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Melaku MD, Yigzaw AA, Kassie YG, Kedimu MW, Wodajeneh HB, Getahun BM, Anley DT, Agidew MM, Zewde EA. Malnutrition and Associated Factors Among Patients With Cirrhosis at a Tertiary Care Center in Addis Ababa Ethiopia: An Ordinal Logistic Regression Analysis. JGH Open 2025; 9:e70107. [PMID: 39897950 PMCID: PMC11782839 DOI: 10.1002/jgh3.70107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 12/09/2024] [Accepted: 01/20/2025] [Indexed: 02/04/2025]
Abstract
Background Cirrhosis is an irreversible stage of liver damage that decreases the ability of the liver to store and metabolize nutrients. Malnutrition is a common problem in patients with cirrhosis and increases the risk of mortality. Aims This study aimed to assess malnutrition and associated factors among patients with cirrhosis at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. Methods A cross-sectional study was conducted at Tikur Anbessa Specialized Hospital. All patients with cirrhosis who were admitted to the hospital from August to November were included. Royal Free Hospital Global Assessment tool (RFH-GA) was used to assess nutritional status. Data were entered in Epi-data software version 4.6.0.2 and analyzed with STATA version 17/MP. Ordinal logistic regression analysis was fitted to determine factors associated with nutritional status. Statistical significance was declared at p value < 0.05. Results The prevalence of moderate malnutrition and severe malnutrition were 36.67% and 14.29%, respectively. Patients with ascites were five times at a higher risk of being severely malnourished (AOR = 5.08; 95% CI = 2.66-9.67). The odds of severe malnutrition decrease by 0.35 times for patients without a history of previous hospitalization (AOR = 0.35; 95% CI = 0.18-0.68). The odds of being in the higher category of nutritional status (severe malnutrition) are 10 times higher for patients with hepatic encephalopathy (AOR = 10.43; 95% CI = 4.66-23.31). As the level of creatinine blood urea nitrogen (Cr-BUN) increases, the risk of malnutrition increases by 2.57 times (AOR = 2.57; 95% CI = 1.02-5.78). Conclusion Malnutrition is high among cirrhotic patients at Tikur Anbessa Specialized Hospital. Ascites, history of hospitalization, Cr-BUN, and hepatic encephalopathy are significant predictors of malnutrition.
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Affiliation(s)
- Metages Damtie Melaku
- Department of Internal Medicine, College of Health SciencesDebre Tabor UniversityDebre TaborEthiopia
| | - Aklog Almaw Yigzaw
- Department of Internal Medicine, College of Health SciencesDebre Tabor UniversityDebre TaborEthiopia
| | | | - Mulugeta Wondmu Kedimu
- Department of Surgery, College of Health SciencesDebre Tabor UniversityDebre TaborEthiopia
| | | | | | - Denekew Tenaw Anley
- Department of Public Health, College of Health SciencesDebre Tabor UniversityDebre TaborEthiopia
| | - Melaku Mekonen Agidew
- Department of Biomedical Sciences, College of Health SciencesDebre Tabor UniversityDebre TaborEthiopia
| | - Edgeit Abebe Zewde
- Department of Biomedical Sciences, College of Health SciencesDebre Tabor UniversityDebre TaborEthiopia
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Granda ML, Luitweiler E, Prince DK, Allegretti AS, Paine C, Pichler R, Sibulesky L, Biggins SW, Kestenbaum B. Proximal Tubule Secretory Clearance, Injury, and Kidney Viability in Cirrhosis. Clin Transl Gastroenterol 2024; 15:e00775. [PMID: 39374041 PMCID: PMC11596343 DOI: 10.14309/ctg.0000000000000775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 09/18/2024] [Indexed: 10/08/2024] Open
Abstract
INTRODUCTION Cirrhosis affects all structures of the kidney, in particular the tubules, which are responsible for secretion of protein-bound metabolites and electrolyte/water homeostasis. Yet, prevailing assessments of kidney function focus solely on glomerular filtration rate (GFR), which may incompletely reflect these processes. We sought to characterize markers of tubular function, injury, and viability in patients with and without cirrhosis. METHODS We recruited outpatients undergoing liver transplantation evaluation for a collection of plasma and 24-hour urine, matching by GFR to control participants without cirrhosis. We measured urinary kidney injury molecule-1, a marker of proximal tubular injury, as well as epidermal growth factor (EGF), a marker of viability necessary for tubular epithelial cell proliferation after injury. We also estimated secretory clearance by measuring several highly secreted endogenous metabolites in urine and plasma. RESULTS We recruited 39 patients with cirrhosis (mean model for end-stage liver disease 17 ± 4, Child-Pugh 8 ± 2, estimated glomerular filtration rate 66 ± 20 mL/min/1.73 m 2 ) and 58 GFR-matched controls without cirrhosis (estimated glomerular filtration rate 66 ± 21 mL/min/1.73 m 2 ). Urinary kidney injury molecule-1 was 4.4-fold higher than controls (95% confidence interval: 2.9-6.5), and EGF averaged 7.41-fold higher than controls (95% confidence interval: 2.15-25.53). We found that of 8 solutes, 5 had significantly greater kidney clearance in cirrhosis (1.3-2.1-fold higher): indoxyl sulfate, p-cresol sulfate, pyridoxic acid, tiglylglycine, and xanthosine. DISCUSSION Cirrhosis was characterized by molecular signs of tubular injury in stable outpatients without acute kidney injury, accompanied by largely preserved tubular secretory clearance and greater signs of tubular viability. Within the limitations of the study, this suggests a phenotype of chronic ischemic injury but with initial preservation of tubular function in cirrhosis.
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Affiliation(s)
- Michael L. Granda
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
- Kidney Research Institute, University of Washington, Seattle, Washington, USA
| | - Eric Luitweiler
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - David K. Prince
- Kidney Research Institute, University of Washington, Seattle, Washington, USA
| | - Andrew S. Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Cary Paine
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Raimund Pichler
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Lena Sibulesky
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, Washington, USA
| | - Scott W. Biggins
- Division of Gastroenterology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Bryan Kestenbaum
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA
- Kidney Research Institute, University of Washington, Seattle, Washington, USA
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Wakil A, Muzahim Y, Awadallah M, Kumar V, Mazzaferro N, Greenberg P, Pyrsopoulos N. Trends of autoimmune liver disease inpatient hospitalization and mortality from 2011 to 2017: A United States nationwide analysis. World J Hepatol 2024; 16:1029-1038. [PMID: 39086532 PMCID: PMC11287613 DOI: 10.4254/wjh.v16.i7.1029] [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: 04/06/2024] [Revised: 05/23/2024] [Accepted: 06/25/2024] [Indexed: 07/26/2024] Open
Abstract
BACKGROUND Autoimmune liver diseases (AiLD) encompass a variety of disorders that target either the liver cells (autoimmune hepatitis, AIH) or the bile ducts [(primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC)]. These conditions can progress to chronic liver disease (CLD), which is characterized by fibrosis, cirrhosis, and hepatocellular carcinoma. Recent studies have indicated a rise in hospitalizations and associated costs for CLD in the US, but information regarding inpatient admissions specifically for AiLD remains limited. AIM To examine the trends and mortality of inpatient hospitalization of AiLD from 2011 to 2017. METHODS This study is a retrospective analysis utilizing the National Inpatient Sample (NIS) databases. All subjects admitted between 2011 and 2017 with a diagnosis of AiLD (AIH, PBC, PSC) were identified using the International Classification of Diseases (ICD-9) and ICD-10 codes. primary AiLD admission was defined if the first admission code was one of the AiLD codes. secondary AiLD admission was defined as having the AiLD diagnosis anywhere in the admission diagnosis (25 diagnoses). Subjects aged 21 years and older were included. The national estimates of hospitalization were derived using sample weights provided by NIS. χ 2 tests for categorical data were used. The primary trend characteristics were in-hospital mortality, hospital charges, and length of stay. RESULTS From 2011 to 2017, hospitalization rates witnessed a significant decline, dropping from 83263 admissions to 74850 admissions (P < 0.05). The patients hospitalized were predominantly elderly (median 53% for age > 65), mostly female (median 59%) (P < 0.05), and primarily Caucasians (median 68%) (P < 0.05). Medicare was the major insurance (median 56%), followed by private payer (median 27%) (P < 0.05). The South was the top geographical distribution for these admissions (median 33%) (P < 0.05), with most admissions taking place in big teaching institutions (median 63%) (P < 0.05). Total charges for admissions rose from 66031 in 2011 to 78987 in 2017 (P < 0.05), while the inpatient mortality rate had a median of 4.9% (P < 0.05), rising from 4.67% in 2011 to 5.43% in 2017. The median length of stay remained relatively stable, changing from 6.94 days (SD = 0.07) in 2011 to 6.51 days (SD = 0.06) in 2017 (P < 0.05). Acute renal failure emerged as the most common risk factor associated with an increased death rate, affecting nearly 68% of patients (P < 0.05). CONCLUSION AiLD-inpatient hospitalization showed a decrease in overall trends over the studied years, however there is a significant increase in financial burden on healthcare with increasing in-hospital costs along with increase in mortality of hospitalized patient with AiLD.
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Affiliation(s)
- Ali Wakil
- Department of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
| | - Yasameen Muzahim
- Department of Gastroenterology and Hepatology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, United States
| | - Mina Awadallah
- Department of Gastroenterology and Hepatology, Rutgers the New Jersey Medical School, Newark, NJ 07103, United States
| | - Vikash Kumar
- Department of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
| | - Natale Mazzaferro
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, United States
| | - Patricia Greenberg
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, United States
| | - Nikolaos Pyrsopoulos
- Department of Gastroenterology and Hepatology, Rutgers the New Jersey Medical School, Newark, NJ 07103, United States.
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Kumar S, Shah S, Singh B, Pradhan A. Comparison Between Creatinine-Modified Pugh Score and Child-Pugh Score for Prognostication in Decompensated Cirrhosis. Cureus 2024; 16:e62311. [PMID: 39006578 PMCID: PMC11246068 DOI: 10.7759/cureus.62311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/13/2024] [Indexed: 07/16/2024] Open
Abstract
Introduction, aim, and objective: Despite recent evidence suggesting the blood creatinine level is a significant predictor of survival in liver cirrhosis patients, the conventional Child-Pugh (CP) score has held a longstanding position as a valuable prognostic indicator in cirrhotic individuals. This study aimed to compare the predictive capabilities of the modified CP score and the traditional CP score in decompensated cirrhosis patients to evaluate their prognostic power. The objective of this study was to assess the prognostic value of the modified and traditional CP scores in individuals with decompensated cirrhosis by assessing their predictive accuracy. METHODS A total of 100 patients diagnosed with decompensated cirrhosis participated in this prospective study. Each patient's Child-Pugh score and class were determined using admission data, with scores ranging from 5 to 15. Serum creatinine was incorporated as the sixth variable to compute the modified CP score, which ranges from 5 to 19. RESULTS The percentages of individuals aged 16-30, 31-40, 41-50, 51-60, and above 60 years were as follows: 16.0%, 29.0%, 26.0%, and 11.0%, respectively. The patients had a mean age of 44.71 years and a standard deviation of 13.40 years. Out of the 100 patients studied, 26% were female and 74% were male. Fifty-two percent of patients had mild hepatic encephalopathy, while 24% had moderate encephalopathy and 24% had severe encephalopathy. In cases of moderate and severe hepatic encephalopathy, the creatinine-modified Pugh score showed a considerably large area under the curve (AUC=0.852) on the receiver operating characteristics (ROC) curve. CONCLUSION When blood creatinine is taken into account, it can enhance the Child-Pugh classification's prognostic usefulness. This is especially true for patients with moderate to severe hepatic encephalopathy, where serum creatinine is a key factor in accurately predicting both survival and complications associated with cirrhosis.
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Affiliation(s)
- Suraj Kumar
- Cardiology, King George's Medical University, Lucknow, IND
| | - Shobhit Shah
- Cardiology, King George's Medical University, Lucknow, IND
| | - Balvir Singh
- Medicine, Autonomous State Medical College, Firozabad, IND
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Nall S, Arshad H, Contractor B, Sunina F, Raja F, Chaudhari SS, Batool S, Amin A. Predictors of Acute Kidney Injury in Patients Hospitalized With Liver Cirrhosis: A Systematic Review and Meta-Analysis. Cureus 2024; 16:e52386. [PMID: 38361702 PMCID: PMC10868655 DOI: 10.7759/cureus.52386] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2024] [Indexed: 01/27/2024] Open
Abstract
Acute kidney injury (AKI) frequently occurs in hospitalized individuals with liver cirrhosis and represents a significant risk factor for early in-hospital mortality, holding crucial clinical and prognostic importance. The objective of this meta-analysis was to assess the risk factors associated with AKI in hospitalized individuals with cirrhosis. This systematic review and meta-analysis was conducted in concordance with guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two independent researchers systematically searched major databases, including MEDLINE/PubMed, Web of Science, and EMBASE, from January 2015 until December 2023. A total of 14 studies were included in this meta-analysis, of which six were prospective, and the remaining were retrospective. Of the 9,659 cirrhosis patients in the 14 included studies, 3,968 had developed AKI with a pooled incidence of 41% (95% confidence interval = 34-47%). Our findings showed that a high Model for End-Stage Liver Disease (MELD) score, infection, high Child-Pugh-Turcotte stage score, high serum creatinine, high serum bilirubin, and low serum albumin were significantly associated with high incidence of AKI in liver cirrhosis patients. The results emphasize the importance of vigilant monitoring in cirrhosis patients to detect any indications of AKI, followed by meticulous and attentive management.
