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Molecular Mechanisms and Therapies for Kidney Diseases

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

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 16813

Special Issue Editor

Faculty of Medical Sciences in Zabrze, Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland
Interests: internal diseases; nephrology; transplantology; hypertensiology

Special Issue Information

Dear Colleagues,

In this issue of IJMS, we would like to present the latest developments in molecular mechanisms of renal disease development and treatment.  What are the reasons for this?

First, kidney diseases have become a global public health problem due to their rapidly increasing prevalence. These diseases affect more than 10% of the world's population due to the global increase in population aging, as well as the increase in the prevalence of their leading causes, such as diabetes, cardiovascular disease and hypertension. As a routine treatment for kidney disease, multidrug therapy is unable to reverse the progression into end-stage renal disease (ESRD) in most patients, and those with ESRD require renal replacement therapy, namely maintenance dialysis or kidney transplantation. Dialysis is not considered an ideal treatment strategy due to the high cost of treatment and adverse effects on patient quality of life. Kidney transplantation allows patients to regain their own kidney function, but a severe shortage of donors and the possibility of organ rejection limit its use. Therefore, it is necessary to search for new and better therapeutic options to alleviate, cure, or prevent kidney disease and to improve patient survival and quality of life. We would like to include papers that provide information on the molecular mechanisms of progression of kidney diseases such as glomerulonephritis - primary and secondary, interstitial nephritis, polycystic kidney disease, their molecular diagnosis and treatment.

Second, acute kidney injury (AKI) has been reported as a common complication among hospitalized patients with coronavirus disease 2019 (COVID-19), with the incidence of AKI ranging from 0.5% to 80%. Understanding the pathophysiology of AKI in the context of COVID-19 is extremely important. The pathway of renal injury in patients infected with severe acute respiratory syndrome virus type 2 (SARS-CoV-2) is multifactorial. We encourage your interest in this topic.

The special issue of ‘Molecular Mechanisms and Therapies for Kidney Diseases’ in the International Journal of Molecular Sciences will contain a selection of research and review papers that will contribute to the understanding of the molecular mechanisms of kidney disease development and diagnosis and new treatments.

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

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Keywords

  • Chronic kidney disease
  • Acute renal failure
  • Glomerulonephritis primary
  • Diabetic kidney disease
  • Interstitial kidney disease
  • Polycystic kidney disease
  • COVID-19 and kidney disease
  • Hypertension
  • Other kidney disease

Published Papers (5 papers)

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Research

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15 pages, 6948 KiB  
Article
Decreased Podocyte Vesicle Transcytosis and Albuminuria in APC C-Terminal Deficiency Mice with Puromycin-Induced Nephrotic Syndrome
by Saaya Hatakeyama, Akihiro Tojo, Hiroshi Satonaka, Nami O. Yamada, Takao Senda and Toshihiko Ishimitsu
Int. J. Mol. Sci. 2021, 22(24), 13412; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413412 - 14 Dec 2021
Cited by 2 | Viewed by 2060
Abstract
In minimal change nephrotic syndrome, podocyte vesicle transport is enhanced. Adenomatous polyposis coli (APC) anchors microtubules to cell membranes and plays an important role in vesicle transport. To clarify the role of APC in vesicle transport in podocytes, nephrotic syndrome was induced by [...] Read more.
In minimal change nephrotic syndrome, podocyte vesicle transport is enhanced. Adenomatous polyposis coli (APC) anchors microtubules to cell membranes and plays an important role in vesicle transport. To clarify the role of APC in vesicle transport in podocytes, nephrotic syndrome was induced by puromycin amino nucleoside (PAN) injection in mice expressing APC1638T lacking the C-terminal of microtubule-binding site (APC1638T mouse); this was examined in renal tissue changes. The kidney size and glomerular area of APC1638T mice were reduced (p = 0.014); however, the number of podocytes was same between wild-type (WT) mice and APC1638T mice. The ultrastructure of podocyte foot process was normal by electron microscopy. When nephrotic syndrome was induced, the kidneys of WT+PAN mice became swollen with many hyaline casts, whereas these changes were inhibited in the kidneys of APC1638T+PAN mice. Electron microscopy showed foot process effacement in both groups; however, APC1638T+PAN mice had fewer vesicles in the basal area of podocytes than WT+PAN mice. Cytoplasmic dynein-1, a motor protein for vesicle transport, and α-tubulin were significantly reduced in APC1638T+PAN mice associated with suppressed urinary albumin excretion compared to WT+PAN mice. In conclusion, APC1638T mice showed reduced albuminuria associated with suppressed podocyte vesicle transport when minimal change nephrotic syndrome was induced. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies for Kidney Diseases)
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19 pages, 4381 KiB  
Article
IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?
by Aurore Devocelle, Lola Lecru, Sophie Ferlicot, Thomas Bessede, Jean-Jacques Candelier, Julien Giron-Michel and Hélène François
Int. J. Mol. Sci. 2021, 22(21), 11698; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111698 - 28 Oct 2021
Cited by 9 | Viewed by 2201
Abstract
Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been implicated in fibrosis protection [...] Read more.
Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been implicated in fibrosis protection in several organs, with little evidence in the kidney. Since endogenous IL-15 expression decreased in nephrectomized human allografts evolving toward fibrosis and kidneys in the unilateral ureteral obstruction (UUO) model, we explored IL-15’s renoprotective role by pharmologically delivering IL-15 coupled or not with its soluble receptor IL-15Rα. Despite the lack of effects on myofibroblast accumulation, both IL-15 treatments prevented tubulointerstitial fibrosis (TIF) in UUO as characterized by reduced collagen and fibronectin deposition. Moreover, IL-15 treatments inhibited collagen and fibronectin secretion by transforming growth factor-β (TGF-β)-treated primary myofibroblast cultures, demonstrating that the antifibrotic effect of IL-15 in UUO acts, in part, through a direct inhibition of ECM synthesis by myofibroblasts. In addition, IL-15 treatments resulted in decreased expression of monocyte chemoattractant protein 1 (MCP-1) and subsequent macrophage infiltration in UUO. Taken together, our study highlights a major role of IL-15 on myofibroblasts and macrophages, two main effector cells in renal fibrosis, demonstrating that IL-15 may represent a new therapeutic option for CKD. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies for Kidney Diseases)
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15 pages, 3402 KiB  
Article
Zebrafish Model as a Screen to Prevent Cyst Inflation in Autosomal Dominant Polycystic Kidney Disease
by Inês Oliveira, Raquel Jacinto, Sara Pestana, Fernando Nolasco, Joaquim Calado, Susana Santos Lopes and Mónica Roxo-Rosa
Int. J. Mol. Sci. 2021, 22(16), 9013; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169013 - 20 Aug 2021
Cited by 1 | Viewed by 3074
Abstract
In autosomal dominant polycystic kidney disease (ADPKD), kidney cyst growth requires the recruitment of CFTR (cystic fibrosis transmembrane conductance regulator), the chloride channel that is defective in cystic fibrosis. We have been studying cyst inflation using the zebrafish Kupffer’s vesicle (KV) as model [...] Read more.
In autosomal dominant polycystic kidney disease (ADPKD), kidney cyst growth requires the recruitment of CFTR (cystic fibrosis transmembrane conductance regulator), the chloride channel that is defective in cystic fibrosis. We have been studying cyst inflation using the zebrafish Kupffer’s vesicle (KV) as model system because we previously demonstrated that knocking down polycystin 2 (PC2) induced a CFTR-mediated enlargement of the organ. We have now quantified the PC2 knockdown by showing that it causes a 73% reduction in the number of KV cilia expressing PC2. According to the literature, this is an essential event in kidney cystogenesis in ADPKD mice. Additionally, we demonstrated that the PC2 knockdown leads to a significant accumulation of CFTR-GFP at the apical region of the KV cells. Furthermore, we determined that KV enlargement is rescued by the injection of Xenopus pkd2 mRNA and by 100 µM tolvaptan treatment, the unique and approved pharmacologic approach for ADPKD management. We expected vasopressin V2 receptor antagonist to lower the cAMP levels of KV-lining cells and, thus, to inactivate CFTR. These findings further support the use of the KV as an in vivo model for screening compounds that may prevent cyst enlargement in this ciliopathy, through CFTR inhibition. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies for Kidney Diseases)
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Review

