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Renal Dysfunction, Uremic Compounds, and Other Factors (3rd Edition)
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Renal Dysfunction, Uremic Compounds, and Other Factors (3rd Edition)

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 5355

Special Issue Editors

Dr. Giovana S. Di Marco

E-Mail Website
Guest Editor
Department of Internal Medicine D, University Hospital Muenster, 48149 Münster, Germany
Interests: nephrology; endothelial dysfunction; cell biology; angiogenesis; risk factors
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marcus Brand

E-Mail Website
Guest Editor
Department of Internal Medicine D, University Hospital Muenster, 48149 Münster, Germany
Interests: nephrology; dialysis; cardiorenal syndrome; angiogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous successful Special Issue "Renal Dysfunction, Uremic Compounds, and Other Factors" (https://www.mdpi.com/journal/ijms/special_issues/Renal_Uremic).

When the kidneys fail, many endogenous substances accumulate in the circulation due to decreased renal clearance and increased production. These substances, including uremic toxins, inflammatory mediators, modified biomolecules, and growth factors, cause a complex local and systemic derangement in metabolism and signaling, affecting nearly all body organs and systems. This occurs not only in the setting of chronic and end-stage renal disease but also due to acute kidney injury. Therefore, identifying uremic compounds and other factors that have a biological effect on cells and tissues is necessary to understand the mechanisms linking kidney disease and other organs and build up better therapeutic strategies.

This Special Issue explores soluble mediators in renal disease (acute and chronic kidney diseases). It includes original articles and review papers reporting on aspects related to their biological effects, disease progression, involvement in inter-organ communication, and therapy. Potential topics include, but are not limited to, the search for new factors/biomarkers, the toxicity of uremic compounds, post-translational modification of proteins and peptides, molecular mechanisms of action, inflammation, the gut microbiome, organ cross-talk, and new techniques and analytical methods for the measurement and detection of soluble compounds or their (toxic) effects.

Dr. Giovana S. Di Marco
Prof. Dr. Marcus Brand
Guest Editors

Manuscript Submission Information

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • renal dysfunction
  • acute kidney disease
  • chronic kidney disease
  • soluble mediators
  • uremic toxins
  • disease progression
  • organ cross-talk
  • therapy
  • new techniques

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Published Papers (3 papers)

