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Sodhi K, Chanchalani G, Tyagi N. Current role of biomarkers in the initiation and weaning of kidney replacement therapy in acute kidney injury. World J Nephrol 2025; 14:99802. [PMID: 40134642 PMCID: PMC11755245 DOI: 10.5527/wjn.v14.i1.99802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/16/2024] [Accepted: 11/12/2024] [Indexed: 01/20/2025] Open
Abstract
The occurrence of acute kidney injury (AKI) in critically ill patients is often associated with increased morbidity and mortality rates. Despite extensive research, a consensus is yet to be arrived, especially regarding the optimal timing and indications for initiation of kidney replacement therapy (KRT) for critically ill patients. There is no clear guidance available on the timing of weaning from KRT. More recently, various biomarkers have produced promising prognostic prediction in such patients, regarding the need for KRT and its termination. Most of these biomarkers are indicative of kidney damage and stress, rather than recovery. However, large-scale validation studies are required to guide the cutoff values of these biomarkers among different patient cohorts so as to identify the optimum timing for KRT. This article reviews the kidney biomarkers in detail and summarizes the individual roles of biomarkers in the decision-making process for initiation and termination of the KRT among critically ill AKI patients and the supportive literature.
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Affiliation(s)
- Kanwalpreet Sodhi
- Department of Critical Care, Deep Hospital, Ludhiana 141002, Punjab, India
| | - Gunjan Chanchalani
- Department of Critical Care Medicine, Karamshibhai Jethabhai Somaiya Hospital and Research Centre, Mumbai 400022, India
| | - Niraj Tyagi
- Department of Critical Care Medicine, Sir Ganga Ram Hospital, New Delhi 110060, Delhi, India
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Ávila M, Mora Sánchez MG, Bernal Amador AS, Paniagua R. The Metabolism of Creatinine and Its Usefulness to Evaluate Kidney Function and Body Composition in Clinical Practice. Biomolecules 2025; 15:41. [PMID: 39858438 PMCID: PMC11764249 DOI: 10.3390/biom15010041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 12/17/2024] [Accepted: 12/23/2024] [Indexed: 01/27/2025] Open
Abstract
Serum creatinine levels are the most used clinical marker to estimate renal function as the glomerular function rate because it is simple, fast, and inexpensive. However, creatinine has limitations, as its levels can be influenced by factors such as advanced age, physical activity, protein-rich diets, male gender, medications, and ethnicity. Serum cystatin C and its combination with serum creatinine may serve as an alternative since these factors do not affect it. Most creatinine synthesis occurs in the muscles, making it a valuable marker for assessing lean body mass within body composition. This measurement is crucial for evaluating and monitoring nutritional status in patients with chronic kidney disease. This review aimed to discuss the literature on creatinine metabolism, its advantages and disadvantages in assessing renal function, and its utility in measuring lean body mass. The variability in the creatinine generation rate among individuals should be considered when assessing the glomerular function rate.
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Affiliation(s)
- Marcela Ávila
- Unidad de Investigación Médica en Enfermedades Nefrológicas, Hospital de Especialidades, CMN SXXI, Instituto Mexicano del Seguro Social, Ciudad de México 06720, Mexico
| | | | | | - Ramón Paniagua
- Unidad de Investigación Médica en Enfermedades Nefrológicas, Hospital de Especialidades, CMN SXXI, Instituto Mexicano del Seguro Social, Ciudad de México 06720, Mexico
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Wang L, Wang X. Diagnostic value of multi-parameter ultrasound evaluation in sepsis complicated by acute kidney injury. Ren Fail 2024; 46:2313861. [PMID: 38344995 PMCID: PMC10863507 DOI: 10.1080/0886022x.2024.2313861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 01/30/2024] [Indexed: 02/15/2024] Open
Abstract
BACKGROUND This study aimed to discuss the diagnostic value of multi-parameter ultrasound evaluation in sepsis complicated with acute kidney injury (AKI). METHODS Patients were divided into an AKI group (n = 50) and a non-injury group (n = 50) based on the presence of AKI. The clinical characteristics were collected, and renal function parameters between the two groups were compared, including 24-h urine volume, serum creatinine, urea, serum cystatin C (CysC), renal parenchymal thickness (RPT), renal artery resistance index (RI), and multi-parameter ultrasound scoring (MPUS). Additionally, logistic regression analysis was conducted to determine the influencing factors of sepsis complicated with AKI. The prediction value was evaluated using a receiver operating characteristic (ROC) curve. RESULTS In the AKI group, creatinine, CysC, urea, MPUS score, RPT, and RI values were significantly higher, while the 24-h urine volume was lower than those in the non-injury group (p < 0.01). Moreover, multivariate logistic analysis indicated that high CysC and RI values were independent risk factors, whereas high 24-h urine volume and low MPUS were independent protective factors for sepsis-induced AKI. The ROC curve demonstrated that RI (AUC = 0.906) was more effective than 24-h urine volume (AUC = 0.797), CysC (AUC = 0.730), and MPUS (AUC = 0.794) in identifying sepsis-induced AKI. CONCLUSION High RI values increase the risk of sepsis-induced AKI, whereas low MPUS may reduce it. RI showed high diagnosis values for sepsis complicated with AKI.
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Affiliation(s)
- Liu Wang
- Department of Ultrasound Medicine, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiang Wang
- Department of Critical Care Medicine, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, China
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Ogorevc N, Slak P, Nikšić S, Novljan G, Fister P, Plut D. Contrast-Enhanced Ultrasound (CEUS) and Ultra-Microangiography (UMA) in Critically Ill Children with Acute Kidney Injury. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1205. [PMID: 39457170 PMCID: PMC11506883 DOI: 10.3390/children11101205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 09/28/2024] [Accepted: 09/29/2024] [Indexed: 10/28/2024]
Abstract
Acute kidney injury (AKI) is an acute condition of impaired kidney function with decreased glomerular filtration rate, which results in dysregulation in volume, electrolyte, and acid-base equilibrium. AKI can be a life-threatening condition and can also lead to chronic kidney disease. It is important to diagnose AKI early in the course of the disease or to predict its development, as this can influence therapeutic decisions, outcome, and, consequently, the prognosis. In clinical practice, an elevated serum creatinine concentration remains the most common laboratory indicator for diagnosing AKI. However, due to the delay in its rise, creatinine levels are often insensitive and inaccurate for early diagnosis. Novel biomarkers of kidney tubular injury and the renal angina index have shown promise in predicting AKI earlier and more accurately. Contrast-enhanced ultrasonography (CEUS) and ultra-microangiography (UMA) are radiological methods that can quantify renal microperfusion and may be able to predict the development of AKI. They have not yet been used for quantifying renal perfusion in children with risk factors for developing AKI. Further research is needed to compare these sonographic techniques with the renal angina index and emerging kidney injury biomarkers for predicting acute kidney injury (AKI) in both children and adults.
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Affiliation(s)
- Nace Ogorevc
- Clinical Radiology Institute, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (P.S.); (D.P.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Peter Slak
- Clinical Radiology Institute, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (P.S.); (D.P.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Stevan Nikšić
- Clinical Radiology Institute, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (P.S.); (D.P.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Gregor Novljan
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Pediatric Nephrology Department, Children’s Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Petja Fister
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Pediatric Intensive Care, Children’s Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Domen Plut
- Clinical Radiology Institute, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; (P.S.); (D.P.)
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
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Miano TA, Barreto EF, McNett M, Martin N, Sakhuja A, Andrews A, Basu RK, Ablordeppey EA. Toward Equitable Kidney Function Estimation in Critical Care Practice: Guidance From the Society of Critical Care Medicine's Diversity, Equity, and Inclusion in Renal Clinical Practice Task Force. Crit Care Med 2024; 52:951-962. [PMID: 38407240 PMCID: PMC11098700 DOI: 10.1097/ccm.0000000000006237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2024]
Abstract
OBJECTIVES Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. DATA SOURCES Literature review and expert consensus. STUDY SELECTION English language publications evaluating GFR assessment and racial disparities. DATA EXTRACTION We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. DATA SYNTHESIS Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. CONCLUSIONS The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population.
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Affiliation(s)
- Todd A. Miano
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Erin F. Barreto
- Department of Pharmacy, Mayo Clinic, Rochester, MN, United States of America
| | - Molly McNett
- College of Nursing, The Ohio State University, Columbus, Ohio
| | - Niels Martin
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ankit Sakhuja
- Division of Data Driven and Digital Medicine, The Charles Bronfman Institute for Personalized Medicine and Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Adair Andrews
- Society of Critical Care Medicine, Mount Prospect, IL
| | - Rajit K. Basu
- Ann & Robert Lurie Children’s Hospital of Chicago, Northwestern University, Chicago, IL, USA
| | - Enyo Ama Ablordeppey
- Washington University School of Medicine, Department of Anesthesiology and Emergency Medicine, St. Louis, Missouri
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Yeh TH, Tu KC, Wang HY, Chen JY. From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease. Int J Mol Sci 2024; 25:1755. [PMID: 38339031 PMCID: PMC10855633 DOI: 10.3390/ijms25031755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 01/28/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open
Abstract
This article provides a thorough overview of the biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI) and acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical applications. This review also highlights the links between renal injury and the pathophysiological mechanisms underlying AKI and AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and the cellular senescence of renal cells. Key signaling pathways, such as Wnt/β-catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The renin-angiotensin-aldosterone system (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating the oxidative stress and cellular changes that promote fibrosis. The clinical evidence suggests that RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.
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Affiliation(s)
- Tzu-Hsuan Yeh
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan; (T.-H.Y.); (H.-Y.W.)
| | - Kuan-Chieh Tu
- Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan;
| | - Hsien-Yi Wang
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan; (T.-H.Y.); (H.-Y.W.)
- Department of Sport Management, College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
| | - Jui-Yi Chen
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan; (T.-H.Y.); (H.-Y.W.)
- Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
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Rossiter A, La A, Koyner JL, Forni LG. New biomarkers in acute kidney injury. Crit Rev Clin Lab Sci 2024; 61:23-44. [PMID: 37668397 DOI: 10.1080/10408363.2023.2242481] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/14/2023] [Accepted: 07/26/2023] [Indexed: 09/06/2023]
Abstract
Acute kidney injury (AKI) is a commonly encountered clinical syndrome. Although it often complicates community acquired illness, it is more common in hospitalized patients, particularly those who are critically ill or who have undergone major surgery. Approximately 20% of hospitalized adult patients develop an AKI during their hospital care, and this rises to nearly 60% in the critically ill, depending on the population being considered. In general, AKI is more common in older adults, in those with preexisting chronic kidney disease and in those with known risk factors for AKI (including diabetes and hypertension). The development of AKI is associated with an increase in both mortality and morbidity, including the development of post-AKI chronic kidney disease. Currently, AKI is defined by a rise in serum creatinine from either a known or derived baseline value and/or oliguria or anuria. However, clinicians may fail to recognize the initial development of AKI because of a delay in the rise of serum creatinine or because of inaccurate urine output monitoring. This, in turn, delays any putative measures to treat AKI or to limit its degree. Consequently, efforts have focused on new biomarkers associated with AKI that may allow early recognition of this syndrome with the intent that this will translate into improved patient outcomes. Here we outline current biomarkers associated with AKI and explore their potential in aiding diagnosis, understanding the pathophysiology and directing therapy.
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Affiliation(s)
- Adam Rossiter
- Critical Care Unit, Royal Surrey Hospital, Guildford, Surry, UK
| | - Ashley La
- Department of Medicine, University of Chicago, Chicago, Illinois, USA
| | - Jay L Koyner
- Department of Medicine, University of Chicago, Chicago, Illinois, USA
| | - Lui G Forni
- Critical Care Unit, Royal Surrey Hospital, Guildford, Surry, UK
- School of Medicine, Department of Clinical & Experimental Medicine, Faculty of Health Sciences, University of Surrey, Surry, UK
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Wang R, Chen H, He M, Xu J. Serum cystatin C is correlated with mortality of traumatic brain injury patients partially mediated by acute kidney injury. Acta Neurol Belg 2023; 123:2235-2241. [PMID: 37171701 PMCID: PMC10175904 DOI: 10.1007/s13760-023-02282-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 05/05/2023] [Indexed: 05/13/2023]
Abstract
BACKGROUND Evaluating risk of poor outcome for Traumatic Brain Injury (TBI) in early stage is necessary to make treatment strategies and decide the need for intensive care. This study is designed to verify the prognostic value of serum cystatin C in TBI patients. METHODS 415 TBI patients admitted to West China hospital were included. Logistic regression was performed to explore risk factors of mortality and testify the correlation between cystatin C and mortality. Mediation analysis was conducted to test whether Acute Kidney Injury (AKI) and brain injury severity mediate the relationship between cystatin C level and mortality. Area under the receiver operating characteristic curve (AUC) was used to evaluate the prognostic value of cystatin C and the constructed model incorporating cystatin C. RESULTS The mortality rate of 415 TBI patients was 48.9%. Non-survivors had lower GCS (5 vs 8, p < 0.001) and higher cystatin C (0.92 vs 0.71, p < 0.001) than survivors. After adjusting confounding effects, multivariate logistic regression indicated GCS (p < 0.001), glucose (p < 0.001), albumin (p = 0.009), cystatin C (p < 0.001) and subdural hematoma (p = 0.042) were independent risk factors of mortality. Mediation analysis showed both AKI and brain injury severity exerted mediating effects on relationship between cystatin C and mortality of included TBI patients. The AUC of combining GCS with cystatin C was 0.862, which was higher than that of GCS alone (Z = 1.7354, p < 0.05). CONCLUSION Both AKI and brain injury severity are mediating variables influencing the relationship between cystatin C and mortality of TBI patients. Serum cystatin C is an effective prognostic marker for TBI patients.
