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1
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Tuchman S, Mulugeta Y, Schwartz GJ, Filler G, de Wildt SN, Mistry K, Sahre M, Pfuma Fletcher E, Azer K, Alzarka BJ, Rahman Archie S, Choi SY, Khurana M, Yao LP, Chand DH. The ADEPT 8 Workshop: Drug Dosing in Pediatric Patients with Renal Impairment. J Pediatr 2025:114624. [PMID: 40280472 DOI: 10.1016/j.jpeds.2025.114624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 03/25/2025] [Accepted: 04/19/2025] [Indexed: 04/29/2025]
Affiliation(s)
- Shamir Tuchman
- Division of Pediatrics and Maternal Health Center for Drug Evaluation and Research U.S..
| | - Yeruk Mulugeta
- Division of Pediatrics and Maternal Health, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
| | - George J Schwartz
- Department of Pediatrics, Golisano Children's Hospital, The University of Rochester School of Medicine and Dentistry
| | - Guido Filler
- Department of Paediatrics, Western University, Schulich School of Medicine and Dentistry
| | | | - Kirtida Mistry
- Division of Cardiology and Nephrology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
| | - Martina Sahre
- Center for Drug Evaluation and Research, U.S. Food and Drug Administration
| | | | - Karim Azer
- Novartis Pharmaceuticals, Northeastern University, Dept of Chemistry, College of Science, Karim Azer is an employee at Novartis Pharmaceuticals
| | - Bakri J Alzarka
- Division of Nephrology, University of Maryland Medical System
| | - Sabrina Rahman Archie
- Division of Pediatrics and Maternal Health; Center for Drug Evaluation and Research; U.S. Food and Drug Administration
| | - Su-Young Choi
- Division of Infectious Disease Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
| | - Mona Khurana
- Division of Pediatrics and Maternal Health, Center for Drug Evaluation and Research; U.S. Food and Drug Administration
| | - Lynne P Yao
- Division of Pediatrics and Maternal Health, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
| | - Deepa H Chand
- Novartis Pharmaceuticals, University of Illinois College of Medicine
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2
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Bosma M, Cobbaert C. Digital metrology in laboratory medicine: a call for bringing order to chaos to facilitate precision diagnostics. Clin Chem Lab Med 2025:cclm-2025-0152. [PMID: 40228294 DOI: 10.1515/cclm-2025-0152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 04/02/2025] [Indexed: 04/16/2025]
Abstract
Laboratory medicine is faced with rapid developments in data exchange, secondary use of data and artificial intelligence. Safe exchange of laboratory data requires a suitable terminology standard. NPU, LOINC and SNOMED CT are increasingly used for this purpose, but none of these terminology standards can currently accommodate safe exchange across the full spectrum of conventional laboratory data. Furthermore, rapid technological advances in, amongst others, the 'omics' area will enforce a shift towards precision diagnostics. These emerging technologies demand an appropriate and future-proof terminology standard. Given the current and future challenges in laboratory terminologies, we here present a concept for digital metrology in laboratory medicine. Terminology standards used in laboratory medicine should be adjusted to the current state of science to allow safe data exchange and interpretation. Essential test information entails the full spectrum of pre-pre-analysis to post-post-analysis. Major improvements needed include sufficient coding detail for the molecular form of the measurand and information on metrological traceability. Furthermore, especially given the advances in precision diagnostics, it will become essential to indicate interrelationships between measurands. Herefore, integration with established taxonomies would allow improved identification of interrelationships between measurands and linkage with scientific information for multidisciplinary data science. Hence, laboratory data can further gain in specificity and value. The time has come to lay the basis for safe data exchange in the era of precision diagnostics, with a global focus. A consensus for digital metrology in laboratory medicine will be essential to move forward with health data exchange within Europe and beyond.
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Affiliation(s)
- Madeleen Bosma
- Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Christa Cobbaert
- Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands
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3
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Kounatidis D, Vallianou NG, Stratigou T, Voukali M, Karampela I, Dalamaga M. The Kidney in Obesity: Current Evidence, Perspectives and Controversies. Curr Obes Rep 2024; 13:680-702. [PMID: 39141201 DOI: 10.1007/s13679-024-00583-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/01/2024] [Indexed: 08/15/2024]
Abstract
PURPOSE OF REVIEW As obesity and chronic kidney disease (CKD) remain a public health issue, we aim to elaborate on their complex relationship regarding pathogenetic mechanisms and therapeutic potential as well. The purpose of this review is to enhance our understanding of the interplay between obesity and CKD in order to timely diagnose and treat obesity-related CKD. RECENT FINDINGS Obesity and CKD pose significant intertwined challenges to global health, affecting a substantial portion of the population worldwide. Obesity is recognized as an independent risk factor, intricately contributing to CKD pathogenesis through mechanisms such as lipotoxicity, chronic inflammation, and insulin resistance. Recent evidence highlights additional factors including hemodynamic changes and intestinal dysbiosis that exacerbate kidney dysfunction in obese individuals, leading to histologic alterations known as obesity-related glomerulopathy (ORG). This narrative review synthesizes current knowledge on the prevalence, pathophysiology, clinical manifestations, and diagnostic strategies of obesity-related kidney disease. Furthermore, it explores mechanistic insights to delineate current therapeutic approaches, future directions for managing this condition and controversies. By elucidating the multifaceted interactions between obesity and kidney health, this review aims to inform clinical practice and stimulate further research to address this global health epidemic effectively.
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Affiliation(s)
- Dimitris Kounatidis
- Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527, Athens, Greece
| | - Natalia G Vallianou
- First Department of Internal Medicine, Sismanogleio General Hospital, 15126, Athens, Greece.
| | - Theodora Stratigou
- Department of Endocrinology, Diabetes and Metabolism, European and National Expertise Center for Rare Endocrine Disorders, Evangelismos General Hospital, 10676, Athens, Greece
| | - Maria Voukali
- First Department of Internal Medicine, Sismanogleio General Hospital, 15126, Athens, Greece
| | - Irene Karampela
- Second Department of Critical Care, Medical School, Attikon General University Hospital, National and Kapodistrian University of Athens, 12462, Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece
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4
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Andersen ES, Röttger R, Brasen CL, Brandslund I. Analytical Performance Specifications for Input Variables: Investigation of the Model of End-Stage Liver Disease. Clin Chem 2024; 70:653-659. [PMID: 38416710 DOI: 10.1093/clinchem/hvae019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 12/26/2023] [Indexed: 03/01/2024]
Abstract
BACKGROUND Artificial intelligence models constitute specific uses of analysis results and, therefore, necessitate evaluation of analytical performance specifications (APS) for this context specifically. The Model of End-stage Liver Disease (MELD) is a clinical prediction model based on measurements of bilirubin, creatinine, and the international normalized ratio (INR). This study evaluates the propagation of error through the MELD, to inform choice of APS for the MELD input variables. METHODS A total of 6093 consecutive MELD scores and underlying analysis results were retrospectively collected. "Desirable analytical variation" based on biological variation as well as current local analytical variation was simulated onto the data set as well as onto a constructed data set, representing a worst-case scenario. Resulting changes in MELD score and risk classification were calculated. RESULTS Biological variation-based APS in the worst-case scenario resulted in 3.26% of scores changing by ≥1 MELD point. In the patient-derived data set, the same variation resulted in 0.92% of samples changing by ≥1 MELD point, and 5.5% of samples changing risk category. Local analytical performance resulted in lower reclassification rates. CONCLUSIONS Error propagation through MELD is complex and includes population-dependent mechanisms. Biological variation-derived APS were acceptable for all uses of the MELD score. Other combinations of APS can yield equally acceptable results. This analysis exemplifies how error propagation through artificial intelligence models can become highly complex. This complexity will necessitate that both model suppliers and clinical laboratories address analytical performance specifications for the specific use case, as these may differ from performance specifications for traditional use of the analyses.
