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Frontiers in Immunology 2022NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of...
NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of decondensed chromatin, called neutrophil extracellular traps (NETs), are released. NETs normally contribute to host immune defense. Accumulating evidence implicates aberrant NET production and/or reduced NET clearance, along with alterations of molecules involved in NETosis pathway, in humans and animals with lupus. The extruded nuclear antigens released by NET are a source of autoantigens, which can contribute to the breakdown of self-tolerance in lupus. Excessive NET can also promote the production of pro-inflammatory cytokine interferon-α, elicit direct cytotoxic effect on various renal cells, and cause capillary necrosis and podocyte loss. Additionally, NET can induce endothelial-to-mesenchymal transdifferentiation, which can promote activated myofibroblasts leading to extracellular matrix production. Thus, aberrant NETosis can play diverse roles, including autoantibody production, inflammation, and tissue damage, at different stages of lupus pathogenesis. Evidence suggests that treatments currently used in lupus may reduce NETosis, suggesting a potential utility of targeting NETosis to treat lupus. In fact, several approaches are being experimented to therapeutically target pathways of NETosis. Future studies should precisely delineate distinct roles of NETosis at different stages of lupus pathogenesis in humans, which would offer a rational basis for NETosis-targeting treatments in the clinic.
Topics: Animals; Autoantigens; Cell Death; Extracellular Traps; Inflammation; Neutrophils
PubMed: 35686129
DOI: 10.3389/fimmu.2022.895216 -
Frontiers in Pharmacology 2023is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years.... (Review)
Review
is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years. Catalpol is the main active compound in Rehmannia roots. Current evidence suggests that catalpol exhibits significant anti-diabetic bioactivity, and thus it has attracted increasing research attention for its potential use in treating DN. However, no studies have systematically evaluated these effects, and its mechanism of action remains unclear. This study aimed to evaluate the effects of catalpol on DN, as well as to summarize its possible mechanisms of action, in DN animal models. We included all DN-related animal studies with catalpol intervention. These studies were retrieved by searching eight databases from their dates of inception to July 2022. In addition, we evaluated the methodological quality of the included studies using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool. Furthermore, we calculated the weighted standard mean difference (SMD) with 95% confidence interval (CI) using the Review Manager 5.3 software and evaluated publication bias using the Stata (12.0) software. A total of 100 studies were retrieved, of which 12 that included 231 animals were finally included in this review. As compared to the control treatment, treatment with catalpol significantly improved renal function in DN animal models by restoring serum creatinine (Scr) ( = 0.0009) and blood urea nitrogen (BUN) ( < 0.00001) levels, reducing proteinuria ( < 0.00001) and fasting blood glucose (FBG) ( < 0.0001), improving kidney indices ( < 0.0001), and alleviating renal pathological changes in the animal models. In addition, it may elicit its effects by reducing inflammation and oxidative stress, improving podocyte apoptosis, regulating lipid metabolism, delaying renal fibrosis, and enhancing autophagy. The preliminary findings of this preclinical systematic review suggest that catalpol elicits significant protective effects against hyperglycemia-induced kidney injury. However, more high-quality studies need to be carried out in the future to overcome the methodological shortcomings identified in this review.
PubMed: 37621314
DOI: 10.3389/fphar.2023.1192694 -
Frontiers in Endocrinology 2023Diabetic kidney disease (DKD) is the main cause of end-stage renal disease worldwide, and there is a lack of effective treatment strategies. Autophagy is a highly... (Review)
Review
Diabetic kidney disease (DKD) is the main cause of end-stage renal disease worldwide, and there is a lack of effective treatment strategies. Autophagy is a highly conserved lysosomal degradation process that maintains homeostasis and energy balance by removing protein aggregates and damaged organelles. Increasing evidence suggests that dysregulated autophagy may contribute to glomerular and tubulointerstitial lesions in the kidney under diabetic conditions. Emerging studies have shown that Chinese herbal medicine and its active compounds may ameliorate diabetic kidney injury by regulating autophagy. In this review, we summarize that dysregulation or insufficiency of autophagy in renal cells, including podocytes, glomerular mesangial cells, and proximal tubular epithelial cells, is a key mechanism for the development of DKD, and focus on the protective effects of Chinese herbal medicine and its active compounds. Moreover, we systematically reviewed the mechanism of autophagy in DKD regulated by Chinese herb compound preparations, single herb and active compounds, so as to provide new drug candidates for clinical treatment of DKD. Finally, we also reviewed the candidate targets of Chinese herbal medicine regulating autophagy for DKD. Therefore, further research on Chinese herbal medicine with autophagy regulation and their targets is of great significance for the realization of new targeted therapies for DKD.