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Affiliation(s)
- Ruoran Wang
- Department of Neurosurgery, West China Hospital, Sichuan University, No.37, Guoxue Alley, Chengdu, 610041, Sichuan Province, China
| | - Hongxu Chen
- Department of Neurosurgery, West China Hospital, Sichuan University, No.37, Guoxue Alley, Chengdu, 610041, Sichuan Province, China
| | - Min He
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
| | - Jianguo Xu
- Department of Neurosurgery, West China Hospital, Sichuan University, No.37, Guoxue Alley, Chengdu, 610041, Sichuan Province, China.
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Wei W, Zhao Y, Zhang Y, Shou S, Jin H. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury. Open Life Sci 2023; 18:20220700. [PMID: 37671089 PMCID: PMC10476484 DOI: 10.1515/biol-2022-0700] [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: 10/12/2022] [Revised: 05/19/2023] [Accepted: 07/30/2023] [Indexed: 09/07/2023] Open
Abstract
Sepsis is a syndrome caused by an imbalance in the inflammatory response of the body caused by an infection that leads to organ dysfunction, with the kidney being one of the most commonly affected organs. Sepsis-related acute kidney injury (SAKI) is strongly linked to increased mortality and poor clinical outcomes. Early diagnosis and treatment can significantly reduce patient mortality. On the other hand, the pathogenesis of SAKI is not fully understood, and early diagnosis of SAKI is a clinical challenge. Therefore, the current review describes biomarkers of acute kidney injury in sepsis and discusses the various pathogenic mechanisms involved in the progression of acute kidney injury in sepsis to develop new clinical treatment avenues.
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Affiliation(s)
- Wei Wei
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin300052, P. R. China
| | - Yibo Zhao
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin300052, P. R. China
| | - Yan Zhang
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin300052, P. R. China
| | - Songtao Shou
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin300052, P. R. China
| | - Heng Jin
- Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin300052, P. R. China
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Roy R, MacDonald J, Dark P, Kalra PA, Green D. The estimation of glomerular filtration in acute and critical illness: Challenges and opportunities. Clin Biochem 2023; 118:110608. [PMID: 37479107 DOI: 10.1016/j.clinbiochem.2023.110608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 06/30/2023] [Accepted: 07/03/2023] [Indexed: 07/23/2023]
Abstract
Recent events have made it apparent that the creatinine based estimating equations for glomerular filtration have their flaws. Some flaws have been known for some time; others have prompted radical modification of the equations themselves. These issues persist in part owing to the behaviour of the creatinine molecule itself, particularly in acute and critical illness. There are significant implications for patient treatment decisions, including drug and fluid therapies and choice of imaging modality (contrast vs. non-contrast CT scan for example). An alternative biomarker, Cystatin C, has been used with some success both alone and in combination with creatinine to help improve the accuracy of particular estimating equations. Problems remain in certain circumstances and costs may limit the more widespread use of the alternative assay. This review will explore both the historical and more recent evidence for glomerular filtration estimation, including options to directly measure glomerular filtration (rather than estimate), perhaps the holy grail for both Biochemistry and Nephrology.
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Affiliation(s)
- Reuben Roy
- The University of Manchester, Manchester, Greater Manchester, United Kingdom.
| | - John MacDonald
- Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, Greater Manchester M6 8HD, United Kingdom
| | - Paul Dark
- The University of Manchester, Manchester, Greater Manchester, United Kingdom
| | - Philip A Kalra
- Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, Greater Manchester M6 8HD, United Kingdom
| | - Darren Green
- Northern Care Alliance NHS Foundation Trust Salford Care Organisation, Salford, Greater Manchester M6 8HD, United Kingdom
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Behal ML, Flannery AH, Barreto EF. Medication Management in the Critically Ill Patient with Acute Kidney Injury. Clin J Am Soc Nephrol 2023; 18:1080-1088. [PMID: 36723347 PMCID: PMC10564345 DOI: 10.2215/cjn.0000000000000101] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 01/20/2023] [Indexed: 02/02/2023]
Abstract
ABSTRACT AKI occurs frequently in critically ill patients. Patients with AKI, including those who require KRT, experience multiple pharmacokinetic and pharmacodynamic perturbations that dynamically influence medication effectiveness and safety. Patients with AKI may experience both subtherapeutic drug concentrations, which lead to ineffective therapy, and supratherapeutic drug concentrations, which increase the risk for toxicity. In critically ill patients with AKI not requiring KRT, conventional GFR estimation equations, especially those based on serum creatinine, have several limitations that can limit the accuracy when used for medication dosing. Alternative methods to estimate kidney function may be informative, including use of measured urinary creatinine clearance, kinetic eGFR, and equations that integrate novel kidney biomarkers. For critically ill patients with AKI requiring KRT, physicochemical properties of the drug, the KRT prescription and circuit configuration, and patient-specific factors each contribute to medication clearance. Evidence-based guidance for medication dosing during AKI requiring KRT is often limited. A working knowledge of the basic tenets of drug elimination during KRT can provide a framework for how to approach decision making when the literature is lacking. Iterative re-evaluation of a patient's progress toward therapeutic goals with a medication must occur over the arc of critical illness, including and especially in the setting of dynamic kidney function.
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Affiliation(s)
- Michael L. Behal
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, Kentucky
| | - Alexander H. Flannery
- Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky
- Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, Kentucky
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12
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Miano TA, Hennessy S, Yang W, Dunn TG, Weisman AR, Oniyide O, Agyekum RS, Turner AP, Ittner CAG, Anderson BJ, Wilson FP, Townsend R, Reilly JP, Giannini HM, Cosgriff CV, Jones TK, Meyer NJ, Shashaty MGS. Association of vancomycin plus piperacillin-tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study. Intensive Care Med 2022; 48:1144-1155. [PMID: 35833959 PMCID: PMC9463324 DOI: 10.1007/s00134-022-06811-0] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 06/28/2022] [Indexed: 01/01/2023]
Abstract
PURPOSE Although dozens of studies have associated vancomycin + piperacillin-tazobactam with increased acute kidney injury (AKI) risk, it is unclear whether the association represents true injury or a pseudotoxicity characterized by isolated effects on creatinine secretion. We tested this hypothesis by contrasting changes in creatinine concentration after antibiotic initiation with changes in cystatin C concentration, a kidney biomarker unaffected by tubular secretion. METHODS We included patients enrolled in the Molecular Epidemiology of SepsiS in the ICU (MESSI) prospective cohort who were treated for ≥ 48 h with vancomycin + piperacillin-tazobactam or vancomycin + cefepime. Kidney function biomarkers [creatinine, cystatin C, and blood urea nitrogen (BUN)] were measured before antibiotic treatment and at day two after initiation. Creatinine-defined AKI and dialysis were examined through day-14, and mortality through day-30. Inverse probability of treatment weighting was used to adjust for confounding. Multiple imputation was used to impute missing baseline covariates. RESULTS The study included 739 patients (vancomycin + piperacillin-tazobactam n = 297, vancomycin + cefepime n = 442), of whom 192 had cystatin C measurements. Vancomycin + piperacillin-tazobactam was associated with a higher percentage increase of creatinine at day-two 8.04% (95% CI 1.21, 15.34) and higher incidence of creatinine-defined AKI: rate ratio (RR) 1.34 (95% CI 1.01, 1.78). In contrast, vancomycin + piperacillin-tazobactam was not associated with change in alternative biomarkers: cystatin C: - 5.63% (95% CI - 18.19, 8.86); BUN: - 4.51% (95% CI - 12.83, 4.59); or clinical outcomes: dialysis: RR 0.63 (95% CI 0.31, 1.29); mortality: RR 1.05 (95%CI 0.79, 1.41). CONCLUSIONS Vancomycin + piperacillin-tazobactam was associated with creatinine-defined AKI, but not changes in alternative kidney biomarkers, dialysis, or mortality, supporting the hypothesis that vancomycin + piperacillin-tazobactam effects on creatinine represent pseudotoxicity.
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Affiliation(s)
- Todd A Miano
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, 423 Guardian Drive, 809 Blockley Hall, Philadelphia, PA, 19104, USA.
- Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
| | - Sean Hennessy
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, 423 Guardian Drive, 809 Blockley Hall, Philadelphia, PA, 19104, USA
- Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Wei Yang
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, 423 Guardian Drive, 809 Blockley Hall, Philadelphia, PA, 19104, USA
- Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Thomas G Dunn
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Ariel R Weisman
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Oluwatosin Oniyide
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Roseline S Agyekum
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Alexandra P Turner
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Caroline A G Ittner
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Brian J Anderson
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - F Perry Wilson
- Section of Nephrology and Clinical and Translational Research Accelerator, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Raymond Townsend
- Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - John P Reilly
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Heather M Giannini
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Christopher V Cosgriff
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Tiffanie K Jones
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Nuala J Meyer
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Michael G S Shashaty
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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13
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Pinsino A, Fabbri M, Braghieri L, Bohn B, Gaudig AJ, Kim A, Takeda K, Naka Y, Sayer GT, Uriel N, Demmer RT, Faillace RT, Husain SA, Mohan S, Colombo PC, Yuzefpolskaya M. The difference between cystatin C- and creatinine-based assessment of kidney function in acute heart failure. ESC Heart Fail 2022; 9:3139-3148. [PMID: 35762103 DOI: 10.1002/ehf2.13975] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 04/03/2022] [Accepted: 05/08/2022] [Indexed: 11/11/2022] Open
Abstract
AIMS Acute heart failure (HF) is associated with muscle mass loss, potentially leading to overestimation of kidney function using serum creatinine-based estimated glomerular filtration rate (eGFRsCr ). Cystatin C-based eGFR (eGFRCysC ) is less muscle mass dependent. Changes in the difference between eGFRCysC and eGFRsCr may reflect muscle mass loss. We investigated the difference between eGFRCysC and eGFRsCr and its association with clinical outcomes in acute HF patients. METHODS AND RESULTS A post hoc analysis was performed in 841 patients enrolled in three trials: Diuretic Optimization Strategy Evaluation (DOSE), Renal Optimization Strategies Evaluation (ROSE), and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF). Intra-individual differences between eGFRs (eGFRdiff ) were calculated as eGFRCysC -eGFRsCr at serial time points during HF admission. We investigated associations of (i) change in eGFRdiff between baseline and day 3 or 4 with readmission-free survival up to day 60; (ii) index hospitalization length of stay (LOS) and readmission with eGFRdiff at day 60. eGFRCysC reclassified 40% of samples to more advanced kidney dysfunction. Median eGFRdiff was -4 [-11 to 1.5] mL/min/1.73 m2 at baseline, became more negative during admission and remained significantly different at day 60. The change in eGFRdiff between baseline and day 3 or 4 was associated with readmission-free survival (adjusted hazard ratio per standard deviation decrease in eGFRdiff : 1.14, P = 0.035). Longer index hospitalization LOS and readmission were associated with more negative eGFRdiff at day 60 (both P ≤ 0.026 in adjusted models). CONCLUSIONS In acute HF, a marked difference between eGFRCysC and eGFRsCr is present at baseline, becomes more pronounced during hospitalization, and is sustained at 60 day follow-up. The change in eGFRdiff during HF admission and eGFRdiff at day 60 are associated with clinical outcomes.
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Affiliation(s)
- Alberto Pinsino
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, NY, USA.,Division of Critical Care Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Matteo Fabbri
- Department of Medicine, NYC Health + Hospitals/Jacobi, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Lorenzo Braghieri
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Bruno Bohn
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA
| | | | - Andrea Kim
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Koji Takeda
- Department of Surgery, Division of Cardiac Surgery, Columbia University Irving Medical Center, New York, NY, USA
| | - Yoshifumi Naka
- Department of Surgery, Division of Cardiac Surgery, Columbia University Irving Medical Center, New York, NY, USA
| | - Gabriel T Sayer
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Nir Uriel
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Ryan T Demmer
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA
| | - Robert T Faillace
- Department of Medicine, NYC Health + Hospitals/Jacobi, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Syed A Husain
- Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, NY, USA
| | - Sumit Mohan
- Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, NY, USA.,Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA
| | - Paolo C Colombo
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Melana Yuzefpolskaya
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, NY, USA
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14
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Evaluation of renal injury and function biomarkers, including symmetric dimethylarginine (SDMA), in the rat passive Heymann nephritis (PHN) model. PLoS One 2022; 17:e0269085. [PMID: 35622875 PMCID: PMC9140233 DOI: 10.1371/journal.pone.0269085] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 05/13/2022] [Indexed: 02/02/2023] Open
Abstract
Symmetric dimethylarginine (SDMA) is a serum biomarker of excretory renal function which consistently correlates with glomerular filtration rate (GFR) across multiple species including rats, dogs, and humans. In human and veterinary clinical settings SDMA demonstrates enhanced sensitivity for detection of declining renal function as compared to other serum biomarkers, but application in preclinical study designs thus far has been limited. The purpose of this study was to determine the performance of serum SDMA in a rat passive Heyman nephritis model of glomerulopathy. In addition to SDMA other biomarkers of excretory renal function were measured including serum creatinine (sCr), blood urea nitrogen (BUN), and cystatin C along with creatinine clearance. Urinary renal biomarkers including microalbumin (μALB), clusterin (CLU), cystatin C, kidney injury marker-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin (OPN) were also measured. PHN was induced using commercial sheep anti-Fx1A serum. Tissue, serum, and urine were collected from groups of control and anti-Fx1A-treated animals for biomarker evaluation, hematology, urinalysis, serum biochemistry, and histologic examination of kidney. Over the course of a 28-day study, concentrations of the urinary biomarkers μALB, CLU, cystatin C, NGAL, KIM-1 and the serum biomarker cystatin C increased significantly in anti-Fx1A-treated rats as compared to controls but no significant increase in serum SDMA, sCr, BUN, or creatinine clearance were noted in anti-Fx1A-treated rats. Given lack of direct GFR measurement or significant change in the renal function biomarkers sCr, BUN, and creatinine clearance, it is unclear if GFR differed significantly between control and anti-Fx1A-treated rats in this study, though urinary biomarkers and histopathologic findings supported renal injury in anti-Fx1A-treated rats over the time course investigated. This study is among the first to investigate serum SDMA in a rat model relevant to preclinical safety assessment and serves to inform future experimental designs and biomarker selection when evaluation of glomerular injury is of priority.
