scholarly journals Mechanisms of COVID-19-induced kidney injury and current pharmacotherapies

2021 ◽  
Author(s):  
Wissam H. Faour ◽  
Ali Choaib ◽  
Elio Issa ◽  
Francesca El Choueiry ◽  
Khodor Shbaklo ◽  
...  
Keyword(s):  
Renal Damage ◽  
Current Knowledge ◽  
Kidney Injury ◽  
Mortality Rates ◽  
Health Crisis ◽  
Significant Evidence ◽  
Kidney Functions ◽  
Shed Light ◽  
High Infectivity

AbstractThe COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness.

scholarly journals The Potential Use of Vitamin C to Prevent Kidney Injury in Patients with COVID-19

Diseases ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 46
Author(s):  
Feng Xu ◽  
Yawei Wen ◽  
Xinge Hu ◽  
Tiannan Wang ◽  
Guoxun Chen
Keyword(s):  
Vitamin C ◽  
Distress Syndrome ◽  
Kidney Injury ◽  
Mortality Rates ◽  
Protective Effects ◽  
Global Public Health ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Renal Functions ◽  
Potential Use

The newly found SARS-CoV-2 has led to the pandemic of COVID-19, which has caused respiratory distress syndrome and even death worldwide. This has become a global public health crisis. Unfortunately, elders and subjects with comorbidities have high mortality rates. One main feature of COVID-19 is the cytokine storm, which can cause damage in cells and tissues including the kidneys. Here, we reviewed the current literature on renal impairments in patients with COVID-19 and analyzed the possible etiology and mechanisms. In addition, we investigated the potential use of vitamin C for the prevention of renal injury in those patients. It appears that vitamin C could be helpful to improve the outcomes of patients with COVID-19. Lastly, we discussed the possible protective effects of vitamin C on renal functions in COVID-19 patients with existing kidney conditions.

scholarly journals Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model

2021 ◽  
Vol 22 (7) ◽  
pp. 3762
Author(s):  
Sarah M. Kedziora ◽  
Kristin Kräker ◽  
Lajos Markó ◽  
Julia Binder ◽  
Meryam Sugulle ◽  
...  
Keyword(s):  
Rat Model ◽  
Renal Damage ◽  
Kidney Injury ◽  
Tissue Growth ◽  
Female Rats ◽  
Male Rats ◽  
Renal Diseases ◽  
Transgenic Rat ◽  
Increased Risk ◽  
Before And After

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.

scholarly journals Protective Role of Nrf2 in Renal Disease

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 39
Author(s):  
Melania Guerrero-Hue ◽  
Sandra Rayego-Mateos ◽  
Cristina Vázquez-Carballo ◽  
Alejandra Palomino-Antolín ◽  
Cristina García-Caballero ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Current Knowledge ◽  
Unmet Need ◽  
Kidney Injury ◽  
Protective Role ◽  
Renal Diseases ◽  
Related Factor ◽  
Ckd Progression ◽  
Protective Mechanisms ◽  
Novel Therapeutic Strategies

Chronic kidney disease (CKD) is one of the fastest-growing causes of death and is predicted to become by 2040 the fifth global cause of death. CKD is characterized by increased oxidative stress and chronic inflammation. However, therapies to slow or prevent CKD progression remain an unmet need. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that plays a key role in protection against oxidative stress and regulation of the inflammatory response. Consequently, the use of compounds targeting Nrf2 has generated growing interest for nephrologists. Pre-clinical and clinical studies have demonstrated that Nrf2-inducing strategies prevent CKD progression and protect from acute kidney injury (AKI). In this article, we review current knowledge on the protective mechanisms mediated by Nrf2 against kidney injury, novel therapeutic strategies to induce Nrf2 activation, and the status of ongoing clinical trials targeting Nrf2 in renal diseases.