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Affiliation(s)
- Scott Nall
- Medicine, Central Michigan University School of Medicine, Saginaw, USA
| | | | - Bianca Contractor
- Internal Medicine, Smt. Nathiba Hargovandas Lakhmichand (NHL) Municipal Medical College, Ahmedabad, IND
| | - Fnu Sunina
- Medicine, Jinnah Postgraduate Medical Centre, Karachi, PAK
| | - Fnu Raja
- Pathology, MetroHealth Medical Center, Cleveland, USA
| | - Sandipkumar S Chaudhari
- Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, USA
- Family Medicine, University of North Dakota School of Medicine and Health Sciences, Fargo, USA
| | - Saima Batool
- Internal Medicine, Hameed Latif Hospital, Lahore, PAK
| | - Adil Amin
- Cardiology, Pakistan Navy Ship (PNS) Shifa, Karachi, PAK
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Musunuri B, Gopal S, Tantry BV, Shenoy S, Shetty AJ. Predictors of Short-term Mortality in Patients of Cirrhosis of Liver Presenting as Acute Kidney Injury: An In-hospital Prospective Observational Study. J Clin Exp Hepatol 2023; 13:989-996. [PMID: 37975056 PMCID: PMC10643502 DOI: 10.1016/j.jceh.2023.05.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 05/29/2023] [Indexed: 11/19/2023] Open
Abstract
Background Acute kidney injury (AKI) is known to be associated with increased short-term mortality among cirrhotic patients. On this background, we designed this study to evaluate various causes of AKI among admitted patients with cirrhosis of liver and predictors of 90-day mortality. Methods One hundred and two consecutive adult patients with cirrhosis of liver with AKI hospitalized between November 2016 and March 2018 were enrolled in this prospective study. Their detailed clinical profile, including biochemical parameters, the etiology of AKI, and their clinical outcome of survival or mortality at 90-days, were recorded. Results The most common causes of AKI were infections, followed by hypovolemia, seen in 55.88% and 31.37% of the patients, respectively. Hepatorenal syndrome (HRS) was seen in 10.78%, while parenchymal renal disease was the least common (1.9%). The in-hospital mortality rate was 28.4%, while 90-day mortality was 39.21%. The HRS group had a high 90-day mortality rate of 54.54%. ROC analysis of various biochemical parameters revealed that serum creatinine (sCr), Model for End-Stage Liver Disease (MELD), International Normalized Ratio (INR), and Neutrophil-Lymphocyte ratio (NLR), followed by Child Turcotte Pugh (CTP), had high area under the curves of 0.785, 0.773, 0.747, 0.740, and 0.718, respectively, for the prediction of 90-day mortality. Conclusion Infection is the commonest cause of AKI in cirrhosis; however, mortality in patients with HRS-AKI is higher than that in those with infection-related AKI. Serum creatinine at admission, INR, NLR, and CTP scores predict short-term mortality among patients with AKI in cirrhosis. Further, large prospective studies are needed to confirm these findings.
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Affiliation(s)
- Balaji Musunuri
- Department of Gastroenterology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Sandeep Gopal
- Department of Gastroenterology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Bailuru V. Tantry
- Department of Gastroenterology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Suresh Shenoy
- Department of Gastroenterology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Anurag J. Shetty
- Department of Gastroenterology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
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Rachid A, Chen B, Zhu G. A preliminary study on the effect of renal function on the metabolism of 18F-FDG in the human cerebellum. Quant Imaging Med Surg 2023; 13:5034-5042. [PMID: 37581043 PMCID: PMC10423388 DOI: 10.21037/qims-22-917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 05/12/2023] [Indexed: 08/16/2023]
Abstract
Background The cerebellum is less affected by normal aging or neurodegenerative diseases, the aim of this paper is to investigate the effect of renal function status on uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in human cerebellum based on independent creatinine (CRE) or blood urea nitrogen (BUN) levels. Methods A total of 253 patients who underwent 18F-FDG PET/CT scans were included. The patients were divided into groups according to renal function status: 201 patients with normal renal function, 16 patients with increase CRE, 36 patients with decrease CRE, and 31 patients with abnormal BUN. The maximum standardized uptake values were obtained in regions of interest (ROIs) for multiple tissue types (right cerebellum, right lobe of liver, right lung, bone marrow and psoas muscle at the level of the fourth lumbar vertebra). Moreover, the selected normal CRE groups were pair-matched with CRE decrease group with respect to age, sex, body mass index and glucose, respectively. Results Among 253 patients who met the inclusion/exclusion criteria, the final analysis included 967 ROIs (244 cerebellum, 191 lungs, 230 muscles, 145 bone marrow, and 157 liver) from 18F-FDG PET/CT scans. Among patients grouped by CRE or BUN levels, the uptake of 18F-FDG by cerebellum was significantly decreased in patients with CRE decrease level (P=0.001). There were no statistically significant differences between the other groups. Matched-pair analysis indicated there were no significant changes in outcomes between the CRE decrease group and the age-, sex-, BMI-, and glucose-matched controls compared to pre-matching. Conclusions In patients with normal renal function and reduced CRE concentration, decrease cerebellar glucose metabolism was observed; however, no abnormal uptake of 18F-FDG was found in the cerebellum and other normal tissues of patients with impaired renal function. Consequently, in the study of cerebellar 18F-FDG metabolism, it may be necessary to consider the influence of blood CRE level.
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Affiliation(s)
- Abdoul Rachid
- Department of Nuclear Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China
- College of International Education, Dalian Medical University, Dalian, China
| | - Bo Chen
- Department of Nuclear Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Guangwen Zhu
- Department of Nuclear Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, China
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Jiao C, Ling D, Bian S, Vassantachart A, Cheng K, Mehta S, Lock D, Zhu Z, Feng M, Thomas H, Scholey JE, Sheng K, Fan Z, Yang W. Contrast-Enhanced Liver Magnetic Resonance Image Synthesis Using Gradient Regularized Multi-Modal Multi-Discrimination Sparse Attention Fusion GAN. Cancers (Basel) 2023; 15:3544. [PMID: 37509207 PMCID: PMC10377331 DOI: 10.3390/cancers15143544] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/03/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023] Open
Abstract
PURPOSES To provide abdominal contrast-enhanced MR image synthesis, we developed an gradient regularized multi-modal multi-discrimination sparse attention fusion generative adversarial network (GRMM-GAN) to avoid repeated contrast injections to patients and facilitate adaptive monitoring. METHODS With IRB approval, 165 abdominal MR studies from 61 liver cancer patients were retrospectively solicited from our institutional database. Each study included T2, T1 pre-contrast (T1pre), and T1 contrast-enhanced (T1ce) images. The GRMM-GAN synthesis pipeline consists of a sparse attention fusion network, an image gradient regularizer (GR), and a generative adversarial network with multi-discrimination. The studies were randomly divided into 115 for training, 20 for validation, and 30 for testing. The two pre-contrast MR modalities, T2 and T1pre images, were adopted as inputs in the training phase. The T1ce image at the portal venous phase was used as an output. The synthesized T1ce images were compared with the ground truth T1ce images. The evaluation metrics include peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and mean squared error (MSE). A Turing test and experts' contours evaluated the image synthesis quality. RESULTS The proposed GRMM-GAN model achieved a PSNR of 28.56, an SSIM of 0.869, and an MSE of 83.27. The proposed model showed statistically significant improvements in all metrics tested with p-values < 0.05 over the state-of-the-art model comparisons. The average Turing test score was 52.33%, which is close to random guessing, supporting the model's effectiveness for clinical application. In the tumor-specific region analysis, the average tumor contrast-to-noise ratio (CNR) of the synthesized MR images was not statistically significant from the real MR images. The average DICE from real vs. synthetic images was 0.90 compared to the inter-operator DICE of 0.91. CONCLUSION We demonstrated the function of a novel multi-modal MR image synthesis neural network GRMM-GAN for T1ce MR synthesis based on pre-contrast T1 and T2 MR images. GRMM-GAN shows promise for avoiding repeated contrast injections during radiation therapy treatment.
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Affiliation(s)
- Changzhe Jiao
- Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA (A.V.); (S.M.)
- Department of Radiation Oncology, UC San Francisco, San Francisco, CA 94143, USA
| | - Diane Ling
- Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA (A.V.); (S.M.)
| | - Shelly Bian
- Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA (A.V.); (S.M.)
| | - April Vassantachart
- Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA (A.V.); (S.M.)
| | - Karen Cheng
- Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA (A.V.); (S.M.)
| | - Shahil Mehta
- Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA (A.V.); (S.M.)
| | - Derrick Lock
- Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA (A.V.); (S.M.)
| | - Zhenyu Zhu
- Guangzhou Institute of Technology, Xidian University, Guangzhou 510555, China;
| | - Mary Feng
- Department of Radiation Oncology, UC San Francisco, San Francisco, CA 94143, USA
| | - Horatio Thomas
- Department of Radiation Oncology, UC San Francisco, San Francisco, CA 94143, USA
| | - Jessica E. Scholey
- Department of Radiation Oncology, UC San Francisco, San Francisco, CA 94143, USA
| | - Ke Sheng
- Department of Radiation Oncology, UC San Francisco, San Francisco, CA 94143, USA
| | - Zhaoyang Fan
- Department of Radiology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Wensha Yang
- Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA (A.V.); (S.M.)
- Department of Radiation Oncology, UC San Francisco, San Francisco, CA 94143, USA
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Xu Y, Dong X, Qin C, Wang F, Cao W, Li J, Yu Y, Zhao L, Tan F, Chen W, Li N, He J. Metabolic biomarkers in lung cancer screening and early diagnosis (Review). Oncol Lett 2023; 25:265. [PMID: 37216157 PMCID: PMC10193366 DOI: 10.3892/ol.2023.13851] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 03/29/2023] [Indexed: 05/24/2023] Open
Abstract
Late diagnosis is one of the major contributing factors to the high mortality rate of lung cancer, which is now the leading cause of cancer-associated mortality worldwide. At present, low-dose CT (LDCT) screening in the high-risk population, in which lung cancer incidence is higher than that of the low-risk population is the predominant diagnostic strategy. Although this has efficiently reduced lung cancer mortality in large randomized trials, LDCT screening has high false-positive rates, resulting in excessive subsequent follow-up procedures and radiation exposure. Complementation of LDCT examination with biofluid-based biomarkers has been documented to increase efficacy, and this type of preliminary screening can potentially reduce potential radioactive damage to low-risk populations and the burden of hospital resources. Several molecular signatures based on components of the biofluid metabolome that can possibly discriminate patients with lung cancer from healthy individuals have been proposed over the past two decades. In the present review, advancements in currently available technologies in metabolomics were reviewed, with particular focus on their possible application in lung cancer screening and early detection.
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Affiliation(s)
- Yongjie Xu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Xuesi Dong
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Chao Qin
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Fei Wang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Wei Cao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Jiang Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Yiwen Yu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Liang Zhao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Fengwei Tan
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Wanqing Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Ni Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Jie He
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
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10
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da Silva MC, Fabiano LC, da Costa Salomão KC, de Freitas PLZ, Neves CQ, Borges SC, de Souza Carvalho MDG, Breithaupt-Faloppa AC, de Thomaz AA, Dos Santos AM, Buttow NC. A Rodent Model of Human-Dose-Equivalent 5-Fluorouracil: Toxicity in the Liver, Kidneys, and Lungs. Antioxidants (Basel) 2023; 12:antiox12051005. [PMID: 37237871 DOI: 10.3390/antiox12051005] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 04/24/2023] [Indexed: 05/28/2023] Open
Abstract
5-Fluorouracil (5-FU) is a chemotherapy drug widely used to treat a range of cancer types, despite the recurrence of adverse reactions. Therefore, information on its side effects when administered at a clinically recommended dose is relevant. On this basis, we examined the effects of the 5-FU clinical treatment on the integrity of the liver, kidneys, and lungs of rats. For this purpose, 14 male Wistar rats were divided into treated and control groups and 5-FU was administered at 15 mg/kg (4 consecutive days), 6 mg/kg (4 alternate days), and 15 mg/kg on the 14th day. On the 15th day, blood, liver, kidney, and lung samples were collected for histological, oxidative stress, and inflammatory evaluations. We observed a reduction in the antioxidant markers and an increase in lipid hydroperoxides (LOOH) in the liver of treated animals. We also detected elevated levels of inflammatory markers, histological lesions, apoptotic cells, and aspartate aminotransferase. Clinical treatment with 5-FU did not promote inflammatory or oxidative alterations in the kidney samples; however, histological and biochemical changes were observed, including increased serum urea and uric acid. 5-FU reduces endogenous antioxidant defenses and increases LOOH levels in the lungs, suggesting oxidative stress. Inflammation and histopathological alterations were also detected. The clinical protocol of 5-FU promotes toxicity in the liver, kidneys, and lungs of healthy rats, resulting in different levels of histological and biochemical alterations. These results will be useful in the search for new adjuvants to attenuate the adverse effects of 5-FU in such organs.
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Affiliation(s)
- Mariana Conceição da Silva
- Biological Physics and Cell Signaling Laboratory, Institute of Biology, Department of Structural and Functional Biology, State University of Campinas, Campinas 13083-970, SP, Brazil
| | - Lilian Catarim Fabiano
- Department of Morphological Science, State University of Maringá, Maringá 87020-900, PR, Brazil
| | | | | | - Camila Quaglio Neves
- Department of Morphological Science, State University of Maringá, Maringá 87020-900, PR, Brazil
| | | | - Maria das Graças de Souza Carvalho
- Biological Physics and Cell Signaling Laboratory, Institute of Biology, Department of Structural and Functional Biology, State University of Campinas, Campinas 13083-970, SP, Brazil
| | - Ana Cristina Breithaupt-Faloppa
- Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-904, SP, Brasil
| | - André Alexandre de Thomaz
- Quantum Electronic Department, Institute of Physics Gleb Wataghin, State University of Campinas, Campinas 13083-872, SP, Brazil
| | - Aline Mara Dos Santos
- Biological Physics and Cell Signaling Laboratory, Institute of Biology, Department of Structural and Functional Biology, State University of Campinas, Campinas 13083-970, SP, Brazil
| | - Nilza Cristina Buttow
- Department of Morphological Science, State University of Maringá, Maringá 87020-900, PR, Brazil
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11
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Stämmler F, Derain-Dubourg L, Lemoine S, Meeusen JW, Dasari S, Lieske JC, Robertson A, Schiffer E. Impact of race-independent equations on estimating glomerular filtration rate for the assessment of kidney dysfunction in liver disease. BMC Nephrol 2023; 24:83. [PMID: 37003973 PMCID: PMC10064726 DOI: 10.1186/s12882-023-03136-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 03/23/2023] [Indexed: 04/03/2023] Open
Abstract
BACKGROUND Altered hemodynamics in liver disease often results in overestimation of glomerular filtration rate (GFR) by creatinine-based GFR estimating (eGFR) equations. Recently, we have validated a novel eGFR equation based on serum myo-inositol, valine, and creatinine quantified by nuclear magnetic resonance spectroscopy in combination with cystatin C, age and sex (GFRNMR). We hypothesized that GFRNMR could improve chronic kidney disease (CKD) classification in the setting of liver disease. RESULTS We conducted a retrospective multicenter study in 205 patients with chronic liver disease (CLD), comparing the performance of GFRNMR to that of validated CKD-EPI eGFR equations, including eGFRcr (based on creatinine) and eGFRcr-cys (based on both creatinine and cystatin C), using measured GFR as reference standard. GFRNMR outperformed all other equations with a low overall median bias (-1 vs. -6 to 4 ml/min/1.73 m2 for the other equations; p < 0.05) and the lowest difference in bias between reduced and preserved liver function (-3 vs. -16 to -8 ml/min/1.73 m2 for other equations). Concordant classification by CKD stage was highest for GFRNMR (59% vs. 48% to 53%) and less biased in estimating CKD severity compared to the other equations. GFRNMR P30 accuracy (83%) was higher than that of eGFRcr (75%; p = 0.019) and comparable to that of eGFRcr-cys (86%; p = 0.578). CONCLUSIONS Addition of myo-inositol and valine to creatinine and cystatin C in GFRNMR further improved GFR estimation in CLD patients and accurately stratified liver disease patients into CKD stages.