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Affiliation(s)
- Eline S Andersen
- Department of Biochemistry and Immunology, Lillebaelt Hospital, Vejle, Denmark
- Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | - Richard Röttger
- Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark
| | - Claus L Brasen
- Department of Biochemistry and Immunology, Lillebaelt Hospital, Vejle, Denmark
- Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | - Ivan Brandslund
- Department of Biochemistry and Immunology, Lillebaelt Hospital, Vejle, Denmark
- Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
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5
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Mondesert E, Bargnoux AS, Portet F, Laoudj-Chenivesse D, Arbogast S, Badiou S, Brun JF, Kuster N, Raynaud de Mauverger E, Cristol JP. Cystatin C for kidney function assessment in patients with facioscapulohumeral muscular dystrophy. Clin Chim Acta 2023; 544:117328. [PMID: 37031784 DOI: 10.1016/j.cca.2023.117328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/28/2023] [Accepted: 03/29/2023] [Indexed: 04/11/2023]
Abstract
BACKGROUND AND AIMS Muscle mass (MM) impairment observed in facioscapulohumeral muscular dystrophy (FSHD) may bias estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcreat). eGFR based on cystatin C (eGFRcys), produced by all nucleated cells, should be an interesting alternative. Main objectives were to compare eGFRcreat and eGRFcys for chronic kidney disease (CKD) staging and for annual eGFR evolution. Secondary objective was to analyse creatinine, cystatin C with measured MM. MATERIAL AND METHODS During 4 years, 159 FSHD patients having one or more creatinine and cystatin C measurements (total samples: n=379), with MM determination by bio-impedancemetry during their follow-up were included. eGFR were determined with CKD-Epi and EKFC equations. RESULTS On first examination samples, mean eGFRcys was significantly lower than mean eGFRcreat of 25.5 and 17.9 ml/min/1.73m2 using CKD-Epi and EKFC equations, respectively. 53.5% (CKD-Epi) and 59.1% (EKFC) of agreement were obtained when using eGFRcys instead of eGFRcreat with reclassifications occurring mainly towards more severe stages. Age was correlated with cystatin C but not with creatinine, MM was correlated with creatinine but not with cystatin C. eGFR decreases >1 ml/min/1.73m2 were more important when using eGFRcys instead of eGFRcreat (CKD-Epi: 37.5 vs 15.4%, p<0.001; EKFC: 34.6 vs 20.2%, p<0.01). CONCLUSION Cystatin C which is independent of MM appears as a promising candidate biomarker for CKD diagnosis and follow-up in FSHD patient.
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Affiliation(s)
- Etienne Mondesert
- Department of Biochemistry, University Hospital of Montpellier, Montpellier, France
| | - Anne-Sophie Bargnoux
- Department of Biochemistry, University Hospital of Montpellier, Montpellier, France; PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France
| | - Florence Portet
- Department of Clinical Physiology, University Hospital of Montpellier, France
| | | | - Sandrine Arbogast
- PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France
| | - Stéphanie Badiou
- Department of Biochemistry, University Hospital of Montpellier, Montpellier, France; PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France
| | - Jean-Frédéric Brun
- PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France; Department of Clinical Physiology, University Hospital of Montpellier, France
| | - Nils Kuster
- Department of Biochemistry, University Hospital of Montpellier, Montpellier, France; PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France
| | - Eric Raynaud de Mauverger
- PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France; Department of Clinical Physiology, University Hospital of Montpellier, France
| | - Jean-Paul Cristol
- Department of Biochemistry, University Hospital of Montpellier, Montpellier, France; PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France.
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6
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Dhont E, Windels C, Snauwaert E, Van Der Heggen T, de Jaeger A, Dhondt L, Delanghe J, Croubels S, Walle JV, De Paepe P, De Cock PA. Reliability of glomerular filtration rate estimating formulas compared to iohexol plasma clearance in critically ill children. Eur J Pediatr 2022; 181:3851-3866. [PMID: 36053381 DOI: 10.1007/s00431-022-04570-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 07/14/2022] [Accepted: 07/18/2022] [Indexed: 11/30/2022]
Abstract
UNLABELLED Accurate renal function assessment is crucial to guide intensive care decision-making and drug dosing. Estimates of glomerular filtration rate (eGFR) are routinely used in critically ill children; however, these formulas were never evaluated against measured GFR (mGFR) in this population. We aimed to assess the reliability of common eGFR formulas compared to iohexol plasma clearance (CLiohexol) in a pediatric intensive care (PICU) population. Secondary outcomes were the prevalence of acute kidney injury (AKI) (by pRIFLE criteria) and augmented renal clearance (ARC) (defined as standard GFR for age + 2 standard deviations (SD)) within 48 h after admission based on mGFR and eGFR by the revised Schwartz formula and the difference between these two methods to diagnose AKI and ARC. In children, between 0 and 15 years of age, without chronic renal disease, GFR was measured by CLiohexol and estimated using 26 formulas based on creatinine (Scr), cystatine C (CysC), and betatrace protein (BTP), early after PICU admission. eGFR and mGFR results were compared for the entire study population and in subgroups according to age, using Bland-Altman analysis with calculation of bias, precision, and accuracy expressed as percentage of eGFR results within 30% (P30) and 10% (P10) of mGFR. CLiohexol was measured in 98 patients. Mean CLiohexol (± SD) was 115 ± 54 ml/min/1.73m2. Most eGFR formulas showed overestimation of mGFR with large bias and poor precision reflected by wide limits of agreement (LoA). Bias was larger with CysC- and BTP-based formulas compared to Scr-based formulas. In the entire study population, none of the eGFR formulas showed the minimal desired P30 > 75%. The widely used revised Schwartz formula overestimated mGFR with a high percentage bias of - 18 ± 51% (95% confidence interval (CI) - 29; - 9), poor precision with 95% LoA from - 120 to 84% and insufficient accuracy reflected by P30 of only 51% (95% CI 41; 61), and P10 of 21% (95% CI 13; 66) in the overall population. Although performance of Scr-based formulas was worst in children below 1 month of age, exclusion of neonates and younger children did not result in improved agreement and accuracy. Based on mGFR, prevalence of AKI and ARC within 48 h was 17% and 45% of patients, respectively. There was poor agreement between revised Schwartz formula and mGFR to diagnose AKI (kappa value of 0.342, p < 0.001; sensitivity of 30%, 95% CI 5; 20%) and ARC (kappa value of 0.342, p < 0.001; sensitivity of 70%, 95% CI 33; 58). CONCLUSION In this proof-of-concept study, eGFR formulas were found to be largely inaccurate in the PICU population. Clinicians should therefore use these formulas with caution to guide drug dosing and therapeutic interventions in critically ill children. More research in subgroup populations is warranted to conclude on generalizability of these study findings. CLINICALTRIALS gov NCT05179564, registered retrospectively on January 5, 2022. WHAT IS KNOWN • Both acute kidney injury and augmented renal clearance may be present in PICU patients and warrant adaptation of therapy, including drug dosing. • Biomarker-based eGFR formulas are widely used for GFR assessment in critically ill children, although endogenous filtration biomarkers have important limitations in PICU patients and eGFR formulas have never been validated against measured GFR in this population. WHAT IS NEW • eGFR formulas were found to be largely inaccurate in the PICU population when compared to measured GFR by iohexol clearance. Clinicians should therefore use these formulas with caution to guide drug dosing and therapeutic interventions in critically ill children. • Iohexol plasma clearance could be considered an alternative for accurate GFR assessment in PICU patients.
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Affiliation(s)
- Evelyn Dhont
- Department of Pediatric Intensive Care, Pediatric Intensive Care 1K12D, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium.