scholarly journals Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1041
Author(s):  
Mohammad Tarek ◽  
Hana Abdelzaher ◽  
Firas Kobeissy ◽  
Hassan A. N. El-Fawal ◽  
Mohammed M. Salama ◽  
...  
Keyword(s):  
Immune Response ◽  
Genetic Factors ◽  
Bioinformatics Analysis ◽  
Expression Patterns ◽  
Spike Protein ◽  
Target Cells ◽  
Health Crisis ◽  
Expression Levels ◽  
Different Populations ◽  
Shed Light

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2’s receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN’s potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

B-cell lymphoma/leukaemia 10 and angiotensin II-induced kidney injury

2019 ◽  
Author(s):  
Lajos Markó ◽  
Joon-Keun Park ◽  
Norbert Henke ◽  
Song Rong ◽  
András Balogh ◽  
...  
Keyword(s):  
B Cell ◽  
Renal Damage ◽  
Cardiac Fibrosis ◽  
Immune Cell ◽  
Cell Lymphoma ◽  
Kidney Injury ◽  
B Cell Lymphoma ◽  
Cell Infiltration ◽  
Tubular Damage ◽  
Ang Ii

Abstract Aims B-cell lymphoma/leukaemia 10 (Bcl10) is a member of the CARMA-Bcl10-MALT1 signalosome, linking angiotensin (Ang) II, and antigen-dependent immune-cell activation to nuclear factor kappa-B signalling. We showed earlier that Bcl10 plays a role in Ang II-induced cardiac fibrosis and remodelling, independent of blood pressure. We now investigated the role of Bcl10 in Ang II-induced renal damage. Methods and results Bcl10 knockout mice (Bcl10 KO) and wild-type (WT) controls were given 1% NaCl in the drinking water and Ang II (1.44 mg/kg/day) for 14 days. Additionally, Bcl10 KO or WT kidneys were transplanted onto WT mice that were challenged by the same protocol for 7 days. Kidneys of Ang II-treated Bcl10 KO mice developed less fibrosis and showed fewer infiltrating cells. Nevertheless, neutrophil gelatinase-associated lipocalin (Ngal) and kidney injury molecule (Kim)1 expression was higher in the kidneys of Ang II-treated Bcl10 KO mice, indicating exacerbated tubular damage. Furthermore, albuminuria was significantly higher in Ang II-treated Bcl10 KO mice accompanied by reduced glomerular nephrin expression and podocyte number. Ang II-treated WT mice transplanted with Bcl10 KO kidney showed more albuminuria and renal Ngal, compared to WT- > WT kidney-transplanted mice, as well as lower podocyte number but similar fibrosis and cell infiltration. Interestingly, mice lacking Bcl10 in the kidney exhibited less Ang II-induced cardiac hypertrophy than controls. Conclusion Bcl10 has multi-faceted actions in Ang II-induced renal damage. On the one hand, global Bcl10 deficiency ameliorates renal fibrosis and cell infiltration; on the other hand, lack of renal Bcl10 aggravates albuminuria and podocyte damage. These data suggest that Bcl10 maintains podocyte integrity and renal function.

scholarly journals Complement Components C3 and C4 Indicate Vasculitis Manifestations to Distinct Renal Compartments in ANCA-Associated Glomerulonephritis

2021 ◽  
Vol 22 (12) ◽  
pp. 6588
Author(s):  
Samy Hakroush ◽  
Désirée Tampe ◽  
Peter Korsten ◽  
Philipp Ströbel ◽  
Björn Tampe
Keyword(s):  
Current Knowledge ◽  
Systemic Disease ◽  
Kidney Injury ◽  
Scoring Systems ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Glomerular Injury ◽  
Tubulointerstitial Injury ◽  
Complement Components ◽  
Tubulointerstitial Lesions ◽  
Low Levels

