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Toxins
Special Issues
Uremic Toxins and Urinary Acute Kidney Injury Biomarkers
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Uremic Toxins and Urinary Acute Kidney Injury Biomarkers

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Uremic Toxins".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 17961

Special Issue Editors

Dr. Joanna Giebułtowicz

E-Mail Website
Guest Editor
Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland
Interests: uremic toxins; analytical methods; bioanalysis; metabolomics
Special Issues, Collections and Topics in MDPI journals
Dr. Wojciech Wołyniec

E-Mail Website
Guest Editor
Department of Occupational, Metabolic and Internal Medicine, Institute of Maritime and Tropical Medicine, Medical University of Gdańsk, 81-519 Gdynia, Poland
Interests: uremic toxins; acute kidney injury; sport; ultramarathon; urinary biomarkers

Special Issue Information

Dear Colleagues,

Uremic toxins are compounds that are usually excreted by the kidneys. In renal failure they accumulate and exert uremic effects, interacting negatively with normal biological functions. Their increased level can cause chronic kidney disease (CKD) progression and is linked to cardiovascular events and mortality. Unfortunately, current conventional dialysis treatment ineffectively removes a number of uremic toxins, mainly due to the large molecular size and high protein affinity. The adverse effects of uremic toxins are related to oxidative stress, inflammation, fibrosis, neurotoxicity, propensity to infection, chronic kidney disease/metabolic bone disease, insulin resistance, and thrombogenicity. However, their harmful action is not yet fully understood. Since the amount of research on uremic toxins in acute kidney injury (AKI) is scarce, we encourage researchers to identify which solutes might impact patient outcomes in AKI, so that pharmacological or renal replacement therapy can be targeted to neutralize these substances.

AKI is related to high mortality, and its diagnosis and prediction remains a challenge. New methods of urine examination have been applied in recent years, including metabolomics, proteomics, transcriptomics, and genomics. As a result, novel biomarkers of AKI were proposed. Since several studies have shown their higher increase not only in AKI, but also in CKD, the search for a new AKI biomarker is ongoing.

The focus of this Special Issue is on uremic toxins and urinary acute kidney injury biomarkers. Submissions are welcome on the following topics:

  • Identification of novel uremic toxins and acute kidney injury markers for diagnosis and prognosis in AKI and CKD. Relation between uremic toxins and urinary AKI biomarkers.
  • Level of uremic toxins in different pathological and physiological states, especially in AKI.
  • Novel effects and molecular mechanisms of action of uremic toxins on animals, various organs, tissues, and cells, especially related to kidney injury and organ disfunction observed in AKI (heart, lungs, liver, intestines, and brain).

Dr. Joanna Giebułtowicz
Dr. Wojciech Wołyniec
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • acute kidney injury
  • chronic kidney disease
  • renal replacement therapy
  • gut–kidney axis
  • glomerular filtration rate
  • renal tubular dysfunction
  • metabolomics
  • LC-MS
  • renal enzymes
  • uremic toxicity

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Published Papers (5 papers)