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Affiliation(s)
- Frank Stämmler
- Department of Research and Development, Numares AG,, Am BioPark 9, 93053, Regensburg, Germany
| | - Laurence Derain-Dubourg
- Department Néphrologie, Dialyse, Hypertension Et Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Université Claude Bernard, Lyon 1, Lyon, France
| | - Sandrine Lemoine
- Department Néphrologie, Dialyse, Hypertension Et Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Université Claude Bernard, Lyon 1, Lyon, France
| | - Jeffrey W Meeusen
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Surendra Dasari
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - John C Lieske
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Andrew Robertson
- Department of Research and Development, Numares AG,, Am BioPark 9, 93053, Regensburg, Germany
| | - Eric Schiffer
- Department of Research and Development, Numares AG,, Am BioPark 9, 93053, Regensburg, Germany.
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12
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McCarthy C, Schoeller D, Brown JC, Gonzalez MC, Varanoske AN, Cataldi D, Shepherd J, Heymsfield SB. D 3 -creatine dilution for skeletal muscle mass measurement: historical development and current status. J Cachexia Sarcopenia Muscle 2022; 13:2595-2607. [PMID: 36059250 PMCID: PMC9745476 DOI: 10.1002/jcsm.13083] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 07/20/2022] [Accepted: 07/26/2022] [Indexed: 12/15/2022] Open
Abstract
The French chemist Michel Eugène Chevreul discovered creatine in meat two centuries ago. Extensive biochemical and physiological studies of this organic molecule followed with confirmation that creatine is found within the cytoplasm and mitochondria of human skeletal muscles. Two groups of investigators exploited these relationships five decades ago by first estimating the creatine pool size in vivo with 14 C and 15 N labelled isotopes. Skeletal muscle mass (kg) was then calculated by dividing the creatine pool size (g) by muscle creatine concentration (g/kg) measured on a single muscle biopsy or estimated from the literature. This approach for quantifying skeletal muscle mass is generating renewed interest with the recent introduction of a practical stable isotope (creatine-(methyl-d3 )) dilution method for estimating the creatine pool size across the full human lifespan. The need for a muscle biopsy has been eliminated by assuming a constant value for whole-body skeletal muscle creatine concentration of 4.3 g/kg wet weight. The current single compartment model of estimating creatine pool size and skeletal muscle mass rests on four main assumptions: tracer absorption is complete; tracer is all retained; tracer is distributed solely in skeletal muscle; and skeletal muscle creatine concentration is known and constant. Three of these assumptions are false to varying degrees. Not all tracer is retained with urinary isotope losses ranging from 0% to 9%; an empirical equation requiring further validation is used to correct for spillage. Not all tracer is distributed in skeletal muscle with non-muscle creatine sources ranging from 2% to 10% with a definitive value lacking. Lastly, skeletal muscle creatine concentration is not constant and varies between muscles (e.g. 3.89-4.62 g/kg), with diets (e.g. vegetarian and omnivore), across age groups (e.g. middle-age, ~4.5 g/kg; old-age, 4.0 g/kg), activity levels (e.g. athletes, ~5 g/kg) and in disease states (e.g. muscular dystrophies, <3 g/kg). Some of the variability in skeletal muscle creatine concentrations can be attributed to heterogeneity in the proportions of wet skeletal muscle as myofibres, connective tissues, and fat. These observations raise serious concerns regarding the accuracy of the deuterated-creatine dilution method for estimating total body skeletal muscle mass as now defined by cadaver analyses of whole wet tissues and in vivo approaches such as magnetic resonance imaging. A new framework is needed in thinking about how this potentially valuable method for measuring the creatine pool size in vivo can be used in the future to study skeletal muscle biology in health and disease.
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Affiliation(s)
- Cassidy McCarthy
- Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeLos AngelesUSA
| | - Dale Schoeller
- Biotechnology Center and Nutritional SciencesUniversity of WisconsinMadisonWisconsinUSA
| | - Justin C. Brown
- Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeLos AngelesUSA
| | - M. Cristina Gonzalez
- Post‐graduate Program in Health and BehaviorCatholic University of PelotasPelotasBrazil
| | - Alyssa N. Varanoske
- Military Nutrition DivisionUS Army Research Institute of Environmental MedicineNatickMassachusettsUSA
- Oak Ridge Institute for Science and EducationOak RidgeTennesseeUSA
| | | | | | - Steven B. Heymsfield
- Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeLos AngelesUSA
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13
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G C, V G, R N, Kaarthikeyan G, S M. Lipid and renal profile in assessing the severity of alcoholic liver disease. Bioinformation 2022; 18:1036-1040. [PMID: 37654846 PMCID: PMC10465763 DOI: 10.6026/973206300181036] [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: 09/02/2022] [Revised: 10/31/2022] [Accepted: 10/31/2022] [Indexed: 09/02/2023] Open
Abstract
Lipid and Renal dysfunction in Alcoholic liver disease (ALD) patients occurs either due to multi-organ involvement or secondary to alcoholism. This study was conducted to evaluate the role of lipid and renal parameters in assessing the severity of progression of ALD. Sixty cases of ALD (two groups based on compensated and decompensated features) and thirty healthy controls for comparison were included. Lipid profile (Total Cholesterol, LDL, HDL and Triglycerides) and renal parameters (serum urea, creatinine and uric acid), total and direct bilirubin, total protein and albumin were measured using automated chemistry analyzer. There was a significant decrease in Total cholesterol ,LDL and HDL levels and increased triglycerides when compared to controls (mean of 128.4 ± 59 vs 155 ± 27.2, 77 ± 44.3 vs 97.4 ± 27.2, 28.3 ± 18 vs 39.5 ± 14.1 and 115.8 ± 70.4 vs 91 ± 38 mg/dL respectively). Lipid profile showed a linear decrease while progressing from compensated to decompensated ALD. Renal parameters revealed a statistically significant decrease in serum urea ,increased creatinine and uric acid levels when compared to controls (17.57±2.96 vs23.73±4.94, 1.12±0.55 vs0.88±0.16,6.60±1.32 vs 4.68±1.40 mg/dL respectively).Total cholesterol and HDL showed a linear decrease when ALD progresses. Serum uric acid showed an early increase in compensated stage of ALD. This study inferred that Total cholesterol, TGL, HDL and uric acid can be used for assessing the severity of progression of ALD.
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Affiliation(s)
| | - Gomathi V
- Institute of Biochemistry, Madras Medical College, RGGGH, Chennai, India
| | - Nachiappan R
- Institute of Biochemistry, Madras Medical College, RGGGH, Chennai, India
| | - Gurumoorthy Kaarthikeyan
- Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai - 77, India
| | - Mahalakshmi S
- Department of Biochemistry, Madurai Medical College, Madurai, Tamilnadu, India
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14
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Hudkova O, Krysiuk I, Drobot L, Latyshko N. Rhabdomyolysis attenuates activity of semicarbazide sensitive amine oxidase as the marker of nephropathy in diabetic rats. UKRAINIAN BIOCHEMICAL JOURNAL 2022. [DOI: 10.15407/ubj94.01.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
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15
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Nguyen M, Mukaneza Y, Tremblay M, Huard G, Tang A, Rose CF, Bémeur C. Renal dysfunction independently predicts muscle mass loss in patients following liver transplantation. CANADIAN LIVER JOURNAL 2022; 5:411-423. [DOI: 10.3138/canlivj-2021-0042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 03/07/2022] [Accepted: 03/13/2022] [Indexed: 11/20/2022]
Abstract
BACKGROUND: Liver transplantation (LT) is the only curative treatment for cirrhosis. However, the presence of complications can impact outcomes following LT. Sarcopenia, or muscle mass loss, is highly prevalent in patients with cirrhosis and is associated with longer hospitalization stays and a higher infection rate post-surgery. We aimed to identify patients at higher risk of early sarcopenia post-LT. METHODS: This retrospective study included 79 cirrhotic patients who underwent LT. Muscle mass was evaluated using the third lumbar spine vertebra skeletal muscle mass index (SMI) and sarcopenia was defined using established cut-off values. Computerized tomography (CT) scans performed within six-month peri-operative period (three months pre- and post-LT) were included in the study. Complications and comorbidities were collected and correlated to SMI post-LT and predictive models for SMI post-LT were constructed. RESULTS: The overall prevalence of sarcopenia was 46% and 62% before and after LT, respectively. Newly developed sarcopenia was found in 42% of patients. Post-LT sarcopenia was associated with longer hospital stays (54±37 vs 29±10 days, p = 0.002), higher number of infection (3±1 vs 1±2, p = 0.027), and greater number of complications (5±2 vs 3±2, p <0.001) compared to absence of sarcopenia. Multivariate analyses showed that the SMI post-LT was independently associated with pre-LT renal function markers, the glomerular filtration rate (GFR) and creatinine (Model 1, GFR: β = 0.33; 95% CI = 0.04–0.17; p = 0.003; Model 2, Creatinine: β = –0.29; 95% CI = –0.10 to –0.02; p = 0.009). CONCLUSIONS: The present study highlights the potential role of renal dysfunction in the development and persistence of sarcopenia after LT.
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Affiliation(s)
- Mimosa Nguyen
- Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada
| | - Yvette Mukaneza
- Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada
| | - Mélanie Tremblay
- Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada
| | - Geneviève Huard
- Centre hospitalier de l’Université de Montréal, Montréal, Québec, Canada
| | - An Tang
- Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada
- Centre hospitalier de l’Université de Montréal, Montréal, Québec, Canada
- Department of Radiology, Radiation Oncology and Nuclear Medicine, Université de Montréal, Montréal, Québec, Canada
| | - Christopher F Rose
- Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada
- Department of Medicine, Université de Montréal, Montréal, Québec, Canada
| | - Chantal Bémeur
- Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada
- Department of Nutrition, Université de Montréal, Montréal, Québec, Canada
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16
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Chan YJ, Chang SS, Wu JL, Wang ST, Yu CS. Association between liver stiffness measurement by transient elastography and chronic kidney disease. Medicine (Baltimore) 2022; 101:e28658. [PMID: 35089208 PMCID: PMC8797510 DOI: 10.1097/md.0000000000028658] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 12/23/2021] [Accepted: 01/04/2022] [Indexed: 01/05/2023] Open
Abstract
ABSTRACT Transient elastography or elastometry (TE) is widely used for clinically cirrhosis and liver steatosis examination. Liver fibrosis and fatty liver had been known to share some co-morbidities that may result in chronic impairment in renal function. We conducted a study to analyze the association between scores of 2 TE parameters, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), with chronic kidney disease among health checkup population.This was a retrospective, cross-sectional study. Our study explored the data of the health checkup population between January 2009 and the end of June 2018 in a regional hospital. All patients were aged more than 18 year-old. Data from a total of 1940 persons were examined in the present study. The estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease (MDRD-simplify-GFR) equation. Chronic kidney disease (CKD) was defined as eGFR < 60 mL/min/1.73 m2.The median of CAP and LSM score was 242, 265.5, and 4.3, 4.95 in non-CKD (eGFR > 60) and CKD (eGFR < 60) group, respectively. In stepwise regression model, we adjust for LSM, CAP, inflammatory markers, serum biochemistry markers of liver function, and metabolic risks factors. The P value of LSM score, ALT, AST, respectively is .005, <.001, and <.001 in this model.The LSM score is an independent factor that could be used to predict renal function impairment according to its correlation with eGFR. This result can further infer that hepatic fibrosis may be a risk factor for CKD.
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Affiliation(s)
- Ya-Ju Chan
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Shy-Shin Chang
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jenny L. Wu
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
| | - Sen-Te Wang
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Health Management Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Cheng-Sheng Yu
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Information Management, Fu Jen Catholic University, New Taipei City, Taiwan
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
- Office of Data Science, Taipei Medical University, Taipei, Taiwan
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17
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Golla K, Mannell H, Benesic A, Dreischulte T, Grill E, Strobach D. Feasibility of the MELD score as a screening tool for pharmacists to identify patients with impaired hepatic function at hospital admission. J Clin Pharm Ther 2022; 47:676-684. [PMID: 35014073 DOI: 10.1111/jcpt.13597] [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: 12/10/2021] [Accepted: 12/23/2021] [Indexed: 11/28/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Hepatic impairment (HI) is a known risk factor for drug safety. The MELD score (Model-for-endstage-liver-disease), calculated from serum creatinine, bilirubin and International Normalized Ratio (INR), is a promising screening tool corresponding to Child-Pugh Score (CPS) for drug adjustment. We tested the feasibility of MELD as an automatic screening tool accounting for correct calculation, interfering factors (IF) and detection of patients corresponding to CPS-B/C potentially requiring drug adjustment. METHODS We retrospectively calculated MELD for a 3-month cohort of surgical patients and assessed need for adjustment of MELD parameters to standard values. IF for INR (oral anticoagulants) and serum creatinine (renal insufficiency (RI; eGFR<60 ml/min/1.73m²); as well as drugs elevating creatinine levels (DECL)) and the number of patients with MELD scores corresponding to CPS-B/C were analysed. For MELD ≥7.5, liver and bile diagnoses were recorded. RESULTS AND DISCUSSION Of 1183 patients, MELD was calculable for 761 (64%; median 7.5, range 6.4-36.8). Parameters had to be adjusted for 690 (91%) patients. IF of parameters were RI in 172 (23%), INR-elevating drugs in 105 (14%) and DECL in 33 (4%) patients. Of 335 (44%) patients with MELD ≥7.5, 122 (36%) had documented liver or bile diagnoses. MELD 10-<15 (corresponding to CPS-B) was found for 105 (14%), MELD ≥15 (corresponding to CPS-C) for 66 (9%) of the 761 patients with a calculated MELD. Referred to all patients, drug adjustments due to possible HI were recommendable for 14% of patients with suspected CPS-B/C. WHAT IS NEW AND CONCLUSION MELD is a feasible screening tool for HI as a risk factor for drug safety at hospital admission when appropriately considering correct parameter adjustment and RI and INR-elevating drugs as IF. Further evaluation of sensitivity and specificity is needed.
