scholarly journals The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

2021 ◽  
pp. 1-17
Author(s):  
Hai Ning Wee ◽  
Jian-Jun Liu ◽  
Jianhong Ching ◽  
Jean-Paul Kovalik ◽  
Su Chi Lim
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Animal Models ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Kynurenine Pathway ◽  
T Cell Subsets ◽  
Renal Diseases ◽  
Tryptophan Degradation

<b><i>Background:</i></b> The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD<sup>+</sup>) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. <b><i>Summary:</i></b> This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD<sup>+</sup> production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. <b><i>Key Messages:</i></b> KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.

scholarly journals Stem cell-based treatment of kidney diseases

2020 ◽  
Vol 245 (10) ◽  
pp. 902-910
Author(s):  
Binbin Pan ◽  
Guoping Fan
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Acute Kidney Injury ◽  
Stem Cell ◽  
Kidney Disease ◽  
Cell Therapy ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Great Promise ◽  
Kidney Organoids

Kidney dysfunction, including chronic kidney disease and acute kidney injury, is a globally prevalent health problem. However, treatment regimens are still lacking, especially for conditions involving kidney fibrosis. Stem cells hold great promise in the treatment of chronic kidney disease and acute kidney injury, but success has been hampered by insufficient incorporation of the stem cells in the injured kidney. Thus, new approaches for the restoration of kidney function after acute or chronic injury have been explored. Recently, kidney organoids have emerged as a useful tool in the treatment of kidney diseases. In this review, we discuss the mechanisms and approaches of cell therapy in acute kidney injury and chronic kidney disease, including diabetic kidney disease and lupus nephritis. We also summarize the potential applications of kidney organoids in the treatment of kidney diseases. Impact statement Stem cells hold great promise in regenerative medicine. Pluripotent stem cells have been differentiated into kidney organoids to understand human kidney development and to dissect renal disease mechanisms. Meanwhile, recent studies have explored the treatment of kidney diseases using a variety of cells, including mesenchymal stem cells and renal derivatives. This mini-review discusses the diverse mechanisms underlying current renal disease treatment via stem cell therapy. We postulate that clinical applications of stem cell therapy for kidney diseases can be readily achieved in the near future.

scholarly journals PROTON PUMP INHIBITORS AND THE RISK OF CHRONIC KIDNEY DISEASES: A CRITICAL REVIEW

2020 ◽  
pp. 11-14
Author(s):  
SHAREEF J. ◽  
SRIDHAR S. B. ◽  
SHARIFF A.
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
End Stage Renal Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Stage Renal Disease ◽  
End Stage

Proton pump inhibitors (PPIs) are most widely used medications for acid related gastrointestinal disorders. Accessible evidence based studies suggest that the increased use of PPI is linked to a greater risk of developing kidney diseases. This review aims to determine the association of kidney disease with the use of proton pump inhibitor with various study designs. PubMed, Scopus and Google Scholar databases as well as a reference list of relevant articles were systematically searched for studies by using the following search terms; ‘proton pump inhibitors’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘end stage renal disease’. Both observational and randomized controlled trials (RCTs) exploring the association of PPI use with kidney disease were eligible for inclusion. A total of 8 articles, including 9 studies (n = 794,349 participants) were identified and included in the review. Majority of the studies showed a higher risk of kidney outcomes in patients taking PPIs, with effect higher of acute kidney injury (4-to 6-fold) compared with chronic kidney disease and end stage renal disease (1.5-to 2.5-fold). However, the studies suggest that the strength of evidence is weak and could not prove causation. The risk increased considerably with the use of high dose of PPIs and prolonged duration of exposure necessitates the monitoring of renal function. Exercising vigilance in PPI use and cessation of proton pump inhibitor when there is no clear indication may be a reasonable approach to reduce the population burden of kidney diseases.