Background: Acute kidney injury (AKI) is a common and severe complication of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) causing progressive chronic kidney disease (CKD), end-stage renal disease (ESRD) or death. Pathogenic ANCAs, in particular proteinase 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response resulting in pauci-immune necrotizing and crescentic glomerulonephritis (GN), a common manifestation of glomerular injury in AAV. However, there is growing evidence that activation of the complement pathway contributes to the pathogenesis and progression of AAV. We here aimed to compare glomerular and tubulointerstitial lesions in ANCA GN and extrarenal manifestation of AAV in association with levels of circulating complement components C3c and C4. Methods: Plasma levels of C3c and C4 in a total number of 53 kidney biopsies with ANCA GN were retrospectively included between 2015 and 2020. Glomerular and tubulointerstitial lesions were evaluated according to established scoring systems for ANCA GN and analogous to the Banff classification. Results: We here show that circulating levels of C3c and C4 in ANCA GN were comparable to the majority of other renal pathologies. Furthermore, hypocomplementemia was only detectable in a minor subset of ANCA GN and not correlated with renal or extrarenal AAV manifestations. However, low levels of circulating C3c correlated with AKI severity in ANCA GN independent of systemic disease activity or extrarenal AAV manifestation. By systematic scoring of glomerular and tubulointerstitial lesions, we provide evidence that low levels of circulating C3c and C4 correlated with vasculitis manifestations to distinct renal compartments in ANCA GN. Conclusions: We here expand our current knowledge about distinct complement components in association with vasculitis manifestations to different renal compartments in ANCA GN. While low levels of C4 correlated with glomerulitis, our observation that low levels of circulating complement component C3c is associated with interstitial vasculitis manifestation reflected by intimal arteritis implicates that C3c contributes to tubulointerstitial injury in ANCA GN.

Assessment of renal function in patients with liver disease

2021 ◽  
Vol 75 (2) ◽  
pp. 138-142
Author(s):  
Vladimír Teplan
Keyword(s):  
Chronic Kidney Disease ◽  
Liver Transplantation ◽  
Renal Function ◽  
Liver Disease ◽  
Filtration Rate ◽  
Renal Damage ◽  
Kidney Injury ◽  
Drug Management ◽  
Function Measurement

Accurate measurement of renal function in serious liver disease is very important not only for the estimation of renal damage (chronic kidney disease – CKD), safe drug management, prediction of illness follow-up, intensive methods including hemodialysis, hemodiafiltration or hemoperfusion, but also for the indication of liver transplantation. All methods of renal function measurement using serum creatinine for the estimation of glomerular filtration rate (GFR) are not accurate: they overestimate the value of GFR; the worse the liver damage is, the higher the level of overestimation; predominantly due to decreased endogenous creatinine production (creatinine generation rate – CGR). Using of cystatin C for GFR in liver disease is mainly promising in acute kidney injury (AKI), but obtained results have not been defi nitive yet and need more relevant data from diff erent methods of GFR estimation.

scholarly journals Preventing Contrast-induced Renal Failure: A Guide

2016 ◽  
Vol 11 (2) ◽  
pp. 98 ◽  
Author(s):  
Michela Faggioni ◽  
◽  
Roxana Mehran ◽  
Keyword(s):  
Risk Factors ◽  
Renal Damage ◽  
Preventive Measures ◽  
Kidney Injury ◽  
Coronary Intervention ◽  
Kidney Dysfunction ◽  
Percutaneous Coronary ◽  
Patients At Risk ◽  
Short And Long Term

Contrast-induced acute kidney injury (CI-AKI) is characterised by a rapid deterioration of renal function within a few days of parenteral administration of contrast media (CM) in the absence of alternative causes. CI-AKI is the most common form of iatrogenic kidney dysfunction with an estimated prevalence of 12 % in patients undergoing percutaneous coronary intervention. Although usually selfresolving, in patients with pre-existing chronic kidney disease (CKD) or concomitant risk factors for renal damage, CI-AKI is associated with increased short- and long-term morbidity and mortality. Therefore, risk stratification based on clinical and peri-procedural characteristics is crucial in selecting patients at risk of CI-AKI who would benefit the most from implementation of preventive measures.

scholarly journals Machine Learning for Mortality Prediction in Pediatric Myocarditis

