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Diagnostics
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Advances in Nephrology
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Advances in Nephrology

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 30 May 2025 | Viewed by 15715

Special Issue Editor

Prof. Dr. Marijn M. Speeckaert

E-Mail Website
Guest Editor
Department of Internal Medicine, Nephrology Division, Ghent University Hospital, 9000 Ghent, Belgium
Interests: proteins; biomarkers; hypertension; acute kidney injury; clinical nephrology; chronic renal failure; diabetes; diabetes mellitus; metabolism; insulin resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acute kidney injury (AKI) is a widespread, epidemic-level problem. AKI is becoming more common in hospitalized patients with acute illnesses and those undergoing major surgery, according to compelling evidence. AKI's consequences are severe, with an increased risk of short- and long-term mortality, incident CKD, and accelerated progression to end-stage renal disease (ESRD).

Chronic kidney disease (CKD) is a major component of noncommunicable chronic diseases, which have reached pandemic proportions and are the leading cause of morbidity and mortality worldwide. Patients with impaired renal function are at increased risk not only of kidney disease progression and the development of ESRD but also of cardiovascular disease and mortality. Unfortunately, CKD is underdiagnosed and undertreated, resulting in missed opportunities for clinical improvement. Early detection and appropriate interventions will improve patient care and prevent or delay progression to ESRD.

We welcome papers in this Special Issue that investigate novel biomarkers, pathophysiological mechanisms, and novel treatments in patients with AKI or CKD.

Prof. Dr. Marijn M. Speeckaert
Guest Editor

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 single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly 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 2600 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.

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Published Papers (6 papers)