scholarly journals Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7113
Author(s):  
Marlene Marisol Perales-Quintana ◽  
Alma L. Saucedo ◽  
Juan Ricardo Lucio-Gutiérrez ◽  
Noemí Waksman ◽  
Gabriela Alarcon-Galvan ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Folic Acid ◽  
Kidney Disease ◽  
Biochemical Parameters ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Control Group ◽  
Organic Osmolytes ◽  
Histological Classification

Background Renal diseases represent a major public health problem. The demonstration that maladaptive repair of acute kidney injury (AKI) can lead to the development of chronic kidney disease (CKD) and end-stage renal disease has generated interest in studying the pathophysiological pathways involved. Animal models of AKI–CKD transition represent important tools to study this pathology. We hypothesized that the administration of multiple doses of folic acid (FA) would lead to a progressive loss of renal function that could be characterized through biochemical parameters, histological classification and nuclear magnetic resonance (NMR) profiling. Methods Wistar rats were divided into groups: the control group received a daily intraperitoneal (I.P.) injection of double-distilled water, the experimental group received a daily I.P. injection of FA (250 mg kg body weight−1). Disease was classified according to blood urea nitrogen level: mild (40–80 mg dL−1), moderate (100–200 mg dL−1) and severe (>200 mg dL−1). We analyzed through biochemical parameters, histological classification and NMR profiling. Results Biochemical markers, pro-inflammatory cytokines and kidney injury biomarkers differed significantly (P < 0.05) between control and experimental groups. Histology revealed that as damage progressed, the degree of tubular injury increased, and the inflammatory infiltrate was more evident. NMR metabolomics and chemometrics revealed differences in urinary metabolites associated with CKD progression. The main physiological pathways affected were those involved in energy production and amino-acid metabolism, together with organic osmolytes. These data suggest that multiple administrations of FA induce a reproducible model of the induction of CKD. This model could help to evaluate new strategies for nephroprotection that could be applied in the clinic.

scholarly journals IL-20 in Acute Kidney Injury: Role in Pathogenesis and Potential as a Therapeutic Target

2020 ◽  
Vol 21 (3) ◽  
pp. 1009
Author(s):  
Tian-Yu Lin ◽  
Yu-Hsiang Hsu
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Risk Factor ◽  
Renal Fibrosis ◽  
Inflammatory Mediator ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Pro Inflammatory Cytokines

Acute kidney injury (AKI) causes over 1 million deaths worldwide every year. AKI is now recognized as a major risk factor in the development and progression of chronic kidney disease (CKD). Diabetes is the main cause of CKD as well. Renal fibrosis and inflammation are hallmarks in kidney diseases. Various cytokines contribute to the progression of renal diseases; thus, many drugs that specifically block cytokine function are designed for disease amelioration. Numerous studies showed IL-20 functions as a pro-inflammatory mediator to regulate cytokine expression in several inflammation-mediated diseases. In this review, we will outline the effects of pro-inflammatory cytokines in the pathogenesis of AKI and CKD. We also discuss the role of IL-20 in kidney diseases and provide a potential therapeutic approach of IL-20 blockade for treating renal diseases.

COVID-19 and Renal Diseases: An Update

2020 ◽  
Vol 22 (1) ◽  
pp. 52-67
Author(s):  
Letícia Bitencourt Cota ◽  
Ana Luisa Pedrosa ◽  
Stephanie Bruna Camilo Soares de Brito ◽  
Ana Cláudia Fontoura Fróes ◽  
Sarah Tayná de Carvalho ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Renal Diseases ◽  
Angiotensin Converting Enzyme 2 ◽  
Immunosuppressive Medications ◽  
Immune Alterations ◽  
Current Scenario

