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Pharmaceuticals
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Advances in the Management of Diabetic Nephropathy
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Advances in the Management of Diabetic Nephropathy

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 20109

Special Issue Editors

Dr. Swayam Prakash Srivastava

E-Mail Website
Guest Editor
Department of Pediatrics (Nephrology), Vascular Biology & Therapeutics, Yale University | YU, New Haven, CT, USA
Interests: kidney fibrosis; diabetic nephropathy; microRNAs in kidneys; molecular and cellular basis of diabetic kidney disease; glomerular diseases; diabetic endothelium and organelle crosstalk in kidneys
Special Issues, Collections and Topics in MDPI journals
Dr. Surya Pandey

E-Mail Website
Guest Editor
Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA
Interests: inflammation; drug–drug interactions; cytokines; chemokines and gut inflammation

Special Issue Information

Dear Colleagues,

Diabetic nephropathy is a serious kidney-related complication of diabetes mellitus. About 25% of people with diabetes eventually develop kidney disease, and diabetes is also a leading cause of end-stage renal disease. The molecular and cellular basis of this renal disease is poorly understood, and this knowledge gap contributes to the suboptimal treatment options available for these patients. Improved understanding of the pathogenesis of diabetic nephropathy is urgently needed to catalyze the development of novel therapeutics. Current therapeutic regimens for these patients include ACE inhibitors, ARBs, and statins that can minimize the effects of the illness but not prevent it. However, side effects to these agents often exceed their overall efficacy. Thus, there is a clear medical need for new therapeutic strategies to improve kidney function in diabetic patients. In this Special Issue of Pharmaceuticals, we are inviting original as well as review articles to deepen our insight into the new pathophysiologic pathways, mechanisms, and advances in therapeutic approaches in the management of diabetic nephropathy.

Dr. Swayam Prakash Srivastava
Dr. Surya Pandey
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 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. Pharmaceuticals 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 2900 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

  • diabetic nephropathy
  • kidney fibrosis
  • microRNAs in kidneys
  • new therapeutic approaches in the management of diabetic kidney disease
  • inflammation
  • glomerular diseases
  • diabetic endothelium
  • organelle crosstalk in kidneys
  • metabolomomics
  • mitochondrial-targeted therapy
  • molecular and cellular basis of diabetic kidney disease
  • chronic kidney disease

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Published Papers (4 papers)

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Research

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16 pages, 5279 KiB  
Article
Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy
by Mohamed M. El-Kady, Reham A. Naggar, Maha Guimei, Iman M. Talaat, Olfat G. Shaker and Maha Saber-Ayad
Pharmaceuticals 2021, 14(7), 608; https://doi.org/10.3390/ph14070608 - 24 Jun 2021
Cited by 10 | Viewed by 5460
Abstract
Diabetic kidney disease (DKD) is still one of the unresolved major complications of diabetes mellitus, which leads ultimately to end-stage renal disease in both type 1 and type 2 diabetes patients. Available drugs that suppress the renin–angiotensin system have partially minimized the disease [...] Read more.
Diabetic kidney disease (DKD) is still one of the unresolved major complications of diabetes mellitus, which leads ultimately to end-stage renal disease in both type 1 and type 2 diabetes patients. Available drugs that suppress the renin–angiotensin system have partially minimized the disease impact. Yet, there is an unmet need for new therapeutic interventions to protect the kidneys of diabetic patients. In DN, glomerular sclerosis and tubulointerstitial fibrosis are mediated through several pathways, of which JAK/STAT is a key one. The current study explored the potential renoprotective effect of the JAK1/JAK2 inhibitor ruxolitinib (at doses of 0.44, 2.2, and 4.4 mg·kg−1) compared to that of enalapril at a dose of 10 mg·kg−1, in a rat model of streptozotocin-induced diabetes mellitus over 8 weeks. The effect of ruxolitinib was assessed by determining urinary albumin/creatinine ratio, serum level of cystatin, and levels of TGF-β1, NF-κB, and TNF-α in renal tissue homogenates by biochemical assays, the glomerular sclerosis and tubulointerstitial fibrosis scores by histological analysis, and fibronectin, TGF-β1, and Vimentin levels by immunohistochemical staining with the respective antibodies. Our results revealed a significant early favorable effect of a two-week ruxolitinib treatment on the renal function, supported by a decline in the proinflammatory biomarkers of DKD. This pre-clinical study suggests that the renoprotective effect of ruxolitinib in the long term should be investigated in animals, as this drug may prove to be a potential option for the treatment of diabetic kidney disease. Full article
(This article belongs to the Special Issue Advances in the Management of Diabetic Nephropathy)
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Review

