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.

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.

scholarly journals Inhibition of PTEN Activity Aggravates Post Renal Fibrosis in Mice with Ischemia Reperfusion-Induced Acute Kidney Injury

2017 ◽  
Vol 43 (5) ◽  
pp. 1841-1854 ◽  
Author(s):  
Jun Zhou ◽  
Jiying  Zhong ◽  
Sen  Lin ◽  
Zhenxing Huang ◽  
Hongtao Chen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Smooth Muscle Actin ◽  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Kidney Injury ◽  
Control Group ◽  
Kidney Fibrosis

Background: Renal fibrosis is a common pathophysiological feature of chronic kidney disease. Acute kidney injury (AKI) is defined as an independent causal factor of chronic kidney disease, with a pathological representation of post renal fibrosis. However, the etiopathogenesis underlying post renal fibrosis induced by AKI is not completely understood. Methods: BALB/c mice were treated with bpv or vehicle controls and were, respectively, the ischemia reperfusion (IR) model group and control group. All of the animals had blood taken from the orbital venous plexus at 24 hours after IR. Six mice in each group were randomly chosen and euthanized 7 days after IR treatment, and the remaining six mice in each group were euthanized 14 days after IR treatment. We examined the effect on post kidney fibrosis of inhibiting PTEN activity in mice in an IR induced AKI experimental model. Results: Compared with vehicle mice, bpv-(PTEN specific inhibitor) treated mice accumulated more bone marrow-derived fibroblasts and myofibroblasts in the kidneys. Inhibition of PTEN activity increased the expression of α-smooth muscle actin and extracellular matrix proteins and post kidney fibrosis. Furthermore, inhibition of PTEN activity resulted in more inflammatory cytokines in the kidneys of mice subjected to IR-induced renal fibrosis. Moreover, inhibition of PTEN activity up-regulated PI3K protein expression and Akt phosphorylation. Conclusions: Our study demonstrated that PTEN played an important role in post renal fibrosis in mice with ischemia reperfusion-induced AKI. These results indicated that the PTEN/PI3K/Akt signaling pathway may serve as a novel therapeutic target for AKI-induced chronic kidney disease.

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 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.

scholarly journals Mild Stage 1 post-operative acute kidney injury: association with chronic kidney disease and long-term survival

2020 ◽  
Author(s):  
Thorir Einarsson Long ◽  
Dadi Helgason ◽  
Solveig Helgadottir ◽  
Gisli Heimir Sigurdsson ◽  
Runolfur Palsson ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Control Group ◽  
Term Survival ◽  
Absolute Increase ◽  
Long Term Survival ◽  
Stage 1

Abstract Background Mild cases of acute kidney injury (AKI) are identified by a small rise in serum creatinine (SCr) according to the KDIGO AKI definition. The aim of this study was to examine the long-term outcomes of individuals with mild AKI. Methods This was a retrospective cohort study of all adult patients who underwent abdominal, cardiothoracic, vascular or orthopaedic surgery at Landspitali–The National University Hospital of Iceland in 1998–2015. Incident chronic kidney disease (CKD), progression of pre-existing CKD and long-term survival were compared between patients with mild Stage 1 AKI (defined as a rise in SCr of ≥26.5 μmol/L within 48 h post-operatively without reaching 1.5× baseline SCr within 7 days), and a propensity score-matched control group without AKI stratified by the presence of CKD. Results Pre- and post-operative SCr values were available for 47 333 (42%) surgeries. Of those, 1161 (2.4%) had mild Stage 1 AKI and 2355 (5%) more severe forms of AKI. Mild Stage 1 AKI was associated with both incident CKD and progression of pre-existing CKD (P &lt; 0.001). After exclusion of post-operative deaths within 30 days, mild Stage 1 AKI was not associated with worse 1-year survival in patients with preserved kidney function (94% versus 94%, P = 0.660), and same was true for patients with pre-operative CKD (83% versus 82%, P = 0.870) compared with their matched individuals. Conclusions Mild Stage 1 AKI is associated with development and progression of CKD, but not with inferior 1-year survival. These findings support the inclusion of a small absolute increase in SCr in the definition of AKI.

scholarly journals Biochemical predictors of chronic kidney disease in children recovering from acute kidney injury

2021 ◽  
Vol 23 (1) ◽  
pp. 65-71
Author(s):  
O. V. Lavrenchuk ◽  
I. V. Bahdasarova ◽  
L. V. Korol ◽  
L. Ya. Myhal
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Disease Duration ◽  
Kidney Injury ◽  
Activity Level ◽  
Control Group ◽  
Healthy Children ◽  
Group 2 ◽  
Group 1

The pressing question today is to find early informative markers for kidney interstitial injury in reconvalescents of acute kidney injury (AKI). The aim of the study was to determine the informativeness of transferrin (TF), ceruloplasmin (CP) presence and activity level of lysosomal enzymes in urine as predictors of chronic kidney disease. Materials and methods. The contents of TF, CP and N-acetyl-β-Dgluosaminindase (NAG) and β-galactosidase (ß-GAL) in the urine of 41 children after AKI were determined. All patients were divided into 2 groups depending on the disease duration – group 1 included 22 patients with 12 months’ duration, group 2 – 19 children with the disease duration of 2 years and more. The control group consisted of 28 conditionally healthy children. Results. The levels of NAG and ß-GAL were 8 and 3 times increased, respectively, in the patients from group 1 in comparison with the control group (P < 0.001). In the group 2 children, the enzyme levels were 4 times higher than the control, and albuminuria was observed at normal GFR (P < 0.001). An inverse correlation was established between GFR indices and activity levels of NAG (r = -0.473) and ß-GAL (r = -0.333), and a direct correlation between activity indices of GAG and ß-GAL (r = 0.845). The presence and high levels of TF in 18.8 % of children in group 1 and in 21.0 % in group 2, as well as urine CP in 72.7 % of patients in group 1 and in 78.9 % in group 2, is indicative of a progressive damage to the kidney glomerular apparatus. Conclusions. The presence and increased quantitative parameters of TF and CP in the urine of children after AKI are early signs of damage to the kidney glomerular apparatus. Four times increased levels of the enzyme activity and albuminuria at unchanged GFR indicate an interstitial kidney injury (P < 0.001). The examinations conducted are non-invasive, relatively low cost and easy to use for children of all ages.

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