Novel Therapies and Surgical Techniques to Improve Kidney Health

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 9383

Special Issue Editor

UWA School of Biomedical Sciences - Dobney Hypertension Centre Level 3, MRF Building, Rear 50 Murray Street, Perth, WA 6000, Australia
Interests: kidney; renal; kidney disease; therapies; surgery

Special Issue Information

Dear Colleagues,

Healthy kidneys are important for the efficient regulation of metabolism. They filter blood, maintain fluid homeostasis, and are crucial in the process of removing toxins through urine. Deteriorating renal function and chronic kidney disease are closely associated with cardiovascular morbidity and mortality. Kidney diseases are commonly divided into two major groups based on the duration of the disease, i.e., acute kidney injury (AKI) and chronic kidney disease (CKD). There is an ever-increasing population of patients suffering from both acute and chronic kidney diseases that disrupt this homeostasis.

The current definition for AKI was first established in 2004 with a standardized set of criteria. The primary dimension assessed is the magnitude of serum creatinine elevation (change from baseline to peak creatinine), with an increasing emphasis on the duration of the AKI. Based on this definition, the global incidence rate of acute kidney injury is 23.2%. Importantly, high levels of circulating IL-6 in patients with acute kidney injury are predictive of an increased mortality rate. In this regard, therapies that target the IL-6 cytokine signaling pathway have been studied with many fruitful results.

Chronic kidney disease is a common disorder that is defined by structural or functional abnormalities of the kidney and/or a sustained reduction in the glomerular filtration rate. As a high-risk condition, the global rise in the prevalence of CKD is alarming. Between 1990 and 2010, chronic kidney disease rose in the rankings from twenty-seventh to eighteenth in the list of causes of total number of global deaths, which was the second largest rise in the list. Once again, therapies targeting IL-6 family cytokines have provided promising outcomes.

It has been reported that 70% of all cases of end-stage renal disease are related to central obesity, diabetes, and/or hypertension. As such, separating kidney disease from other conditions such as obesity, diabetes, and hypertension is difficult because they are all entwined. The global prevalence of obesity continues to increase, with over 600 million adults and over 100 million children estimated to be obese worldwide. Obesity causes a number of structural changes in the kidneys, including fewer nephrons and abnormal renal tubular exchange. Of significant concern, a high body mass index (BMI) contributed to approximately 7% of deaths globally in 2015, with cardiovascular disease and diabetes being the two leading causes. Diabetes can result in kidney diseases such as diabetic nephropathy, athero-embolic renal disease, ischemic nephropathy, and interstitial fibrosis. There is also a high prevalence of hypertension amongst the obese population. Kidney disease can also progress the propensity for hypertension to increase the activity of the sympathetic nervous system (SNS) or the renin–angiotensin–aldosterone system (RAAS). Activation of the SNS via afferent signals of sensory renal nerves is an early event in the pathophysiology of kidney disease. Surgical procedures such as renal denervation may be beneficial to prevent neurogenic hypertension and may halt the progression of kidney damage and failure.

This Special Issue aims to concentrate on the numerous therapies and surgical techniques that are currently in use to improve kidney health. We will also consider reviews on interesting hypotheses for future interventions to assist with improving and preventing kidney disease.

Dr. Vance Matthews
Guest Editor

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Published Papers (4 papers)