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38 pages, 1136 KiB  
Review
Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists
by Agata Winiarska, Monika Knysak, Katarzyna Nabrdalik, Janusz Gumprecht and Tomasz Stompór
Int. J. Mol. Sci. 2021, 22(19), 10822; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910822 - 06 Oct 2021
Cited by 63 | Viewed by 6145
Abstract
The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early [...] Read more.
The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) agonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R agonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies for Kidney Diseases)
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Other

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12 pages, 4882 KiB  
Case Report
Atypical Hemolytic Uremic Syndrome (aHUS) and Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID)—Two Diseases That Exacerbate Each Other: Case Report
by Anna Bogdał, Andrzej Badeński, Małgorzata Pac, Anna Wójcicka, Marta Badeńska, Agnieszka Didyk, Elżbieta Trembecka-Dubel, Nel Dąbrowska-Leonik, Małgorzata Walaszczyk, Natalia Matysiak, Aurelia Morawiec-Knysak, Tomasz Szczepański and Maria Szczepańska
Int. J. Mol. Sci. 2021, 22(17), 9479; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179479 - 31 Aug 2021
Cited by 2 | Viewed by 2575
Abstract
Hemolytic uremic syndrome (HUS) is defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Atypical HUS (aHUS), distinguished by its etiology, is caused by uncontrolled overactivation of the alternative complement pathway. The correct diagnosis of aHUS is complex [...] Read more.
Hemolytic uremic syndrome (HUS) is defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Atypical HUS (aHUS), distinguished by its etiology, is caused by uncontrolled overactivation of the alternative complement pathway. The correct diagnosis of aHUS is complex and involves various gene mutations. Severe combined immunodeficiency (SCID), characterized by severe T-cell lymphocytopenia and a lack of antigen-specific T-cell and B-cell immune responses, is of seldom occurrence. In 10–15% of pediatric patients, SCID is caused by adenosine deaminase (ADA) deficiency. The authors describe the case of a boy who suffered from both aHUS and ADA-deficient SCID. At the age of 9 months, the patient presented acute kidney injury with anuria and coagulopathy. The diagnosis of aHUS was established on the basis of alternative complement pathway deregulation and disease-associated gene mutations. Further examination revealed immune system failure and, at the age of 13 months, the ADA deficiency was confirmed by genetic tests and the boy was diagnosed with ADA-SCID. ADA SCID has recently been described as a possible triggering factor of aHUS development and progression. However, more research is required in this field. Nevertheless, it is crucial in clinical practice to be aware of these two co-existing life-threatening diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies for Kidney Diseases)
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