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Research

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17 pages, 2127 KiB  
Article
Severe Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Patients on Chronic Hemodialysis—Reconsidering the Relationship with Thrombo-Inflammation and Oxidative Stress
by Srdjan Nikolovski, Branislava Medic Brkic, Katarina Savic Vujovic, Ivana Cirkovic, Nina Jovanovic, Bhavana Reddy, Omer Iqbal, Chongyu Zhang, Jawed Fareed and Vinod Bansal
Diagnostics 2024, 14(21), 2406; https://doi.org/10.3390/diagnostics14212406 - 29 Oct 2024
Viewed by 801
Abstract
Background/Objectives: Besides a multitude of consequences patients on chronic renal replacement therapy have, anemia is one of the most prominent factors making a significant number of patients dependent on erythropoiesis-stimulating agent (ESA) therapy. The aim of this study was to examine the relationship [...] Read more.
Background/Objectives: Besides a multitude of consequences patients on chronic renal replacement therapy have, anemia is one of the most prominent factors making a significant number of patients dependent on erythropoiesis-stimulating agent (ESA) therapy. The aim of this study was to examine the relationship between the levels of a broad spectrum of thrombo-inflammatory and oxidative stress-related biomarkers and the presence and level of ESA hyporesponsiveness in patients undergoing regular chronic hemodialysis. Methods: This cross-sectional study included 96 patients treated with chronic hemodialysis. Levels of several thrombo-inflammatory and oxidative stress-related biomarkers, as well as demographic, clinical, and laboratory analyses, were collected and analyzed based on the calculated value of the ESA-hyporesponsiveness index (EHRI). Results: In the analyzed sample, 58 patients received ESAs. Of all the investigated parameters, only body mass index (BMI), level of plasminogen activator inhibitor-1, and level of L-type fatty acid binding protein (L-FABP) were observed as significant predictors of EHRI. A significant diagnostic potential for ESA resistance has been observed in BMI and L-FABP between ESA-resistant and ESA-non-resistant groups of patients (p = 0.004, area under the curve 0.763 and p = 0.014, area under the curve 0.712, respectively) with the cut-off values of 25.46 kg/m2 and 5355.24 ng/mL, respectively. Having a BMI of 25.46 kg/m2 or less and an L-FABP level higher than 5355.24 ng/mL were observed as significant predictors of ESA resistance (odds ratio 9.857 and 6.125, respectively). Conclusions: EHRI was positively predicted by low BMI and high levels of plasminogen activator inhibitor-1 and L-FABP. High levels of L-FABP and low BMI have been observed as strong predictors of ESA resistance. Full article
(This article belongs to the Special Issue Advances in Nephrology)
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10 pages, 246 KiB  
Article
The Association between Echocardiographic Parameters of Heart Failure with Preserved Ejection Fraction and Fluid Status Biomarkers in Hemodialysis Patients
by Mariusz Lupa, Agnieszka Pardała, Anna Bednarek, Jolanta Mrochem-Kwarciak, Regina Deja, Katarzyna Mizia-Stec and Aureliusz Kolonko
Diagnostics 2024, 14(12), 1310; https://doi.org/10.3390/diagnostics14121310 - 20 Jun 2024
Viewed by 1389
Abstract
Overhydration and cardiac function abnormalities are common in hemodialysis patients. The association of N-terminal prohormone for brain natriuretic peptide (NT-proBNP) and other fluid status biomarkers with echocardiographic parameters of heart failure with preserved ejection fraction (HFpEF) is scarcely investigated in this population. A [...] Read more.
Overhydration and cardiac function abnormalities are common in hemodialysis patients. The association of N-terminal prohormone for brain natriuretic peptide (NT-proBNP) and other fluid status biomarkers with echocardiographic parameters of heart failure with preserved ejection fraction (HFpEF) is scarcely investigated in this population. A total of 100 separate measurements performed in 50 dialysis patients (29 male, aged 60 ± 17 years) in NYHA class II/II and preserved left ventricle ejection fraction were analyzed. Plasma levels of NT-proBNP, mid-regional prohormone for atrial natriuretic peptide (MR-proANP) and copeptin (CPP) were measured. The E/e’ ratio as an index of HFpEF and other echocardiographic parameters were calculated. An E/e’ ratio >9 was associated with higher median right ventricular systolic pressure (RVSP) and LVMI values. Left atrium volume index (LAVI) as well as NT-proBNP and MR-proANP, but not CPP levels were significantly higher in this group. In a stepwise multivariate analysis, only CPP and IL-6 levels were found to be independently associated with the E/e’ ratio in the study group, whereas NT-proBNP and MR-proANP were associated only with left heart structure parameters and LVEF. Of the analyzed biomarkers, only the CPP level was found to be independently associated with the E/e’ ratio in maintenance hemodialysis patients. Full article