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15
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The Most Promising Biomarkers of Allogeneic Kidney Transplant Rejection. J Immunol Res 2022; 2022:6572338. [PMID: 35669103 PMCID: PMC9167141 DOI: 10.1155/2022/6572338] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/30/2022] [Indexed: 12/13/2022] Open
Abstract
Clinical transplantology is a constantly evolving field of medicine. Kidney transplantation has become standard clinical practice, and it has a significant impact on reducing mortality and improving the quality of life of patients. Allogenic transplantation induces an immune response, which may lead to the rejection of the transplanted organ. The gold standard for evaluating rejection of the transplanted kidney by the recipient's organism is a biopsy of this organ. However, due to the high invasiveness of this procedure, alternative diagnostic methods are being sought. Therefore, the biomarkers may play an essential predictive role in transplant rejection. A review of the most promising biomarkers for early diagnosis and prognosis prediction of allogenic kidney transplant rejection summarizes novel data on neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), C-X-C motif chemokine 10 (CXCL-10), cystatin C (CysC), osteopontin (OPN), and clusterin (CLU) and analyses the dynamics of changes of the biomarkers mentioned above in kidney diseases and the mechanism of rejection of the transplanted kidney.
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16
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Hasson D, Menon S, Gist KM. Improving acute kidney injury diagnostic precision using biomarkers. Pract Lab Med 2022; 30:e00272. [PMID: 35494424 PMCID: PMC9046880 DOI: 10.1016/j.plabm.2022.e00272] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 03/08/2022] [Accepted: 03/21/2022] [Indexed: 01/20/2023] Open
Abstract
Acute kidney injury (AKI) is common in hospitalized patients of all ages and is associated with significant morbidity and mortality. Accurate prediction and early identification of AKI is of utmost importance because no therapy exists to mitigate AKI once it has occurred. Yet, serum creatinine lacks adequate sensitivity and specificity, and quantification of urine output is challenging in incontinent children without indwelling bladder catheters. Integration of clinically available biomarkers have the potential to delineate unique AKI phenotypes that could have important prognostic and therapeutic implications. Plasma Cystatin C, urine neutrophil gelatinase associated lipocalin (NGAL) and the urinary product of tissue inhibitor metalloproteinase (TIMP-2) and insulin growth factor binding protein-7 (IGFBP7) are clinically available. These biomarkers have been studied in heterogenous populations across the age spectrum and in a variety of clinical settings for prediction of AKI. The purpose of this review is to describe and discuss the clinically available AKI biomarkers including how they have been used to delineate AKI phenotypes.
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Affiliation(s)
- Denise Hasson
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Shina Menon
- Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, USA
| | - Katja M. Gist
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA
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17
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Barreto JN, Reid JM, Thompson CA, Mara KC, Rule AD, Kashani KB, Leung N, Larson T, McGovern RM, Witzig TE, Barreto EF. Prospective evaluation of high-dose methotrexate pharmacokinetics in adult patients with lymphoma using novel determinants of kidney function. Clin Transl Sci 2022; 15:105-117. [PMID: 34378331 PMCID: PMC8742646 DOI: 10.1111/cts.13125] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/06/2021] [Accepted: 07/10/2021] [Indexed: 12/14/2022] Open
Abstract
High-dose methotrexate (HDMTX) pharmacokinetics (PKs), including the best estimated glomerular filtration rate (eGFR) equation that reflects methotrexate (MTX) clearance, requires investigation. This prospective, observational, single-center study evaluated adult patients with lymphoma treated with HDMTX. Samples were collected at predefined time points up to 96 h postinfusion. MTX and 7-hydroxy-MTX PKs were estimated by standard noncompartmental analysis. Linear regression determined which serum creatinine- or cystatin C-based eGFR equation best predicted MTX clearance. The 80 included patients had a median (interquartile range [IQR]) age of 68.6 years (IQR 59.2-75.6), 54 (67.5%) were men, and 74 (92.5%) were White. The median (IQR) dose of MTX was 7.6 (IQR 4.8-11.3) grams. Median clearance was similar across three dosing levels at 4.5-5.6 L/h and was consistent with linear PKs. Liver function, weight, age, sex, concomitant chemotherapy, and number of previous MTX doses did not impact clearance. MTX area under the curve (AUC) values varied over a fourfold range and appeared to increase in proportion to the dose. The eGFRcys (ml/min) equation most closely correlated with MTX clearance in both the entire cohort and after excluding outlier MTX clearance values (r = 0.31 and 0.51, respectively). HDMTX as a 4-h infusion displays high interpatient pharmacokinetic variability. Population PK modeling to optimize MTX AUC attainment requires further evaluation. The cystatin C-based eGFR equation most closely estimated MTX clearance and should be investigated for dosing and monitoring in adults requiring MTX as part of lymphoma management.
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Affiliation(s)
| | - Joel M. Reid
- Department of Molecular Pharmacology and Experimental TherapeuticsMayo ClinicRochesterMinnesotaUSA,Department of OncologyMayo ClinicRochesterMinnesotaUSA
| | - Carrie A. Thompson
- Division of HematologyDepartment of Internal MedicineMayo ClinicRochesterMinnesotaUSA
| | - Kristin C. Mara
- Division of Biomedical Statistics and InformaticsDepartment of Health Sciences ResearchMayo ClinicRochesterMinnesotaUSA
| | - Andrew D. Rule
- Division of Nephrology and HypertensionDepartment of Internal MedicineMayo ClinicRochesterMinnesotaUSA
| | - Kianoush B. Kashani
- Division of Nephrology and HypertensionDepartment of Internal MedicineMayo ClinicRochesterMinnesotaUSA
| | - Nelson Leung
- Division of Nephrology and HypertensionDepartment of Internal MedicineMayo ClinicRochesterMinnesotaUSA
| | - Thomas R. Larson
- Department of Molecular Pharmacology and Experimental TherapeuticsMayo ClinicRochesterMinnesotaUSA
| | | | - Thomas E. Witzig
- Division of HematologyDepartment of Internal MedicineMayo ClinicRochesterMinnesotaUSA
| | - Erin F. Barreto
- Department of PharmacyMayo ClinicRochesterMinnesotaUSA,Robert D. and Patricia E. Kern Center for the Science of Health Care DeliveryMayo ClinicRochesterMinnesotaUSA
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18
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Xin Q, Xie T, Chen R, Wang H, Zhang X, Wang S, Liu C, Zhang J. Predictive nomogram model for major adverse kidney events within 30 days in sepsis patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2022; 13:1024500. [PMID: 36589822 PMCID: PMC9800518 DOI: 10.3389/fendo.2022.1024500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 12/06/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND In sepsis patients, Type 2 Diabetes Mellitus (T2DM) was associated with an increased risk of kidney injury. Furthermore, kidney damage is among the dangerous complications, with a high mortality rate in sepsis patients. However, the underlying predictive model on the prediction of major adverse kidney events within 30 days (MAKE30) in sepsis patients with T2DM has not been reported by any study. METHODS A total of 406 sepsis patients with T2DM were retrospectively enrolled and divided into a non-MAKE30 group (261 cases) and a MAKE30 group (145 cases). In sepsis patients with T2DM, univariate and multivariate logistic regression analyses were conducted to identify independent predictors of MAKE30. Based on the findings of multivariate logistic regression analysis, the corresponding nomogram was constructed. The nomogram was evaluated using the calibration curve, Receiver Operating Characteristic (ROC) curve, and decision curve analysis. A composite of death, new Renal Replacement Therapy (RRT), or Persistent Renal Dysfunction (PRD) comprised MAKE30. Finally, subgroup analyses of the nomogram for 30-day mortality, new RRT, and PRD were performed. RESULTS In sepsis patients with T2DM, Mean Arterial Pressure (MAP), Platelet (PLT), cystatin C, High-Density Lipoprotein (HDL), and apolipoprotein E (apoE) were independent predictors for MAKE30. According to the ROC curve, calibration curve, and decision curve analysis, the nomogram model based on those predictors had satisfactory discrimination (AUC = 0.916), good calibration, and clinical application. Additionally, in sepsis patients with T2DM, the nomogram model exhibited a high ability to predict the occurrence of 30-day mortality (AUC = 0.822), new RRT (AUC = 0.874), and PRD (AUC = 0.801). CONCLUSION The nomogram model, which is available within 24 hours after admission, had a robust and accurate assessment for the MAKE30 occurrence, and it provided information to better manage sepsis patients with T2DM.
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Affiliation(s)
- Qi Xin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Tonghui Xie
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Rui Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Hai Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xing Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Shufeng Wang
- Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- *Correspondence: Shufeng Wang, ; Chang Liu, ; Jingyao Zhang,
| | - Chang Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Department of Surgical Intensive Care Unit, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- *Correspondence: Shufeng Wang, ; Chang Liu, ; Jingyao Zhang,
| | - Jingyao Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Department of Surgical Intensive Care Unit, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- *Correspondence: Shufeng Wang, ; Chang Liu, ; Jingyao Zhang,
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19
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Wang RR, He M, Gui X, Kang Y. A nomogram based on serum cystatin C for predicting acute kidney injury in patients with traumatic brain injury. Ren Fail 2021; 43:206-215. [PMID: 33478333 PMCID: PMC7833079 DOI: 10.1080/0886022x.2021.1871919] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 12/26/2020] [Accepted: 12/26/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a common complication in traumatic brain injury (TBI) patients and is associated with unfavorable outcome of these patients. We designed this study to explore the value of serum cystatin C, an indicator of renal function, on predicting AKI after suffering TBI. METHODS Patients confirmed with TBI and hospitalized in the West China Hospital of Sichuan University between January 2015 and December 2019 were included. Patients were divided into two groups according to occurrence of AKI. Univariate and multivariate logistic regression analyses were sequentially utilized to find risk factors of AKI in included TBI patients. Nomogram composed of discovered risk factors for predicting AKI was constructed. Receiver operating characteristics (ROC) curves were drawn and area under the ROC curve (AUC) were calculated to evaluate the predictive value of cystatin C alone and the constructed nomogram. RESULTS Among 234 included TBI patients, 55 were divided into AKI group. AKI group had shorter length of stay (p < 0.001) and higher in-hospital mortality (p < 0.001). Multivariate logistic regression analysis showed absolute lymphocyte count (p = 0.034), serum creatinine (p < 0.001), serum cystatin C (p = 0.017) and transfusion of red blood cell (p = 0.005) were independently associated with development of AKI after TBI. While hypertonic saline use was not associated with the development of AKI (p = 0.067). The AUC of single cystatin C and predictive nomogram were 0.804 and 0.925, respectively. CONCLUSION Higher serum cystatin C is associated with development of AKI in TBI patients. Predictive nomogram incorporating cystatin C is beneficial for physicians to evaluate possibilities of AKI and consequently adjust treatment strategies to avoid occurrence of AKI.
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Affiliation(s)
- Ruo Ran Wang
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Min He
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Xiying Gui
- Department of Critical Care Medicine, Tibet Autonomous Region People’s Hospital, Lhasa, China
| | - Yan Kang
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
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20
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Al-Amodi HS, Abdelsattar S, Kasemy ZA, Bedair HM, Elbarbary HS, Kamel HFM. Potential Value of TNF-α (-376 G/A) Polymorphism and Cystatin C (CysC) in the Diagnosis of Sepsis Associated Acute Kidney Injury (S-AK I) and Prediction of Mortality in Critically Ill patients. Front Mol Biosci 2021; 8:751299. [PMID: 34692772 PMCID: PMC8526786 DOI: 10.3389/fmolb.2021.751299] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 09/20/2021] [Indexed: 12/29/2022] Open
Abstract
Sepsis Associated Kidney Injury represents a major health concern as it is frequently associated with increased risk of mortality and morbidity. We aimed to evaluate the potential value of TNF-α (-376 G/A) and cystatin C in the diagnosis of S-AKI and prediction of mortality in critically ill patients. This study included 200 critically ill patients and 200 healthy controls. Patients were categorized into 116 with acute septic shock and 84 with sepsis, from which 142 (71%) developed S-AKI. Genotyping of TNF-α (-376 G/A) was performed by RT-PCR and serum CysC was assessed by Enzyme Linked Immunosorbent Assay. Our results showed a highly significant difference in the genotype frequencies of TNF-α (-376 G/A) SNP between S-AKI and non-AKI patients (p < 0.001). Additionally, sCysC levels were significantly higher in the S-AKI group (p = 0.011). The combination of both sCysC and TNF-α (-376 G/A) together had a better diagnostic ability for S-AKI than sCysC alone (AUC = 0.610, 0.838, respectively). Both GA and AA genotypes were independent predictors of S-AKI (p= < 0.001, p = 0.002 respectively). Additionally, sCysC was significantly associated with the risk of S-AKI development (Odds Ratio = 1.111). Both genotypes and sCysC were significant predictors of non-survival (p < 0.001), suggesting their potential role in the diagnosis of S-AKI and prediction of mortality.