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Research

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14 pages, 313 KiB  
Article
Biomarkers of Uremic Cardiotoxicity
by Bojan Stopic, Sandra Dragicevic, Branislava Medic-Brkic, Aleksandra Nikolic, Marko Stojanovic, Sreten Budisavljevic and Nada Dimkovic
Toxins 2021, 13(9), 639; https://doi.org/10.3390/toxins13090639 - 10 Sep 2021
Cited by 4 | Viewed by 3090
Abstract
Cardiovascular (CV) morbidity and mortality increase along with the progression of chronic kidney disease (CKD). The potential novel biomarkers of cardiotoxicity have been tested with the aim of the early detection of patients at high CV risk, and among them are markers of [...] Read more.
Cardiovascular (CV) morbidity and mortality increase along with the progression of chronic kidney disease (CKD). The potential novel biomarkers of cardiotoxicity have been tested with the aim of the early detection of patients at high CV risk, and among them are markers of inflammation, oxidative stress, acute renal injury, and microRNAs. The study analyzed biomarkers in non-dialysis-dependent (NDD; stage 3a–4 CKD) and dialysis-dependent (DD) CKD patients. The prospective cohort study included 87 patients who were followed for 18 months, during which period newly occurred CV events were recorded. Cox regression analysis confirmed serum albumin, urea, interventricular septum thickness diameter (IVST), the use of calcium antagonist, and erythropoiesis-stimulating agent to be significant predictors of CV outcome. No significant difference was observed in biomarkers of inflammation, oxidative stress, acute kidney injury (IL-18, CRP, ferritin, IMA, SOD, NGAL, and KIM-1), and miR-133a, in regards to the presence/absence of CV event, CV death, and left ventricular hypertrophy. Serum albumin, urea, IVST, and the use of calcium antagonist and erythropoiesis-stimulating agents were confirmed to be factors associated with CV events in CKD patients. Apart from traditional risk factors, new research is needed to define novel and reliable biomarkers of cardiotoxicity in CKD patients. Full article
(This article belongs to the Special Issue Uremic Toxins and Urinary Acute Kidney Injury Biomarkers)
13 pages, 1661 KiB  
Article
Evaluation of Salivary Indoxyl Sulfate with Proteinuria for Predicting Graft Deterioration in Kidney Transplant Recipients
by Natalia Korytowska, Aleksandra Wyczałkowska-Tomasik, Leszek Pączek and Joanna Giebułtowicz
Toxins 2021, 13(8), 571; https://doi.org/10.3390/toxins13080571 - 16 Aug 2021
Cited by 7 | Viewed by 2979
Abstract
Acute kidney injury (AKI) is a significant risk factor for developing chronic kidney disease and progression to end-stage renal disease in elderly patients. AKI is also a relatively common complication after kidney transplantation (KTx) associated with graft failure. Since the lifespan of a [...] Read more.
Acute kidney injury (AKI) is a significant risk factor for developing chronic kidney disease and progression to end-stage renal disease in elderly patients. AKI is also a relatively common complication after kidney transplantation (KTx) associated with graft failure. Since the lifespan of a transplanted kidney is limited, the risk of the loss/deterioration of graft function (DoGF) should be estimated to apply the preventive treatment. The collection of saliva and urine is more convenient than collecting blood and can be performed at home. The study aimed to verify whether non-invasive biomarkers, determined in saliva and urine, may be useful in the prediction of DoGF in kidney transplant recipients (KTRs) (n = 92). Salivary and serum toxins (p-cresol sulfate, pCS; indoxyl sulfate, IS) concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urinary proteins, hemoglobin, and glucose were measured using a semi-quantitative strip test. Salivary IS (odds ratio (OR) = 1.19), and proteinuria (OR = 3.69) were demonstrated as independent factors for the prediction of DoGF. Satisfactory discriminatory power (area under the receiver operating characteristic curve (AUC) = 0.71 ± 0.07) and calibration of the model were obtained. The model showed that categories of the increasing probability of the risk of DoGF are associated with the decreased risk of graft survival. The non-invasive diagnostic biomarkers are a useful screening tool to identify high-risk patients for DoGF. Full article
(This article belongs to the Special Issue Uremic Toxins and Urinary Acute Kidney Injury Biomarkers)
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17 pages, 929 KiB  
Article
Post-Contrast Acute Kidney Injury in Patients with Various Stages of Chronic Kidney Disease—Is Fear Justified?
by Inga Chomicka, Marlena Kwiatkowska, Alicja Lesniak and Jolanta Malyszko
Toxins 2021, 13(6), 395; https://doi.org/10.3390/toxins13060395 - 1 Jun 2021
Cited by 5 | Viewed by 3376
Abstract
Post-contrast acute kidney injury (PC-AKI) is one of the side effects of iodinated contrast media, including those used in computed tomography. Its incidence seems exaggerated, and thus we decided to try estimate that number and investigate its significance in our clinical practice. We [...] Read more.
Post-contrast acute kidney injury (PC-AKI) is one of the side effects of iodinated contrast media, including those used in computed tomography. Its incidence seems exaggerated, and thus we decided to try estimate that number and investigate its significance in our clinical practice. We analyzed all computed tomographies performed in our clinic in 2019, including data about the patient and the procedure. In each case, we recorded the parameters of kidney function (serum creatinine concentration and eGFR) in four time intervals: before the test, immediately after the test, 14–28 days after the test, and over 28 days after the test. Patients who did not have a follow-up after computed tomography were excluded. After reviewing 706 CT scans performed in 2019, we included 284 patients undergoing contrast-enhanced CT and 67 non-enhanced CT in the final analysis. On this basis, we created two comparable groups in terms of age, gender, the severity of chronic kidney disease, and the number of comorbidities. We found that AKI was more common in the non-enhanced CT population (25.4% vs. 17.9%). In terms of our experience, it seems that PC-AKI is not a great risk for patients, even those with chronic kidney disease. Consequently, the fear of using contrast agents is not justified. Full article
(This article belongs to the Special Issue Uremic Toxins and Urinary Acute Kidney Injury Biomarkers)
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Review