- Faculty of Medicine and Health Sciences, Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium.
| | - Charlotte Windels
- Department of General Practice and Primary Health Care, Ghent University, Ghent, Belgium
| | - Evelien Snauwaert
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
| | - Tatjana Van Der Heggen
- Faculty of Medicine and Health Sciences, Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium
| | - Annick de Jaeger
- Department of Pediatric Intensive Care, Pediatric Intensive Care 1K12D, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium
| | - Laura Dhondt
- Faculty of Veterinary Medicine, Department of Pathobiology, Pharmacology and Zoological Medicine, Ghent University, Ghent, Belgium
| | - Joris Delanghe
- Faculty of Medicine and Health Sciences, Department of Diagnostic Sciences, Ghent University, Ghent, Belgium
| | - Siska Croubels
- Faculty of Veterinary Medicine, Department of Pathobiology, Pharmacology and Zoological Medicine, Ghent University, Ghent, Belgium
| | - Johan Vande Walle
- Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
| | - Peter De Paepe
- Faculty of Medicine and Health Sciences, Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium
- Department of Pharmacy, Ghent University Hospital, Ghent, Belgium
| | - Pieter A De Cock
- Department of Pediatric Intensive Care, Pediatric Intensive Care 1K12D, Ghent University Hospital, C. Heymanslaan 10, 9000, Ghent, Belgium
- Faculty of Medicine and Health Sciences, Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium
- Department of Pharmacy, Ghent University Hospital, Ghent, Belgium
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7
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Krzyzanski W, Smits A, Van Den Anker J, Allegaert K. Population Model of Serum Creatinine as Time-Dependent Covariate in Neonates. AAPS JOURNAL 2021; 23:86. [PMID: 34142253 DOI: 10.1208/s12248-021-00612-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 05/19/2021] [Indexed: 11/30/2022]
Abstract
Serum creatinine (sCr) is a commonly measured biomarker to estimate glomerular filtration rate (GFR) and therefore widely used as a covariate in population pharmacokinetic models of renally excreted drugs. In neonates, sCr dynamically changes during the first few weeks after birth. Missing covariates are a common problem in pharmacokinetic modeling of neonates due to the limited availability of blood sampling in number and volume. The objective of this work is to develop a parsimonious population model describing time courses of sCr in neonates with the intent to be incorporated into pharmacokinetic models of various drugs where sCr values are sparse or missing. The data for model development consisted of sCr measurements in 1080 newborns with a gestational age of 24-42 weeks. The model is based on a pharmacokinetic model of sCr that involves GFR, backflow of creatinine from the renal tubules, and urinary flow. Gestational age is the only covariate explaining between-subject variability of sCr. The model adequately describes distinct features of the sCr time course such as a peak and decline to a plateau. For a neonate with a GA of 35 weeks, the typical value of sCr at birth was 0.584 mg/dL, the peak (0.794 mg/dL) occurred 2.3 days after birth, to reach a plateau of 0.255 mg/dL approximately after 24.7 days. Model simulations reveal that in neonates with a similar postnatal age, sCr decreases with increasing GA. In summary, our model is designed to be a part of full random effects pharmacokinetic models where sCr is a significant covariate.
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Affiliation(s)
- Wojciech Krzyzanski
- Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA.
| | - Anne Smits
- Department of Development and Regeneration, KU Leuven, Leuven, Belgium.,Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium
| | - John Van Den Anker
- Division of Clinical Pharmacology, Children's National Hospital, Washington, District of Columbia, USA.,Division of Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland
| | - Karel Allegaert
- Department of Development and Regeneration, KU Leuven, Leuven, Belgium.,Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000, Leuven, Belgium.,Department of Hospital Pharmacy, Erasmus MC University Medical Center, 3015, Rotterdam, The Netherlands
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8
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Dhont E, Van Der Heggen T, De Jaeger A, Vande Walle J, De Paepe P, De Cock PA. Augmented renal clearance in pediatric intensive care: are we undertreating our sickest patients? Pediatr Nephrol 2020; 35:25-39. [PMID: 30374606 DOI: 10.1007/s00467-018-4120-2] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 10/04/2018] [Accepted: 10/16/2018] [Indexed: 10/28/2022]
Abstract
Many critically ill patients display a supraphysiological renal function with enhanced renal perfusion and glomerular hyperfiltration. This phenomenon described as augmented renal clearance (ARC) may result in enhanced drug elimination through renal excretion mechanisms. Augmented renal clearance seems to be triggered by systemic inflammation and therapeutic interventions in intensive care. There is growing evidence that ARC is not restricted to the adult intensive care population, but is also prevalent in critically ill children. Augmented renal clearance is often overlooked due to the lack of reliable methods to assess renal function in critically ill children. Standard equations to calculate glomerular filtration rate (GFR) are developed for patients who have a steady-state creatinine production and a stable renal function. Those formulas are not reliable in critically ill patients with acutely changing GFR and tend to underestimate true GFR in patients with ARC. Tools for real-time, continuous, and non-invasive measurement of fluctuating GFR are most needed to identify changes in kidney function during critical illness and therapeutic interventions. Such devices are currently being validated and hold a strong potential to become the standard of practice. In the meantime, urinary creatinine clearance is considered the most reliable method to detect ARC in critically ill patients. Augmented renal clearance is clearly associated with subtherapeutic antimicrobial concentrations and subsequent therapeutic failure. This warrants the need for adjusted dosing regimens to optimize pharmacokinetic and pharmacodynamic target attainment. This review aims to summarize current knowledge on ARC in critically ill children, to give insight into its possible pathophysiological mechanism, to evaluate screening methods for ARC in the pediatric intensive care population, and to illustrate the effect of ARC on drug exposure, therapeutic efficacy, and clinical outcome.
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Affiliation(s)
- Evelyn Dhont
- Department of Pediatric Intensive Care, Ghent University Hospital, Ghent, Belgium. .,Pediatric Intensive Care 1K12D, Ghent University Hospital, Heymanslaan 10, 9000, Ghent, Belgium.
| | | | - Annick De Jaeger
- Department of Pediatric Intensive Care, Ghent University Hospital, Ghent, Belgium
| | - Johan Vande Walle
- Department of Pediatrics, Ghent University Hospital, Ghent, Belgium.,Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium
| | - Peter De Paepe
- Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium
| | - Pieter A De Cock
- Department of Pediatric Intensive Care, Ghent University Hospital, Ghent, Belgium.,Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.,Department of Pharmacy, Ghent University Hospital, Ghent, Belgium
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9
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Barreto EF, Rule AD, Murad MH, Kashani KB, Lieske JC, Erwin PJ, Steckelberg JM, Gajic O, Reid JM, Kane-Gill SL. Prediction of the Renal Elimination of Drugs With Cystatin C vs Creatinine: A Systematic Review. Mayo Clin Proc 2019; 94:500-514. [PMID: 30713050 DOI: 10.1016/j.mayocp.2018.08.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Revised: 07/05/2018] [Accepted: 08/07/2018] [Indexed: 01/08/2023]
Abstract
Serum cystatin C has been proposed as a kidney biomarker to inform drug dosing. We conducted a systematic review to synthesize available data for the association between serum cystatin C and drug pharmacokinetics, dosing, and clinical outcomes in adults (≥18 years). PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, and Scopus were systematically searched from 1946 to September 2017 to identify candidate studies. Studies of cystatin C as a predictor for acute kidney injury or for management of contrast-associated acute kidney injury were excluded. Also, studies were excluded if drug concentrations were unavailable and if a reference standard for drug dosing (eg, serum creatinine) was not concurrently reported. The outcomes of interest included drug clearance (L/h), concentrations (mg/L), target level achievement (%), therapeutic failure (%), and drug toxicity (%). We included 28 articles that evaluated 16 different medications in 3455 participants. Vancomycin was the most well-studied drug. Overall, cystatin C-based estimated glomerular filtration rate (eGFRCystatin C) was more predictive of drug levels and drug clearance than eGFRCreatinine. In only one study were target attainment and outcomes compared between 2 drug-dosing regimens, one based on eGFRCreatinine-Cystatin C and one dosed with the Cockcroft-Gault creatinine clearance equation. Compared with eGFRCreatinine, use of eGFRCystatin C to predict elimination of medications via the kidney was as accurate, if not superior, in most studies, but infrequently were data on target attainment or clinical outcomes reported. Drug-specific dosing protocols that use cystatin C to estimate kidney function should be tested for clinical application.
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Affiliation(s)
- Erin F Barreto
- Department of Pharmacy, Mayo Clinic, Rochester, MN; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
| | - Andrew D Rule
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Division of Epidemiology, Mayo Clinic, Rochester, MN
| | - M Hassan Murad
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Kianoush B Kashani
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
| | - John C Lieske
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | | | | | - Ognjen Gajic
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
| | - Joel M Reid
- Division of Medical Oncology, Mayo Clinic, Rochester, MN; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN
| | - Sandra L Kane-Gill
- Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA
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10
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Krintus M, Fernandez JA, Chesters C, Colla R, Ford C, Frattolillo D, Köller U, Mairesse J, Jimenez DM, Motol J, Padmore K, Sharrod-Cole H, Sypniewska G. Analytical Performance of 10 High-Volume Clinical Chemistry Assays on the Alinity c System. Lab Med 2019; 50:e1-e8. [PMID: 30247580 DOI: 10.1093/labmed/lmy053] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Background Early access for routine testing with the Alinity c clinical chemistry system (Abbot Laboratories) presented the opportunity to characterize the analytical performance of multiple analytes across clinical laboratories in Europe. Methods A total of 8 laboratories from 7 European countries evaluated 10 high-volume chemistry assays on the Alinity c system for imprecision, linearity, and accuracy by method comparison to the routine ARCHITECT (Abbott Laboratories) method. Results Within-run precision was less than 4% coefficient of variation (CV), with total imprecision less than 5.6% CV for 5- and 20-day evaluations. Linearity met expectations, and method comparison showed strong correlation between the Alinity and ARCHITECT methods, with overall linear correlation coefficient between 0.980 to 1.000 and slopes of the regression line between 0.963 and 1.034. Mean percentage difference between the results of assays run on the ARCHITECT and the Alinity ranged between -1.7% and 2.15%. Conclusions Our results demonstrated acceptable key analytical performance across all assays tested at each participating laboratory.