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Affiliation(s)
- Hiba S Al-Amodi
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt
| | - Zeinab A. Kasemy
- Department of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt
| | - Hanan M. Bedair
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebine Elkoum, Egypt
| | - Hany S. Elbarbary
- Department of Internal Medicine, Renal Unit, Faculty of Medicine, Menoufia University, Shebine Elkoum, Egypt
- Department of Internal Medicine, Renal Unit, Faculty of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Hala F. M. Kamel
- Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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21
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Wu Y, Wang S, Xu X. Correlation of Serum Cystatin C with Renal Function in Gout Patients with Renal Injury. J Interferon Cytokine Res 2021; 41:329-335. [PMID: 34435875 DOI: 10.1089/jir.2021.0034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The gout-induced continuous deposition of urate in the kidney tissues is the main cause of renal injury, for which cystatin C (Cys C) is an important indicator. This research analyzed the correlation between general renal injury indicators and serum Cys C level, and further investigated the potential of Cys C in renal injury diagnosis. A total of 140 gout patients with renal injury (GRI) were recruited and grouped by their glomerular filtration rate (GFR). Urea nitrogen, uric acid, creatinine, and Cys C levels in the serum were evaluated. The diagnostic efficacy of serum Cys C was evaluated by the nonparametric receiver operating characteristic analysis. Serum Cys C level was increased with decreased GFR in GRI. Urea nitrogen, uric acid, and creatinine levels in the serum showed positive correlations with Cys C level. The area under the curve for serum Cys C was 0.8589 (P < 0.001). In conclusion, this research demonstrated that the serum Cys C level was a precise diagnostic marker for GFR and renal damage evaluation, and showed a significant diagnostic value for renal injury in patients with gout.
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Affiliation(s)
- Yanqun Wu
- Department of Immune Rheumatology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, Shandong, China
| | - Shunhua Wang
- Department of Immune Rheumatology, Qingdao Municipal Hospital, Qingdao, Shandong, China
| | - Xiaoqing Xu
- Surgery Department Consulting Area, Qingdao Municipal Hospital, Qingdao, Shandong, China
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22
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Yildirim C, Ozger HS, Yasar E, Tombul N, Gulbahar O, Yildiz M, Bozdayi G, Derici U, Dizbay M. Early predictors of acute kidney injury in COVID-19 patients. Nephrology (Carlton) 2021; 26:513-521. [PMID: 33502771 PMCID: PMC8014704 DOI: 10.1111/nep.13856] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 12/11/2020] [Accepted: 01/22/2021] [Indexed: 12/26/2022]
Abstract
Aim This study aims to determine the frequency of COVID‐19 related AKI and to identify the early predictors of AKI. Methods This study is a single‐center, retrospective, observational study. Hospitalized COVID‐19 patients between 24/03/2020 and 31/05/2020 were included in the study. All patients were evaluated for renal dysfunctions with urine dipstick, protein/creatinine ratio, albumin/creatinine ratio in spot urine, serum cystatin C, serum creatinine level on hospital admission, and 28th day of hospital admission. To assess the utility of these parameters to predict AKI, a receiver‐operating characteristic curve was generated and the area under the curve (AUC) was calculated. Results 348 patients were included. The average incidence of AKI was 4.9% (n = 17). The incidence of AKI in mild, moderate and severe COVID‐19 cases was 1.3% (n = 4), 9.0% (n = 3) and 76.9% (n = 10), respectively. Proteinuria was detected in 7.8% (n = 27) of patients with a urine dipstick test. In spot urine analysis, proteinuria was found in 20.1% (n = 70) of patients. The frequency of persistent proteinuria was 5.2% (n = 18). The AUC alue of serum cystatin C, D‐dimer and albumin/creatinine ratio to predict COVID‐19 related AKI were 0.96 (0.90 to 1.0), 0.94 (0.89–0.98), and 0.95 (0.91–0.98). Conclusion In COVID‐19 patients with normal serum creatinine levels on hospital admission, albuminuria, serum cystatin C and D‐dimer levels may be an early predictor of COVID‐19 related AKI and these patients should be monitored closely for AKI. Since the sample size in the AKI group was small, our study results should be confirmed with larger cohort studies. This observational single‐center study assessed the frequency and predictors of acute kidney injury in 348 hospitalized patients with COVID‐19. In this cohort, AKI was diagnosed in 4.9% of patients and proteinuria (spot urine analysis) in 20%. Albuminuria/creatinine ratio, cystatin C‐ and D‐dimer were identified as potential predictors of AKI on admission.
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Affiliation(s)
- Cigdem Yildirim
- Infectious Disease and Clinical Microbiology Department, Gazi University School of Medicine, Ankara, Turkey
| | - Hasan Selcuk Ozger
- Infectious Disease and Clinical Microbiology Department, Gazi University School of Medicine, Ankara, Turkey
| | - Emre Yasar
- Nephrology Department, Gazi University School of Medicine, Ankara, Turkey
| | - Nazrin Tombul
- Medical Biochemistry Department, Gazi University School of Medicine, Ankara, Turkey
| | - Ozlem Gulbahar
- Medical Biochemistry Department, Gazi University School of Medicine, Ankara, Turkey
| | - Mehmet Yildiz
- Infectious Disease and Clinical Microbiology Department, Gazi University School of Medicine, Ankara, Turkey
| | - Gulendam Bozdayi
- Medical Microbiology Department, Gazi University School of Medicine, Ankara, Turkey
| | - Ulver Derici
- Nephrology Department, Gazi University School of Medicine, Ankara, Turkey
| | - Murat Dizbay
- Infectious Disease and Clinical Microbiology Department, Gazi University School of Medicine, Ankara, Turkey
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Hansson M, Gustafsson R, Jacquet C, Chebaane N, Satchell S, Thunberg T, Ahlm C, Fors Connolly AM. Cystatin C and α-1-Microglobulin Predict Severe Acute Kidney Injury in Patients with Hemorrhagic Fever with Renal Syndrome. Pathogens 2020; 9:pathogens9080666. [PMID: 32824680 PMCID: PMC7460112 DOI: 10.3390/pathogens9080666] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 08/11/2020] [Accepted: 08/13/2020] [Indexed: 12/29/2022] Open
Abstract
Puumala orthohantavirus causes hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury (AKI), an abrupt decrease in renal function. Creatinine is routinely used to detect and quantify AKI; however, early AKI may not be reflected in increased creatinine levels. Therefore, kidney injury markers that can predict AKI are needed. The potential of the kidney injury markers urea, cystatin C, α1-microglobulin (A1M) and neutrophil gelatinase-associated lipocalin (NGAL) to detect early AKI during HFRS was studied by quantifying the levels of these markers in consecutively obtained plasma (P) and urine samples (U) for 44 HFRS patients. P-cystatin C and U-A1M levels were significantly increased during early HFRS compared to follow-up. In a receiver operating characteristic (ROC) curve analysis, P-cystatin C, U-A1M and P-urea predicted severe AKI with area under the curve 0.72, 0.73 and 0.71, respectively, whereas the traditional kidney injury biomarkers creatinine and U-albumin did not predict AKI. Nearly half of the HFRS patients (41%) fulfilled the criteria for shrunken pore syndrome, which was associated with the level of inflammation as measured by P-CRP. P-cystatin C and U-A1M are more sensitive and earlier markers compared to creatinine in predicting kidney injury during HFRS.
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Affiliation(s)
- Magnus Hansson
- Clinical Chemistry, Karolinska University Hospital, 17176 Stockholm, Sweden;
- Department of Laboratory Medicine, Karolinska Institutet, 17177 Stockholm, Sweden
| | - Rasmus Gustafsson
- Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden;
| | - Chloé Jacquet
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
- Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden
| | - Nedia Chebaane
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
| | - Simon Satchell
- Bristol Renal, Bristol Medical School, University of Bristol, Bristol BS1 3NY, UK;
| | - Therese Thunberg
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
| | - Clas Ahlm
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
| | - Anne-Marie Fors Connolly
- Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden; (C.J.); (N.C.); (T.T.); (C.A.)
- Molecular Infection Medicine Sweden (MIMS), Umeå University, 90187 Umeå, Sweden
- Correspondence:
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Teaford HR, Rule AD, Mara KC, Kashani KB, Lieske JC, Schreier DJ, Wieruszewski PM, Barreto EF. Patterns of Cystatin C Uptake and Use Across and Within Hospitals. Mayo Clin Proc 2020; 95:1649-1659. [PMID: 32753139 PMCID: PMC7412578 DOI: 10.1016/j.mayocp.2020.03.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 02/23/2020] [Accepted: 03/04/2020] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To characterize the use of cystatin C (cysC) across and within hospitals. PATIENTS AND METHODS This 2-part study first evaluated access to cysC testing across 129 hospitals in the state of Minnesota, using a telephone-based survey. Second, granular data from a single center (Mayo Clinic) with on-site, rapid-turnaround testing (<1 day) and automated estimated glomerular filtration rate (eGFR) reporting was used to describe temporal patterns. The characteristics of hospitals that offered cysC testing and of patients who underwent rapid cysC testing at Mayo Clinic between January 1, 2011, and March 31, 2018, were described. Poisson regression analyzed temporal trends in cysC testing. RESULTS Of the 114 hospitals (88%) that responded to the statewide survey, cysC was available in 91 (80%), but only 3 of 91 (3%) reported a turnaround time of <1 day. At Mayo Clinic, cysC use increased from 0.74 tests per 1000 patient-days in 2011 to 14 tests per 1000 patient-days in 2018 (P=.004). Of the 3774 patients with cysC tests, the mean first available eGFR was 46 mL/min per 1.73 m2 using cysC and 59 mL/min per 1.73 m2 using serum creatinine (P<.001). CysC testing was used across all intensities of care and was ordered by a variety of specialties. Nephrology was consulted in only 42% of cases. CONCLUSION In the hospital, rapid-turnaround cysC testing is necessary for practical use but was not widely available in Minnesota. When available, a marked increase in cysC testing was observed over the study timeframe. Additional research is needed to determine optimal strategies for implementation of cysC within hospitals.
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Affiliation(s)
| | - Andrew D Rule
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Division of Epidemiology, Mayo Clinic, Rochester, MN
| | - Kristin C Mara
- Division of Biomedical Statistics and Informatics, 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
| | | | | | - 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.
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Eiamcharoenying J, Kulvichit W, Lumlertgul N, Chaiwatanarat T, Peerapornratana S, Srisawat N. The role of serum cystatin C in estimation of renal function in survivors of critical illness. J Crit Care 2020; 59:201-206. [PMID: 32688168 DOI: 10.1016/j.jcrc.2020.07.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 03/24/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Estimating renal function by serum creatinine after critical illness is a challenging problem. However, the role of cystatin C for estimation of the renal function in survivors of critical illness is unknown. We aimed to compare the performance of serum cystatin C- and serum creatinine-based eGFR against a reference GFR using 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) in survivors of critical illness. MATERIAL AND METHODS Survivors of critical illness with stable hemodynamics and renal functions were recruited. Their serum creatinine and cystatin C levels were measured. eGFR were calculated by using various equations: 1)CKD-EPI SCysC; 2) Thai eGFR SCysC; 3)CKD-EPI SCr; 4)Thai eGFR SCr; 5)MDRD Caucasian SCr; 6)CKD-EPI SCr-SCysC. The 99mTc-DTPA plasma clearance was used as a standard eGFR. RESULTS Forty-two patients were included. The bias (median percentage difference) between standard GFR and SCysC-based eGFR were 41.97% (95%CI 33.1% to 48.5%) for CKD-EPI SCysC and 31.72% (95%CI 21.1% to 34.9%) for Thai eGFR SCysC. While, the bias between standard GFR and SCr-based eGFR were -11.37 (95%CI -20.9 to 1.6) for CKD-EPI SCr, -18.30 (95%CI -26.3 to -10.6) for Thai eGFR SCr, and -27.17 (-43.7 to -19.1) for MDRD Caucasian SCr. CONCLUSION In survivors of critical illness, we demonstrated limitations of estimating GFR by both currently available SCysC and SCr-based equations. Therefore, further studies are still needed to develop better eGFR equations.
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Affiliation(s)
- Jirarat Eiamcharoenying
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Win Kulvichit
- Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Critical Care Nephrology Research Unit, Chulalongkorn University, Bangkok, Thailand
| | - Nuttha Lumlertgul
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Critical Care Nephrology Research Unit, Chulalongkorn University, Bangkok, Thailand
| | - Tawatchai Chaiwatanarat
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sadudee Peerapornratana
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Critical Care Nephrology Research Unit, Chulalongkorn University, Bangkok, Thailand
| | - Nattachai Srisawat
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Critical Care Nephrology Research Unit, Chulalongkorn University, Bangkok, Thailand; Academy of Science, Royal Society of Thailand, Bangkok, Thailand; Tropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand.