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Research

15 pages, 55921 KiB  
Article
The Effect of SGLT2 Inhibition on Diabetic Kidney Disease in a Model of Diabetic Retinopathy
by Jennifer Rose Matthews, Markus P. Schlaich, Elizabeth Piroska Rakoczy, Vance Bruce Matthews and Lakshini Yasaswi Herat
Biomedicines 2022, 10(3), 522; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030522 - 23 Feb 2022
Cited by 9 | Viewed by 2417
Abstract
Diabetic kidney disease (DKD) is a chronic disorder characterized by elevated urine albumin excretion, reduced glomerular filtration rate, or both. At present, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are the standard care for the treatment of DKD, resulting in improved outcomes. However, [...] Read more.
Diabetic kidney disease (DKD) is a chronic disorder characterized by elevated urine albumin excretion, reduced glomerular filtration rate, or both. At present, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are the standard care for the treatment of DKD, resulting in improved outcomes. However, alternative treatments may be required because although the standard treatments have been found to slow the progression of DKD, they have not been found to halt the disease. In the past decade, sodium glucose co-transporter 2 (SGLT2) inhibitors have been widely researched in the area of cardiovascular disease and diabetes and have been shown to improve cardiovascular outcomes. SGLT2 inhibitors including canagliflozin and dapagliflozin have been shown to slow the progression of kidney disease. There is currently an omission of literature where three SGLT2 inhibitors have been simultaneously compared in a rodent diabetic model. After diabetic Akimba mice were treated with SGLT2 inhibitors for 8 weeks, there was not only a beneficial impact on the pancreas, signified by an increase in the islet mass and increased plasma insulin levels, but also on the kidneys, signified by a reduction in average kidney to body weight ratio and improvement in renal histology. These findings suggest that SGLT2 inhibition promotes improvement in both pancreatic and kidney health. Full article
(This article belongs to the Special Issue Novel Therapies and Surgical Techniques to Improve Kidney Health)
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13 pages, 2539 KiB  
Article
Pharmacologically Inhibiting Glycogen Synthase Kinase-3β Ameliorates Renal Inflammation and Nephrotoxicity in an Animal Model of Cisplatin-Induced Acute Kidney Injury
by Chung-Hsi Hsing, Cheng-Chieh Tsai, Chia-Ling Chen, Yu-Hui Lin, Po-Chun Tseng, Rahmat Dani Satria and Chiou-Feng Lin
Biomedicines 2021, 9(8), 887; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9080887 - 25 Jul 2021
Cited by 5 | Viewed by 2074
Abstract
The adverse effect of cisplatin administration causes acute kidney injury (AKI) following renal inflammation and nephrotoxicity, characterized by proximal tubular cell apoptosis and necrosis. Pro-apoptotic and pro-inflammatory roles of glycogen synthase kinase (GSK)-3β have been reported. This study investigated the therapeutic blockade of [...] Read more.
The adverse effect of cisplatin administration causes acute kidney injury (AKI) following renal inflammation and nephrotoxicity, characterized by proximal tubular cell apoptosis and necrosis. Pro-apoptotic and pro-inflammatory roles of glycogen synthase kinase (GSK)-3β have been reported. This study investigated the therapeutic blockade of GSK-3β in cisplatin-induced AKI. A renal cisplatin nephrotoxicity model showed activation of GSK-3β in vivo, particularly in proximal tubular epithelial cells. Pharmacologically inhibiting GSK-3β abolished cisplatin nephrotoxicity, including proximal tubular injury, cell cytotoxicity, and biochemical dysfunction. Additionally, GSK-3β inhibitor treatment ameliorated renal inflammation by reducing immune cell infiltration, cell adhesion molecule expression, and pro-inflammatory cytokine/chemokine production. Cisplatin treatment caused GSK-3β activation in vitro in the human renal proximal tubular epithelial cell line HK-2, whereas either pharmacological administration of GSK-3β inhibitors or genetic transduction of GSK-3β short-hairpin RNA impeded cisplatin-induced cytotoxicity. These results indicate that cisplatin activates GSK-3β followed by GSK-3β-mediated renal inflammation and nephrotoxicity, contributing to AKI. Full article
(This article belongs to the Special Issue Novel Therapies and Surgical Techniques to Improve Kidney Health)
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19 pages, 2381 KiB  
Article
Delayed Contralateral Nephrectomy Halted Post-Ischemic Renal Fibrosis Progression and Inhibited the Ischemia-Induced Fibromir Upregulation in Mice