(This article belongs to the Special Issue Advances in Nephrology)
13 pages, 2818 KiB  
Article
Ratio of Extracellular to Intracellular Water Is Associated with Permanent Catheter Patency Survival in Patients Receiving Maintenance Hemodialysis
by Moo-Jun Kim, Jae-Wan Jeon, Hae-Ri Kim, Hyerim Park, Suyeon Han, Yunkyeong Hwang, Heewon Park, Kyungho Park, Eu-Jin Lee, Young-Rok Ham, Ki-Ryang Na, Kang-Wook Lee and Dae-Eun Choi
Diagnostics 2023, 13(15), 2545; https://doi.org/10.3390/diagnostics13152545 - 31 Jul 2023
Cited by 1 | Viewed by 1248
Abstract
Patients undergoing dialysis through a permanent catheter often experience infection or malfunction. However, few studies have clarified the predictors of permanent catheter patency survival in patients undergoing hemodialysis. We assessed the relationship between the parameters of body composition monitoring (BCM), determined before the [...] Read more.
Patients undergoing dialysis through a permanent catheter often experience infection or malfunction. However, few studies have clarified the predictors of permanent catheter patency survival in patients undergoing hemodialysis. We assessed the relationship between the parameters of body composition monitoring (BCM), determined before the initiation of dialysis, and the patency survival of the permanent catheters inserted in 179 patients who commenced hemodialysis between 14 January 2020 and 31 August 2021. The relationships between permanent catheter patency at 6 weeks and BCM parameters, laboratory tests, age, sex, comorbidities, and medications at baseline were studied using Kaplan–Meier survival curves. Permanent catheter patency was observed to be superior at high extracellular-to-intracellular (ECW/ICW) ratio (p < 0.005). After adjustment for covariates, the ECW/ICW ratio remained an independent factor associated with permanent catheter patency survival. When patients with non-patent catheters were subdivided into infection and malfunction groups, and the associations of BCM parameters were evaluated in those groups, the ECW/ICW ratio was not significantly associated with permanent catheter patency survival in the infection group (p = 0.327); instead, a significant association was found for the lean tissue index (p < 0.001). In the malfunction group, the ECW/ICW ratio remained significantly associated with permanent catheter patency survival (p < 0.001). Full article
(This article belongs to the Special Issue Advances in Nephrology)
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17 pages, 1110 KiB  
Article
Potential of Urine Biomarkers CHI3L1, NGAL, TIMP-2, IGFBP7, and Combinations as Complementary Diagnostic Tools for Acute Kidney Injury after Pediatric Cardiac Surgery: A Prospective Cohort Study
by Wim Vandenberghe, Jorien De Loor, Katrien Francois, Kristof Vandekerckhove, Ingrid Herck, Johan Vande Walle, Harlinde Peperstraete, Thierry Bové, Daniël De Wolf, Lieve Nuytinck, Jan J. De Waele, Evelyne Meyer and Eric A. J. Hoste
Diagnostics 2023, 13(6), 1047; https://doi.org/10.3390/diagnostics13061047 - 9 Mar 2023
Cited by 4 | Viewed by 2381
Abstract
Acute kidney injury (AKI) is common after pediatric cardiac surgery (CS). Several urine biomarkers have been validated to detect AKI earlier. The objective of this study was to evaluate urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® as predictors for AKI ≥ 1 [...] Read more.
Acute kidney injury (AKI) is common after pediatric cardiac surgery (CS). Several urine biomarkers have been validated to detect AKI earlier. The objective of this study was to evaluate urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® as predictors for AKI ≥ 1 in pediatric CS after 48 h and AKI ≥ 2 after 12 h. Pediatric patients (age < 18 year; body weight ≥ 2 kg) requiring CS were prospectively included. Urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® were measured during surgery and intensive care unit (ICU) stay and corrected for urine dilution. One hundred and one pediatric patients were included. AKI ≥ 1 within 48 h after ICU admission occurred in 62.4% and AKI ≥ 2 within 12 h in 30.7%. All damage biomarkers predicted AKI ≥ 1 within 48 h after ICU admission, when corrected for urine dilution: CHI3L1 (AUC-ROC: 0.642 (95% CI, 0.535–0.741)), NGAL (0.765 (0.664–0.848)), TIMP-2 (0.778 (0.662–0.868)), IGFBP7 (0.796 (0.682–0.883)), NephroCheck® (0.734 (0.614–0.832)). Similarly, AKI ≥ 2 within 12 h was predicted by all damage biomarkers when corrected for urine dilution: uCHI3L1 (AUC-ROC: 0.686 (95% CI, 0.580–0.780)), NGAL (0.714 (0.609–0.804)), TIMP-2 (0.830 (0.722–0.909)), IGFBP7 (0.834 (0.725–0.912)), NephroCheck® (0.774 (0.658–0.865)). After pediatric cardiac surgery, the damage biomarkers urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® reliably predict AKI after correction for urine dilution. Full article
(This article belongs to the Special Issue Advances in Nephrology)
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Review