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Khalil R, Elghadban H, Abdelsalam M, Tawfik M. Kidney injury molecule-1: A potential marker of renal recovery after laparoscopic sleeve gastrectomy. Kidney Res Clin Pract 2020; 39:162-171. [PMID: 32487784 PMCID: PMC7321680 DOI: 10.23876/j.krcp.19.109] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 02/27/2020] [Accepted: 02/27/2020] [Indexed: 12/19/2022] Open
Abstract
Background Bariatric surgeries were reported to improve diabetes and hypertension; however, the effect on renal recovery has not been fully explored. The aim of this study was to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) in morbidly obese patients on renal function, degree of albuminuria, and kidney injury molecule-1 (KIM-1) level. Methods This was a prospective observational study conducted at Mansoura University Hospitals from January to June 2017. Forty-four morbidly obese patients (29 females and 15 males) who met the 1991 WHO criteria for obesity surgery were included. Patients underwent surgical LSG for treatment of morbid obesity, and all were followed for 6 months after surgery. Demographic, clinical, and laboratory data were collected and compared before and after surgery. Primary endpoints were the differences of albuminuria, estimated glomerular filtration rate (eGFR) and serum KIM-1 between baseline (pre-surgery) and 6-month post-surgery values. Results Six-month post-surgery data showed significant reduction of body mass index, HbA1c, microalbuminuria, and serum KIM-1, and a significant increase in eGFR (all, P < 0.001). The serum KIM-1 level positively correlated with microalbuminuria and serum creatinine (r = 0.596, P = 0.001 and r = 0.402, P = 0.034, respectively). Postoperative data showed that patients with microalbuminuria had significantly lower eGFR and higher KIM-1 values than those without microalbuminuria (P = 0.003 and 0.049, respectively). Conclusion We showed potential benefits of LSG against obesity-associated kidney damage. This is evidenced by improving eGFR and reducing levels of both KIM-1 and microalbuminuria. The serum level of KIM-1 may be a potential marker for renal recovery after LSG.
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Affiliation(s)
- Rania Khalil
- Biochemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt
| | - Hosam Elghadban
- General Surgery Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Moustafa Abdelsalam
- Internal Medicine Department, Mansoura Nephrology and Dialysis Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mona Tawfik
- Internal Medicine Department, Mansoura Nephrology and Dialysis Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Uhel F, Peters-Sengers H, Falahi F, Scicluna BP, van Vught LA, Bonten MJ, Cremer OL, Schultz MJ, van der Poll T. Mortality and host response aberrations associated with transient and persistent acute kidney injury in critically ill patients with sepsis: a prospective cohort study. Intensive Care Med 2020; 46:1576-1589. [PMID: 32514599 PMCID: PMC7381452 DOI: 10.1007/s00134-020-06119-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 05/14/2020] [Indexed: 12/26/2022]
Abstract
Purpose Sepsis is the most frequent cause of acute kidney injury (AKI). The “Acute Disease Quality Initiative Workgroup” recently proposed new definitions for AKI, classifying it as transient or persistent. We investigated the incidence, mortality, and host response aberrations associated with transient and persistent AKI in sepsis patients. Methods A total of 1545 patients admitted with sepsis to 2 intensive care units in the Netherlands were stratified according to the presence (defined by any urine or creatinine RIFLE criterion within the first 48 h) and evolution of AKI (with persistent defined as remaining > 48 h). We determined 30-day mortality by logistic regression adjusting for confounding variables and analyzed 16 plasma biomarkers reflecting pathways involved in sepsis pathogenesis (n = 866) and blood leukocyte transcriptomes (n = 392). Results AKI occurred in 37.7% of patients, of which 18.4% was transient and 81.6% persistent. On admission, patients with persistent AKI had higher disease severity scores and more frequently had severe (injury or failure) RIFLE AKI stages than transient AKI patients. Persistent AKI, but not transient AKI, was associated with increased mortality by day 30 and up to 1 year. Persistent AKI was associated with enhanced and sustained inflammatory and procoagulant responses during the first 4 days, and a more severe loss of vascular integrity compared with transient AKI. Baseline blood gene expression showed minimal differences with respect to the presence or evolution of AKI. Conclusion Persistent AKI is independently associated with sepsis mortality, as well as with sustained inflammatory and procoagulant responses, and loss of vascular integrity as compared with transient AKI. Electronic supplementary material The online version of this article (10.1007/s00134-020-06119-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Fabrice Uhel
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Room G2-130; Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Hessel Peters-Sengers
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Room G2-130; Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Fahimeh Falahi
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Room G2-130; Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Brendon P Scicluna
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Room G2-130; Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Lonneke A van Vught
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Room G2-130; Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Marc J Bonten
- Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Olaf L Cremer
- Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marcus J Schultz
- Department of Intensive Care Medicine, and Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand
- Nuffield Department of medicine, University of Oxford, Oxford, UK
| | - Tom van der Poll
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Room G2-130; Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Division of Infectious Diseases, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Teaford HR, Barreto JN, Vollmer KJ, Rule AD, Barreto EF. Cystatin C: A Primer for Pharmacists. PHARMACY 2020; 8:E35. [PMID: 32182861 PMCID: PMC7151673 DOI: 10.3390/pharmacy8010035] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 02/22/2020] [Accepted: 03/05/2020] [Indexed: 12/20/2022] Open
Abstract
Pharmacists are at the forefront of dosing and monitoring medications eliminated by or toxic to the kidney. To evaluate the effectiveness and safety of these medications, accurate measurement of kidney function is paramount. The mainstay of kidney assessment for drug dosing and monitoring is serum creatinine (SCr)-based estimation equations. Yet, SCr has known limitations including its insensitivity to underlying changes in kidney function and the numerous non-kidney factors that are incompletely accounted for in equations to estimate glomerular filtration rate (eGFR). Serum cystatin C (cysC) is a biomarker that can serve as an adjunct or alternative to SCr to evaluate kidney function for drug dosing. Pharmacists must be educated about the strengths and limitations of cysC prior to applying it to medication management. Not all patient populations have been studied and some evaluations demonstrated large variations in the relationship between cysC and GFR. Use of eGFR equations incorporating cysC should be reserved for drug management in scenarios with demonstrated outcomes, including to improve pharmacodynamic target attainment for antibiotics or reduce drug toxicity. This article provides an overview of cysC, discusses evidence around its use in medication dosing and in special populations, and describes practical considerations for application and implementation.
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Affiliation(s)
- Hilary R. Teaford
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, USA; (H.R.T.); (J.N.B.)
| | - Jason N. Barreto
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, USA; (H.R.T.); (J.N.B.)
| | - Kathryn J. Vollmer
- College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311, USA;
| | - Andrew D. Rule
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA;
- Division of Epidemiology, Mayo Clinic, Rochester, MN 55905, USA
| | - Erin F. Barreto
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, USA; (H.R.T.); (J.N.B.)
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, USA
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Deng Y, Wang L, Hou Y, Ma J, Chi R, Ye H, Zhai Y, Zhang D, Gao L, Hu L, Hou T, Li J, Tan N, Chen C. The influence of glycemic status on the performance of cystatin C for acute kidney injury detection in the critically ill. Ren Fail 2019; 41:139-149. [PMID: 30942122 PMCID: PMC6450510 DOI: 10.1080/0886022x.2019.1586722] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE Serum cystatin C (sCysC) used clinically for detecting early acute kidney injury (AKI) was reported to be independently associated with hemoglobin (HbA1c) levels, diabetes, and prediabetes. We aimed to assess the influence of HbA1c levels, diabetes, or prediabetes on the performance of sCysC for AKI detection in critically ill adults. METHODS A prospective observational study was conducted in a mixed medical-surgical intensive care unit (ICU). Patients were divided into four quartiles based on levels of HbA1c or serum glucose at ICU admission, respectively. Additionally, patients were stratified into four subgroups according to HbA1c levels and history of diabetes, namely recognized diabetes (previous diagnosis of diabetes), unrecognized diabetes, prediabetes, and normal glycemic status. Comparisons were made using the area under the receiver operator characteristic curve (AUC) for AKI detection, and reassessed after patient stratification by above-mentioned glycemic status. RESULTS Multivariable linear regression revealed that HbA1c levels and history of diabetes were positively related with sCysC (all p < .05). Although stratification for above-mentioned glycemic status displayed no significant difference between AUC of sCysC (all p > .05), sCysC yielded the highest AUCs for detecting AKI in diabetic patients. Moreover, higher optimal cutoff values of sCysC to detect AKI were observed in patients with versus without diabetes. CONCLUSION Glycemic status has no significant impact on the accuracy of sCysC for AKI detection in critically ill adults and a higher optimal cutoff value of sCysC for AKI detection should be considered in diabetic patients.
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Affiliation(s)
- Yujun Deng
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People's Republic of China
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
| | - Lin Wang
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
- Shantou University Medical College, Shantou, People's Republic of China
| | - Yating Hou
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
| | - Jianchao Ma
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
| | - Ruibin Chi
- Department of Critical Care Medicine, Xiaolan Hospital of Southern Medical University, Zhongshan, People’s Republic of China
| | - Heng Ye
- Department of Critical Care Medicine, Guangzhou Nansha Central Hospital, Nansha, People’s Republic of China
| | - Yiling Zhai
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
| | - Danqing Zhang
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
| | - Lu Gao
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
| | - Linhui Hu
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
| | - Tieying Hou
- Department of Clinical Laboratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
| | - Jinghua Li
- Department of Clinical Laboratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
| | - Ning Tan
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People's Republic of China
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Key Laboratory of Coronary Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China
- Ning Tan The Second School of Clinical Medicine, Southern Medical University, Guangzhou510280, Guangdong, People's Republic of China; Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Key Laboratory of Coronary Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou510100, Guangdong, People's Republic of China
| | - Chunbo Chen
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People's Republic of China
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China
- CONTACT Chunbo Chen The Second School of Clinical Medicine, Southern Medical University, Guangzhou510280, Guangdong, People's Republic of China; Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou510080, Guangdong Province, People’s Republic of China; National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou510515, Guangdong Province, P.R. China
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A study of the utility of novel non-invasive urinary and serum biomarkers of blunt kidney injury in a rat model: NGAL, KIM-1, and IL-18. Cent Eur J Immunol 2019; 44:219-225. [PMID: 31871414 PMCID: PMC6925560 DOI: 10.5114/ceji.2019.89592] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2017] [Accepted: 05/08/2017] [Indexed: 12/05/2022] Open
Abstract
This study investigated changes in the concentrations of serum and urine neutrophil gelatinase lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), and cystatin-C (Cys-C) induced by parenchymal and tubular damage following blunt kidney trauma, as well as their potential utility as biomarkers in the detection and follow-up of patients with suspected blunt renal trauma. Three-month-old male Sprague-Dawley rats (n = 18) were divided into three groups (n = 6 in each): group 1: control group (no intervention); group 2: sham group (explorative surgery and exposure of the left kidneys); and group 3: trauma group (explorative surgery and induction of blunt renal trauma of the left kidneys). Serum and urine samples were collected before and 12-24, 36-48, and 60-72 hours later for NGAL, KIM-1, IL-18, and Cys-C measurements. In the trauma group, there was a statistically significant increase in post-operative NGAL, KIM-1, and IL-18 values after 12-24 h and 36-48 h, as compared with pre-operative values. There was also a statistically significant increase in post-operative serum and urine Cys-C values after 60-72 h, as compared with pre-operative values. NGAL, KIM-1, and IL-18 may represent novel non-invasive descriptive candidate biomarkers of early-stage tubular damage in children with renal trauma.
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Nasonova SN, Zhirov IV, Ledyakhova MV, Sharf TV, Bosykh EG, Masenko VP, Tereshchenko SN. Early diagnosis of acute renal injury in patients with acute decompensation of chronic heart failure. TERAPEVT ARKH 2019; 91:67-73. [PMID: 31094479 DOI: 10.26442/00403660.2019.04.000168] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
AIM To study the possibilities of previously diagnosing acute renal damage in patients with acute decompensation of chronic heart failure with reduced systolic function using biomarkers of acute renal injury. MATERIALS AND METHODS The study included 60 patients (62.0±11.1 years) with HADS (BNP >500 pg/ml) and a reduced left ventricular ejection fraction (LV 27.05% [23.25; 32.75], c FC III-IV NYHA). The level of creatinine, urea, uric acid, albumin in serum was determined in all patients, as well as a number of biomarkers: lipocalin associated with neutrophil gelatinase (NGAL) and cystatin C (CysC) in serum; kidney damage molecule-1 (KIM-1) and angiotensinogen (AGT) in the urine. RESULTS AKI is determined based on changes in serum creatinine concentration or diuresis value. The results obtained indicate a high specificity and sensitivity of the use of biomarkers for the diagnosis of AKI in patients with ADHF. NGAL AUC - 0.833 (p<0.001), Se - 82.8%, Sp - 4.2%. CysC AUC - 0.823 (p<0.001), Se - 79.3%, Sp - 74.2%. KIM-1 AUC - 0.782 (p<0.001), Se - 75.9%, Sp - 74.2%. AGT AUC - 0.829 (p<0.001), Se - 82.8%, Sp - 77.4%. In a multifactorial regression analysis, it was found that with NGAL greater than 157.35 ng/ml, the risk of AKI increases 13.1 times (95% CI 1.365-126.431), with an increase in KIM-1, the risk of the development of AKI increases 20.6 times (95% CI 1.802-235.524), and with an increase in AGT more than 14.31 leng/ml, the risk of AKI increases 32.8 times (95% CI 2.752-390.110). CONCLUSION Acute kidney injury develops in 48.3% of patients hospitalized with acute decompensation of chronic heart failure. Patients with acute decompensation of chronic heart failure and AKI have significantly higher serum NGAL and CysC, KIM-1 and AGT values in the urine compared with patients without impairing renal function. These biomarkers can serve both for the early diagnosis of acute kidney damage and the prediction of AKI in patients with acute decompensation of chronic heart failure.