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Affiliation(s)
- Magdalena Krintus
- Department of Laboratory Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland
| | - Jon Ardanza Fernandez
- Department of Biochemistry, Core Laboratory, Hospital Universitario de Álava, Vitoria, Spain
| | | | - Rossana Colla
- Azienda USL di Reggio Emilia, Ospedale di Guastalla U.O. Laboratorio Analisi, Guastalla, Italy
| | - Clare Ford
- Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom
| | - Daniele Frattolillo
- Azienda USL di Reggio Emilia, Ospedale di Guastalla U.O. Laboratorio Analisi, Guastalla, Italy
| | - Ursula Köller
- Institute for Laboratory Diagnostics, Vienna Hospital Association, Hospital Hietzing, Vienna, Austria
| | | | - Daniel Martinez Jimenez
- Department of Biochemistry, Core Laboratory, Hospital Universitario de Álava, Vitoria, Spain
| | | | | | | | - Grazyna Sypniewska
- Department of Laboratory Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland
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Delanghe JR, De Buyzere ML. Twenty years of European IVD regulations and its aimed traceability - where are we? Clin Chim Acta 2018; 483:263-264. [DOI: 10.1016/j.cca.2018.05.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 05/08/2018] [Indexed: 10/16/2022]
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Jansen RT, Cobbaert CM, Weykamp C, Thelen M. The quest for equivalence of test results: the pilgrimage of the Dutch Calibration 2.000 program for metrological traceability. ACTA ACUST UNITED AC 2018; 56:1673-1684. [DOI: 10.1515/cclm-2017-0796] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 11/17/2017] [Indexed: 01/02/2023]
Abstract
Abstract
Calibration 2.000 was initiated 20 years ago for standardization and harmonization of medical tests. The program also intended to evaluate adequate implementation of the In Vitro Diagnostics (IVD) 98/79/EC directive, in order to ensure that medical tests are fit-for-clinical purpose. The Calibration 2.000 initiative led to ongoing verification of test standardization and harmonization in the Netherlands using commutable external quality assessment (EQA)-tools and a type 1 EQA-design, where feasible. National support was guaranteed by involving all laboratory professionals as well as laboratory technicians responsible for EQA and quality officers. A category 1 EQA-system for general chemistry analytes, harmonizers for specific analytes like hGH and IGF-1, and commutable materials for other EQA-sections have been developed and structurally introduced in the EQA-schemes. The type 1 EQA-design facilitates the dialogue between individual specialists in laboratory medicine and the IVD-industry to reduce lot-to-lot variation and to improve standardization. In such a way, Calibration 2.000 sheds light on the metrological traceability challenges that we are facing and helps the laboratory community to get the issues on the table and resolved. The need for commutable trueness verifiers and/or harmonizers for other medical tests is now seen as paramount. Much knowledge is present in the Netherlands and for general chemistry, humoral immunology and protein chemistry, a few endocrinology tests, and various therapeutic drug monitoring (TDM) tests, commutable materials are available. Also the multi sample evaluation scoring system (MUSE) and the category 1 EQA-design offer many possibilities for permanent education of laboratory professionals to further improve the between and within laboratory variation and the test equivalence.
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Affiliation(s)
- Rob T.P. Jansen
- SKML , Mercator 1, Toernooiveld 214 , 6525EC Nijmegen , The Netherlands
| | | | - Cas Weykamp
- Queen Beatrix Hospital , MCA Laboratory , Winterswijk , The Netherlands
| | - Marc Thelen
- Amphia Hospital, Clinical Chemistry and Haematology , Breda , The Netherlands
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Nusshag C, Weigand MA, Zeier M, Morath C, Brenner T. Issues of Acute Kidney Injury Staging and Management in Sepsis and Critical Illness: A Narrative Review. Int J Mol Sci 2017; 18:E1387. [PMID: 28657585 PMCID: PMC5535880 DOI: 10.3390/ijms18071387] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 06/24/2017] [Accepted: 06/24/2017] [Indexed: 12/19/2022] Open
Abstract
Acute kidney injury (AKI) has a high incidence on intensive care units around the world and is a major complication in critically ill patients suffering from sepsis or septic shock. The short- and long-term complications are thereby devastating and impair the quality of life. Especially in terms of AKI staging, the determination of kidney function and the timing of dialytic AKI management outside of life-threatening indications are ongoing matters of debate. Despite several studies, a major problem remains in distinguishing between beneficial and unnecessary "early" or even harmful renal replacement therapy (RRT). The latter might prolong disease course and renal recovery. AKI scores, however, provide an insufficient outcome-predicting ability and the related estimation of kidney function via serum creatinine or blood urea nitrogen (BUN)/urea is not reliable in AKI and critical illness. Kidney independent alterations of creatinine- and BUN/urea-levels further complicate the situation. This review critically assesses the current AKI staging, issues and pitfalls of the determination of kidney function and RRT timing, as well as the potential harm reflected by unnecessary RRT. A better understanding is mandatory to improve future study designs and avoid unnecessary RRT for higher patient safety and lower health care costs.
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Affiliation(s)
- Christian Nusshag
- Department of Nephrology, Heidelberg University Hospital, 162, Im Neuenheimer Feld, D-69120 Heidelberg, Germany.
| | - Markus A Weigand
- Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, D-69120 Heidelberg, Germany.
| | - Martin Zeier
- Department of Nephrology, Heidelberg University Hospital, 162, Im Neuenheimer Feld, D-69120 Heidelberg, Germany.
| | - Christian Morath
- Department of Nephrology, Heidelberg University Hospital, 162, Im Neuenheimer Feld, D-69120 Heidelberg, Germany.
| | - Thorsten Brenner
- Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, D-69120 Heidelberg, Germany.
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Lee ES, Collier CP, White CA. Creatinine Assay Attainment of Analytical Performance Goals Following Implementation of IDMS Standardization: Further Improvements Required. Can J Kidney Health Dis 2017; 4:2054358117693353. [PMID: 28321322 PMCID: PMC5347424 DOI: 10.1177/2054358117693353] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 12/09/2016] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND The international initiative to standardize creatinine (Cr) assays by tracing reference materials to Isotope Dilution Mass Spectrometry (IDMS) assigned values was implemented to reduce interlaboratory variability and improve assay accuracy. OBJECTIVE The aims of this study were to examine whether IDMS standardization has improved Cr assay accuracy (bias), interlaboratory variability (precision), total error (TE), and attainment of recommended analytical performance goals. METHODS External Quality Assessment (EQA) data (n = 66 challenge vials) from Ontario, Canada, were analyzed. The bias, precision, TE, and the number of EQA challenge vials meeting performance goals were determined by assay manufacturer before (n = 32) and after (n = 34) IDMS implementation. RESULTS The challenge vials with the worst bias and precision were spiked with known common interfering substances (glucose and bilirubin). IDMS standardization improved assay bias (10.4%-1.6%, P < .001), but precision remained unchanged (5.0%-4.7%, P = .5) with performance goals not consistently being met. Precision and TE goals based on biologic variation were attained by only 29% to 69% and 32% to 62% of challenge vials. CONCLUSIONS While IDMS standardization has improved Cr assay accuracy and thus reduced TE, significant interlaboratory variability remains. Contemporary Cr assays do not currently meet the standards required to allow for accurate and consistent estimated glomerular filtration rate assessment and chronic kidney disease diagnosis across laboratories. Further improvements in Cr assay performance are needed.
