = 27) and healthy controls (n = 20) were recruited in the study. Different VOCs profiles were obtained from patients and control. Developed methodology offers the opportunity to examine the metabolic profile associated with glomerulopathy. Four compounds found in elevated amounts in the patients group, i.e., methyl hexadecanoate; 9-hexadecen-1-ol; 6,10-dimethyl-5,9-undecadien-2-one and 2-pentanone were proposed as markers of glomerular diseases.

The influence of genetic variations and drug interactions based on metabo-lism of antidepressants and anticonvulsants

2020 ◽  
Vol 21 ◽  
Author(s):  
Merve Demirbugen Oz ◽  
Fezile Ozdemir ◽  
Halit Sinan Suzen
Keyword(s):  
Personalized Medicine ◽  
Drug Interactions ◽  
Clinical Outcomes ◽  
Cytochromes P450 ◽  
Treatment Strategies ◽  
Genetic Variations ◽  
Metabolizing Enzymes ◽  
Drug Metabolizing Enzyme ◽  
Clinically Significant ◽  
Metabolizing Enzyme

Background:: Antidepressant (AD) and anticonvulsants (AC) medications are widely prescribed to treat neuro-psychiatric disorders and a broad range of other comorbidities. Interpatient variability in response to a given drug is a large challenge in psychiatry and neurology. Clinically similar patient’s often experience vastly different outcomes (higher or lower levels than the therapeutic range and/or adverse effects) from the same drug at similar doses. The variability in drug response is highly complex and can be attributed to the polymedication, genetic polymorphisms modulating drug-metabolizing enzyme activities (cytochromes P450, CYP), physiological and environmental factors. These identified sources of variability in drug responses makes biotransformation center of personalized treatment strategies. Objective:: The main objective of this review is deeply discuss the role of biotransformation in the occurrence of antidepres-sant and anticonvulsant induced inter individual variabilities with the focus of genetic variations and drug interactions. Methods:: We conducted an extensive search of the literature related to biotransformation of the antidepressant and anticon-vulsant agents available on relationships between genetic differences and interactions on available databases. Results:: In the present review, we provided an overview of documented clinically significant pharmacokinetic drug interac-tions, physiological and environmental differences. We further discuss the significance of genetic variations in drug metabo-lizing enzymes to underline the need for using information on both genotype and drug interactions towards implementing better clinical outcomes through personalized medicine in neurology and psychiatry. Conclusions:: The genetic variations in drug metabolizing enzymes underline the need for using information on both geno-type and drug interactions towards implementing better clinical outcomes through personalized medicine in neurology and psychiatry.

scholarly journals Elastin imaging enables noninvasive staging and treatment monitoring of kidney fibrosis

2019 ◽  
Vol 11 (486) ◽  
pp. eaat4865 ◽  
Author(s):  
Qinxue Sun ◽  
Maike Baues ◽  
Barbara M. Klinkhammer ◽  
Josef Ehling ◽  
Sonja Djudjaj ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Matrix Protein ◽  
Kidney Diseases ◽  
Therapeutic Interventions ◽  
Extracellular Matrix Protein ◽  
Imaging Method ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Common Endpoint ◽  
Routine Assessment

Fibrosis is the common endpoint and currently the best predictor of progression of chronic kidney diseases (CKDs). Despite several drawbacks, biopsies remain the only available means to specifically assess the extent of renal fibrosis. Here, we show that molecular imaging of the extracellular matrix protein elastin allows for noninvasive staging and longitudinal monitoring of renal fibrosis. Elastin was hardly expressed in healthy mouse, rat, and human kidneys, whereas it was highly up-regulated in cortical, medullar, and perivascular regions in progressive CKD. Compared to a clinically relevant control contrast agent, the elastin-specific magnetic resonance imaging agent ESMA specifically detected elastin expression in multiple mouse models of renal fibrosis and also in fibrotic human kidneys. Elastin imaging allowed for repetitive and reproducible assessment of renal fibrosis, and it enabled longitudinal monitoring of therapeutic interventions, accurately capturing anti-fibrotic therapy effects. Last, in a model of reversible renal injury, elastin imaging detected ensuing fibrosis not identifiable via routine assessment of kidney function. Elastin imaging thus has the potential to become a noninvasive, specific imaging method to assess renal fibrosis.

Relation Between Drug-Metabolizing Activity and Phospholipids in Hepatic Microsomes. I. Effects of Phenobarbital, Carbon Tetrachloride, and Actinomycin D

1972 ◽  
Vol 50 (6) ◽  
pp. 568-575 ◽  
Author(s):  
S. D. Cooper ◽  
G. Feuer
Keyword(s):  
Enzyme Activity ◽  
Carbon Tetrachloride ◽  
Actinomycin D ◽  
Microsomal Protein ◽  
Phospholipid Content ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Drug Metabolizing Enzyme ◽  
Hepatic Microsomes ◽  
Metabolizing Enzyme

The treatment of rats with phenobarbital caused a significant increase in hepatic microsomal content of protein and phospholipid in parallel with the induction of drug-metabolizing enzymes. In contrast, carbon tetrachloride significantly reduced microsomal protein, phospholipid, and drug-metabolizing enzyme activity. The opposing actions of these compounds were manifested mainly in the phosphatidylethanolamine, phosphatidylcholine, and lysophosphatidylcholine fractions.Actinomycin D was found to block all the effects of phenobarbital except for the increase in lysophosphatidylcholine which was inhibited only by about 50%. Actinomycin D alone significantly decreased drug-metabolizing enzyme activity and microsomal phospholipid content.

scholarly journals PHENOBARBITAL-INDUCED SYNTHESIS OF THE MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEM AND ITS RELATIONSHIP TO THE PROLIFERATION OF ENDOPLASMIC MEMBRANES

1965 ◽  
Vol 25 (3) ◽  
pp. 627-639 ◽  
Author(s):  
Sten Orrenius ◽  
Jan L. E. Ericsson ◽  
Lars Ernster
Keyword(s):  
Liver Microsomes ◽  
Enzyme Synthesis ◽  
Metabolizing Enzymes ◽  
Ultrastructural Studies ◽  
Oxidative Demethylation ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Phenobarbital Administration ◽  
Parenchymal Cells

Liver microsomes, isolated from rats which had been treated with phenobarbital in vivo, were found to exhibit increased activities of oxidative demethylation and TPNH-cytochrome c reductase and an increased amount of CO-binding pigment. Simultaneous administration of actinomycin D or puromycin abolished the phenobarbital-induced enzyme synthesis. Increased rate of Pi32 incorporation into microsomal phospholipid was the first sign of phenobarbital stimulation and appeared 3 hours after a single injection of this drug. Microsomes were divided into smooth-surfaced and rough-surfaced vesicle fractions. The fraction consisting of smooth-surfaced vesicles exhibited the greatest increase in protein content and oxidative demethylation activity after phenobarbital administration in vivo. Ultrastructural studies revealed that drug treatment also gave rise to proliferation of the endoplasmic reticulum in the hepatic parenchymal cells, first noticed after two phenobarbital injections. The phenobarbital-induced synthesis of the metabolizing enzymes is discussed with special reference to the relationship to the stimulated synthesis of the endoplasmic membranes.

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