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Research

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21 pages, 5882 KiB  
Article
Integrated Multi-Omics Analysis Unveils Distinct Molecular Subtypes and a Robust Immune–Metabolic Prognostic Model in Clear Cell Renal Cell Carcinoma
by Yilin Zhu, Shihui Yu, Dan Yang, Tian Yu, Yi Liu and Wenlong Du
Int. J. Mol. Sci. 2025, 26(7), 3125; https://doi.org/10.3390/ijms26073125 - 28 Mar 2025
Cited by 1 | Viewed by 690
Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by significant clinical and molecular heterogeneity, with immune and metabolic processes playing crucial roles in tumor progression and influencing patient outcomes. This study aims to elucidate the molecular subtypes of ccRCC by employing non-negative matrix [...] Read more.
Clear cell renal cell carcinoma (ccRCC) is characterized by significant clinical and molecular heterogeneity, with immune and metabolic processes playing crucial roles in tumor progression and influencing patient outcomes. This study aims to elucidate the molecular subtypes of ccRCC by employing non-negative matrix factorization (NMF) clustering on differentially expressed genes (DEGs), thereby identifying distinct transcriptional profiles, immune cell infiltration patterns, and subsequent survival outcomes. Utilizing NMF clustering, we identified two molecular subtypes of ccRCC. We developed a prognostic model using LASSO–Cox regression, validated with multiple datasets and quantitative reverse transcription polymerase chain reaction (qRT-PCR), incorporating ten immunity- and metabolism-related genes (IMRGs) for overall survival (OS) prediction. Immune cell infiltration and tumor mutational burden (TMB) analyses were performed to explore differences between high- and low-risk groups, while Gene Set Enrichment Analysis (GSEA) provided insights into relevant biological pathways. The findings revealed that subtype C1, characterized by a “cold” tumor microenvironment, correlates with better prognostic outcomes compared to subtype C2, which exhibits an immunologically active environment and worse survival prospects. High-risk patients demonstrated poorer OS associated with alterations in immune and metabolic pathways. Immune checkpoint analysis indicated the upregulation of CTLA4, LAG3, and LGALS9 in high-risk patients, suggesting potential therapeutic targets. A nomogram integrating IMRG risk scores with clinical factors displayed high predictive accuracy for 1-, 3-, and 5-year OS. These findings provide novel insights into the molecular heterogeneity of ccRCC and emphasize the interconnected roles of immune dysregulation and metabolic alterations in tumor progression. By identifying key prognostic biomarkers and potential therapeutic targets, this study paves the way for innovative strategies aimed at harnessing immune and metabolic pathways for better clinical outcomes in ccRCC patients. Full article
(This article belongs to the Special Issue Renal Dysfunction, Uremic Compounds, and Other Factors (3rd Edition))
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17 pages, 1553 KiB  
Article
Metabolic Pathways Affected in Patients Undergoing Hemodialysis and Their Relationship with Inflammation
by María Peris-Fernández, Marta Isabel Roca-Marugán, Julià L. Amengual, Ángel Balaguer-Timor, Iris Viejo-Boyano, Amparo Soldevila-Orient, Ramon Devesa-Such, Pilar Sánchez-Pérez and Julio Hernández-Jaras
Int. J. Mol. Sci. 2024, 25(17), 9364; https://doi.org/10.3390/ijms25179364 - 29 Aug 2024
Cited by 1 | Viewed by 1741
Abstract
Worldwide, 3.9 million individuals rely on kidney replacement therapy. They experience heightened susceptibility to cardiovascular diseases and mortality, alongside an increased risk of infections and malignancies, with inflammation being key to explaining this intensified risk. This study utilized semi-targeted metabolomics to explore novel [...] Read more.
Worldwide, 3.9 million individuals rely on kidney replacement therapy. They experience heightened susceptibility to cardiovascular diseases and mortality, alongside an increased risk of infections and malignancies, with inflammation being key to explaining this intensified risk. This study utilized semi-targeted metabolomics to explore novel metabolic pathways related to inflammation in this population. We collected pre- and post-session blood samples of patients who had already undergone one year of chronic hemodialysis and used liquid chromatography and high-resolution mass spectrometry to perform a metabolomic analysis. Afterwards, we employed both univariate (Mann–Whitney test) and multivariate (logistic regression with LASSO regularization) to identify metabolites associated with inflammation. In the univariate analysis, indole-3-acetaldehyde, 2-ketobutyric acid, and urocanic acid showed statistically significant decreases in median concentrations in the presence of inflammation. In the multivariate analysis, metabolites positively associated with inflammation included allantoin, taurodeoxycholic acid, norepinephrine, pyroglutamic acid, and L-hydroorotic acid. Conversely, metabolites showing negative associations with inflammation included benzoic acid, indole-3-acetaldehyde, methionine, citrulline, alphaketoglutarate, n-acetyl-ornithine, and 3-4-dihydroxibenzeneacetic acid. Non-inflamed patients exhibit preserved autophagy and reduced mitochondrial dysfunction. Understanding inflammation in this group hinges on the metabolism of arginine and the urea cycle. Additionally, the microbiota, particularly uricase-producing bacteria and those metabolizing tryptophan, play critical roles. Full article
(This article belongs to the Special Issue Renal Dysfunction, Uremic Compounds, and Other Factors (3rd Edition))
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Review

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13 pages, 696 KiB  
Review
Updates on C3 Glomerulopathy in Kidney Transplantation: Pathogenesis and Treatment Options
by Giulia Bartoli, Andrea Dello Strologo, Giuseppe Grandaliano and Francesco Pesce
Int. J. Mol. Sci. 2024, 25(12), 6508; https://doi.org/10.3390/ijms25126508 - 13 Jun 2024
Cited by 5 | Viewed by 2314
Abstract
C3 glomerulopathy is a rare disease, characterized by an abnormal activation of the complement’s alternative pathway that leads to the accumulation of the C3 component in the kidney. The disease recurs in more than half of kidney transplant recipients, with a significant impact [...] Read more.
C3 glomerulopathy is a rare disease, characterized by an abnormal activation of the complement’s alternative pathway that leads to the accumulation of the C3 component in the kidney. The disease recurs in more than half of kidney transplant recipients, with a significant impact on graft survival. Recurrence of the primary disease represents the second cause of graft loss after organ rejection. In C3 glomerulopathy, there are several risk factors which can promote a recurrence during transplantation, such as delayed graft function, infection and monoclonal gammopathy. All these events can trigger the alternative complement pathway. In this review, we summarize the impact of C3 glomerulopathy on kidney grafts and present the latest treatment options. The most widely used treatments for the disease include corticosteroids and mycophenolate mofetil, which are already used chronically by kidney transplant recipients; thus, additional treatments for C3 glomerulopathy are required. Currently, several studies using anti-complement drugs (i.e., eculizumab, Ravalizumab, avacopan) for C3 glomerulopathy in kidney transplant patients are ongoing with encouraging results. Full article
(This article belongs to the Special Issue Renal Dysfunction, Uremic Compounds, and Other Factors (3rd Edition))
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