Background: It becomes increasingly evident that the SARS-CoV-2 infection is not limited to the respiratory system. In addition to being a target of the virus, the kidney also seems to have substantial influence on the outcomes of the disease. Methods: Data was obtained by a comprehensive and non-systematic search in the PubMed, Cochrane, Scopus and SciELO databases, using mainly the terms “SARS-CoV-2”, “COVID-19”, “chronic kidney disease”, “renal transplantation”, acute kidney injury” and “renal dysfunction”. Discussion: The membrane-bound angiotensin converting enzyme 2 is the receptor for SARS-CoV-2, and this interaction may lead to an imbalance of the Renin Angiotensin System (RAS), associated with worse clinical presentations of COVID-19, including acute pulmonary injury, hyperinflammatory state and hematological alterations. In the framework of renal diseases, development of acute kidney injury is associated mostly with immune alterations and direct cytopathic lesions by the virus, leading to higher mortality. As for chronic kidney disease, the patients at a non-terminal stage have worse prog-nosis, while the hemodialysis patients appear to have mild courses of COVID-19, probably due to lower chances of being affected by the cytokine storm. Furthermore, the current scenario is unfavorable to kidney donation and transplantation. The relationship between COVID-19 and immunosuppression in kidney transplantation recipients has been greatly discussed to determine whether it increases mortality and how it interacts with immunosuppressive medications. Conclusion: The kidney and the RAS exert fundamental roles in the SARS-CoV-2 infection and more research is required to have a complete understanding on the repercussions caused by COVID-19 in renal diseases.

Malignancy-associated kidney disease

2016 ◽  
Vol 6 (1) ◽  
pp. 0-0
Author(s):  
K Kozłowska ◽  
J. Małyszko
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Nephrotic Syndrome ◽  
Renal Replacement Therapy ◽  
Kidney Disease ◽  
Replacement Therapy ◽  
Tubulointerstitial Nephritis ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Electrolyte Abnormalities

Malignancy or its treatment affect kidney in several ways. The most common are acute kidney injury and chronic kidney disease. Other form of kidney diseases can also be present such as nephrotic syndrome, tubulointerstitial nephritis, thrombotic microangipathy etc. In addition, electrolyte abnormalities such as hypercalcemia, hyponatremia and hypernatremia, hypokalemia and hyperkalemia, and hypomagnesemia. are observed. Treatment of malignancy associated kidney disease is usually symptomatic. Cessation of the offending agent or other supportive measures if needed i.e. renal replacement therapy are also implemented.

scholarly journals Found in Translation: Reasons for Optimism in the Pursuit to Prevent Chronic Kidney Disease After Acute Kidney Injury

2019 ◽  
Vol 6 ◽  
pp. 205435811986874
Author(s):  
Samuel A. Silver ◽  
Casimiro Gerarduzzi
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Animal Models ◽  
Kidney Injury ◽  
Narrative Review ◽  
Sources Of Information ◽  
Stage Renal Disease ◽  
End Stage ◽  
Injury Progression

Purpose of review: The current review will discuss on the progress of studying the transition phase between acute kidney injury (AKI) and chronic kidney disease (CKD) through improved animal models, common AKI and CKD pathways, and how human studies may inform different translational approaches. Sources of information: PubMed and Google Scholar. Methods: A narrative review was performed using the main terms “acute kidney injury,” “chronic kidney disease,” “end-stage renal disease,” “animal models,” “review,” “decision-making,” and “translational research.” Key findings: The last decade has shown much progress in the study of AKI, including evidence of a pathophysiological link between AKI and CKD. We are now in a phase of redesigning animal models and discovering mechanisms that can replicate the pathological conditions of the AKI-to-CKD continuum. Translating these findings into the clinic is a barrier that must be overcome. To this end, current efforts include prediction of AKI onset and maladaptive repair, detecting patients susceptible to the progression of chronic maladaptive repair, and understanding shared signaling mechanisms between AKI and CKD. Limitations: This is a narrative review of the literature that is partially influenced by the knowledge, perspectives, and experiences of the authors and their research background. Implications: Overall, this new knowledge from the AKI-to-CKD continuum will help bridge the discontinuity that exists between animal models and patients, resulting in more effective translational biomarkers and therapeutics to test in known AKI pathologies thereby preventing the chronicity of kidney injury progression.