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Affiliation(s)
- Elizabeth Sunmin Lee
- Division of Nephrology, Department of Medicine, Queen’s University, Kingston, Ontario, Canada
| | - Christine P. Collier
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
| | - Christine A. White
- Division of Nephrology, Department of Medicine, Queen’s University, Kingston, Ontario, Canada
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Küme T, Sağlam B, Ergon C, Sisman AR. Evaluation and comparison of Abbott Jaffe and enzymatic creatinine methods: Could the old method meet the new requirements? J Clin Lab Anal 2017; 32. [PMID: 28205269 DOI: 10.1002/jcla.22168] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 01/14/2017] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND The aim of this study is to evaluate and compare the analytical performance characteristics of the two creatinine methods based on the Jaffe and enzymatic methods. METHODS Two original creatinine methods, Jaffe and enzymatic, were evaluated on Architect c16000 automated analyzer via limit of detection (LOD) and limit of quantitation (LOQ), linearity, intra-assay and inter-assay precision, and comparability in serum and urine samples. The method comparison and bias estimation using patient samples according to CLSI guideline were performed on 230 serum and 141 urine samples by analyzing on the same auto-analyzer. RESULTS The LODs were determined as 0.1 mg/dL for both serum methods and as 0.25 and 0.07 mg/dL for the Jaffe and the enzymatic urine method respectively. The LOQs were similar with 0.05 mg/dL value for both serum methods, and enzymatic urine method had a lower LOQ than Jaffe urine method, values at 0.5 and 2 mg/dL respectively. Both methods were linear up to 65 mg/dL for serum and 260 mg/dL for urine. The intra-assay and inter-assay precision data were under desirable levels in both methods. The higher correlations were determined between two methods in serum and urine (r=.9994, r=.9998 respectively). On the other hand, Jaffe method gave the higher creatinine results than enzymatic method, especially at the low concentrations in both serum and urine. CONCLUSIONS Both Jaffe and enzymatic methods were found to meet the analytical performance requirements in routine use. However, enzymatic method was found to have better performance in low creatinine levels.
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Affiliation(s)
- Tuncay Küme
- Medical Biochemistry Department, Dokuz Eylül University Medical Faculty, Izmir, Turkey.,Central Laboratory, Dokuz Eylül University Hospital, Izmir, Turkey
| | - Barıs Sağlam
- Biochemistry Laboratory, Biga State Hospital, Çanakkale, Turkey
| | - Cem Ergon
- Central Laboratory, Dokuz Eylül University Hospital, Izmir, Turkey.,Medical Microbiology Department, Dokuz Eylül University Medical Faculty, Izmir, Turkey
| | - Ali Rıza Sisman
- Medical Biochemistry Department, Dokuz Eylül University Medical Faculty, Izmir, Turkey.,Central Laboratory, Dokuz Eylül University Hospital, Izmir, Turkey
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Lee E, Collier CP, White CA. Interlaboratory Variability in Plasma Creatinine Measurement and the Relation with Estimated Glomerular Filtration Rate and Chronic Kidney Disease Diagnosis. Clin J Am Soc Nephrol 2017; 12:29-37. [PMID: 27827312 PMCID: PMC5220660 DOI: 10.2215/cjn.05400516] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Accepted: 10/04/2016] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES The tracing of creatinine (Cr) reference materials to isotope dilution mass spectrometry-assigned values was implemented worldwide to reduce interlaboratory variability and improve assay accuracy. The aims of this study were to examine the current extent of interlaboratory variability and its effect on eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Leftover plasma from 2-3 consecutive days was obtained from 53 intensive care unit patients with a range of kidney functions. Individual patient samples were pooled and split and sent to 12 different laboratories for Cr measurement. For each patient, the mean Cr and Chronic Kidney Disease Epidemiology Collaboration eGFR (eGFR-EPI), assuming a 65-year-old nonblack woman, were determined. Interlaboratory variability was assessed by the range and SD of Cr and eGFR-EPI. This was repeated after stratifying by assay type and by the median Cr of 1.36 mg/dl. For patients whose eGFR-EPI range included 60 ml/min per 1.73 m2, the percentage of laboratories with eGFR-EPI<60 ml/min per 1.73 m2 was determined. RESULTS The mean±SD of the Cr and eGFR-EPI ranges were 0.20±0.09 mg/dl and 14±9 ml/min per 1.73 m2 for Cr<1.36 mg/dl. Jaffe Cr results were an average 0.1 mg/dl (Cr≥1.36 mg/dl) and 0.05 mg/dl (Cr<1.36 mg/dl) higher than enzymatic results (P<0.001 for both). Ten patients had an eGFR-EPI range that included 60 ml/min per 1.73 m2. Their median eGFR-EPI range was 15 ml/min per 1.73 m2. There was significant discordance in the diagnosis of CKD (eGFR-EPI<60 ml/min per 1.73 m2), with laboratories using Jaffe Cr methods making the diagnosis more frequently than those using enzymatic Cr methods (60% versus 39%). CONCLUSIONS Significant interlaboratory variability in Cr measurement still exists. Jaffe assays yield higher Cr values than enzymatic assays, leading to lower eGFR-EPIs and more frequent CKD diagnoses. Further improvements in assay performance are required to standardize patient CKD diagnosis and to facilitate longitudinal Cr monitoring across laboratories.
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Affiliation(s)
| | - Christine P. Collier
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Nicoletto BB, Krolikowski TC, Crispim D, Canani LH. Serum and Urinary Progranulin in Diabetic Kidney Disease. PLoS One 2016; 11:e0165177. [PMID: 27776152 PMCID: PMC5077076 DOI: 10.1371/journal.pone.0165177] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 10/08/2016] [Indexed: 01/10/2023] Open
Abstract
Progranulin has been recognized as an adipokine related to obesity, insulin resistance and type 2 diabetes mellitus (T2DM). There are scarce data regarding progranulin and kidney disease, but there are some data linking diabetic kidney disease (DKD) and increased progranulin levels. We aimed to better describe the relationship between serum and urinary progranulin levels and DKD in T2DM. This is a case-control study including four groups of subjects: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2; 2) Albuminuric DKD cases: T2DM patients with urinary albumin excretion (UAE) ≥30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; 3) Diabetic controls: T2DM patients with UAE <30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; and 4) Non-diabetic controls: individuals without T2DM. Progranulin was determined by enzyme-linked immunosorbent assay. One hundred and fourteen patients were included (23 advanced DKD cases, 25 albuminuric DKD cases, 40 diabetic controls and 26 non-diabetic controls). Serum progranulin was increased in advanced DKD compared to other groups [70.84 (59.04–83.16) vs. albuminuric cases 57.16 (42.24–67.38), diabetic controls 57.28 (42.08–70.47) and non-diabetic controls 44.54 (41.44–53.32) ng/mL; p<0.001]. Urinary progranulin was decreased in advanced DKD cases compared to albuminuric cases [10.62 (6.30–16.08) vs. 20.94 (12.35–30.22); diabetic controls 14.06 (9.88–20.82) and non-diabetic controls 13.51 (7.94–24.36) ng/mL; p = 0.017]. There was a positive correlation between serum progranulin and body mass index (r = 0.27; p = 0.004), waist circumference (r = 0.25; p = 0.007); body fat percentage (r = 0.20; p = 0.042), high-sensitive C reactive protein (r = 0.35; p<0.001) and interleukin-6 (r = 0.37; p<0.001) and a negative correlation with eGFR (r = -0.22; p = 0.023). Urinary progranulin was positively associated with albuminuria (r = 0.25; p = 0.010). In conclusion, progranulin is affected by a decrease in eGFR, being at a higher concentration in serum and lower in urine of DKD patients with T2DM and eGFR <60 mL/min/1.73m2. It is also associated with markers of obesity and inflammation.
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Affiliation(s)
- Bruna Bellincanta Nicoletto
- Post Graduate Medical Sciences Program: Endocrinology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- * E-mail:
| | - Thaiana Cirino Krolikowski
- Nutrition Course, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Daisy Crispim
- Post Graduate Medical Sciences Program: Endocrinology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Luis Henrique Canani
- Post Graduate Medical Sciences Program: Endocrinology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
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18
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Evaluation of bilirubin interference and accuracy of six creatinine assays compared with isotope dilution–liquid chromatography mass spectrometry. Clin Biochem 2016; 49:274-81. [DOI: 10.1016/j.clinbiochem.2015.10.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 10/23/2015] [Accepted: 10/25/2015] [Indexed: 12/27/2022]
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Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children. Antimicrob Agents Chemother 2015; 59:7027-35. [PMID: 26349821 DOI: 10.1128/aac.01368-15] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 08/29/2015] [Indexed: 11/20/2022] Open
Abstract
There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].).