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Affiliation(s)
- S N Nasonova
- National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - I V Zhirov
- National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia.,Russian Medical Academy Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - M V Ledyakhova
- National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - T V Sharf
- National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - E G Bosykh
- National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - V P Masenko
- National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - S N Tereshchenko
- National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia.,Russian Medical Academy Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia
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Che M, Wang X, Xie B, Huang R, Liu S, Yan Y, Zhu M, Lu R, Qian J, Zhang W, Gu L, Mou S, Ni Z, Xue S. Use of Both Serum Cystatin C and Creatinine as Diagnostic Criteria for Cardiac Surgery-Associated Acute Kidney Injury and Its Correlation with Long-Term Major Adverse Events. Kidney Blood Press Res 2019; 44:415-425. [PMID: 31189155 DOI: 10.1159/000499647] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Cardiac surgery-associated acute kidney injury (CSA-AKI) was traditionally defined as an increase in serum creatinine (sCr) after cardiac surgery. Recently, serum cystatin C (sCyC) has been proposed to be a better biomarker in the prediction of AKI. The clinical utility and performance of combining sCyC and sCr in patients with AKI, particularly for the prediction of long-term outcomes, remain unknown. METHODS We measured sCyC together with sCr in 628 patients undergoing cardiac surgery. sCyC and sCr were assessed at baseline and 24 and 48 h after surgery. CSA-AKI determined by sCr (CSA-AKIsCr) was defined as an sCr increase greater than 0.3 mg/dL or 50% from baseline. Major adverse events (MAEs; including death of any cause and dialysis) at 3 years were assessed. RESULTS CSA-AKIsCr developed in 178 patients (28.3%). Three-year follow-up was available for 621 patients; MAEs occurred in 42 patients (6.8%). An increase in sCyC concentration ≥30% within 48 h after surgery was detected in 228 patients (36.3%). This was the best sCyC cutoff for CSA-AKIsCr detection (negative predictive value = 88.8%, positive predictive value = 58.3%). To evaluate the use of both sCyC and sCr as CSA-AKI diagnostic criteria, we stratified patients into 3 groups: non-CSA-AKI, CSA-AKI detected by a single marker, and CSA-AKI detected by both markers. By multivariable logistic regression analysis, the independent predictors of MAEs at 3 years were group 2 (non-CSA-AKI group as the reference, CSA-AKI detected by a single marker: odds ratio [OR] = 3.48, 95% confidence interval [CI]: 1.27-9.58, p = 0.016), group 3 (CSA-AKI detected by both markers: OR = 5.12, 95% CI: 2.01-13.09; p = 0.001), and baseline glomerular filtration rate (OR = 2.24; 95% CI: 1.27-3.95; p = 0.005). CONCLUSION Combining sCyC and sCr to diagnose CSA-AKI would be beneficial for risk stratification and prognosis in patients after cardiac surgery.
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Affiliation(s)
- Miaolin Che
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xudong Wang
- Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Bo Xie
- Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ritai Huang
- Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shang Liu
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yucheng Yan
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Mingli Zhu
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Renhua Lu
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jiaqi Qian
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Weiming Zhang
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Leyi Gu
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shan Mou
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhaohui Ni
- Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China,
| | - Song Xue
- Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Hall PS, Mitchell ED, Smith AF, Cairns DA, Messenger M, Hutchinson M, Wright J, Vinall-Collier K, Corps C, Hamilton P, Meads D, Lewington A. The future for diagnostic tests of acute kidney injury in critical care: evidence synthesis, care pathway analysis and research prioritisation. Health Technol Assess 2019; 22:1-274. [PMID: 29862965 DOI: 10.3310/hta22320] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is highly prevalent in hospital inpatient populations, leading to significant mortality and morbidity, reduced quality of life and high short- and long-term health-care costs for the NHS. New diagnostic tests may offer an earlier diagnosis or improved care, but evidence of benefit to patients and of value to the NHS is required before national adoption. OBJECTIVES To evaluate the potential for AKI in vitro diagnostic tests to enhance the NHS care of patients admitted to the intensive care unit (ICU) and identify an efficient supporting research strategy. DATA SOURCES We searched ClinicalTrials.gov, The Cochrane Library databases, Embase, Health Management Information Consortium, International Clinical Trials Registry Platform, MEDLINE, metaRegister of Current Controlled Trials, PubMed and Web of Science databases from their inception dates until September 2014 (review 1), November 2015 (review 2) and July 2015 (economic model). Details of databases used for each review and coverage dates are listed in the main report. REVIEW METHODS The AKI-Diagnostics project included horizon scanning, systematic reviewing, meta-analysis of sensitivity and specificity, appraisal of analytical validity, care pathway analysis, model-based lifetime economic evaluation from a UK NHS perspective and value of information (VOI) analysis. RESULTS The horizon-scanning search identified 152 potential tests and biomarkers. Three tests, Nephrocheck® (Astute Medical, Inc., San Diego, CA, USA), NGAL and cystatin C, were subjected to detailed review. The meta-analysis was limited by variable reporting standards, study quality and heterogeneity, but sensitivity was between 0.54 and 0.92 and specificity was between 0.49 and 0.95 depending on the test. A bespoke critical appraisal framework demonstrated that analytical validity was also poorly reported in many instances. In the economic model the incremental cost-effectiveness ratios ranged from £11,476 to £19,324 per quality-adjusted life-year (QALY), with a probability of cost-effectiveness between 48% and 54% when tests were compared with current standard care. LIMITATIONS The major limitation in the evidence on tests was the heterogeneity between studies in the definitions of AKI and the timing of testing. CONCLUSIONS Diagnostic tests for AKI in the ICU offer the potential to improve patient care and add value to the NHS, but cost-effectiveness remains highly uncertain. Further research should focus on the mechanisms by which a new test might change current care processes in the ICU and the subsequent cost and QALY implications. The VOI analysis suggested that further observational research to better define the prevalence of AKI developing in the ICU would be worthwhile. A formal randomised controlled trial of biomarker use linked to a standardised AKI care pathway is necessary to provide definitive evidence on whether or not adoption of tests by the NHS would be of value. STUDY REGISTRATION The systematic review within this study is registered as PROSPERO CRD42014013919. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Peter S Hall
- Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK
| | | | - Alison F Smith
- Academy of Primary Care, Hull York Medical School, Hull, UK.,National Institute for Health Research (NIHR) Diagnostic Evidence Co-operative Leeds, Leeds, UK
| | - David A Cairns
- Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Michael Messenger
- National Institute for Health Research (NIHR) Diagnostic Evidence Co-operative Leeds, Leeds, UK
| | | | - Judy Wright
- Academy of Primary Care, Hull York Medical School, Hull, UK
| | | | | | - Patrick Hamilton
- Manchester Institute of Nephrology and Transplantation, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - David Meads
- Academy of Primary Care, Hull York Medical School, Hull, UK
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Ravn B, Rimes-Stigare C, Bell M, Hansson M, Hansson LO, Martling CR, Larsson A, Mårtensson J. Creatinine versus cystatin C based glomerular filtration rate in critically ill patients. J Crit Care 2019; 52:136-140. [PMID: 31039451 DOI: 10.1016/j.jcrc.2019.04.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 04/02/2019] [Accepted: 04/03/2019] [Indexed: 01/29/2023]
Affiliation(s)
- Bo Ravn
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden..
| | - Claire Rimes-Stigare
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden
| | - Max Bell
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden
| | - Magnus Hansson
- Department of Laboratory Medicine (LABMED), H5, Division of Clinical Chemistry, C1 74 Karolinska Universitetssjukhuset Huddinge, 14186 Stockholm, Sweden
| | - Lars-Olof Hansson
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, 751 85 Uppsala, Sweden
| | - Claes-Roland Martling
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden
| | - Anders Larsson
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, 751 85 Uppsala, Sweden
| | - Johan Mårtensson
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden
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Barreto EF. Reply to letter regarding: "Validation of the sarcopenia index to assess muscle mass in the critically ill: A novel application of kidney function markers". Clin Nutr 2019; 38:1478. [PMID: 30902486 DOI: 10.1016/j.clnu.2019.02.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 02/27/2019] [Indexed: 10/27/2022]
Affiliation(s)
- Erin F Barreto
- Department of Pharmacy, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
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36
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Zhang D, Gao L, Ye H, Chi R, Wang L, Hu L, Ouyang X, Hou Y, Deng Y, Long Y, Xiong W, Chen C. Impact of thyroid function on cystatin C in detecting acute kidney injury: a prospective, observational study. BMC Nephrol 2019; 20:41. [PMID: 30727972 PMCID: PMC6364411 DOI: 10.1186/s12882-019-1201-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 01/03/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Cystatin C (Cys C) used clinically for detecting early acute kidney injury (AKI) was reported to be associated with thyroid function. Therefore, whether the performance of Cys C is affected by thyroid hormones has raised concern in critically ill patients. This study aimed to investigate the impact of thyroid hormones on the diagnostic and predictive accuracy of Cys C for AKI, and hence optimize the clinical application of Cys C. METHODS A prospective observational study was conducted in the general intensive care units (ICUs). Serum creatinine (SCr), Cys C, and thyroid function were documented for all patients at ICU admission. Patients were separated into five quintiles based on free triiodothyronine (FT3) and total triiodothyronine (TT3), and two categories according to the presence of low T3 syndrome or not. The impact of thyroid function on the performance of Cys C in diagnosing and predicting AKI was assessed by area under the receiver operating characteristic curve (AUC). RESULTS The AKI incidence was 30.0% (402/1339); 225 patients had AKI upon entry, and 177 patients developed AKI during the subsequent 7 days. The AUCs for Cys C in detecting total AKI, established AKI, and later-onset AKI was 0.753, 0.797, and 0.669, respectively. The multiple linear regression analysis demonstrated that TT3 and FT3 were independently associated with Cys C. Overall, although Cys C did not yield any significant difference in AUCs for detecting AKI among patients with different thyroid hormones, the optimal cut-off value of Cys C to detect AKI was markedly different between patients with and without low T3 syndrome. CONCLUSIONS The thyroid function had no significant impact on the diagnostic and predictive accuracy of Cys C in detecting AKI in ICU patients. However, the optimal cut-off value of Cys C to detect AKI could be affected by thyroid function.
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Affiliation(s)
- Danqing Zhang
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080 Guangdong Province People’s Republic of China
- Department of Critical Care, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangdong, 510080 Guangdong Province People’s Republic of China
- Shantou University Medical College, 22 Xinling Road, Shantou, 515063 Guangdong Province People’s Republic of China
| | - Lu Gao
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080 Guangdong Province People’s Republic of China
| | - Heng Ye
- Department of Critical Care Medicine, Guangzhou Nansha Central Hospital, Guangzhou, 511400 Guangdong Province People’s Republic of China
| | - Ruibin Chi
- Department of Critical Care Medicine, Xiaolan Hospital of Southern Medical University, Zhongshan, 528415 Guangdong Province People’s Republic of China
| | - Lin Wang
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080 Guangdong Province People’s Republic of China
| | - Linhui Hu
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080 Guangdong Province People’s Republic of China
| | - Xin Ouyang
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080 Guangdong Province People’s Republic of China
| | - Yating Hou
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080 Guangdong Province People’s Republic of China
| | - Yujun Deng
- Department of Critical Care, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangdong, 510080 Guangdong Province People’s Republic of China
| | - Yi Long
- Department of Critical Care, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangdong, 510080 Guangdong Province People’s Republic of China
| | - Weiping Xiong
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080 Guangdong Province People’s Republic of China
| | - Chunbo Chen
- Department of Intensive Care Unit of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080 Guangdong Province People’s Republic of China
- Department of Critical Care, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangdong, 510080 Guangdong Province People’s Republic of China
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 Guangdong Province People’s Republic of China
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Barreto EF, Kanderi T, DiCecco SR, Lopez-Ruiz A, Poyant JO, Mara KC, Heimgartner J, Gajic O, Rule AD, Nystrom EM, Kashani KB. Sarcopenia Index Is a Simple Objective Screening Tool for Malnutrition in the Critically Ill. JPEN J Parenter Enteral Nutr 2018; 43:780-788. [PMID: 30561031 DOI: 10.1002/jpen.1492] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 10/19/2018] [Accepted: 11/14/2018] [Indexed: 01/04/2023]
Abstract
BACKGROUND Reliable and valid tools to screen for malnutrition in the intensive care unit (ICU) remain elusive. The sarcopenia index (SI) [(serum creatinine/serum cystatin C) × 100], could be an inexpensive, objective tool to predict malnutrition. We evaluated the SI as a screening tool for malnutrition in the ICU and compared it with the modified-NUTRIC score. MATERIALS AND METHODS This was a historical cohort study of ICU patients with stable kidney function admitted to Mayo Clinic ICUs between 2008 and 2015. Malnutrition was defined by the Subjective Global Assessment. Diagnostic performance was evaluated with the area under the receiver operating characteristic curve (AUC) and multivariable logistic regression. RESULTS Of the 398 included patients, 181 (45%) had malnutrition, with 34 (9%) scored as severely malnourished. The SI was significantly lower in malnourished patients than in well-nourished patients (64 ± 27 vs 72 ± 25; P = 0.002), and reductions in SI corresponded to increased malnutrition severity (P = 0.001). As a screening tool, the SI was an indicator of malnutrition risk (AUC 0.61) and performed slightly better than the more complex modified-NUTRIC score (AUC = 0.57). SI cutoffs of 101 and 43 had >90% sensitivity and >90% specificity, respectively, for the prediction of malnutrition. Patients with a low SI (≤43) had a significantly higher risk of mortality (HR = 2.61, 95% CI 1.06-6.48, P = 0.038). CONCLUSION The frequency of malnutrition was high in this critically ill population, and it was associated with a poor prognosis. The SI could be used to assess nutrition risk in ICU patients.