by Beáta Róka, Pál Tod, Tamás Kaucsár, Éva Nóra Bukosza, Imre Vörös, Zoltán V. Varga, Balázs Petrovich, Bence Ágg, Péter Ferdinandy, Gábor Szénási and Péter Hamar
Biomedicines 2021, 9(7), 815; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9070815 - 14 Jul 2021
Cited by 2 | Viewed by 2226
Abstract
(1) Background: Ischemia reperfusion (IR) is the leading cause of acute kidney injury (AKI) and results in predisposition to chronic kidney disease. We demonstrated that delayed contralateral nephrectomy (Nx) greatly improved the function of the IR-injured kidney and decelerated fibrosis progression. Our aim [...] Read more.
(1) Background: Ischemia reperfusion (IR) is the leading cause of acute kidney injury (AKI) and results in predisposition to chronic kidney disease. We demonstrated that delayed contralateral nephrectomy (Nx) greatly improved the function of the IR-injured kidney and decelerated fibrosis progression. Our aim was to identify microRNAs (miRNA/miR) involved in this process. (2) Methods: NMRI mice were subjected to 30 min of renal IR and one week later to Nx/sham surgery. The experiments were conducted for 7–28 days after IR. On day 8, multiplex renal miRNA profiling was performed. Expression of nine miRNAs was determined with qPCR at all time points. Based on the target prediction, plexin-A2 and Cd2AP were measured by Western blot. (3) Results: On day 8 after IR, the expression of 20/1195 miRNAs doubled, and 9/13 selected miRNAs were upregulated at all time points. Nx reduced the expression of several ischemia-induced pro-fibrotic miRNAs (fibromirs), such as miR-142a-duplex, miR-146a-5p, miR-199a-duplex, miR-214-3p and miR-223-3p, in the injured kidneys at various time points. Plexin-A2 was upregulated by IR on day 10, while Cd2AP was unchanged. (4) Conclusion: Nx delayed fibrosis progression and decreased the expression of ischemia-induced fibromirs. The protein expression of plexin-A2 and Cd2AP is mainly regulated by factors other than miRNAs. Full article
(This article belongs to the Special Issue Novel Therapies and Surgical Techniques to Improve Kidney Health)
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18 pages, 2969 KiB  
Article
The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion
by Karol Tejchman, Adam Nowacki, Katarzyna Kotfis, Edyta Skwirczynska, Maciej Kotowski, Labib Zair, Marek Ostrowski and Jerzy Sienko
Biomedicines 2021, 9(4), 417; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9040417 - 13 Apr 2021
Cited by 6 | Viewed by 1892
Abstract
Ischemia-reperfusion injury (IRI) occurring after renal transplantation is a complex biochemical process that can be monitored by specific biomarkers. The roles of those are not yet fully elucidated. The aim of this study was to analyze the concentrations of endothelins (ET-1, ET-2, and [...] Read more.
Ischemia-reperfusion injury (IRI) occurring after renal transplantation is a complex biochemical process that can be monitored by specific biomarkers. The roles of those are not yet fully elucidated. The aim of this study was to analyze the concentrations of endothelins (ET-1, ET-2, and ET-3), interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) during the reperfusion of human kidneys grafted from brain dead donors and later transplanted. The study group (n = 44) was analyzed according to the method of kidney storage: Group 1 underwent hypothermic machine perfusion (HMP) in the LifePort perfusion pump (n = 22), and Group 2 underwent static cold storage (SCS) (n = 22). The analysis of kidney function was performed daily during the first seven days after transplantation. The kidneys in Group 1 were characterized by higher absolute concentrations of ET-1, IL-18, and NGAL, as well as a lower concentration of ET-2 (p = 0.017) and ET-3. The relative increase of ET-1 (p = 0.033), ET-2, and ET-3 during reperfusion was lower in this group, while the relative decrease of NGAL was higher. Group 1 was also characterized by significant decrease of IL-18 (p = 0.026) and a tendency for better kidney function based on the higher total diuresis, higher glomerular filtration rate (GFR), higher potassium level, lower serum creatinine, and lower urea concentration during the seven-day postoperative observation period. The long-term beneficial impact of hypothermic machine perfusion on the outcome of transplanted kidneys may rely on the early modified proceedings and intensity of ischemia-reperfusion injury reflected by the dynamics of the concentrations of examined biomarkers. Full article
(This article belongs to the Special Issue Novel Therapies and Surgical Techniques to Improve Kidney Health)
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