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19 pages, 2054 KiB  
Review
Regulation of the Homeostatic Unfolded Protein Response in Diabetic Nephropathy
by Hongjie Wang, Srikanth Karnati and Thati Madhusudhan
Pharmaceuticals 2022, 15(4), 401; https://doi.org/10.3390/ph15040401 - 25 Mar 2022
Cited by 8 | Viewed by 3210
Abstract
A growing body of scientific evidence indicates that protein homeostasis, also designated as proteostasis, is causatively linked to chronic diabetic nephropathy (DN). Experimental studies have demonstrated that the insulin signaling in podocytes maintain the homeostatic unfolded protein response (UPR). Insulin signaling via the [...] Read more.
A growing body of scientific evidence indicates that protein homeostasis, also designated as proteostasis, is causatively linked to chronic diabetic nephropathy (DN). Experimental studies have demonstrated that the insulin signaling in podocytes maintain the homeostatic unfolded protein response (UPR). Insulin signaling via the insulin receptor non-canonically activates the spliced X-box binding protein-1 (sXBP1), a highly conserved endoplasmic reticulum (ER) transcription factor, which regulates the expression of genes that control proteostasis. Defective insulin signaling in mouse models of diabetes or the genetic disruption of the insulin signaling pathway in podocytes propagates hyperglycemia induced maladaptive UPR and DN. Insulin resistance in podocytes specifically promotes activating transcription factor 6 (ATF6) dependent pathogenic UPR. Akin to insulin, recent studies have identified that the cytoprotective effect of anticoagulant serine protease-activated protein C (aPC) in DN is mediated by sXBP1. In mouse models of DN, treatment with chemical chaperones that improve protein folding provides an additional benefit on top of currently used ACE inhibitors. Understanding the molecular mechanisms that transmute renal cell specific adaptive responses and that deteriorate renal function in diabetes will enable researchers to develop new therapeutic regimens for DN. Within this review, we focus on the current understanding of homeostatic mechanisms by which UPR is regulated in DN. Full article
(This article belongs to the Special Issue Advances in the Management of Diabetic Nephropathy)
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18 pages, 27284 KiB  
Review
Coronavirus Disease (COVID)-19 and Diabetic Kidney Disease
by Swayam Prakash Srivastava, Rohit Srivastava, Subhash Chand and Julie E. Goodwin
Pharmaceuticals 2021, 14(8), 751; https://doi.org/10.3390/ph14080751 - 30 Jul 2021
Cited by 13 | Viewed by 5110
Abstract
The present review describes COVID-19 severity in diabetes and diabetic kidney disease. We discuss the crucial effect of COVID-19-associated cytokine storm and linked injuries and associated severe mesenchymal activation in tubular epithelial cells, endothelial cells, and macrophages that influence neighboring cell homeostasis, resulting [...] Read more.
The present review describes COVID-19 severity in diabetes and diabetic kidney disease. We discuss the crucial effect of COVID-19-associated cytokine storm and linked injuries and associated severe mesenchymal activation in tubular epithelial cells, endothelial cells, and macrophages that influence neighboring cell homeostasis, resulting in severe proteinuria and organ fibrosis in diabetes. Altered microRNA expression disrupts cellular homeostasis and the renin-angiotensin-system, targets reno-protective signaling proteins, such as angiotensin-converting enzyme 2 (ACE2) and MAS1 receptor (MAS), and facilitates viral entry and replication in kidney cells. COVID-19-associated endotheliopathy that interacts with other cell types, such as neutrophils, platelets, and macrophages, is one factor that accelerates prethrombotic reactions and thrombus formation, resulting in organ failures in diabetes. Apart from targeting vital signaling through ACE2 and MAS, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are also associated with higher profibrotic dipeptidyl transferase-4 (DPP-4)-mediated mechanisms and suppression of AMP-activated protein kinase (AMPK) activation in kidney cells. Lowered DPP-4 levels and restoration of AMPK levels are organ-protective, suggesting a pathogenic role of DPP-4 and a protective role of AMPK in diabetic COVID-19 patients. In addition to standard care provided to COVID-19 patients, we urgently need novel drug therapies that support the stability and function of both organs and cell types in diabetes. Full article
(This article belongs to the Special Issue Advances in the Management of Diabetic Nephropathy)
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17 pages, 371 KiB  
Review
Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease
by Nina Vodošek Hojs, Sebastjan Bevc, Robert Ekart, Nejc Piko, Tadej Petreski and Radovan Hojs
Pharmaceuticals 2021, 14(6), 561; https://doi.org/10.3390/ph14060561 - 11 Jun 2021
Cited by 22 | Viewed by 5218
Abstract
Diabetes mellitus is a global health issue and main cause of chronic kidney disease. Both diseases are also linked through high cardiovascular morbidity and mortality. Diabetic kidney disease (DKD) is present in up to 40% of diabetic patients; therefore, prevention and treatment of [...] Read more.
Diabetes mellitus is a global health issue and main cause of chronic kidney disease. Both diseases are also linked through high cardiovascular morbidity and mortality. Diabetic kidney disease (DKD) is present in up to 40% of diabetic patients; therefore, prevention and treatment of DKD are of utmost importance. Much research has been dedicated to the optimization of DKD treatment. In the last few years, mineralocorticoid receptor antagonists (MRA) have experienced a renaissance in this field with the development of non-steroidal MRA. Steroidal MRA have known cardiorenal benefits, but their use is limited by side effects, especially hyperkalemia. Non-steroidal MRA still block the damaging effects of mineralocorticoid receptor overactivation (extracellular fluid volume expansion, inflammation, fibrosis), but with fewer side effects (hormonal, hyperkalemia) than steroidal MRA. This review article summarizes the current knowledge and newer research conducted on MRA in DKD. Full article
(This article belongs to the Special Issue Advances in the Management of Diabetic Nephropathy)
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