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Affiliation(s)
- Kathrin Golla
- Hospital Pharmacy, University Hospital, LMU Munich, Munich, Germany.,Doctoral Program Clinical Pharmacy, University Hospital, LMU Munich, Munich, Germany
| | - Hanna Mannell
- Doctoral Program Clinical Pharmacy, University Hospital, LMU Munich, Munich, Germany
| | - Andreas Benesic
- Department of Internal Medicine - Gastroenterology, Krankenhaus GmbH Weilheim-Schongau, Schongau, Germany
| | - Tobias Dreischulte
- Institute of General Practice and Family Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Eva Grill
- Institute for Medical Information Processing, Biometrics and Epidemiology, LMU Munich, Munich, Germany
| | - Dorothea Strobach
- Hospital Pharmacy, University Hospital, LMU Munich, Munich, Germany.,Doctoral Program Clinical Pharmacy, University Hospital, LMU Munich, Munich, Germany
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18
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Reed TJ, D'Ambrosio D, Knollmann-Ritschel BE. Educational Case: Evaluating a patient with cirrhosis. Acad Pathol 2022; 9:100031. [PMID: 35813091 PMCID: PMC9257346 DOI: 10.1016/j.acpath.2022.100031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 01/02/2022] [Accepted: 01/22/2022] [Indexed: 11/15/2022] Open
Affiliation(s)
| | - Danielle D'Ambrosio
- Corresponding author. Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
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19
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Colistin-Induced Acute Kidney Injury and the Effect on Survival in Patients with Multidrug-Resistant Gram-Negative Infections: Significance of Drug Doses Adjusted to Ideal Body Weight. Int J Nephrol 2021; 2021:7795096. [PMID: 34966562 PMCID: PMC8712152 DOI: 10.1155/2021/7795096] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 12/04/2021] [Indexed: 12/31/2022] Open
Abstract
Background Colistin is a lifesaving treatment for multidrug-resistant Gram-negative bacterial (MDR-GNB) infections along with its well-known nephrotoxicity. The controversy of colistin-induced acute kidney injury (AKI) on mortality is noted. This study aimed to determine the risk factors and impact of AKI on the survival and significance of colistin dosage. Methods A retrospective cohort study was performed in adult patients who received intravenous colistin for MDR-GNB treatment between June 2015 and June 2017. Factors influencing colistin-induced AKI and survival were evaluated by Cox regression analysis. Cut-off levels of the colistin dose per ideal body weight (IBW) that significantly affected clinical outcomes were assessed with linearity trends and receiver operating characteristic analyses. Results AKI occurred in 68.5% of 412 enrolled patients with an incidence rate of 10.6 per 100 patients-days and a median time was 6 (3–13) days. Stages I–III of AKI were 38.3, 24.5, and 37.2%. Factors associated with colistin-induced AKI were advanced age, high serum bilirubin, AKI presented before colistin administration, increased daily colistin doses per IBW, and concomitant use of nephrotoxic drugs. Colistin-induced AKI was related to mortality (HR 1.74, 95% CI 1.06–2.86, p=0.028). In the non-AKI before colistin usage subgroup, the total dose and total dose/IBW were >1,500–2,000 mg and 30–35 mg/kg to benefit mortality reduction but were <2,500–3,000 mg and 45–50 mg/kg for risk reduction of AKI. A daily colistin dose/IBW >4.5 mg/kg/day also increased the risk of AKI. In the AKI developed before colistin subgroup, the cut-off values of total colistin dose >1250–1350 mg and total dose/IBW >23.5–24 mg/kg demonstrated significant risks of AKI. Conclusion The incidence of AKI after colistin administration was high and impacted mortality. Prevention and early correction of these related factors are mandatory. Careful use of colistin was also both beneficial in mortality and AKI reductions.
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20
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El Hassani M, Simard C, Pilote S, Cloutier I, Soufsaf S, Marsot A. Consideration of height-based tobramycin dosing regimens for the treatment of adult cystic fibrosis pulmonary exacerbations. Br J Clin Pharmacol 2021; 88:2246-2255. [PMID: 34820875 DOI: 10.1111/bcp.15154] [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: 09/01/2021] [Revised: 11/10/2021] [Accepted: 11/12/2021] [Indexed: 11/30/2022] Open
Abstract
AIMS Some population pharmacokinetic models have been developed using height to explain some of the interindividual variability in tobramycin pharmacokinetics in cystic fibrosis patients. However, their predictive performance when extrapolated to other clinical centres is unclear. Therefore, the aim of this study was to externally evaluate the predictability of tobramycin population pharmacokinetic models with an independent dataset and perform simulations using previously recommended height-based dosing regimens. METHODS A literature search was conducted through the PubMed database to identify relevant population pharmacokinetic models. Tobramycin plasma concentration data from April 2014 to November 2019 were retrospectively collected from the Institut universitaire de cardiologie et de pneumologie de Québec, Canada. External evaluations were performed using NONMEM® v7.5 and RStudio® v1.3.1073. Monte Carlo simulations were performed to evaluate the probability of target attainment of Cmax /MIC ratios for several dosing regimens. RESULTS The validation dataset included 27 patients and 143 concentration samples. Three models were evaluated. Only the ones by Crass et al. and Alghanem et al. performed satisfactorily in terms of prediction-based diagnostics with MDPE values of -3.4% and 29.3% and MDAPE values of 19.0 and 29.5%, respectively. In simulation-based evaluations, both pcVPC and NPDE showed no evidence of model misspecification. Our simulations suggest that patients treated with a once-daily dose of 3.4 mg/cm should produce peak and trough levels consistent with current guidelines. CONCLUSION Our results show that the models by Crass et al. and Alghanem et al. are appropriate for simulation-based applications to aid individualized dosing in our population and that height-based dosing regimens could be considered in cystic fibrosis patients.
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Affiliation(s)
- Mehdi El Hassani
- Faculté de pharmacie, Université de Montréal, Canada.,Laboratoire de suivi thérapeutique pharmacologique et pharmacocinétique, Faculté de pharmacie, Université de Montréal, Canada
| | - Chantale Simard
- Faculté de pharmacie, Université Laval, Canada.,Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec, Canada
| | - Sylvie Pilote
- Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec, Canada
| | - Isabelle Cloutier
- Faculté de pharmacie, Université Laval, Canada.,Département de pharmacie, Institut universitaire de cardiologie et de pneumologie de Québec, Canada
| | - Sara Soufsaf
- Faculté de pharmacie, Université de Montréal, Canada
| | - Amélie Marsot
- Faculté de pharmacie, Université de Montréal, Canada.,Laboratoire de suivi thérapeutique pharmacologique et pharmacocinétique, Faculté de pharmacie, Université de Montréal, Canada
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21
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Doba S, Buzlama A. Protective effect of three developed gel formulations: Chitosan, Chitosan with Taurine and Chitosan with Dexpanthenol, on the acute overdose of Diclofenac sodium in preclinical studies. RESEARCH JOURNAL OF PHARMACY AND TECHNOLOGY 2021:4341-4348. [DOI: 10.52711/0974-360x.2021.00754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Objectives: To investigate the tissue-protective effects of three gel formulations (chitosan, chitosan with taurine or chitosan with dexpanthenol) as active substances against an acute overdose of diclofenac sodium. Methods: White outbred conventional male rats were allocated to five experimental groups: the first is an intact group that did not receive any drug, the second group is a control group that received 50mg/kg of diclofenac sodium once orally, the third, fourth and fifth groups are an experimental group that received our studied drugs at a dose of 0.16ml/100mg b.w. once orally 1 hr. before diclofenac sodium, the third group received chitosan-based gel 1%, the fourth group received chitosan-based gel 1% with 4% taurine and the fifth group chitosan-based gel 1% with 0.43% dexpanthenol. Blood samples were taken for biochemical, hematological and blood coagulation system tests on day 7th after administration of diclofenac sodium. Results: An acute overdose of diclofenac sodium caused marked extensive tissue necrosis in the liver, bleeding in the gastrointestinal tract and inflammatory process, these marks were evidenced by different changes in the test of the blood samples. Significantly 73.6% of the blood indicators were improved by the administration of chitosan-based gel 1% with 0.43% dexpanthenol, while 57.8% were improved by chitosan-based gel 1% with 4% taurine and 68.4% by chitosan-based gel 1%. Conclusion: Chitosan-based gel 1% with dexpanthenol 0.43% can help in mitigating hepatic injury, gastrointestinal bleeding, and systemic and local intestinal inflammation caused by an acute overdose of diclofenac sodium.
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Affiliation(s)
- Solaiman Doba
- Department of Pharmacology and Clinical Pharmacology, Faculty of Pharmacy, Voronezh State University, Russia
| | - Anna Buzlama
- Department of Pharmacology and Clinical Pharmacology, Faculty of Pharmacy, Voronezh State University, Russia
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22
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Nazeer SS, Sreedevi TP, Jayasree RS. Autofluorescence spectroscopy and multivariate analysis for predicting the induced damages to other organs due to liver fibrosis. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2021; 257:119741. [PMID: 33872953 DOI: 10.1016/j.saa.2021.119741] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 03/17/2021] [Accepted: 03/19/2021] [Indexed: 06/12/2023]
Abstract
When our liver does not work well, it can induce damage to other organs causing their dysfunction. With this background, we aim to study the effect of liver fibrosis on other organs such as heart, lungs, kidney and spleen by assessing the variations in the inherent emission property of the tissue, using fluorescence spectroscopy. Fluorescence emission spectra from excised organs of liver fibrosis induced rats were collected at excitation wavelengths 320 and 410 nm. Optical redox ratio derived from the spectral data supported by multivariate statistical analysis, principal component analysis followed by linear discriminant analysis (PCA-LDA) distinguished between control and fibrosis induced groups. The two different excitation wavelength provided variations in the endogenous flurophores collagen, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), lipopigments and porphyrins. Additionally, evaluation of redox ratio provided variations in tissue metabolic activity of different organs. The PCA-LDA modelling yielded a sensitivity of 85 to 97% and specificity of 80 to 96% on 320 nm excitation and a sensitivity of 72 to 100% and specificity of 59 to 100% on 410 nm excitation. Fluorescence emission spectral study along with multivariate analysis paved way to identify the biochemical alterations caused to other organs due to the development of liver fibrosis, which could lead to their damage and dysfunction.
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Affiliation(s)
- Shaiju S Nazeer
- Department of Chemistry, Indian Institute of Space Sciences and Technology, Thiruvananthapuram, Kerala, India; Division of Biophotonics and Imaging, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
| | - T P Sreedevi
- Department of Optoelectronics and Communication, Thangal Kunju Musaliar Institute of Technology, Kollam, Kerala, India
| | - Ramapurath S Jayasree
- Division of Biophotonics and Imaging, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.
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Lang M, Lang AL, Tsui BQ, Wang W, Erly BK, Shen B, Kapoor B. Renal-function change after transjugular intra-hepatic portosystemic shunt placement and its relationship with survival: a single-center experience. Gastroenterol Rep (Oxf) 2021; 9:306-312. [PMID: 34567562 PMCID: PMC8460113 DOI: 10.1093/gastro/goaa081] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 09/15/2020] [Accepted: 09/27/2020] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND The effect of transjugular intra-hepatic portosystemic shunt (TIPS) placement on renal function and the correlation of post-TIPS Cr with mortality remain unclear. This study aimed to assess the effect of TIPS placement on renal function and to examine the relationship between post-TIPS Cr and mortality risk. METHODS A total of 593 patients who underwent de novo TIPS placement between 2004 and 2017 at a single institution were included in the study. The pre-TIPS Cr level (T0; within 7 days before TIPS placement) and post-TIPS Cr levels, at 1-2 days (T1), 5-12 days (T2), and 15-40 days (T3), were collected. Predictors of Cr change after TIPS placement and the 1-year mortality rate were analysed using multivariable linear-regression and Cox proportional-hazards models, respectively. RESULTS Overall, 21.4% of patients (n = 127) had elevated baseline Cr (≥1.5 mg/dL; mean, 2.51 ± 1.49 mg/dL) and 78.6% (n = 466) had normal baseline Cr (<1.5 mg/dL; mean, 0.92 ± 0.26 mg/dL). Patients with elevated pre-TIPS Cr demonstrated a decrease in post-TIPS Cr (difference, -0.60 mg/dL), whereas patients with normal baseline Cr exhibited no change (difference, <0.01 mg/dL). The 30-day, 90-day, and 1-year mortality rates were 13%, 20%, and 32%, respectively. Variceal bleeding as a TIPS-placement indication (hazard ratio = 1.731; P = 0.036), higher T0 Cr (hazard ratio = 1.834; P = 0.012), and higher T3 Cr (hazard ratio = 3.524; P < 0.001) were associated with higher 1-year mortality risk. CONCLUSION TIPS placement improved renal function in patients with baseline renal dysfunction and the post-TIPS Cr level was a strong predictor of 1-year mortality risk.
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Affiliation(s)
- Min Lang
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Angela L. Lang
- Department of Anesthesia, Critical Care, and Pain Management, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Brian Q. Tsui
- Department of Radiology, UCLA Medical Center, Los Angeles, CA, USA
| | - Weiping Wang
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Brian K. Erly
- Colorado School of Public Health, Aurora, Colorado, USA
| | - Bo Shen
- The Inflammatory Bowel Disease Center at Columbia, Columbia University Irving Medical Center, New York, NY, USA
| | - Baljendra Kapoor
- Division of Vascular and Interventional Radiology, Imaging Institute, Cleveland Clinic, Cleveland, OH, USA
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El-Makarem MAERA, Mousa MM, Ayaad LA, Keryakos HKH. Comparative study of various glomerular filtration rate estimating equations in Egyptian patients with hepatitis C virus-related liver cirrhosis: a single-center observational study. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00093-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Accurate assessment of GFR is critical in patients with chronic liver disease for early detection of renal disease. Cystatin C is a marker of GFR that seems to be more accurate than creatinine. The aim of the study is to assess of the performance of creatinine and cystatin C-based GFR equations in Egyptian patients with hepatitis C virus (HCV)-related liver cirrhosis as compared to measured creatinine clearance. GFR was estimated using five equations; three that were based on serum creatinine, another that was based on serum cystatin C, and a third that was based on both in 120 patients with HCV-related liver cirrhosis as well as 60 age- and sex-matched healthy controls. The bias, precision, and accuracy of each equation were determined as compared to measured creatinine clearance using the traditional equation U*V/P.