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42 pages, 2355 KiB  
Review
Unveiling the Hidden Power of Uromodulin: A Promising Potential Biomarker for Kidney Diseases
by Raïsa Thielemans, Reinhart Speeckaert, Charlotte Delrue, Sander De Bruyne, Matthijs Oyaert and Marijn M. Speeckaert
Diagnostics 2023, 13(19), 3077; https://doi.org/10.3390/diagnostics13193077 - 28 Sep 2023
Cited by 14 | Viewed by 5129
Abstract
Uromodulin, also known as Tamm-Horsfall protein, represents the predominant urinary protein in healthy individuals. Over the years, studies have revealed compelling associations between urinary and serum concentrations of uromodulin and various parameters, encompassing kidney function, graft survival, cardiovascular disease, glucose metabolism, and overall [...] Read more.
Uromodulin, also known as Tamm-Horsfall protein, represents the predominant urinary protein in healthy individuals. Over the years, studies have revealed compelling associations between urinary and serum concentrations of uromodulin and various parameters, encompassing kidney function, graft survival, cardiovascular disease, glucose metabolism, and overall mortality. Consequently, there has been a growing interest in uromodulin as a novel and effective biomarker with potential applications in diverse clinical settings. Reduced urinary uromodulin levels have been linked to an elevated risk of acute kidney injury (AKI) following cardiac surgery. In the context of chronic kidney disease (CKD) of different etiologies, urinary uromodulin levels tend to decrease significantly and are strongly correlated with variations in estimated glomerular filtration rate. The presence of uromodulin in the serum, attributable to basolateral epithelial cell leakage in the thick ascending limb, has been observed. This serum uromodulin level is closely associated with kidney function and histological severity, suggesting its potential as a biomarker capable of reflecting disease severity across a spectrum of kidney disorders. The UMOD gene has emerged as a prominent locus linked to kidney function parameters and CKD risk within the general population. Extensive research in multiple disciplines has underscored the biological significance of the top UMOD gene variants, which have also been associated with hypertension and kidney stones, thus highlighting the diverse and significant impact of uromodulin on kidney-related conditions. UMOD gene mutations are implicated in uromodulin-associated kidney disease, while polymorphisms in the UMOD gene show a significant association with CKD. In conclusion, uromodulin holds great promise as an informative biomarker, providing valuable insights into kidney function and disease progression in various clinical scenarios. The identification of UMOD gene variants further strengthens its relevance as a potential target for better understanding kidney-related pathologies and devising novel therapeutic strategies. Future investigations into the roles of uromodulin and regulatory mechanisms are likely to yield even more profound implications for kidney disease diagnosis, risk assessment, and management. Full article
(This article belongs to the Special Issue Advances in Nephrology)
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27 pages, 1369 KiB  
Review
Urinary Extracellular Vesicles in Chronic Kidney Disease: From Bench to Bedside?
by Charlotte Delrue, Sander De Bruyne, Reinhart Speeckaert and Marijn M. Speeckaert
Diagnostics 2023, 13(3), 443; https://doi.org/10.3390/diagnostics13030443 - 26 Jan 2023
Cited by 12 | Viewed by 3442
Abstract
Extracellular vesicles are a diverse group of particles that include exosomes, microvesicles, and apoptotic bodies and are defined by size, composition, site of origin, and density. They incorporate various bioactive molecules from their cell of origin during formation, such as soluble proteins, membrane [...] Read more.
Extracellular vesicles are a diverse group of particles that include exosomes, microvesicles, and apoptotic bodies and are defined by size, composition, site of origin, and density. They incorporate various bioactive molecules from their cell of origin during formation, such as soluble proteins, membrane receptors, nucleic acids (mRNAs and miRNAs), and lipids, which can then be transferred to target cells. Extracellular vesicles/exosomes have been extensively studied as a critical factor in pathophysiological processes of human diseases. Urinary extracellular vesicles could be a promising liquid biopsy for determining the pattern and/or severity of kidney histologic injury. The signature of urinary extracellular vesicles may pave the way for noninvasive methods to supplement existing testing methods for diagnosing kidney diseases. We discuss the potential role of urinary extracellular vesicles in various chronic kidney diseases in this review, highlighting open questions and discussing the potential for future research. Full article
(This article belongs to the Special Issue Advances in Nephrology)
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