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Affiliation(s)
- Erin F Barreto
- Department of Pharmacy, Mayo Clinic, Rochester, Minnesota, USA.,Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota, USA
| | - Tejaswi Kanderi
- Department of Internal Medicine, UPMC Pinnacle, Harrisburg, Pennsylvania, USA
| | - Sara R DiCecco
- Clinical Nutrition, Mayo Clinic, Rochester, Minnesota, USA
| | - Arnaldo Lopez-Ruiz
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Janelle O Poyant
- Department of Pharmacy, Tufts Medical Center, Boston, Massachusetts, USA
| | - Kristin C Mara
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Ognjen Gajic
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Andrew D Rule
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.,Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Erin M Nystrom
- Department of Pharmacy, Mayo Clinic, Rochester, Minnesota, USA
| | - Kianoush B Kashani
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA.,Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
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Lee CW, Kou HW, Chou HS, Chou HH, Huang SF, Chang CH, Wu CH, Yu MC, Tsai HI. A combination of SOFA score and biomarkers gives a better prediction of septic AKI and in-hospital mortality in critically ill surgical patients: a pilot study. World J Emerg Surg 2018; 13:41. [PMID: 30214469 PMCID: PMC6131912 DOI: 10.1186/s13017-018-0202-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 08/27/2018] [Indexed: 12/17/2022] Open
Abstract
Background Sepsis is a syndrome characterized by a constellation of clinical manifestations and a significantly high mortality rate in the surgical intensive care unit (ICU). It is frequently complicated by acute kidney injury (AKI), which, in turn, increases the risk of mortality. Therefore, it is of paramount importance to identify those septic patients at risk for the development of AKI and mortality. The objective of this pilot study was to evaluate several different biomarkers, including NGAL, calprotectin, KIM-1, cystatin C, and GDF-15, along with SOFA scores, in predicting the development of septic AKI and associated in-hospital mortality in critically ill surgical patients. Methods Patients admitted to the surgical ICU were prospectively enrolled, having given signed informed consent. Their blood and urine samples were obtained and subjected to enzyme-linked immunosorbent assay (ELISA) to determine the levels of various novel biomarkers. The clinical data and survival outcome were recorded and analyzed. Results A total of 33 patients were enrolled in the study. Most patients received surgery prior to ICU admission, with abdominal surgery being the most common type of procedure (27 patients (81.8%)). In the study, 22 patients had a diagnosis of sepsis with varying degrees of AKI, while the remaining 11 were free of sepsis. Statistical analysis demonstrated that in patients with septic AKI versus those without, the following were significantly higher: serum NGAL (447.5 ± 35.7 ng/mL vs. 256.5 ± 31.8 ng/mL, P value 0.001), calprotectin (1030.3 ± 298.6 pg/mL vs. 248.1 ± 210.7 pg/mL, P value 0.049), urinary NGAL (434.2 ± 31.5 ng/mL vs. 208.3 ± 39.5 ng/mL, P value < 0.001), and SOFA score (11.5 ± 1.2 vs. 4.4 ± 0.5, P value < 0.001). On the other hand, serum NGAL (428.2 ± 32.3 ng/mL vs. 300.4 ± 44.3 ng/mL, P value 0.029) and urinary NGAL (422.3 ± 33.7 ng/mL vs. 230.8 ± 42.2 ng/mL, P value 0.001), together with SOFA scores (10.6 ± 1.4 vs. 5.6 ± 0.8, P value 0.003), were statistically higher in cases of in-hospital mortality. A combination of serum NGAL, urinary NGAL, and SOFA scores could predict in-hospital mortality with an AUROC of 0.911. Conclusions This pilot study demonstrated a promising panel that allows an early diagnosis, high sensitivity, and specificity and a prognostic value for septic AKI and in-hospital mortality in surgical ICU. Further study is warranted to validate our findings. Electronic supplementary material The online version of this article (10.1186/s13017-018-0202-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Chao-Wei Lee
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China.,2College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China.,3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China
| | - Hao-Wei Kou
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China
| | - Hong-Shiue Chou
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China
| | - Hsu-Huan Chou
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China
| | - Song-Fong Huang
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China
| | - Chih-Hsiang Chang
- Division of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China
| | - Chun-Hsing Wu
- 3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China
| | - Ming-Chin Yu
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China.,2College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China
| | - Hsin-I Tsai
- 3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China.,Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China
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39
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Teo SH, Endre ZH. Biomarkers in acute kidney injury (AKI). Best Pract Res Clin Anaesthesiol 2018; 31:331-344. [PMID: 29248140 DOI: 10.1016/j.bpa.2017.10.003] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 10/25/2017] [Indexed: 12/14/2022]
Abstract
Acute kidney injury is common in critically ill patients and portends a significant impact on mortality, progressive chronic kidney disease, and cardiovascular disease and mortality. Though most physicians alter therapy depending on changes in serum creatinine, this often represents delayed intervention. Various AKI biomarkers have been discovered and validated to improve timely detection, differentiation and stratification into risk groups for progressive renal decline, need for renal replacement therapy or death. This chapter will review AKI biomarkers validated over the past decade. We also describe the clinical performance of the biomarkers. We suggest that using AKI biomarkers to complement serum creatinine (or cystatin C) and urine output will better integrate patient care through earlier recognition and clinical outcome prediction after AKI.
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Affiliation(s)
- Su Hooi Teo
- Department of Nephrology, Singapore General Hospital, Singapore
| | - Zoltán Huba Endre
- Department of Nephrology, Prince of Wales Hospital, High Street, Randwick, Sydney, 2031, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; Department of Medicine, University of Otago-Christchurch; Christchurch, New Zealand; School of Medicine, University of Queensland, Brisbane, Australia.
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40
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Klein SJ, Brandtner AK, Lehner GF, Ulmer H, Bagshaw SM, Wiedermann CJ, Joannidis M. Biomarkers for prediction of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis. Intensive Care Med 2018. [PMID: 29541790 PMCID: PMC5861176 DOI: 10.1007/s00134-018-5126-8] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Purpose Acute kidney injury (AKI) frequently occurs in critically ill patients and often precipitates use of renal replacement therapy (RRT). However, the ideal circumstances for whether and when to start RRT remain unclear. We performed evidence synthesis of the available literature to evaluate the value of biomarkers to predict receipt of RRT for AKI. Methods We conducted a PRISMA-guided systematic review and meta-analysis including all trials evaluating biomarker performance for prediction of RRT in AKI. A systematic search was applied in MEDLINE, Embase, and CENTRAL databases from inception to September 2017. All studies reporting an area under the curve (AUC) for a biomarker to predict initiation of RRT were included. Results Sixty-three studies comprising 15,928 critically ill patients (median per study 122.5 [31–1439]) met eligibility. Forty-one studies evaluating 13 different biomarkers were included. Of these biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) had the largest body of evidence. The pooled AUCs for urine and blood NGAL were 0.720 (95% CI 0.638–0.803) and 0.755 (0.706–0.803), respectively. Blood creatinine and cystatin C had pooled AUCs of 0.764 (0.732–0.796) and 0.768 (0.729–0.807), respectively. For urine biomarkers, interleukin-18, cystatin C, and the product of tissue inhibitor of metalloproteinase-2 and insulin growth factor binding protein-7 showed pooled AUCs of 0.668 (0.606–0.729), 0.722 (0.575–0.868), and 0.857 (0.789–0.925), respectively. Conclusion Though several biomarkers showed promise and reasonable prediction of RRT use for critically ill patients with AKI, the strength of evidence currently precludes their routine use to guide decision-making on when to initiate RRT. Electronic supplementary material The online version of this article (10.1007/s00134-018-5126-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Sebastian J Klein
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Anna K Brandtner
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Georg F Lehner
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Hanno Ulmer
- Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, Innsbruck, Austria
| | - Sean M Bagshaw
- Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | | | - Michael Joannidis
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
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Singal AK, Jackson B, Pereira GB, Russ KB, Fitzmorris PS, Kakati D, Axley P, Ravi S, Seay T, Ramachandra Rao SP, Mehta R, Kuo YF, Singh KP, Agarwal A. Biomarkers of Renal Injury in Cirrhosis: Association with Acute Kidney Injury and Recovery after Liver Transplantation. Nephron Clin Pract 2017; 138:1-12. [PMID: 28873373 DOI: 10.1159/000479074] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2017] [Accepted: 06/26/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND To define urine or serum biomarkers in predicting renal function recovery after liver transplantation (LT). METHODS Adults listed for LT (February 2011-July 2014) and with modified diet for renal disease-6 (MDRD-6) <60 mL/min provided urine/blood samples at baseline and serially until LT for biomarkers in serum (pg/mL) and urine (pg/mg creatinine). RESULTS Of 271 LT listed patients (mean age 57 years, 63% males, median listing MELD 17.5), 1 year acute kidney injury (AKI) probability was 49%, with odds of 1.3-, 3.0-, 4.6-, and 8.5-fold times for listing MELD 16-20, 21-25, 26-30, and >30, compared to MELD <16. Thirty-seven people died over 1 year from the time of listing, with twofold increased odds with AKI. Among 67 patients with MDRD <60, only urinary epidermal growth factor was different comparing AKI (increase in serum creatinine ≥0.3 mg/dL from baseline within past 3 months) vs. no AKI (2,254 vs. 4,253, p = 0.003). Differences between acute tubular necrosis (ATN) and hepatorenal syndrome could not be ascertained for a small sample of 3 patients with ATN. Analyzing 15 of 43 receiving LT and MDRD-6 <30 prior to LT, biomarkers were not different comparing 5 patients recovering renal function (MDRD-6 >50 mL/min) at 6 months vs. 10 without recovery. CONCLUSIONS AKI is common among LT listed patients, with a negative impact on transplant-free survival. Serum and urine biomarkers are not associated with the recovery of renal function after LT. Multicenter studies are suggested to (a) develop strategies to reduce the development of AKI and (b) derive novel biomarkers for use in accurately predicting renal recovery after LT.
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Affiliation(s)
- Ashwani K Singal
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama, Birmingham, AL, USA
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Breidthardt T, Sabti Z, Ziller R, Rassouli F, Twerenbold R, Kozhuharov N, Gayat E, Shrestha S, Barata S, Badertscher P, Boeddinghaus J, Nestelberger T, Mueller C. Diagnostic and prognostic value of cystatin C in acute heart failure. Clin Biochem 2017; 50:1007-1013. [PMID: 28756070 DOI: 10.1016/j.clinbiochem.2017.07.016] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 07/24/2017] [Accepted: 07/25/2017] [Indexed: 01/07/2023]
Abstract
BACKGROUND The accurate early diagnosis of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Cystatin C might improve the early detection of AKI. METHODS 207 patients presenting to the emergency department with AHF were enrolled. Cystatin C was measured in plasma in a blinded fashion at presentation and serially thereafter. The potential of Cystatin C levels to predict AKI was assessed as the primary endpoint. Long-term mortality was assessed as a secondary endpoint. RESULTS At presentation, creatinine (140μmol/L [91-203] vs. 97μmol/L [76-132], p<0.01) and Cystatin C (2.00mg/L [1.30-3.08] vs. 1.45mg/L [1.00-1.90], p<0.01) levels were significantly higher in AKI compared to Non-AKI patients. The diagnostic accuracy for AKI quantified by the area under the receiver operating characteristic curve was mediocre and comparable for both markers (creatinine 0.68; 95%CI 0.58-78 vs. Cystatin C 0.67; 95%CI 0.58-0.76). Serial measurements of Cystatin C did not further increase the prognostic accuracy for AKI. Cystatin C levels were significantly higher in decedents than in survivors (1.90mg/L [1.30-2.70] vs. 1.30mg/L [1.0-1.6], p<0.001). The combination of Cystatin C and BNP levels significantly improved the prediction of mortality provided by either parameter alone. In multivariable regression analysis Cystatin C remained independently associated with mortality (HR 1.41; 95%CI 1.02-1.95). CONCLUSION Plasma Cystatin C levels do not adequately predict AKI in patients with AHF. However, in multivariable regression analysis Cystatin C predicted mortality after the adjustment for baseline renal function, AKI, BNP levels and heart failure risk factors.
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Affiliation(s)
- Tobias Breidthardt
- Department of Internal Medicine, University of Basel, Switzerland; Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland.
| | - Zaid Sabti
- Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Cardiology all at the University Hospital Basel, University of Basel, Switzerland
| | - Ronny Ziller
- Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Geriatric Medicine, Spital Interlaken, Switzerland
| | - Frank Rassouli
- Medical University Clinic, Kantonsspital, Aarau, Switzerland
| | - Raphael Twerenbold
- Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Cardiology all at the University Hospital Basel, University of Basel, Switzerland; Department of General and Interventional Cardiology, Hamburg University Heart Center, Hamburg, Germany
| | - Nikola Kozhuharov
- Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Cardiology all at the University Hospital Basel, University of Basel, Switzerland
| | - Etienne Gayat
- Hôpital Lariboisière APHP, University of Paris, France
| | - Samyut Shrestha
- Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Cardiology all at the University Hospital Basel, University of Basel, Switzerland
| | - Sara Barata
- Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Cardiology all at the University Hospital Basel, University of Basel, Switzerland
| | - Patrick Badertscher
- Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Cardiology all at the University Hospital Basel, University of Basel, Switzerland
| | - Jasper Boeddinghaus
- Department of Internal Medicine, University of Basel, Switzerland; Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Cardiology all at the University Hospital Basel, University of Basel, Switzerland
| | - Thomas Nestelberger
- Department of Internal Medicine, University of Basel, Switzerland; Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Cardiology all at the University Hospital Basel, University of Basel, Switzerland
| | - Christian Mueller
- Cardiovascular Research Institute Basel (CRIB), University of Basel, Switzerland; Department of Cardiology all at the University Hospital Basel, University of Basel, Switzerland
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Torres Aguilar O, Maya Quintá R, Rodríguez Prieto G, Leal M, Castilleja Leal J. Early initiation of renal replacement therapy in acute renal injury. MEDICINA UNIVERSITARIA 2017. [DOI: 10.1016/j.rmu.2017.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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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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45
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Deng Y, Yuan J, Chi R, Ye H, Zhou D, Wang S, Mai C, Nie Z, Wang L, Zhai Y, Gao L, Zhang D, Hu L, Deng Y, Chen C. The Incidence, Risk Factors and Outcomes of Postoperative Acute Kidney Injury in Neurosurgical Critically Ill Patients. Sci Rep 2017; 7:4245. [PMID: 28652590 PMCID: PMC5484679 DOI: 10.1038/s41598-017-04627-3] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 05/17/2017] [Indexed: 02/08/2023] Open
Abstract
We investigated the incidence, perioperative risk factors, and outcomes of postoperative acute kidney injury (AKI) in neurosurgical critically ill patients. A prospective multicenter cohort study was conducted, enrolling adult patients who underwent neurosurgical procedure and admitted to the neurosurgical intensive care units (ICU). Postoperative AKI was diagnosed within 7 days after surgery based on the Kidney Disease Improving Global Outcomes criteria. Of 624 enrolled patients, postoperative AKI occurred in 84 patients. AKI was associated with increased rates of ICU and in-hospital mortality, postoperative renal replacement therapy, postoperative tracheotomy, and postoperative tracheal reintubation. Patients who developed AKI had higher total ICU costs, prolonged length of hospital and ICU stay, and longer duration of postoperative mechanical ventilation. Multivariate analysis identified postoperative reoperation (adjusted odds ratio [OR] 5.70 [95% CI, 1.61–20.14]), postoperative concentration of serum cystatin C (adjusted OR 4.53 [95% CI, 1.98–10.39]), use of mannitol during operation (adjusted OR 1.97 [95% CI, 1.13–3.43]), postoperative APACHE II score (adjusted OR 1.11 [95% CI, 1.06–1.16]), and intraoperative estimated blood loss (adjusted OR 1.04 [95% CI, 1.00–1.08]) as independent risk factors for postoperative AKI. Postoperative AKI in neurosurgical critically ill cohort is prevalent and associated with adverse in-hospital outcomes.