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Luna-Záizar H, Virgen-Montelongo M, Cortez-Álvarez CR, Ruiz-Quezada SL, Escutia-Gutiérrez R, García-Lemus CR, Mendizabal-Ruiz AP. In vitro interference by acetaminophen, aspirin, and metamizole in serum measurements of glucose, urea, and creatinine. Clin Biochem 2015; 48:538-41. [DOI: 10.1016/j.clinbiochem.2015.01.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Revised: 01/09/2015] [Accepted: 01/13/2015] [Indexed: 10/24/2022]
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Pipili C, Cholongitas E. Renal dysfunction in patients with cirrhosis: Where do we stand? World J Gastrointest Pharmacol Ther 2014; 5:156-168. [PMID: 25133044 PMCID: PMC4133441 DOI: 10.4292/wjgpt.v5.i3.156] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 02/08/2014] [Accepted: 05/08/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with cirrhosis and renal failure are high-risk patients who can hardly be grouped to form precise instructions for diagnosis and treatment. When it comes to evaluate renal function in patients with cirrhosis, determination of acute kidney injury (AKI), chronic kidney disease (CKD) or AKI on CKD should be made. First it should be excluded the prerenal causes of AKI. All cirrhotic patients should undergo renal ultrasound for measurement of renal resistive index in every stage of liver dysfunction and urine microscopy for differentiation of all causes of AKI. If there is history of dehydration on the ground of normal renal ultrasound and urine microscopy the diuretics should be withdrawn and plasma volume expansion should be tried with albumin. If the patient does not respond, the correct diagnosis is HRS. In case there is recent use of nephrotoxic agents or contrast media and examination shows shock, granular cast in urinary sediment and proteinuria above 0.5 g daily, acute tubular necrosis is the prominent diagnosis. Renal biopsy should be performed when glomerular filtration rate is between 30-60 mL/min and there are signs of parenchymal renal disease. The acute renal function is preferable to be assessed with modified AKIN. Patients with AKIN stage 1 and serum creatinine ≥ 1.5 mg/dL should be at close surveillance. Management options include hemodynamic monitoring and management of fluid balance and infections, potentially driving to HRS. Terlipressin is the treatment of choice in case of established HRS, administered until there are signs of improvement, but not more than two weeks. Midodrine is the alternative for therapy continuation or when terlipressin is unavailable. Norepinephrine has shown similar effect with terlipressin in patients being in Intensive Care Unit, but with much lower cost than that of terlipressin. If the patient meets the requirements for transplantation, dialysis and transjugular intrahepatic portosystemic shunt are the bridging therapies to keep the transplant candidate in the best clinical status. The present review clarifies the latest therapeutic modalities and the proposed recommendations and algorithms in order to be applied in clinical practice.
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Ghys L, Paepe D, Smets P, Lefebvre H, Delanghe J, Daminet S. Cystatin C: a new renal marker and its potential use in small animal medicine. J Vet Intern Med 2014; 28:1152-64. [PMID: 24814357 PMCID: PMC4857948 DOI: 10.1111/jvim.12366] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 02/27/2014] [Accepted: 03/18/2014] [Indexed: 01/01/2023] Open
Abstract
The occurrence of chronic kidney disease is underestimated in both human and veterinary medicine. Glomerular filtration rate (GFR) is considered the gold standard for evaluating kidney function. However, GFR assessment is time-consuming and labor-intensive and therefore not routinely used in practice. The commonly used indirect GFR markers, serum creatinine (sCr) and urea, are not sufficiently sensitive or specific to detect early renal dysfunction. Serum cystatin C (sCysC), a proteinase inhibitor, has most of the properties required for an endogenous GFR marker. In human medicine, numerous studies have evaluated its potential use as a GFR marker in several populations. In veterinary medicine, this marker is gaining interest. The measurement is easy, which makes it an interesting parameter for clinical use. This review summarizes current knowledge about cystatin C (CysC) in humans, dogs, and cats, including its history, assays, relationship with GFR, and biological and clinical variations in both human and veterinary medicine.
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Affiliation(s)
- L. Ghys
- Department of Medicine and Clinical Biology of Small AnimalsFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
| | - D. Paepe
- Department of Medicine and Clinical Biology of Small AnimalsFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
| | - P. Smets
- Department of Medicine and Clinical Biology of Small AnimalsFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
| | - H. Lefebvre
- Clinical Research UnitNational Veterinary School of ToulouseToulouse Cedex 3France
| | - J. Delanghe
- Department of Clinical Chemistry, Microbiology and ImmunologyFaculty of Health Medicine and Life SciencesGhent UniversityGhentBelgium
| | - S. Daminet
- Department of Medicine and Clinical Biology of Small AnimalsFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
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Montañés Bermúdez R, Gràcia Garcia S, Fraga Rodríguez G, Escribano Subias J, Diez de los Ríos Carrasco M, Alonso Melgar A, García Nieto V. Documento de consenso: recomendaciones sobre la utilización de ecuaciones para la estimación del filtrado glomerular en niños. An Pediatr (Barc) 2014; 80:326.e1-326.e13. [DOI: 10.1016/j.anpedi.2013.06.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Accepted: 06/19/2013] [Indexed: 01/07/2023] Open
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External quality assurance programs as a tool for verifying standardization of measurement procedures: Pilot collaboration in Europe. Clin Chim Acta 2014; 432:82-9. [DOI: 10.1016/j.cca.2013.11.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2013] [Revised: 10/22/2013] [Accepted: 11/08/2013] [Indexed: 11/16/2022]
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Jansen R, Jassam N, Thomas A, Perich C, Fernandez-Calle P, Faria AP, Correia H, Barth JH, Weykamp C, Cobbaert C, Thelen M, Ricós C. A category 1 EQA scheme for comparison of laboratory performance and method performance: An international pilot study in the framework of the Calibration 2000 project. Clin Chim Acta 2014; 432:90-8. [DOI: 10.1016/j.cca.2013.11.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2013] [Revised: 11/05/2013] [Accepted: 11/05/2013] [Indexed: 11/16/2022]
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Filler G, Yasin A, Medeiros M. Methods of assessing renal function. Pediatr Nephrol 2014; 29:183-92. [PMID: 23417278 DOI: 10.1007/s00467-013-2426-7] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2012] [Revised: 01/14/2013] [Accepted: 01/17/2013] [Indexed: 12/15/2022]
Abstract
Accurate assessment of renal function is critical for appropriate drug dosing of renally excreted compounds. Glomerular filtration rate (GFR) is considered the best marker of kidney function. Inulin clearance forms the gold standard for measuring GFR, both in adults and in children. The method is invasive, cumbersome, and smaller children require urinary catheterization for accurate timed urine collections. Nuclear medicine methods replaced inulin clearance in the 1970s after (51)Cr EDTA clearance was introduced. Inulin has no plasma protein binding, whereas all commonly used radioisotopes have a small amount of plasma protein binding that leads to lower values. Only iohexol does not have significant plasma protein binding. The underestimation due to plasma protein binding is partially offset by overestimation due to the use of non-compartmental pharmacokinetic modeling of the plasma disappearance of the radioisotope. The problem could be overcome with a urinary nuclear medicine clearance method, but these have not been validated in children. Endogenous markers of GFR include serum creatinine and low molecular weight proteins such as cystatin C and beta-trace protein. Of these, estimation of GFR using cystatin C appears to be the most promising, although its accuracy in pregnancy and in the neonatal period may be limited.