2021 ◽  
Vol 9 ◽  
Author(s):  
Fu-Sheng Chou ◽  
Laxmi V. Ghimire
Keyword(s):  
Machine Learning ◽  
Linear Regression ◽  
Regression Model ◽  
Current Knowledge ◽  
External Validation ◽  
Model Development ◽  
Kidney Injury ◽  
High Specificity ◽  
Mortality Prediction ◽  
Linear Regression Models

Background: Pediatric myocarditis is a rare disease. The etiologies are multiple. Mortality associated with the disease is 5–8%. Prognostic factors were identified with the use of national hospitalization databases. Applying these identified risk factors for mortality prediction has not been reported.Methods: We used the Kids' Inpatient Database for this project. We manually curated fourteen variables as predictors of mortality based on the current knowledge of the disease, and compared performance of mortality prediction between linear regression models and a machine learning (ML) model. For ML, the random forest algorithm was chosen because of the categorical nature of the variables. Based on variable importance scores, a reduced model was also developed for comparison.Results: We identified 4,144 patients from the database for randomization into the primary (for model development) and testing (for external validation) datasets. We found that the conventional logistic regression model had low sensitivity (~50%) despite high specificity (>95%) or overall accuracy. On the other hand, the ML model struck a good balance between sensitivity (89.9%) and specificity (85.8%). The reduced ML model with top five variables (mechanical ventilation, cardiac arrest, ECMO, acute kidney injury, ventricular fibrillation) were sufficient to approximate the prediction performance of the full model.Conclusions: The ML algorithm performs superiorly when compared to the linear regression model for mortality prediction in pediatric myocarditis in this retrospective dataset. Prospective studies are warranted to further validate the applicability of our model in clinical settings.

scholarly journals Risk factors and mortality in patients with sepsis, septic and non septic acute kidney injury in ICU

2019 ◽  
Vol 41 (4) ◽  
pp. 462-471 ◽  
Author(s):  
Kellen Hyde Elias Pinheiro ◽  
Franciana Aguiar Azêdo ◽  
Kelsy Catherina Nema Areco ◽  
Sandra Maria Rodrigues Laranja
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Mortality Rates ◽  
Icu Patients ◽  
Septic Acute Kidney Injury ◽  
Observational Cohort ◽  
Worse Prognosis

Abstract Acute kidney injury (AKI) has an incidence rate of 5-6% among intensive care unit (ICU) patients and sepsis is the most frequent etiology. Aims: To assess patients in the ICU that developed AKI, AKI on chronic kidney disease (CKD), and/or sepsis, and identify the risk factors and outcomes of these diseases. Methods: A prospective observational cohort quantitative study that included patients who stayed in the ICU > 48 hours and had not been on dialysis previously was carried out. Results: 302 patients were included and divided into: no sepsis and no AKI (nsnAKI), sepsis alone (S), septic AKI (sAKI), non-septic AKI (nsAKI), septic AKI on CKD (sAKI/CKD), and non-septic AKI on CKD (nsAKI/CKD). It was observed that 94% of the patients developed some degree of AKI. Kidney Disease Improving Global Outcomes (KDIGO) stage 3 was predominant in the septic groups (p = 0.018). Nephrologist follow-up in the non-septic patients was only 23% vs. 54% in the septic groups (p < 0.001). Dialysis was performed in 8% of the non-septic and 37% of the septic groups (p < 0.001). Mechanical ventilation (MV) requirement was higher in the septic groups (p < 0.001). Mortality was 38 and 39% in the sAKI and sAKI/CKD groups vs 16% and 0% in the nsAKI and nsAKI/CKD groups, respectively (p < 0.001). Conclusions: Patients with sAKI and sAKI/CKD had worse prognosis than those with nsAKI and nsAKI/CKD. The nephrologist was not contacted in a large number of AKI cases, except for KDIGO stage 3, which directly influenced mortality rates. The urine output was considerably impaired, ICU stay was longer, use of MV and mortality were higher when kidney injury was combined with sepsis.

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