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Affiliation(s)
- Yujun Deng
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Jie Yuan
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Ruibin Chi
- Department of Critical Care Medicine, Xiaolan Hospital of Southern Medical University, Zhongshan, 528415, Guangdong, P.R. China
| | - Heng Ye
- Department of Critical Care Medicine, Guangzhou Nansha Central Hospital, Nansha, 511400, Guangdong, P.R. China
| | - Dong Zhou
- Department of Neurosurgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P.R. China
| | - Sheng Wang
- Department of Anesthesiology, Guangdong Cardiovascular Institute and Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P.R. China
| | - Cong Mai
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Zhiqiang Nie
- Department of Cardiovascular Epidemiology, Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P.R. China
| | - Lin Wang
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Yiling Zhai
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Lu Gao
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Danqing Zhang
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Linhui Hu
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China
| | - Yiyu Deng
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China.
| | - Chunbo Chen
- Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, P.R. China.
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Leem AY, Park MS, Park BH, Jung WJ, Chung KS, Kim SY, Kim EY, Jung JY, Kang YA, Kim YS, Kim SK, Chang J, Song JH. Value of Serum Cystatin C Measurement in the Diagnosis of Sepsis-Induced Kidney Injury and Prediction of Renal Function Recovery. Yonsei Med J 2017; 58:604-612. [PMID: 28332367 PMCID: PMC5368147 DOI: 10.3349/ymj.2017.58.3.604] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 01/16/2017] [Accepted: 01/23/2017] [Indexed: 01/18/2023] Open
Abstract
PURPOSE Acute kidney injury (AKI) is common in critically ill patients. Serum cystatin C has emerged as a reliable marker of AKI. We sought to assess the value of serum cystatin C for early detection and prediction of renal function recovery in patients with sepsis. MATERIALS AND METHODS Sepsis patients (113 AKI patients and 49 non-AKI patients) admitted to the intensive care unit (ICU) were included. Serum creatinine and cystatin C levels and glomerular filtration rate were measured on days 0, 1, 3, and 7. RESULTS Serum cystatin C levels were significantly higher in AKI patients than in non-AKI patients at all time points. Multivariate analysis showed that only serum cystatin C levels on day 0 were associated with AKI development [odds ratio (OR)=19.30; 95% confidence interval (CI)= 2.58-144.50, p<0.001]. Linear mixed model analysis showed significant variation in cystatin C levels between the recovery and non-recovery groups over time (p=0.001). High levels of serum cystatin C at day 0 (OR=1.64; 95% CI=1.00-2.68, p=0.048) were associated with recovery of AKI. CONCLUSION Serum cystatin C level was found to be associated with the development and worsening of AKI in ICU patients with sepsis.
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Affiliation(s)
- Ah Young Leem
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Moo Suk Park
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Hoon Park
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Won Jai Jung
- Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Kyung Soo Chung
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Song Yee Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Young Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Ye Jung
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Ae Kang
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Sam Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Se Kyu Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Joon Chang
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Joo Han Song
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Institute of Chest Disease, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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Mohamed F, Buckley NA, Pickering JW, Wunnapuk K, Dissanayake S, Chathuranga U, Gawarammana I, Jayamanne S, Endre ZH. Nephrotoxicity-induced proteinuria increases biomarker diagnostic thresholds in acute kidney injury. BMC Nephrol 2017; 18:122. [PMID: 28372541 PMCID: PMC5379711 DOI: 10.1186/s12882-017-0532-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Accepted: 03/24/2017] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Paraquat ingestion is frequently fatal. While biomarkers of kidney damage increase during paraquat-induced acute kidney injury (AKI), significant concurrent proteinuria may alter diagnostic thresholds for diagnosis and prognosis to an unknown extent. This study evaluated the effect of albuminuria on biomarker cutoffs for diagnosis and outcome prediction. METHODS This was a multi-centre prospective clinical study of patients following acute paraquat self-poisoning in 5 Sri Lankan hospitals. Biomarker concentrations were quantified using ELISA and microbead assays and correlated with urinary albumin. Functional-AKI was defined by the Acute Kidney Injury Network serum creatinine definition and alternatively by a ≥50% increase in serum cystatin C. Albuminuria was defined as albumin-creatinine ratio >30 mg/g. The study outcomes were compared with a retrospective analysis of a pre-clinical study of paraquat-induced nephrotoxicity with appropriate controls. RESULTS Albuminuria was detected in 34 of 50 patients, and increased with functional-AKI severity. The concentrations of uNGAL, uCysC, uClusterin, uβ2M, and uKIM-1 were higher in albuminuric compared to non-albuminuric patients (p < 0.001). Albuminuria correlated with biomarker concentration (r > 0.6, p < 0.01) and was associated with death (p = 0.006). Optimal biomarker cutoffs for prediction of death were higher in the albuminuric group. Similar outcomes with more detailed analysis were obtained in experimental paraquat nephrotoxicity. CONCLUSION Albuminuria was associated with paraquat-induced nephrotoxicity and increased excretion of low-molecular weight protein biomarkers. AKI biomarker cutoffs for diagnosis, outcome prediction and AKI stratification increased in the presence of albuminuria. This may lead to over-diagnosis of AKI in conditions independently associated with proteinuria.
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Affiliation(s)
- Fahim Mohamed
- South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. .,Department of Pharmacy, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka. .,Department of Nephrology, Prince Of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia. .,TACT Research Group, Department of Pharmacology, SOMS, Sydney Medical School, University of Sydney NSW, Sydney, Australia. .,SACTRC, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
| | - Nicholas A Buckley
- South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka.,TACT Research Group, Department of Pharmacology, SOMS, Sydney Medical School, University of Sydney NSW, Sydney, Australia
| | - John W Pickering
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.,Emergency Department, Christchurch Hospital, Christchurch, New Zealand
| | - Klintean Wunnapuk
- Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sandamali Dissanayake
- South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka
| | - Umesh Chathuranga
- South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka
| | - Indika Gawarammana
- South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka
| | - Shaluka Jayamanne
- South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka
| | - Zoltan H Endre
- Department of Nephrology, Prince Of Wales Hospital and Clinical School, University of New South Wales, Sydney, Australia.,Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
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Pianta TJ, Pickering JW, Succar L, Chin M, Davidson T, Buckley NA, Mohamed F, Endre ZH. Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy. Kidney Blood Press Res 2017; 42:62-75. [PMID: 28315878 DOI: 10.1159/000469715] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 12/21/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. METHODS In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1), and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague-Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. RESULTS In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16-34%)], relative increases were ≥ 50% in 9 patients (35%) for pCysC compared with 2 (8%) for sCr (p = 0.04) and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC), but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. CONCLUSIONS In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.
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Affiliation(s)
- Timothy J Pianta
- Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.,Northern Clinical School, University of Melbourne, Melbourne, Victoria, Australia
| | | | - Lena Succar
- Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Melvin Chin
- Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Trent Davidson
- Anatomical Pathology, SEALS, Prince of Wales Hospital, Randwick, New South Wales, Australia
| | - Nicholas A Buckley
- Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.,Clinical Pharmacology, University of Sydney, Sydney, New South Wales, Australia
| | - Fahim Mohamed
- Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.,Clinical Pharmacology, University of Sydney, Sydney, New South Wales, Australia
| | - Zoltan H Endre
- Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.,Medicine, University of Otago, Christchurch, New Zealand
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The discrepancy between serum creatinine and cystatin C can predict renal function after treatment for postrenal acute kidney injury: multicenter study and pooled data analysis. Clin Exp Nephrol 2017; 21:852-857. [PMID: 28258496 DOI: 10.1007/s10157-016-1377-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 12/20/2016] [Indexed: 10/20/2022]
Abstract
BACKGROUND Although serum cystatin C and creatinine are used as practical markers of renal function, the discrepancy between them in postrenal acute kidney injury (AKI) cases was reported. The aim of this study was to determine whether the preoperative serum cystatin C (pre-CysC) level could predict clinical outcomes after treatment in patients with postrenal AKI. METHODS Patients who underwent urological interventions with postrenal AKI were enrolled in this prospective observational study. Associations among preoperative serum creatinine (pre-sCr), pre-CysC, and nadir postoperative serum creatinine (post-sCr) were evaluated. In addition, based on our results in combination with detailed data from the literature, a predictive equation for postoperative serum creatinine (post-sCr) was developed by simple regression analysis and validated using Bland-Altman plots. RESULTS Finally, 19 patients were eligible for analysis in this study. The value calculated by subtracting pre-CysC (mg/L) from pre-sCr (mg/dl) had a strong correlation to the decrement of serum creatinine (r = 0.9508, p < 0.0001). We added the data of 16 patients obtained from the literature to our series, which were totally randomized into 2 groups, training set and validation set in a 2:1 ratio (n = 23 and 12, respectively) to develop and validate a predictive equation for post-sCr. The mean difference between the predictive and actual post-sCr, -0.68 mg/dl (95% CI -1.62 to 0.26) in the validation set was within the limits of agreement. CONCLUSION We showed that the discrepancy between pre-sCr and pre-CysC could predict improvement of renal function after intervention in patients with postrenal AKI.
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Lins E Lins FLDM, Mayor P, Silva Filho E, Imbeloni AA, Bandeira da Silva W, Monteiro MVB, Nunes-Pinheiro DCS, Monteiro FOB. Renal biochemistry variables and ultrasonographic imaging in healthy Squirrel monkeys (Saimiri collinsi). Vet Clin Pathol 2017; 46:126-131. [PMID: 28165629 DOI: 10.1111/vcp.12454] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND The combined use of renal biochemistry and ultrasonographic imaging may improve the correct management of renal disease. Although renal disease is frequently observed in nonhuman primates, renal function markers have not yet been studied in Squirrel monkeys (Saimiri collinsi). OBJECTIVES The aim of this study was to establish normal renal biochemistry variables and ultrasonographic features in Squirrel monkeys. MATERIAL AND METHODS Renal biochemistry variables and ultrasonographic images were documented in 29 healthy Squirrel monkeys (15 males and 14 females). Urea, serum creatinine (SCr), and uric acid (UA) concentrations were measured by kinetic assay. Cystatin C (CysC) was analyzed by immunonephelometry. A multiple frequency linear array probe (5-12 MHz) was used for ultrasonographic imaging. The studied indicators of renal function were related to sex, age, and body mass. RESULTS Serum creatinine was influenced by sex and body mass. Serum concentration of urea, UA, and CysC were not influenced by sex, age, and body mass. Ultrasonographic images provided accurate and comprehensive data for making clinical decisions for Squirrel monkeys. The total renal volume was only influenced by the body mass nested in sex and was positively correlated to body mass. Right renal volume was bigger than the left one. CONCLUSION Normative standards for the renal evaluation, including biochemistry and ultrasonography, in the Squirrel monkey have been established correlated to age, sex, and body mass.
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Affiliation(s)
| | - Pedro Mayor
- Postgraduate Program in Heath and Animal Production on the Amazon (PPGSPAA), Federal Rural University of the Amazon (UFRA), Belem, Brazil.,Department of Animal Health and Anatomy, Autonomous University of Barcelona, Barcelona, Spain
| | - Ednaldo Silva Filho
- Postgraduate Program in Heath and Animal Production on the Amazon (PPGSPAA), Federal Rural University of the Amazon (UFRA), Belem, Brazil
| | - Aline Amaral Imbeloni
- National Primate Center (CENP), Health Surveillance Secretariat, Ministry of Health, Ananindeua, Brazil
| | - Wellington Bandeira da Silva
- Postgraduate Program in Heath and Animal Production on the Amazon (PPGSPAA), Federal Rural University of the Amazon (UFRA), Belem, Brazil.,National Primate Center (CENP), Health Surveillance Secretariat, Ministry of Health, Ananindeua, Brazil
| | | | | | - Frederico Ozanan Barros Monteiro
- Postgraduate Program in Heath and Animal Production on the Amazon (PPGSPAA), Federal Rural University of the Amazon (UFRA), Belem, Brazil
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