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Affiliation(s)
- Guido Filler
- Department of Pediatrics, Children's Hospital, London Health Science Centre, University of Western Ontario, 800 Commissioners Road East, London, Ontario, Canada, N6A 5W9,
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Devenport NA, Blenkhorn DJ, Weston DJ, Reynolds JC, Creaser CS. Direct determination of urinary creatinine by reactive-thermal desorption-extractive electrospray-ion mobility-tandem mass spectrometry. Anal Chem 2013; 86:357-61. [PMID: 24279641 PMCID: PMC3953925 DOI: 10.1021/ac403133t] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
A direct, ambient ionization method has been developed for the determination of creatinine in urine that combines derivatization and thermal desorption with extractive electrospray ionization and ion mobility-mass spectrometry. The volatility of creatinine was enhanced by a rapid on-probe aqueous acylation reaction, using a custom-made thermal desorption probe, allowing thermal desorption and ionization of the monoacylated derivative. The monoacyl creatinine [M + H](+) ion (m/z 156) was subjected to mass-to-charge selection and collision induced dissociation to remove the acyl group, generating the protonated creatinine [M + H](+) product ion at m/z 114 before an ion mobility separation was applied to reduce chemical noise. Stable isotope dilution using creatinine-d3 as internal standard was used for quantitative measurements. The direct on-probe derivatization allows high sample throughput with a typical cycle time of 1 min per sample. The method shows good linearity (R(2) = 0.986) and repeatability (%RSD 8-10%) in the range of 0.25-2.0 mg/mL. The creatinine concentrations in diluted urine samples from a healthy individual were determined to contain a mean concentration of 1.44 mg/mL creatinine with a precision (%RSD) of 9.9%. The reactive ambient ionization approach demonstrated here has potential for the determination of involatile analytes in urine and other biofluids.
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Affiliation(s)
- Neil A Devenport
- Centre for Analytical Science, Department of Chemistry, Loughborough University , Loughborough, Leicestershire LE11 3TU, United Kingdom
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Factors other than the glomerular filtration rate that determine the serum beta-2-microglobulin level. PLoS One 2013; 8:e72073. [PMID: 23991042 PMCID: PMC3750024 DOI: 10.1371/journal.pone.0072073] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Accepted: 07/09/2013] [Indexed: 11/22/2022] Open
Abstract
Background β2-microglobulin has been increasingly investigated as a diagnostic marker of kidney function and a prognostic marker of adverse outcomes. To date, non-renal determinants of β2-microglobulin levels have not been well described. Non-renal determinants are important for the interpretation and appraisal of the diagnostic and prognostic value of any endogenous kidney function marker. Methods This cross-sectional analysis was performed within the framework of the www.seniorlabor.ch study, which includes subjectively healthy individuals aged ≥60 years. Factors known or suspected to have a non-renal association with kidney function markers were investigated for a non-renal association with serum β2-microglobulin. As a marker of kidney function, the Berlin Initiative Study equation 2 for the estimation of the estimated glomerular filtration rate (eGFRBIS2) in the elderly was employed. Results A total of 1302 participants (714 females and 588 males) were enrolled in the study. The use of a multivariate regression model adjusting for age, gender and kidney function (eGFRBIS2) revealed age, male gender, and C-reactive protein level to be positively associated with β2-microglobulin levels. In addition, there was an inverse non-renal relationship between systolic blood pressure, total cholesterol and current smoking status. No association with markers of diabetes mellitus, body stature, nutritional risk, thyroid function or calcium and phosphate levels was observed. Conclusions Serum β2-microglobulin levels in elderly subjects are related to several non-renal factors. These non-renal factors are not congruent to those known from other markers (i.e. cystatin C and creatinine) and remind of classical cardiovascular risk factors.
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Zitta S, Schrabmair W, Reibnegger G, Meinitzer A, Wagner D, Estelberger W, Rosenkranz AR. Glomerular filtration rate (GFR) determination via individual kinetics of the inulin-like polyfructosan sinistrin versus creatinine-based population-derived regression formulae. BMC Nephrol 2013; 14:159. [PMID: 23876053 PMCID: PMC3726368 DOI: 10.1186/1471-2369-14-159] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Accepted: 07/18/2013] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND In renal patients estimation of GFR is routinely done by means of population-based formulae using serum creatinine levels. For GFR determination in the creatinine-blind regions or in cases of reno-hepatic syndrome as well as in critical cases of live kidney donors individualized measurements of GFR (mGFR) employing the kinetics of exogenous filtration markers such as the inulin-like polyfructosan sinistrin are necessary. The goal of this study is to compare mGFR values with the eGFR values gained by the Modification of Diet in Renal Disease (MDRD4) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formulae. METHODS In 170 subjects comprising persons with normal renal function or with various stages of kidney diseases (CKD 1-4) GFR was measured by application of intravenous bolus of sinistrin and assessment of temporal plasma concentration profiles by means of pharmacokinetic methods (mGFR). Comparisons of mGFR with MDRD4- and CKD-EPI-derived eGFR values were performed by means of linear regression and Bland-Altman analyses. RESULTS Reasonable agreement of mGFR and eGFR values was observed in patients with poor renal function [GFR below 60 (ml/min)/1.73 m²]. In cases of normal or mildly impaired renal function, GFR determination by MDRD4 or CKD-EPI tends to underestimate GFR. Notably, there is practically no difference between the two eGFR methods. CONCLUSIONS For routine purposes or for epidemiological studies in cases of poor renal function eGFR methods are generally reliable. But in creatinine-blind ranges [GFR above 60 (ml/min)/1.73 m²] eGFR values are unreliable and should be replaced by clinically and physiologically suitable methods for mGFR determination. CONSORT http://www.consort-statement.org/index.aspx?o=1190.
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Affiliation(s)
- Sabine Zitta
- Department of Internal Medicine, Clinical Division of Nephrology, Medical University Graz, Graz, Austria.
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Cheuiche AV, Soares AA, Camargo EG, Weinert LS, Camargo JL, Silveiro SP. Comparison between IDMS-traceable Jaffe and enzymatic creatinine assays for estimation of glomerular filtration rate by the CKD-EPI equation in healthy and diabetic subjects. Clin Biochem 2013; 46:1423-9. [PMID: 23747959 DOI: 10.1016/j.clinbiochem.2013.05.067] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Revised: 04/23/2013] [Accepted: 05/25/2013] [Indexed: 12/17/2022]
Abstract
OBJECTIVES The aim of this paper was to compare the agreement between creatinine measured by Jaffe and enzymatic methods and their putative influence on eGFR as calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy and diabetic individuals. DESIGN AND METHODS Cross-sectional study conducted in 123 adult southern Brazilians with GFR>60 mL/min/1.73 m² (53 patients with type 2 diabetes, 70 healthy volunteers). Mean age was 49±16 years (range of 19-86). Most were female (55%) and white (83%). Creatinine was measured by a traceable Jaffe method (Modular P, Roche Diagnostic) and by an enzymatic method (CREA plus, Roche/Hitachi 917). GFR was measured by the ⁵¹Cr-EDTA single-injection method. RESULTS Serum creatinine measured by the Jaffe and enzymatic methods was similar in healthy subjects (0.79±0.16 vs. 0.79±0.15 mg/dL, respectively, P=0.76), and diabetic patients (0.96±0.22 vs. 0.92±0.29 mg/dL, respectively, P=0.17). However, the correlation between the two methods was higher in the healthy group (r=0.90 vs. 0.76, P<0.001). The difference between Jaffe creatinine and enzymatic creatinine was <10% in 63% of cases in the healthy group and 40% of cases in the diabetes group (P=0.018). In the subset of patients with diabetes, eGFR based on enzymatic assay results showed better agreement with measured GFR than did eGFR based on Jaffe results. CONCLUSION Jaffe and enzymatic creatinine methods show adequate agreement in healthy subjects, but in the presence of diabetes, the enzymatic method performed slightly better.
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Affiliation(s)
- Amanda Veiga Cheuiche
- Graduate Program in Medical Science: Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil
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De Souza VC, Rabilloud M, Cochat P, Selistre L, Hadj-Aissa A, Kassai B, Ranchin B, Berg U, Herthelius M, Dubourg L. Schwartz formula: is one k-coefficient adequate for all children? PLoS One 2012; 7:e53439. [PMID: 23285295 PMCID: PMC3532344 DOI: 10.1371/journal.pone.0053439] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2012] [Accepted: 11/28/2012] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND/OBJECTIVE Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population. PATIENTS/METHODS We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort. RESULTS In Schwartz-Lyon formula, k was estimated at 32.5 in boys <13 years and all girls and at 36.5 in boys aged ≥13 years. The performance of this formula was higher than that of 2009-Schwartz formula in children <13 years. This was first supported by a statistically significant reduction of the overestimation of the measured glomerular filtration rate in both cohorts, by better 10% and 30% accuracies, and by a better concordance correlation coefficient. CONCLUSIONS The performance and simplicity of Schwartz formula are strong arguments for its routine use in children and adolescents. The specific coefficient for children aged <13 years further improves this performance.