Results
The mean measured creatinine clearance was 51.39 ± 16.05 ml/min per 1.73 m2. The CKD-EPI creatinine-cystatin C equation had the greatest precision (7.5 ml/min per 1.73 m2), and highest accuracy (68 and 93% within 10% and 30% of measured GFR, respectively), but not the lowest bias (5.4 ml/min per 1.73 m2). The CKD-EPI creatinine-cystatin C equation remained accurate even in both males (69 and 90% within 10% and 30% of measured GFR, respectively) and females (68 and 97% within 10% and 30% of measured GFR, respectively). The CKD-EPI creatinine-cystatin C equation remained accurate even when the measured GFR was ≥ 60 ml/min per 1.73 m2 (60 and 90% within 10% and 30% of measured GFR, respectively with precision 10.5 ml/min per 1.73 m2).
Conclusion
CKD-EPI creatinine-cystatin C equation is more accurate at predicting GFR in HCV-related liver cirrhosis than creatinine- and cystatin-C alone based equations.
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Shankar V, Raj A, Singhal S, Sahni R, Goyal N, Venuthurimilli A, Olson MT, Chatterji C. Doppler-derived renal resistive index helps predict acute kidney injury in patients undergoing living-related liver transplantation. Clin Transplant 2021; 35:e14263. [PMID: 33608962 DOI: 10.1111/ctr.14263] [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: 10/30/2020] [Revised: 01/24/2021] [Accepted: 02/13/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Acute kidney injury (AKI) is commonly associated with increased postoperative morbidity in liver transplant (LT) recipients. The aim of this study was to identify the role of renal resistive index (RRI) in predicting AKI and to study the factors associated with AKI in LT recipients. PATIENTS AND METHODS We performed a single-center, prospective study, including adult living donor LT recipients at our center between January 2018 and September 2019 with no preoperative renal dysfunction. RRI was calculated on ultrasound doppler once preoperatively, and once daily in the postoperative period through postoperative day (POD) six. Patients were grouped into AKI and non-AKI groups for comparison. RESULTS Fifty patients were included in the study (mean age, 44 years; 20% females). AKI developed in 25 patients (50%). Both groups were similar in baseline characteristics. RRI of ≥ 0.69 on POD 2 predicted AKI (sensitivity 88%; specificity 92%). RRI on the day before AKI diagnosis (0.71 vs. 0.65) and on the day of diagnosis (0.72 vs. 0.65) were significantly increased relative to preoperative baseline. CONCLUSIONS Doppler-derived RRI is a rapid, non-invasive, and bedside procedure capable of predicting the occurrence of postoperative AKI in LT recipients.
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Affiliation(s)
- Vijay Shankar
- Department of Anesthesiology and Critical Care, Indraprastha Apollo Hospital, New Delhi, India
| | - Anupam Raj
- Department of Anesthesiology and Critical Care, Indraprastha Apollo Hospital, New Delhi, India
| | - Saurabh Singhal
- Liver Transplant and Hepatopancreaticobiliary Unit, Indraprastha Apollo Hospital, New Delhi, India
| | - Reeti Sahni
- Department of Radiology, Indraprastha Apollo Hospital, New Delhi, India
| | - Neerav Goyal
- Liver Transplant and Hepatopancreaticobiliary Unit, Indraprastha Apollo Hospital, New Delhi, India
| | - Arun Venuthurimilli
- Liver Transplant and Hepatopancreaticobiliary Unit, Indraprastha Apollo Hospital, New Delhi, India
| | - Michael T Olson
- Department of Surgery, University of Arizona College of Medicine -Phoenix Campus, Phoenix, AZ, USA
| | - Chitra Chatterji
- Department of Anesthesiology and Critical Care, Indraprastha Apollo Hospital, New Delhi, India
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Cedeño Y, Miranda M, Orjales I, Herrero-Latorre C, Suárez M, Luna D, López-Alonso M. Trace Element Levels in Serum Are Potentially Valuable Diagnostic Markers in Dogs. Animals (Basel) 2020; 10:E2316. [PMID: 33297385 PMCID: PMC7762272 DOI: 10.3390/ani10122316] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/26/2020] [Accepted: 12/04/2020] [Indexed: 01/04/2023] Open
Abstract
The objective of this study was to obtain information about the role of trace element imbalance in the pathogenesis of certain diseases in dogs and to evaluate the suitability of trace element profiling as an additional tool in the diagnosis. Serum trace element concentrations (copper, molybdenum, selenium and zinc) were measured in a cohort of healthy (control) dogs (n = 42) and dogs affected by hepatic (n = 25), gastrointestinal (n = 24), inflammatory/infection (n = 24), and renal (n = 22) diseases. These data were analyzed together with data on basic biochemical parameters (alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine, albumin, globulin, and glucose) by using chemometric techniques. The chemometric analysis revealed distinctive association patterns between trace elements and biochemical parameters for each clinical disorders. The findings provide clear evidence for the important role of trace elements in disease, particularly in relation to acute phase reactions, with serum copper providing an indirect measurement of ceruloplasmin (positive acute-phase protein) and serum selenium and zinc acting as negative acute phase reactants. Molybdenum may also be a suitable marker of incipient renal disease. Thus, the analysis of trace element profiles, by multielement techniques, in a single serum sample would be a valuable additional tool for the diagnosis of certain diseases.
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Affiliation(s)
- Yolanda Cedeño
- Department of Animal Pathology, Faculty of Veterinary, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain; (Y.C.); (D.L.); (M.L.-A.)
- Faculty of Veterinary Medicine, Universidad Central del Ecuador, EC170521 Quito, Ecuador
| | - Marta Miranda
- Department of Anatomy, Animal Production and Clinical Veterinary Sciences, Faculty of Veterinary, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain; (I.O.); (M.S.)
- Rof-Codina Veterinary Teaching Hospital, Faculty of Veterinary, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain
| | - Inmaculada Orjales
- Department of Anatomy, Animal Production and Clinical Veterinary Sciences, Faculty of Veterinary, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain; (I.O.); (M.S.)
- Rof-Codina Veterinary Teaching Hospital, Faculty of Veterinary, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain
| | - Carlos Herrero-Latorre
- Research Institute on Chemical and Biological Analysis, Analytical Chemistry, Nutrition and Bromatology Department, Faculty of Sciences, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain;
| | - Maruska Suárez
- Department of Anatomy, Animal Production and Clinical Veterinary Sciences, Faculty of Veterinary, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain; (I.O.); (M.S.)
- Rof-Codina Veterinary Teaching Hospital, Faculty of Veterinary, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain
| | - Diego Luna
- Department of Animal Pathology, Faculty of Veterinary, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain; (Y.C.); (D.L.); (M.L.-A.)
- Faculty of Veterinary Medicine, Universidad Central del Ecuador, EC170521 Quito, Ecuador
| | - Marta López-Alonso
- Department of Animal Pathology, Faculty of Veterinary, Campus Terra, Universidade de Santiago de Compostela, 27002 Lugo, Spain; (Y.C.); (D.L.); (M.L.-A.)
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Tassinari R, Narciso L, Tait S, Busani L, Martinelli A, Di Virgilio A, Carli F, Deodati A, La Rocca C, Maranghi F. Juvenile Toxicity Rodent Model to Study Toxicological Effects of Bisphenol A (BPA) at Dose Levels Derived From Italian Children Biomonitoring Study. Toxicol Sci 2020; 173:387-401. [PMID: 31697385 DOI: 10.1093/toxsci/kfz226] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Bisphenol A (BPA) is a plasticizer with endocrine disrupting properties particularly relevant for children health. Recently BPA has been associated with metabolic dysfunctions but no data are yet available in specific, long-term studies. This study aimed to evaluate BPA modes of action and hazards during animal juvenile life-stage, corresponding to childhood. Immature Sprague-Dawley rats of both sexes were orally treated with 0 (vehicle only-olive oil), 2, 6, and 18 mg/kg bw per day of BPA for 28 days, from weaning to sexual maturity. Dose levels were obtained from the PERSUADED biomonitoring study in Italian children. Both no-observed-adverse-effect-level (NOAEL)/low-observed-adverse-effect-level (LOAEL) and estimated benchmark dose (BMD) approaches were applied. General toxicity, parameters of sexual development, endocrine/reproductive/functional liver and kidney biomarkers, histopathology of target tissues, and gene expression in hypothalamic-pituitary area and liver were studied. No mortality or general toxicity occurred. Sex-specific alterations were observed in liver, thyroid, spleen, leptin/adiponectin serum levels, and hypothalamic-pituitary gene expression. Thyroid homeostasis and liver were the most sensitive targets of BPA exposure in the peripubertal phase. The proposed LOAEL was 2 mg/kg bw, considering as critical effect the liver endpoints, kidney weight in male and adrenal histomorphometrical alterations and osteopontin upregulation in female rats. The BMD lower bounds were 0.05 and 1.33 mg/kg bw in males and females, considering liver and thyroid biomarkers, respectively. Overall, BPA evaluation at dose levels derived from children biomonitoring study allowed to identify sex-specific, targeted toxicological effects that may have significant impact on risk assessment for children.
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Affiliation(s)
| | | | | | | | - Andrea Martinelli
- Experimental Animal Welfare Sector, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Antonio Di Virgilio
- Experimental Animal Welfare Sector, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Fabrizia Carli
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Annalisa Deodati
- Dipartimento Pediatrico Universitario Ospedaliero "Bambino Gesù".,Children's Hospital-Tor Vergata University, Rome, Italy
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Matsinkou RS, Oumbe VAS, Ngondi JL, Oben JE. Protective effects of peel extracts of Irvingia wombolu on metabolic disorders in streptozotocin-induced diabetic rats. CLINICAL PHYTOSCIENCE 2020. [DOI: 10.1186/s40816-020-00218-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
AbstractBackgroundDiabetes is widely recognized as associated with several structural and functional liver, kidney, and heart abnormalities. Therefore, the present study was conducted to evaluate the protective effect of peel extracts ofIrvingia womboluagainst diabetes complications.MethodsDiabetes was induced by intravenous administration of streptozotocin (STZ) (50 mg/kg) through the right jugular vein on rats and animals with blood glucose values of at least 250 mg/dl received orally aqueous extract of peel (AEP), hydroethanolic extract of peel (HEP), tolbutamide and DMSO 10%. Their effects on the concentration of blood glucose, total cholesterol, HDL-C, LDL-C, triglycerides, malondialdehyde (MDA) and activities of catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in diabetic and normal rats were investigated using standard methods.ResultsTwenty-one days of treatment with AEP and HEP at a dose of 400 mg/kg significantly (P < 0,05) reduced the fasting blood glucose to a point of reaching normal value. The antihyperlipidemic assessment of extracts revealed a significant (P < 0,05) decrease in total cholesterol, triglycerides, LDL levels, and a significant (P < 0,05) increase in HDL level in the plasma of treated diabetic rats. Furthermore, plasma biomarkers of liver and kidney dysfunction were significantly reduced in treated diabetic rats. We also observed increased activities of catalase, SOD, and reduced glutathione in diabetic treated rats.ConclusionThe present findings suggest that AEP and HEP have a protective effect on liver, kidney, and heart in experimental diabetic rats which can be beneficial in the management of diabetes and its complications.
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Reese T, Fard-Aghaie MH, Makridis G, Kantas A, Wagner KC, Malagó M, Robles-Campos R, Hernandez-Alejandro R, de Santibañes E, Clavien PA, Petrowsky H, Linecker M, Oldhafer KJ. Renal Impairment Is Associated with Reduced Outcome After Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy. J Gastrointest Surg 2020; 24:2500-2507. [PMID: 31745902 DOI: 10.1007/s11605-019-04419-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 09/16/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Impaired postoperative renal function is associated with increased morbidity and mortality after liver resection. The role of impaired renal function in the two-stage hepatectomy setting of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is unknown. METHODS An international multicenter cohort of ALPPS patients captured in the ALPPS Registry was analyzed. Particular attention was drawn to the renal function in the interstage interval to determine outcome after stage 2 surgery. Interstage renal impairment (RI) was defined as an increase of serum creatinine of ≥ 0.3 mg/dl referring to a preoperative value or an increase of serum creatinine of ≥ 1.5× of the preoperative value on the fifth postoperative day after stage 1. RESULTS A total of 705 patients were identified of which 7.5% had an interstage RI. Patients developing an interstage RI were significantly older. During stage 1, a longer operation time, higher rate of intraoperative transfusions, and additional procedures were observed in patients that developed interstage RI. After stage 1, interstage RI patients had more major complications and higher interstage mortality (1% vs. 8%, p < 0.001). Furthermore, these patients developed more and severe complications after completion of stage 2. Mortality of patients with interstage RI was 38% vs. 8% without interstage RI. In 41% of patients with interstage RI, the renal function recovered before stage 2; however, the mortality after stage 2 remained 28% in those patients. Risk factors for the development of an interstage RI were age over 67 years, prolonged operative time, and additional procedure during stage 1. CONCLUSION This study shows that interstage RI is a predictor for interstage and post-stage 2 morbidity and perioperative mortality. The causality of impaired renal function on outcome, however, remains unknown. Interstage RI may directly cause adverse outcome but may also be a surrogate marker for major complications.
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Affiliation(s)
- Tim Reese
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Rübenkamp 220, 22291, Hamburg, Germany
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Mohammad H Fard-Aghaie
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Rübenkamp 220, 22291, Hamburg, Germany
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Georgios Makridis
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Rübenkamp 220, 22291, Hamburg, Germany
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Alexandros Kantas
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Rübenkamp 220, 22291, Hamburg, Germany
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Kim C Wagner
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Rübenkamp 220, 22291, Hamburg, Germany
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Massimo Malagó
- Department of HPB and Liver Transplant Surgery, Royal Free Hospital, University College London, London, UK
| | | | | | - Eduardo de Santibañes
- Department of Surgery, Division of HPB Surgery, Liver Transplant Unit, Italian Hospital Buenos Aires, Buenos Aires, Argentina
| | - Pierre-Alain Clavien
- Department of Surgery and Transplantation, Swiss HPB and Transplant Center, University Hospital Zurich, Zurich, Switzerland
| | - Henrik Petrowsky
- Department of Surgery and Transplantation, Swiss HPB and Transplant Center, University Hospital Zurich, Zurich, Switzerland
| | - Michael Linecker
- Department of Surgery and Transplantation, Swiss HPB and Transplant Center, University Hospital Zurich, Zurich, Switzerland
| | - Karl J Oldhafer
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Rübenkamp 220, 22291, Hamburg, Germany.
- Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany.
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Lacquaniti A, Campo S, Casuscelli Di Tocco T, Rovito S, Bucca M, Ragusa A, Monardo P. Acute and chronic kidney disease after pediatric liver transplantation: An underestimated problem. Clin Transplant 2020; 34:e14082. [PMID: 32949054 DOI: 10.1111/ctr.14082] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 08/02/2020] [Accepted: 08/15/2020] [Indexed: 12/13/2022]
Abstract
Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), but whereas renal dysfunction in adult transplant patients is well documented, little is known about its prevalence in childhood. It is a challenge to accurately evaluate renal function in patients with liver disease, due to several confounding factors. Creatinine-based equations estimating glomerular filtration rate, validated in nephropathic patients without hepatic issues, are frequently inaccurate in end-stage liver disease, underestimating the real impact of renal disease. Moreover, whereas renal issues observed within 1 year from LTx were often related to acute injuries, kidney damage observed after 5-7 years from LTx, is due to chronic, irreversible mechanisms. Most immunosuppression protocols are based on calcineurin inhibitors (CNIs) and corticosteroids, but mycophenolate mofetil or sirolimus could play significant roles, also in children. Early diagnosis and personalized treatment represent the bases of kidney disease management, in order to minimize its close relation with increased mortality. This review analyzed acute and chronic kidney damage after pediatric LTx, also discussing the impact of pre-existent renal disease. The main immunosuppressant strategies have been reviewed, highlighting their impact on kidney function. Different methods assessing renal function were reported, with the potential application of new renal biomarkers.
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Affiliation(s)
- Antonio Lacquaniti
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Susanna Campo
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Teresa Casuscelli Di Tocco
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Stefania Rovito
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Maurizio Bucca
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Antonino Ragusa
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Paolo Monardo
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
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Rawat D, Shrivastava S, Naik RA, Chhonker SK, Koiri RK. SIRT1-mediated amelioration of oxidative stress in kidney of alcohol-aflatoxin-B1-induced hepatocellular carcinoma by resveratrol is catalase dependent and GPx independent. J Biochem Mol Toxicol 2020; 34:e22576. [PMID: 32640115 DOI: 10.1002/jbt.22576] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 05/10/2020] [Accepted: 06/23/2020] [Indexed: 01/18/2023]
Abstract
Hepatocellular carcinoma (HCC) is a type of primary liver cancer and dietary exposure to aflatoxins is a major risk factor of HCC. The current study aimed to assess the role of resveratrol and nicotinamide in renal toxicity during alcohol-aflatoxin-B1-induced HCC. The results revealed that resveratrol treatment normalized the level of urea, lipid peroxidation, lactate and lactate dehydrogenase, which were increased in HCC. It also downregulated the increased expression of sirtuin 1 in HCC kidney. Furthermore, amelioration of oxidative stress in kidney of HCC rats by resveratrol was observed to be catalase dependent and glutathione peroxidase independent.
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Affiliation(s)
- Divya Rawat
- Biochemistry Laboratory, Department of Zoology, Dr Harisingh Gour Vishwavidyalaya, Sagar, India
| | - Somi Shrivastava
- Biochemistry Laboratory, Department of Zoology, Dr Harisingh Gour Vishwavidyalaya, Sagar, India
| | - Rayees Ahmad Naik
- Biochemistry Laboratory, Department of Zoology, Dr Harisingh Gour Vishwavidyalaya, Sagar, India
| | - Saurabh Kumar Chhonker
- Biochemistry Laboratory, Department of Zoology, Dr Harisingh Gour Vishwavidyalaya, Sagar, India
| | - Raj Kumar Koiri
- Biochemistry Laboratory, Department of Zoology, Dr Harisingh Gour Vishwavidyalaya, Sagar, India
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Racial/Ethnic Disparities in Access and Outcomes of Simultaneous Liver-Kidney Transplant Among Liver Transplant Candidates With Renal Dysfunction in the United States. Transplantation 2020; 103:1663-1674. [PMID: 30720678 DOI: 10.1097/tp.0000000000002574] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Since the Model for End-stage Liver Disease (MELD) allocation system was implemented, the proportion of simultaneous liver-kidney transplantation (SLKT) has increased significantly. However, whether racial/ethnic disparities exist in access to SLKT and post-SLKT survival remains understudied. METHODS A retrospective cohort of patients aged ≥18 years with renal dysfunction on the liver transplant (LT) waiting list was obtained from Organ Procurement and Transplantation Network. Renal dysfunction was defined as estimated glomerular filtration rate <60 mL/min/1.73 m at listing for LT. Multilevel time-to-competing-events regression adjusting for center effect was used to examine the likelihood of receiving SLKT. Inverse probability of treatment weighted survival analyses were used to analyze posttransplant mortality outcomes. RESULTS For patients with renal dysfunction at listing for LT, not listed for simultaneous kidney transplant, non-Hispanic black (NHB) and Hispanic patients were more likely to receive SLKT than non-Hispanic white (NHW) patients (NHB: multivariable-adjusted hazard ratio [aHR] 2.57; 95% confidence interval [CI], 1.42-4.65; Hispanic: aHR, 2.03; 95% CI, 1.14-3.60). For post-SLKT outcomes, compared to NHW patients, NHB patients had a lower mortality risk before 24 months (aHR, 0.80; 95% CI, 0.65-0.97) but had a higher mortality risk (aHR, 2.00; 95% CI, 1.59-2.55) afterward; in contrast, Hispanic patients had a lower overall mortality risk than NHW patients (aHR, 0.61; 95% CI, 0.51-0.74). CONCLUSIONS In the MELD era, racial/ethnic differences exist in access and survival of SLKT for patients with renal dysfunction at listing for LT. Future studies are warranted to examine whether these differences remain in the post-SLK allocation policy era.
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Zoccali C, Blankestijn PJ, Bruchfeld A, Capasso G, Fliser D, Fouque D, Goumenos D, Ketteler M, Massy Z, Rychlık I, Jose Soler M, Stevens K, Spasovski G, Wanner C. Children of a lesser god: exclusion of chronic kidney disease patients from clinical trials. Nephrol Dial Transplant 2020; 34:1112-1114. [PMID: 30815678 DOI: 10.1093/ndt/gfz023] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Indexed: 01/28/2023] Open
Abstract
The exclusion of chronic kidney disease (CKD) patients from clinical trials-particularly cardiovascular trials-remains a long-standing, unsolved problem, which prevents the optimization of clinical care in these patients. The situation recalls the insufficient recruitment of women in cardiovascular trials until the 1980s, a problem that was only resolved following regulatory interventions. Regulatory agencies are in a unique position to promote recruitment of CKD patients in clinical trials. The main stakeholders, namely patients' associations and scientific societies, should make major lobbying efforts to persuade these agencies that the issue is an absolute public health priority.
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Affiliation(s)
| | - Peter J Blankestijn
- Department of Nephrology, University Medical Center, Utrecht, The Netherlands
| | - Annette Bruchfeld
- Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | | | - Danilo Fliser
- Internal Medicine IV, Renal and Hypertensive Disease, University Medical Center, Homburg/Saar, Germany
| | - Denis Fouque
- Department of Nephrology, Dialysis, Nutrition, Centre Hospitalier Lyon Sud, Pierre Bénite Cedex, France
| | - Dimitrios Goumenos
- Department of Nephrology and Renal Transplantation, Patras University Hospital, Patras, Greece
| | | | - Ziad Massy
- Division of Nephrology, Ambroise Paré Hospital, Paris Ile de France West University (UVSQ), Villejuif, France
| | - Ivan Rychlık
- First Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Maria Jose Soler
- Department of Nephrology, Hospital Universitari Vall d'Hebron, Nephrology Research Group, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
| | - Kate Stevens
- Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, UK
| | - Goce Spasovski
- Department of Nephrology, Medical Faculty, University of Skopje, Skopje, Former Yugoslav Republic of Macedonia
| | - Christoph Wanner
- Division of Nephrology, University of Würzburg, Würzburg, Germany
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Sinner B, Banas M, Brunete-Lorenzo C, Zant R, Knoppke B, Scherer MN, Graf BM, Lunz D. Acute Kidney Injury and Renal Regional Oxygen Saturation During Pediatric Liver Transplantation. Ann Transplant 2020; 25:e919717. [PMID: 31988274 PMCID: PMC7006365 DOI: 10.12659/aot.919717] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Background Kidney injury is a complication among children undergoing liver transplantation (pLTx). Cystatin C serum concentration seems to be superior to creatinine-based determination of kidney injury in adults and children. Near-infrared spectroscopy (NIRS) technology provides non-invasive and real-time measurement of renal tissue oxygenation. Here, we compared renal tissue oximetry (rSrO2) with conventional diagnostic criteria cystatin C and creatinine concentration in children undergoing pLTx. Material/Methods rSrO2 was measured intraoperatively in children undergoing pLTx over the left kidney, and was statistically compared with pre- and postoperative serum creatinine and cystatin C concentrations. Results rSrO2 was affected by hemoglobin concentration, bilirubin concentration, and FiO2. Statistical analysis demonstrated that rSrO2 was significantly reduced in children with preoperative pathologic increased cystatin C concentrations compared to children without (63.7±4.3 vs. 53.4±4.9, p<0.05). We did not detect a significant difference in rSrO2 between children who developed postoperative renal impairment, either determined by increased postoperative cystatin C concentration, creatinine concentration, or the pRIFLE criteria. Intraoperative increase or decrease in rSrO2 did not predict the development of postoperative kidney injury. Conclusions In children with liver failure undergoing pLTx, a preoperative decrease in rSrO2 indicates compromised renal function. However, intraoperative rSrO2 is not predictive of postoperative kidney injury.
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Affiliation(s)
- Barbara Sinner
- Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany
| | - Miriam Banas
- Department of Nephrology, University Hospital Regensburg, Regensburg, Germany
| | | | - Robert Zant
- Department of Pediatric Cardiology, University Hospital Erlangen, Erlangen, Germany
| | - Birgit Knoppke
- KUNO University Children's Hospital, Regensburg, Germany
| | - Marcus N Scherer
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Bernhard M Graf
- Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany
| | - Dirk Lunz
- Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany
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Wyawahare M, Krishna Reddy SS, Priyamvada PS, Rajendiran S. Utility of Urinary Neutrophil gelatinase associated lipocalin (NGAL) in decompensated cirrhosis. Indian J Nephrol 2020; 30:391-397. [PMID: 33840958 PMCID: PMC8023034 DOI: 10.4103/ijn.ijn_254_19] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 08/29/2019] [Accepted: 11/10/2019] [Indexed: 01/23/2023] Open
Abstract
Background and Aims: Renal failure occurring in the setting of cirrhosis increases mortality by more than threefold. Serum creatinine, the conventional marker for renal dysfunction has inherent limitations in identifying and categorizing renal dysfunction in patients with chronic liver disease (CLD). Neutrophil gelatinase associated lipocalin (NGAL) is a novel biomarker which gets upregulated as early as 2-6 hours following the insult to renal tubules. In this study, we aim to check the utility of uNGAL to identify the different phenotypes of renal dysfunction in patients with CLD. We also intend to assess the utility of NGAL to predict 90-day transplant-free survival in patients with CLD. Methods: A total number of 120 adult patients, with cirrhosis of liver were recruited. Those with pre-existing renal parenchymal disease, receiving nephrotoxic medications, spontaneous bacterial peritonitis, septic shock, proteinuria, hematuria, urinary tract infection and anuria were excluded. Urine samples for NGAL was measured at admission and at 48 hours thereafter. Patients were followed up for 90 days post admission. Results: Among the study population, 16 patients (13.3%) had normal kidney function, 43 (35.8%) had prerenal azotemia and 54 (45%) had Hepatorenal Syndrome (HRS - AKI) and 7 (5.8%) had acute tubular necrosis (ATN). Urinary NGAL (uNGAL) levels were considerably lower in patients with normal kidney function and prerenal azotemia. An uNGAL level of 124 ng/ml on admission could distinguish severe forms of renal injury, with a sensitivity of 86% and specificity of 84%. The non survivors had higher uNGAL levels at admission [209.6 ng/ml (118.7-376.8) vs. 123 (33.6-344.3); P = 0.013].The receiver operated curves for uNGAL and serum creatinine at admission did not show any significant difference for predicting 90 day mortality (AUC for uNGAL: 0.632 vs 0.580 for serum creatinine; difference in AUC 0.053, P value 0.17). Conclusion: uNGAL levels are elevated in patients with HRS-AKI and ATN. A higher uNGAL level at admission was suggestive of severe renal dysfunction. An elevated uNGAL on admission is associated with inferior survival. However, uNGAL is not superior to serum creatinine in predicting 90-day mortality.
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Nour HF, El Malah T. Rapid naked-eye colorimetric detection of gaseous alkaline analytes using rhodamine B hydrazone-coated silica strips. NEW J CHEM 2020. [DOI: 10.1039/d0nj01044h] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Development of rhodamine B hydrazone-coated silica strips for rapid detection of alkaline vapors by the naked-eye or using a smartphone camera.