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7 pages, 810 KiB  
Review
Establishing Cell Models to Understand Cellular Toxicity: Lessons Learned from an Unconventional Cell Type
by Tino Vollmer and Bernd Stegmayr
Toxins 2022, 14(1), 54; https://doi.org/10.3390/toxins14010054 - 12 Jan 2022
Viewed by 2956
Abstract
The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with [...] Read more.
The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with the expected reactions in human patients and studies on one organ system are limited in capturing the complexity of the uremic situation. In this narrative review, we present aspects relevant for cellular toxicity research based on our previous establishment of a human spermatozoa-based cell model, as follows: (i) applicability to compare the effects of more than 100 uremic substances, (ii) detection of the protective effects of uremic substances by the cellular responses towards the uremic milieu, (iii) inclusion of the drug milieu for cellular function, and (iv) transferability for clinical application, e.g., hemodialysis. Our technique allows the estimation of cell viability, vitality, and physiological state, not only restricted to acute or chronic kidney toxicity but also for other conditions, such as intoxications of unknown substances. The cellular models can clarify molecular mechanisms of action of toxins related to human physiology and therapy. Identification of uremic toxins retained during acute and chronic kidney injury enables further research on the removal or degradation of such products. Full article
(This article belongs to the Special Issue Uremic Toxins and Urinary Acute Kidney Injury Biomarkers)
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13 pages, 575 KiB  
Review
Acute Kidney Injury and Organ Dysfunction: What Is the Role of Uremic Toxins?
by Jesús Iván Lara-Prado, Fabiola Pazos-Pérez, Carlos Enrique Méndez-Landa, Dulce Paola Grajales-García, José Alfredo Feria-Ramírez, Juan José Salazar-González, Mario Cruz-Romero and Alejandro Treviño-Becerra
Toxins 2021, 13(8), 551; https://doi.org/10.3390/toxins13080551 - 9 Aug 2021
Cited by 8 | Viewed by 4504
Abstract
Acute kidney injury (AKI), defined as an abrupt increase in serum creatinine, a reduced urinary output, or both, is experiencing considerable evolution in terms of our understanding of the pathophysiological mechanisms and its impact on other organs. Oxidative stress and reactive oxygen species [...] Read more.
Acute kidney injury (AKI), defined as an abrupt increase in serum creatinine, a reduced urinary output, or both, is experiencing considerable evolution in terms of our understanding of the pathophysiological mechanisms and its impact on other organs. Oxidative stress and reactive oxygen species (ROS) are main contributors to organ dysfunction in AKI, but they are not alone. The precise mechanisms behind multi-organ dysfunction are not yet fully accounted for. The building up of uremic toxins specific to AKI might be a plausible explanation for these disturbances. However, controversies have arisen around their effects in organs other than the kidney, because animal models usually depict AKI as a kidney-specific injury. Meanwhile, humans present AKI frequently in association with multi-organ failure (MOF). Until now, medium-molecular-weight molecules, such as inflammatory cytokines, have been proven to play a role in endothelial and epithelial injury, leading to increased permeability and capillary leakage, mainly in pulmonary and intestinal tissues. Full article
(This article belongs to the Special Issue Uremic Toxins and Urinary Acute Kidney Injury Biomarkers)
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