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Affiliation(s)
- Vandrea Carla De Souza
- Centre de Référence des Maladies Rénales Rares, Service de Néphrologie et Rhumatologie Pédiatriques, Hospices Civils de Lyon, Lyon, France.
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Evaluation of NGAL Test™, a fully-automated neutrophil gelatinase-associated lipocalin (NGAL) immunoassay on Beckman Coulter AU 5822. ACTA ACUST UNITED AC 2012; 50:1581-4. [DOI: 10.1515/cclm.2011.839] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2011] [Accepted: 12/05/2011] [Indexed: 11/15/2022]
Abstract
AbstractThe neutrophil gelatinase associated lipocalin (NGAL) has been identified as the most promising biomarker of acute kidney injury (AKI). This study was aimed to evaluate a NGAL immunoassay on Beckman Coulter AU 5822.NGAL Test™ (BioPorto Diagnostics A/S) is a particle-enhanced turbidimetric immunoassay. The within-and between-run imprecision were assessed on three urine samples. The linearity was assessed by serially diluting two urine samples with low and high NGAL concentration. The comparison study was performed with Abbott ARCHITECT NGAL, on 70 urine samples.The within-run imprecision was comprised between 1.0% and 2.3%, whereas the between-run imprecision was between 1.2% and 2.0%. The linearity was excellent in the range between 18 ng/mL and 790 ng/mL (r=1.000; p<0.001). A highly significant agreement was observed between NGAL Test™ on Beckman Coulter AU5822 and Abbott ARCHITECT NGAL (r=0.925; p<0.001), although the method exhibited a bias of +65%. Excellent sensitivity and specificity against the ARCHITECT values were found at 200 ng/mL.This analytical evaluation attests that the NGAL Test™ has several technical and analytical advantages, including no manual pretreatment, low volume of sample (i.e., 3 μL), fast turnaround time (approx. 10 min), low imprecision, wide dynamic range, optimal linearity.
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Vilhelmsdotter Allander S, Marké LÅ, Wihlen B, Svensson M, Elinder CG, Larsson A. Regional variation in use of exogenous and endogenous glomerular filtration rate (GFR) markers in Sweden. Ups J Med Sci 2012; 117:273-8. [PMID: 22401136 PMCID: PMC3410286 DOI: 10.3109/03009734.2012.664179] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Markers of renal function (glomerular filtration rate (GFR)) are frequently used in the Swedish health care. GFR is usually estimated based on plasma creatinine concentration, but plasma cystatin C concentration, creatinine clearance, iohexol clearance, and (51)Cr-EDTA clearance are also used. These markers are all part of the daily patient care, but there is little specific information on the clinical use of these markers. The aim of this study was to compare the use of these various GFR markers in different parts of Sweden and potential changes over time. METHODS Retrospective study using questionnaires to collect information for the years 2006-2009 divided per county on the specific use of GFR markers with type of test reports. RESULTS Plasma/serum creatinine concentration (96%) is by far the dominating GFR marker in Sweden, while cystatin C concentration (3.5%), creatinine clearance (0.1%), iohexol clearance (0.1%), and 51Cr-EDTA clearance (0.1%) are less frequently used. The use of GFR markers, including creatinine, continues to increase on a national level with the exception of creatinine clearance and 51Cr-EDTA clearance. There were considerable variations between different counties in the use of GFR markers and the type of test reports that the laboratories provided. CONCLUSIONS The inter-county variations of GFR markers used in Sweden are large and indicate that savings associated with optimized test utilization in this regard could be substantial. Regional habits and traditions are likely to influence the variations in GFR marker use.
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Affiliation(s)
| | | | | | - Maria Svensson
- Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Carl-Gustaf Elinder
- Nephrology Unit, Department of Clinical Sciences Intervention and Technology, Karolinska Institute, Stockholm, Sweden
| | - Anders Larsson
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Blackburn GL, Magerowski G. The Impact of Renal Function on Outcomes of Bariatric Surgery. J Am Soc Nephrol 2012; 23:769-70. [DOI: 10.1681/asn.2012030306] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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Panteghini M. Implementation of standardization in clinical practice: not always an easy task. Clin Chem Lab Med 2012; 50:1237-41. [DOI: 10.1515/cclm.2011.791] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2011] [Accepted: 10/26/2011] [Indexed: 11/15/2022]
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Filler G, Huang SHS, Yasin A. The usefulness of cystatin C and related formulae in pediatrics. Clin Chem Lab Med 2012; 50:2081-91. [DOI: 10.1515/cclm-2012-0257] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Accepted: 05/21/2012] [Indexed: 11/15/2022]
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Kuster N, Bargnoux AS, Pageaux GP, Cristol JP. Limitations of compensated Jaffe creatinine assays in cirrhotic patients. Clin Biochem 2011; 45:320-5. [PMID: 22178107 DOI: 10.1016/j.clinbiochem.2011.11.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2011] [Revised: 11/09/2011] [Accepted: 11/21/2011] [Indexed: 12/14/2022]
Abstract
OBJECTIVES This study aimed to evaluate the impact of two creatinine measurement methods on the Model for End Stage Liver Disease (MELD) score and glomerular filtration rate estimation (eGFR) in cirrhotic patients. We focused on ID-MS traceable method such as compensated Jaffe (cJafCreat) and enzymatic (EnzCreat) methods. DESIGN AND METHODS Potential protein-related interferences in creatinine determination were evaluated using dialysates spiked with albumin. MELD score, CKD-EPI formula creatinine-based eGFR and cystatin C-based eGFR were evaluated in 100 cirrhotic patients. RESULTS In vitro model demonstrated that low protein levels result in an underestimation of creatinine levels using cJafCreat. In patients, cJafCreat created a negative bias of -6.1 μmol/L that led to higher eGFR and lower MELD scores. CONCLUSIONS cJafCreat contributes to an overestimation of renal function in cirrhotic patients and may alter cirrhosis-severity assessment. Compensated Jaffe assays should therefore be replaced by enzymatic methods.
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Affiliation(s)
- Nils Kuster
- Laboratoire de Biochimie, CHRU Montpellier, France
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Hannemann A, Friedrich N, Dittmann K, Spielhagen C, Wallaschofski H, Völzke H, Rettig R, Endlich K, Lendeckel U, Stracke S, Nauck M. Age- and sex-specific reference limits for creatinine, cystatin C and the estimated glomerular filtration rate. Clin Chem Lab Med 2011; 50:919-26. [PMID: 22080819 DOI: 10.1515/cclm.2011.788] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Accepted: 10/21/2011] [Indexed: 11/15/2022]
Abstract
BACKGROUND Early detection of patients with chronic kidney disease is of great importance. This study developed reference limits for serum creatinine and serum cystatin C concentrations and for the estimated glomerular filtration rate (eGFR) in healthy subjects from the general population aged 25-65 years. METHODS This study defined a reference population including 985 subjects from the first follow-up of the Study of Health in Pomerania. Serum creatinine was measured with a modified kinetic Jaffé method. Serum cystatin C was measured with a nephelometric assay. The eGFR was calculated from serum creatinine according to the Cockcroft-Gault (eGFR(CG)) and the Modification of Diet in Renal Disease (eGFR(MDRD)) equation, respectively, as well as from serum cystatin C according to the formula by Larsson (eGFR(Larsson)). Non-parametric quantile regression was used to estimate the reference limits. For serum creatinine and serum cystatin C the 95th percentile and for eGFR(CG), eGFR(MDRD) and eGFR(Larsson) the 5th percentile were selected as reference limits. All data was weighted to reflect the age- and sex-structure of the German population in 2008. RESULTS The reference limits for serum creatinine (men: 1.11-1.23 mg/dL; women: 0.93-1.00 mg/dL) and serum cystatin C levels (men: 0.92-1.04 mg/L; women: 0.84-1.02 mg/L) increased with advancing age. The reference limits for eGFR decreased with increasing age (eGFR(CG) men: 106.0-64.7 mL/min, women 84.4-57.9 mL/min; eGFR(MDRD) men: 82.5-62.2 mL/min/1.73 m², women 75.0-58.2 mL/min/1.73 m²; eGFR(Larsson) men: 85.5-72.9 mL/min, women 94.5-75.7 mL/min). CONCLUSIONS This study presents age- and sex-specific reference limits for five measures of renal function based on quantile regression models.
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Affiliation(s)
- Anke Hannemann
- Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
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