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Affiliation(s)
- Hany F. Nour
- Photochemistry Department, Chemical Industries Research Division
- National Research Centre
- Cairo
- Egypt
| | - Tamer El Malah
- Photochemistry Department, Chemical Industries Research Division
- National Research Centre
- Cairo
- Egypt
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Bhandari P, Shah Z, Patel K, Patel R. Contrast-induced acute kidney injury following coronary angiography in patients with end-stage liver disease. J Community Hosp Intern Med Perspect 2019; 9:403-409. [PMID: 31723384 PMCID: PMC6830185 DOI: 10.1080/20009666.2019.1661148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 08/19/2019] [Indexed: 12/28/2022] Open
Abstract
Background: Contrast-induced acute kidney injury (CIAKI) following coronary angiography is frequently observed in the general population. End-stage liver disease (ESLD) patients are at a particularly increased risk for development of CIAKI following coronary angiography due to preexisting renal hypoperfusion. Methods: We performed a retrospective study of 544 consecutive cardiac catheterizations in ESLD patients from December 2003 to May 2013 to calculate the incidence of CIAKI post-coronary angiography and to identify risk factors for CIAKI. CIAKI was defined as a serum creatinine increase of either ≥ 25% or ≥ 0.5 mg/dL from baseline within 72 hours. Multivariable and Cox regression analysis was performed for development of CIAKI and all-cause mortality, respectively. Results: Overall, 179 cases of coronary angiography were included in the final analysis. CIAKI occurred in 23% of patients. All-cause mortality was 52% in the CIAKI group and 37% in the non-CIAKI group, with a mean follow-up of 2.2 ± 3.8 years. Multivariable analysis identified intensive care unit admission (OR 2.72, CI 1.05–7.01, p < 0.05) and baseline estimated glomerular filtration rate (OR 1.02, CI 1.002–1.035, p < 0.05) as independent predictors of CIAKI. Cox regression analysis identified pre-angiography beta-blocker use (HR 2.13, CI 1.04–4.38, p < 0.05), international normalized ratio (HR 1.37, CI 1.05–1.78, p < 0.05) and Mehran risk score (HR 1.13, CI 1.02–1.25, p < 0.05) as independent predictors of all-cause mortality. Conclusions: CIAKI in ESLD patients undergoing coronary angiography occurs at a moderately elevated rate when compared to the general population.
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Affiliation(s)
- Priyanka Bhandari
- Departmant of Internal Medicine, Mount Sinai Elmhurst Hospital, New York, USA
| | - Zeel Shah
- Departmant of Internal Medicine, Mount Sinai Elmhurst Hospital, New York, USA
| | - Kush Patel
- Department of Family Medicine, Southside Northwell Hospital, New York, USA
| | - Ruchir Patel
- Departmant of Internal Medicine, Henry Ford Hospital, Michigan, USA
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Lima C, de Paiva Haddad LB, de Melo PDV, Malbouisson LM, do Carmo LPF, D'Albuquerque LAC, Macedo E. Early detection of acute kidney injury in the perioperative period of liver transplant with neutrophil gelatinase-associated lipocalin. BMC Nephrol 2019; 20:367. [PMID: 31615452 PMCID: PMC6794911 DOI: 10.1186/s12882-019-1566-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 09/26/2019] [Indexed: 12/28/2022] Open
Abstract
Background Acute kidney injury (AKI) is a common complication in patients undergoing liver transplant (LT) and is associated with high morbidity and mortality. We aim to evaluate the pattern of urine and plasma neutrophil gelatinase-associated lipocalin (NGAL) elevation during the perioperative period of LT and to assess it as a prognostic marker for AKI progression, need for dialysis and mortality. Methods We assessed NGAL levels before induction of anesthesia, after portal reperfusion and at 6, 18, 24, and 48 h after surgery. Patients were monitored daily during the first week after LT. Results Of 100 enrolled patients undergoing liver transplant, 59 developed severe AKI based on the KDIGO serum creatinine (sCr) criterion; 34 were dialysed, and 21 died within 60 days after LT. Applying a cut-off value of 136 ng/ml, UNGAL values 6 h after surgery was a good predictor of AKI development within 7 days after surgery, having a positive predictive value (PPV) of 80% with an AUC of 0.76 (95% CI 0.67–0.86). PNGAL at 18 h after LT was also a good predictor of AKI in the first week, having a PPV of 81% and AUC of 0.74 (95% CI 0.60–0.88). Based on PNGAL and UNGAL cut-off criteria levels, time to AKI diagnosis was 28 and 23 h earlier than by sCr, respectively. The best times to assess the need for dialysis were 18 h after LT by PNGAL and 06 h after LT by UNGAL. Conclusion In conclusion, the plasma and urine NGAL elevation pattern in the perioperative period of the liver transplant can predict AKI diagnosis earlier. UNGAL was an early independent predictor of AKI development and need for dialysis. Further studies are needed to assess whether the clinical use of biomarkers can improve patient outcomes. Trial registration Registered at Clinical Trials (clinicaltrials.gov) in March 24th, 2014 by title “Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)” and identifier NCT02095431, retrospectively registered.
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Affiliation(s)
- Camila Lima
- Department of Internal Medicine, Nephrology Division, University of Sao Paulo, Present Address: 419 Av. Dr Enéas de Carvalho Aguiar, third floor - room 340, 05403-000, Cerqueira Cesar, São Paulo, Brazil. .,Department of Medical Surgical Nursing, University of Sao Paulo Nursing School, Sao Paulo, Brazil.
| | - Luciana Bertocco de Paiva Haddad
- Department of Gastrointestinal Surgery, Clinical Surgery Division, University of Sao Paulo, Sao Paulo, Brazil.,Present Address: La Jolla, San Diego, USA
| | | | - Luiz Marcelo Malbouisson
- Department of Anaesthesiology, Clinical Surgery Division, University of Sao Paulo, Sao Paulo, Brazil
| | - Lilian Pires Freitas do Carmo
- Department of Internal Medicine, Nephrology Division, University of Sao Paulo, Present Address: 419 Av. Dr Enéas de Carvalho Aguiar, third floor - room 340, 05403-000, Cerqueira Cesar, São Paulo, Brazil
| | | | - Etienne Macedo
- Department of Internal Medicine, Nephrology Division, University of Sao Paulo, Present Address: 419 Av. Dr Enéas de Carvalho Aguiar, third floor - room 340, 05403-000, Cerqueira Cesar, São Paulo, Brazil.,Department of Medicine, Nephrology Division, University of California San Diego, San Diego, USA
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Xie F, Dong J, Zhu Y, Wang K, Liu X, Chen D, Meng Q. HIF1a Inhibitor Rescues Acute-on-Chronic Liver Failure. Ann Hepatol 2019; 18:757-764. [PMID: 31402229 DOI: 10.1016/j.aohep.2019.03.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 02/01/2019] [Accepted: 03/06/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION AND OBJECTIVES Hypoxia-inducible factor-1α is critically involved in the pathogenesis of liver diseases. Its inhibitor genistein attenuated D-galactosamine (D-GalN)-induced liver damage. However, the role of genistein in acute-on-chronic liver failure (ACLF) is unclear. The influence of genistein on reactive oxygen species (ROS) and hepatocyte functions were evaluated in a rat model of ACLF. MATERIAL AND METHODS Genistein [20mg/ (kg. day)]/coenzyme Q10 [10mg/ (kg. day)]/lipoic acid [20mg/ (kg. day)] was administered via the intra-gastric route daily for 6 weeks as co-treatment to the rats in the experimental groups. Then, 100μg/kg LPS combined with 0.5g/kg D-GalN was injected intraperitoneally to attack the rats. RESULTS Genistein significantly attenuated LPS/D-GalN-induced ACLF, characterized by ameliorated gross appearance and microscopic histopathology of liver, reduced AST level in serum, whereas increased levels of ATP, ADP/O, and respiratory control ratio (RCR) in mitochondria. Genistein suppressed necrosis and ROS production. CONCLUSION These results suggested that genistein could protect against ACLF through inhibiting cellular ROS production and necrosis, improving RCR, and decreasing permeability transition pores in mitochondrial, which was similar as mitochondrial protective agent coenzyme Q10.
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Affiliation(s)
- Fang Xie
- Beijing You an Hospital, Capital Medical University, Beijing, China; Beijing Institute of Hepatology, Beijing, P.R. China
| | - Jinling Dong
- Beijing You an Hospital, Capital Medical University, Beijing, China
| | - Yueke Zhu
- Beijing You an Hospital, Capital Medical University, Beijing, China
| | - Kefei Wang
- Beijing You an Hospital, Capital Medical University, Beijing, China
| | - Xuemei Liu
- Beijing You an Hospital, Capital Medical University, Beijing, China
| | - Dexi Chen
- Beijing You an Hospital, Capital Medical University, Beijing, China; Beijing Institute of Hepatology, Beijing, P.R. China
| | - Qinghua Meng
- Beijing You an Hospital, Capital Medical University, Beijing, China.
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Papazafiropoulou A, Melidonis A. Antidiabetic agents in patients with hepatic impairment. World J Meta-Anal 2019; 7:380-388. [DOI: 10.13105/wjma.v7.i8.380] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 08/07/2019] [Accepted: 08/20/2019] [Indexed: 02/06/2023] Open
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Mirza AC, Panchal SS. Safety evaluation of syringic acid: subacute oral toxicity studies in Wistar rats. Heliyon 2019; 5:e02129. [PMID: 31463381 PMCID: PMC6706588 DOI: 10.1016/j.heliyon.2019.e02129] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/20/2019] [Accepted: 07/18/2019] [Indexed: 02/05/2023] Open
Abstract
Syringic acid (SA) is a phenolic acid and have been investigated for diverse pharmacological activities, but the safety and/or mechanism of toxicity is still lacking in the literature. Subacute toxicity studies will add value to its pharmacological profile and support its exploration as a future medicine. According to OECD TG 407 (OECD, 2008), rats were divided into 3 groups (n = 12). The dose of SA was decided by limit test. Treatment and satellite groups received SA (1000 mg/kg/day, p.o for 14 days), whereas an equal volume of vehicle was given to control groups. In order to access reversibility, satellite groups were kept for another 14 days post-treatment. The toxic signs, mortality and body weight changes were recorded. On day 15 and 29 the rats were anesthetized to collect blood for estimation of hematological and biochemical parameters and then sacrificed to collect internal body organ for weighing and histopathological studies. SA has no major adverse effect on the body weight, food intake, erythropoiesis, leucopoiesis and on internal body organs which was confirmed by evaluating various biochemical and hematological parameters, relative body organ weight and histopathological studies. Therefore, SA could be considered safe over limited period of time and this study may help researchers in establishing the doses for the longer-term subchronic studies. Further, subchronic and chronic toxicity studies are required to evaluate safety on long term use.
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Affiliation(s)
- Anwarbaig C. Mirza
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Sarkhej-Ghandinagar Highway, Ahmedabad, 382481, Gujarat, India
- Department of Pharmacology, School of Pharmacy, AI's Kalsekar Technical Campus, Navi Mumbai, 410206, Maharashtra, India
| | - Shital S. Panchal
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Sarkhej-Ghandinagar Highway, Ahmedabad, 382481, Gujarat, India
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Jain V, Burford C, Alexander EC, Sutton H, Dhawan A, Joshi D, Davenport M, Heaton N, Hadzic N, Samyn M. Prognostic markers at adolescence in patients requiring liver transplantation for biliary atresia in adulthood. J Hepatol 2019; 71:71-77. [PMID: 30876944 DOI: 10.1016/j.jhep.2019.03.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 02/14/2019] [Accepted: 03/04/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND & AIMS In patients with biliary atresia (BA), the rate of native liver survival (NLS) to adulthood has been reported as 14-44% worldwide. Complications related to portal hypertension (PHT) and cholangitis are common in adulthood. For those requiring liver transplantation (LT), the timing can be challenging. The aim of this study was to identify variables that could predict whether young people with BA would require LT when they are >16 years of age. METHODS This study was a single-centre retrospective analysis of 397 patients who underwent Kasai portoenterostomy (KP) between 1980-96 in the UK. After KP, 111/397 (28%) demonstrated NLS until 16 years of age. At final follow-up, 67 showed NLS when >16 years old (Group 1) and 22 required LT when >16 years old (Group 2). Laboratory, clinical and radiological parameters were collected for both groups at a median age of 16.06 years (13.6-17.4 years). RESULTS The need for LT when >16 years old was associated with higher total bilirubin (hazard ratio 1.03, p = 0.019) and lower creatinine (hazard ratio 0.95, p = 0.040), at 16 years, on multivariate analysis. Receiver-operating characteristic curve analysis demonstrated that a total bilirubin level of ≥21 µmol/L at 16 years old (AUROC = 0.848) predicted the need for LT when >16 years old, with 85% sensitivity and 74% specificity. Cholangitis episode(s) during adolescence were associated with a 5-fold increased risk of needing LT when >16 years old. The presence of PHT or gastro-oesophageal varices in patients <16 years old was associated with a 7-fold and 8.6-fold increase in the risk of needing LT, respectively. CONCLUSIONS BA in adulthood requires specialised management. Adult liver disease scoring models are not appropriate for this cohort. Bilirubin ≥21 µmol/L, PHT or gastro-oesophageal varices at 16 years, and cholangitis in adolescence, can predict the need for future LT in young people with BA. Low creatinine at 16 years also has potential prognostic value. LAY SUMMARY Patients with biliary atresia commonly require liver transplantation before reaching adulthood. Those who reach adulthood with their own liver are still at risk of needing a transplant. This study aimed to identify tests that could help clinicians predict which patients with biliary atresia who reach the age of 16 without a transplant will require one in later life. The study found that the presence of bilirubin ≥21 µmol/L, lower creatinine levels, and a history of portal hypertension or gastro-oesophageal varices at 16 years, as well as cholangitis in adolescence, could predict the future likelihood of needing a liver transplant for young people with biliary atresia.
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Affiliation(s)
- Vandana Jain
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital, London, UK.
| | - Charlotte Burford
- Faculty of Life Sciences and Medicine, Kings College London, London, UK
| | - Emma C Alexander
- Faculty of Life Sciences and Medicine, Kings College London, London, UK
| | - Harry Sutton
- Faculty of Life Sciences and Medicine, Kings College London, London, UK
| | - Anil Dhawan
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital, London, UK
| | - Deepak Joshi
- Institute of Liver Studies, Kings College Hospital, London, UK
| | - Mark Davenport
- Department of Paediatric Surgery, Kings College Hospital, London, UK
| | - Nigel Heaton
- Liver Transplant Surgery, Institute of Liver Studies, Kings College Hospital, London, UK
| | - Nedim Hadzic
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital, London, UK
| | - Marianne Samyn
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital, London, UK
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43
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Deep A, Saxena R, Jose B. Acute kidney injury in children with chronic liver disease. Pediatr Nephrol 2019; 34:45-59. [PMID: 29497824 PMCID: PMC6244855 DOI: 10.1007/s00467-018-3893-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 01/10/2018] [Accepted: 01/11/2018] [Indexed: 12/16/2022]
Abstract
Acute kidney injury (AKI) is a common accompaniment in patients with liver disease. The causes, risk factors, manifestations and management of AKI in these patients vary according to the liver disease in question (acute liver failure, acute-on-chronic liver failure, post-liver transplantation or metabolic liver disease). There are multiple causes of AKI in patients with liver disease-pre-renal, acute tubular necrosis, post-renal, drug-induced renal failure and hepatorenal syndrome (HRS). Definitions of AKI in liver failure are periodically revised and updated, but pediatric definitions have still to see the light of the day. As our understanding of the pathophysiology of liver disease and renal involvement improves, treatment modalities have become more advanced and rationalized. Treatment includes reversing precipitating factors, such as infections and gastrointestinal bleeding, volume expansion, paracentesis and vasoconstrictors. This approach is tried and tested in adults. A pediatric tailored approach is still lacking due to inadequate numbers of patients, differences in causes of AKI and paucity of literature. In this review, we attempt to explore the pathophysiological basis, treatment modalities and controversies in the diagnosis and treatment of AKI in pediatric patients with chronic liver disease and discuss our own personal practice. We recognize that, although it is not a very commonly encountered entity in pediatric population, HRS has specific diagnostic criteria and treatment modalities that differ from other causes of AKI in patients with chronic liver disease; hence among the etiologies of kidney injury in patients with chronic liver disease, we focus here on HRS.