scholarly journals Mitochondrial DNA-Mediated Inflammation in Acute Kidney Injury and Chronic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Lini Jin ◽  
Binfeng Yu ◽  
Ines Armando ◽  
Fei Han
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Mitochondrial Dna ◽  
Kidney Disease ◽  
Inflammatory Responses ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Inflammasome Activation ◽  
Mtdna Copy Number ◽  
And Function

The integrity and function of mitochondria are essential for normal kidney physiology. Mitochondrial DNA (mtDNA) has been widely a concern in recent years because its abnormalities may result in disruption of aerobic respiration, cellular dysfunction, and even cell death. Particularly, aberrant mtDNA copy number (mtDNA-CN) is associated with the development of acute kidney injury and chronic kidney disease, and urinary mtDNA-CN shows the potential to be a promising indicator for clinical diagnosis and evaluation of kidney function. Several lines of evidence suggest that mtDNA may also trigger innate immunity, leading to kidney inflammation and fibrosis. In mechanism, mtDNA can be released into the cytoplasm under cell stress and recognized by multiple DNA-sensing mechanisms, including Toll-like receptor 9 (TLR9), cytosolic cGAS-stimulator of interferon genes (STING) signaling, and inflammasome activation, which then mediate downstream inflammatory cascades. In this review, we summarize the characteristics of these mtDNA-sensing pathways mediating inflammatory responses and their role in the pathogenesis of acute kidney injury, nondiabetic chronic kidney disease, and diabetic kidney disease. In addition, we highlight targeting of mtDNA-mediated inflammatory pathways as a novel therapeutic target for these kidney diseases.

scholarly journals Connexin 43: a New Therapeutic Target Against Chronic Kidney Disease

2018 ◽  
Vol 49 (3) ◽  
pp. 998-1009 ◽  
Author(s):  
Niki Prakoura ◽  
Panagiotis Kavvadas ◽  
Christos E.  Chadjichristos
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Animal Models ◽  
Renal Disease ◽  
Connexin 43 ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Kidney Diseases ◽  
In Vivo Studies ◽  
Renal Diseases

Chronic kidney disease is an incurable to date pathology with a continuously growing incidence that contributes to the increase of the number of deaths worldwide. With currently no efficient prognostic or therapeutic options being available, the only possibility for treatment of end-stage renal disease is renal replacement therapy through dialysis or transplantation. Understanding the molecular mechanisms participating in the progression of renal diseases and uncovering the pathways implicated will permit the identification of novel and more efficient targets of therapy. Connexin43 was recently identified as a novel player in the development of chronic kidney disease. It was found de novo expressed and/or differentially localized in various renal cell populations during progression of renal disease, indicating an abnormal connexin signaling, both in patients and animal models. Subsequent in vivo studies demonstrated that connexin43 is involved in mediating inflammatory and fibrotic processes contributing to renal damage. Genetic, pharmaco-genetic or peptide-based inhibition of connexin43 in animal models and cell culture systems was successful in preventing the progression of the pathology and preserving the cell phenotypes. This review will summarize the recent advances on connexin43 in the field of kidney diseases and discuss the potential of future connexin43-based therapies against chronic kidney disease.

scholarly journals Deprivation and kidney disease—a predictor of poor outcomes

2019 ◽  
Vol 13 (2) ◽  
pp. 128-132
Author(s):  
Greg D Guthrie ◽  
Samira Bell
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Confounding Factors ◽  
Growing Body ◽  
Poor Outcomes

Abstract There is a growing body of evidence for the role of deprivation in a broad spectrum of diseases including renal disease. Deprivation has been demonstrated to be associated with poorer outcomes across a range of renal diseases including acute kidney injury (AKI), chronic kidney disease and transplantation. In this issue of Clinical Kidney Journal, Hounkpatin et al. describe the association of socioeconomic deprivation with incidence, mortality and resolution of AKI in a large UK cohort. Investigating deprivation as a factor influencing either incidence or outcome of disease is challenging due to variations in measures of deprivation used and other confounding factors that may be contributing to the observed differences. In this editorial, we review the current literature examining the role of deprivation in renal disease.

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