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Affiliation(s)
- Akash Deep
- Paediatric Intensive Care Unit (PICU), King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
| | - Romit Saxena
- Paediatric Intensive Care Unit (PICU), King’s College Hospital, Denmark Hill, London, SE5 9RS UK
| | - Bipin Jose
- Paediatric Intensive Care Unit (PICU), King’s College Hospital, Denmark Hill, London, SE5 9RS UK
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44
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Hong YS, Ryu S, Chang Y, Caínzos-Achirica M, Kwon MJ, Zhao D, Shafi T, Lazo M, Pastor-Barriuso R, Shin H, Cho J, Guallar E. Hepatitis B virus infection and development of chronic kidney disease: a cohort study. BMC Nephrol 2018; 19:353. [PMID: 30537940 PMCID: PMC6288894 DOI: 10.1186/s12882-018-1154-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 11/23/2018] [Indexed: 02/07/2023] Open
Abstract
Background The effect of chronic hepatitis B virus (HBV) infection on the risk of chronic kidney disease (CKD) is controversial. We examined the prospective association between hepatitis B surface antigen (HBsAg) serology status and incident CKD in a large cohort of men and women. Methods Cohort study of 299,913 adults free of CKD at baseline who underwent health screening exams between January 2002 and December 2016 in South Korea. Incident CKD was defined as the development of an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 and/or proteinuria. Results Over 1,673,701 person-years of follow-up, we observed 13,924 incident cases of CKD (3225 cases of eGFR < 60 ml/min/1.73m2 and 11,072 cases of proteinuria). In fully adjusted models comparing positive to negative HBsAg participants, the hazard ratio (HR, 95% confidence interval) for incident CKD was 1.11 (1.03–1.21; P = 0.01). The corresponding HR for incident proteinuria and for eGFR < 60 ml/min/1.73m2 were 1.23 (1.12–1.35; P < 0.001) and 0.89 (0.73–1.07; P = 0.21), respectively. The associations were similar across categories of liver enzyme levels at baseline. Conclusion In this large cohort, HBsAg positive serology was associated with higher risk of incident CKD, and we provide novel evidence that this association was due to a higher incidence of proteinuria in HBsAg positive participants. Our study adds to the growing body of evidence suggesting that chronic HBV infection may be a contributor to the increasing incidence of CKD. Electronic supplementary material The online version of this article (10.1186/s12882-018-1154-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yun Soo Hong
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health, Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health, Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Miguel Caínzos-Achirica
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.,Ciccarone Center for the Prevention of Heart Disease, Department of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.,Bellvitge University Hospital, Barcelona, Spain.,RTI Health Solutions, Pharmacoepidemiology and Risk Management, Barcelona, Spain
| | - Min-Jung Kwon
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.,Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Di Zhao
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Tariq Shafi
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.,Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mariana Lazo
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Roberto Pastor-Barriuso
- National Center for Epidemiology, Carlos III Institute of Health and Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Hocheol Shin
- Department of Family Medicine, Kangbuk Samsung Hospital and Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Juhee Cho
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. .,Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. .,Department of Health Sciences and Technology, Samsung Advanced Institute for Health, Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
| | - Eliseo Guallar
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
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A dose Dependent hepatoprotective and nephroprotective activity of eucalyptus oil on Streptozotocin induced diabetic mice model. CLINICAL PHYTOSCIENCE 2018. [DOI: 10.1186/s40816-018-0067-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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46
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Yeung ACY, Morozov A, Robertson FP, Fuller BJ, Davidson BR. Neutrophil Gelatinase-Associated Lipocalin (NGAL) in predicting acute kidney injury following orthotopic liver transplantation: A systematic review. Int J Surg 2018; 59:48-54. [PMID: 30273683 DOI: 10.1016/j.ijsu.2018.09.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2018] [Revised: 07/30/2018] [Accepted: 09/07/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Acute kidney injury (AKI) is common after orthotopic liver transplantation (OLT) usually occurring early post-transplant. Multiple causes include graft preservation injury, blood loss, hypotension but also severity of recipient liver disease. Early intervention in AKI has both short and long term patient benefits. Unfortunately there are no current clinical biomarkers of early AKI. AIM To assess the value of NGAL in predicting AKI following OLT. METHODS Ovid MEDLINE and EMBASE were searched between the years of 2000 and 2017 for studies using keywords: Neutrophil Gelatinase Associated Lipocalin or NGAL variants combined with synonyms for liver transplantation. RESULTS 96 studies were identified. 11 studies including 563 patients were considered suitable for analysis. Both urinary (uNGAL) and plasma NGAL (pNGAL) measurement were found to predict AKI after liver transplantation. Optimal reported area under the receiver-operator characteristics curve (AUROC) values of 0.5-0.83 and 0.54-0.86 respectively. CONCLUSIONS NGAL is a good predictor of early AKI post OLT although there is considerable variation in the published results. Further studies with prospectively defined cut-off values, standardized definitions of AKI and rigorous data reporting should be conducted to establish its clinical usefulness and limitations.
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Affiliation(s)
- Arthur C Y Yeung
- Department of Surgery and Interventional Science, Royal Free Campus, University College London, 9th Floor Royal Free London NHS Foundation Trust, Pond Street, NW3 2QG, UK
| | - Andrew Morozov
- Department of Surgery and Interventional Science, Royal Free Campus, University College London, 9th Floor Royal Free London NHS Foundation Trust, Pond Street, NW3 2QG, UK
| | - Francis P Robertson
- Department of Surgery and Interventional Science, Royal Free Campus, University College London, 9th Floor Royal Free London NHS Foundation Trust, Pond Street, NW3 2QG, UK.
| | - Barry J Fuller
- Department of Surgery and Interventional Science, Royal Free Campus, University College London, 9th Floor Royal Free London NHS Foundation Trust, Pond Street, NW3 2QG, UK
| | - Brian R Davidson
- Department of Surgery and Interventional Science, Royal Free Campus, University College London, 9th Floor Royal Free London NHS Foundation Trust, Pond Street, NW3 2QG, UK
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47
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Hepatic Rac1 GTPase contributes to liver-mediated basal immune homeostasis and LPS-induced endotoxemia. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2018; 1865:1277-1292. [DOI: 10.1016/j.bbamcr.2018.06.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 05/30/2018] [Accepted: 06/17/2018] [Indexed: 12/16/2022]
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48
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Panic G, Coulibaly JT, Harvey N, Keiser J, Swann J. Characterizing the Biochemical Response to Schistosoma mansoni Infection and Treatment with Praziquantel in Preschool and School Aged Children. J Proteome Res 2018; 17:2028-2033. [PMID: 29701975 DOI: 10.1021/acs.jproteome.7b00910] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Schistosomiasis is a widespread chronic neglected tropical disease prevalent mostly in children in under-resourced rural areas. Its pathological effects have been clinically characterized, yet the molecular-level effects are understudied. In this study, the biochemical effects of Schistosoma mansoni infection and praziquantel treatment were studied in 130 preschool aged and 159 school aged infected children and 11 noninfected children in Azaguié, Côte d'Ivoire. Urine samples were collected prior to receiving 20, 40, or 60 mg/kg of praziquantel or a placebo, as well as 24 h post-treatment, and at the 3-week follow up. Urinary metabolic phenotypes were measured using 1H NMR spectroscopy, and metabolic variation associated with S. mansoni infection and praziquantel administration was identified using multivariate statistical techniques. Discriminatory metabolic signatures were detected between heavily infected and noninfected children at baseline as well as according to the dose of praziquantel administered 24 h post treatment. These signatures were primarily associated with the metabolic activity of the gut microbiota, gut health and growth biomarkers and energy and liver metabolism. These analyses provide insights into the metabolic phenotype of schistosomiasis and treatment with praziquantel in two important demographics.
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Affiliation(s)
- Gordana Panic
- Department of Medical Parasitology and Infection Biology , Swiss Tropical and Public Health Institute , CH-4002 Basel , Switzerland.,University of Basel , CH-4003 Basel , Switzerland
| | - Jean T Coulibaly
- Department of Medical Parasitology and Infection Biology , Swiss Tropical and Public Health Institute , CH-4002 Basel , Switzerland.,University of Basel , CH-4003 Basel , Switzerland.,Unité de Formation et de Recherche Biosciences , Université Félix Houphouët-Boigny , 01 BP V34 , Abidjan 01 , Côte d'Ivoire
| | - Nikita Harvey
- Division of Integrative Systems Medicine and Digestive Diseases , Department of Surgery and Cancer, Imperial College London , London SW7 2AZ , United Kingdom
| | - Jennifer Keiser
- Department of Medical Parasitology and Infection Biology , Swiss Tropical and Public Health Institute , CH-4002 Basel , Switzerland.,University of Basel , CH-4003 Basel , Switzerland
| | - Jonathan Swann
- Division of Integrative Systems Medicine and Digestive Diseases , Department of Surgery and Cancer, Imperial College London , London SW7 2AZ , United Kingdom
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Pandey CK, Saluja V, Gaurav K, Tandon M, Pandey VK, Bhadoria AS. K time & maximum amplitude of thromboelastogram predict post-central venous cannulation bleeding in patients with cirrhosis: A pilot study. Indian J Med Res 2018; 145:84-89. [PMID: 28574019 PMCID: PMC5460579 DOI: 10.4103/ijmr.ijmr_749_14] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background & objectives: Coagulation and haemostasis are dynamic processes. The haemostatic changes in liver disease affect all aspects of coagulation. The prothrombin time (PT)/international normalized ratio (INR) was developed to monitor oral anticoagulant therapy and the activated partial thromboplastin time to investigate inheritable single factor deficiencies. Viscoelastic tests such as thromboelastogram (TEG) give information about dynamics of clot formation (coagulation factor and anticoagulant activity), clot strength (platelets and fibrinogen) and clot stability (finbrinolysis and factor XIII). Administration of blood products before invasive procedures is still guided by INR and platelet count in patients of liver disease. This study was aimed to evaluate the validity of TEG to predict post-procedural bleed after central venous cannulation in patients with cirrhosis. Methods: Ninety patients aged 20-70 yr diagnosed with liver cirrhosis requiring elective central venous catheter (CVC) insertion were studied. Platelet count, INR, serum creatinine, TEG and Child-Turcotte-Pugh (CTP) score were recorded before the procedure. Right-sided internal jugular vein was cannulated. On the basis of presence or absence of post-procedural bleed, patients were divided into bleeding and non-bleeding groups. The CTP score, component of TEG (R - reaction time, K - coagulation time, MA - maximum amplitude and α - angle) and laboratory parameters of both the groups were compared. Results: Bleeding was seen more when CTP scores were ≥10 (P=0.05). The K time of 3.05 min or more on thromboelastograph was a significant predictor of bleeding [area under the curve (AUC) 0.694, P=0.047]. MA of 48.8 mm or more was a significant predictor of non-bleeding. INR ≥2.6 was a significant predictor of bleeding (AUC 0.765, P=0.005). K time had a low-positive predictive value of 20 per cent and the positive and negative likelihood ratios of 1.87 and 0.48, respectively. Interpretation & conclusions: Our results show that the cut-off value for INR ≥2.6 and K time ≥3.05 min predict bleeding and MA ≥48.8 mm predicts non-bleeding in patients with cirrhosis undergoing central venous pressure catheter cannulation.
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Affiliation(s)
- Chandra K Pandey
- Department of Anaesthesia & Critical Care, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Vandana Saluja
- Department of Anaesthesia & Critical Care, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Kumar Gaurav
- Department of Anaesthesia & Critical Care, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Manish Tandon
- Department of Anaesthesia & Critical Care, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Vijay K Pandey
- Department of Anaesthesia & Critical Care, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Ajeet S Bhadoria
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
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50
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Buccolieri A, Serra A, Giancane G, Manno D. Colloidal solution of silver nanoparticles for label-free colorimetric sensing of ammonia in aqueous solutions. BEILSTEIN JOURNAL OF NANOTECHNOLOGY 2018; 9:499-507. [PMID: 29515962 PMCID: PMC5815292 DOI: 10.3762/bjnano.9.48] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 01/26/2018] [Indexed: 03/30/2024]
Abstract
Silver nanoparticles were synthesized in the presence of saccharides and ammonia (NH3) in the concentration range from 10-2 to 103 ppm to develop an optical sensor for NH3 in aqueous solutions. Ammonia affects the features of the nanoparticles obtained in a concentration-dependent manner as determined by UV-vis absorption analysis and TEM observations. Structural and morphological analysis provides the basis for the production of a colorimetric label-free sensor for ammonia. Overall, surface plasmon resonance increases when ammonia concentration rises, although the functional trend is not the same over the entire investigated ammonia concentration range. Three different ranges have been identified: very low ammonia concentrations from 0.01 to 0.2 ppm, high ammonia concentrations from 20 to 350 ppm and, most importantly, the intermediate or physiological range of ammonia from 0.5 to 10 ppm.
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Affiliation(s)
- Alessandro Buccolieri
- GFA-Gruppo di Fisica Applicata, Dipartimento di Matematica e Fisica “E. De Giorgi”, Università del Salento Lecce, Italy
| | - Antonio Serra
- GFA-Gruppo di Fisica Applicata, Dipartimento di Matematica e Fisica “E. De Giorgi”, Università del Salento Lecce, Italy
| | - Gabriele Giancane
- GFA-Gruppo di Fisica Applicata, Dipartimento di Matematica e Fisica “E. De Giorgi”, Università del Salento Lecce, Italy
| | - Daniela Manno
- GFA-Gruppo di Fisica Applicata, Dipartimento di Matematica e Fisica “E. De Giorgi”, Università del Salento Lecce, Italy
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