Topics: Humans; Diabetic Nephropathies; Drugs, Chinese Herbal; Kidney; Podocytes; Autophagy; Diabetes Mellitus
PubMed: 36942026
DOI: 10.3389/fendo.2023.1142805 -
Journal of Nephrology Dec 2023Severe acute respiratory syndrome coronavirus 2 infection has caused significant morbidity and mortality. Vaccines produced against this virus have proven highly... (Review)
Review
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 infection has caused significant morbidity and mortality. Vaccines produced against this virus have proven highly effective. However, adverse events following vaccination have also been reported. One of them is nephrotic syndrome, that can be associated with different pathologic pictures. This review aims to provide a wider understanding of incidence, etiopathogenesis, and management of nephrotic syndrome following vaccination against SARS-CoV-2.
METHODS AND RESULTS
A literature search was undertaken using appropriate keywords in various databases like PubMed, Google Scholar, Europe PMC, and Science Direct. Twenty-one articles were included following qualitative assessment. Data of 74 patients from these articles were included.
DISCUSSION
The pathogenesis of nephrotic syndrome following COVID vaccination has been widely attributed to the activation of angiotensin-converting enzyme-2 receptors, leading to podocyte effacement. Relapses have also been reported in patients with prior history of nephrotic syndrome following COVID-19 vaccination. A renal biopsy is necessary to identify the histopathological picture. Management of COVID-19 vaccine-induced nephrotic syndrome was mainly reported as successfully attainable with corticosteroids and supportive management.
CONCLUSION
Further investigations will help in establishing an early diagnosis and salvaging kidney function.
Topics: Humans; COVID-19; COVID-19 Vaccines; Nephrotic Syndrome; SARS-CoV-2; Vaccination
PubMed: 37505405
DOI: 10.1007/s40620-023-01710-z -
International Journal of Molecular... Jun 2022Alport syndrome (AS) is the second most common cause of inherited chronic kidney disease. This disorder is caused by genetic variants on , and genes. These genes... (Review)
Review
Alport syndrome (AS) is the second most common cause of inherited chronic kidney disease. This disorder is caused by genetic variants on , and genes. These genes encode the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). The heterodimer COL4A3A4A5 constitutes the majority of the GBM, and it is essential for the normal function of the glomerular filtration barrier (GFB). Alterations in any of collagen type IV constituents cause disruption of the GMB structure, allowing leakage of red blood cells and albumin into the urine, and compromise the architecture of the GFB, inducing inflammation and fibrosis, thus resulting in kidney damage and loss of renal function. The advances in DNA sequencing technologies, such as next-generation sequencing, allow an accurate diagnose of AS. Due to the important risk of the development of progressive kidney disease in AS patients, which can be delayed or possibly prevented by timely initiation of therapy, an early diagnosis of this condition is mandatory. Conventional biomarkers such as albuminuria and serum creatinine increase relatively late in AS. A panel of biomarkers that might detect early renal damage, monitor therapy, and reflect the prognosis would have special interest in clinical practice. The aim of this systematic review is to summarize the biomarkers of renal damage in AS as described in the literature. We found that urinary Podocin and Vascular Endothelial Growth Factor A are important markers of podocyte injury. Urinary Epidermal Growth Factor has been related to tubular damage, interstitial fibrosis and rapid progression of the disease. Inflammatory markers such as Transforming Growth Factor Beta 1, High Motility Group Box 1 and Urinary Monocyte Chemoattractant Protein- 1 are also increased in AS and indicate a higher risk of kidney disease progression. Studies suggest that miRNA-21 is elevated when renal damage occurs. Novel techniques, such as proteomics and microRNAs, are promising.
Topics: Biomarkers; Collagen Type IV; Fibrosis; Humans; Kidney; Nephritis, Hereditary; Vascular Endothelial Growth Factor A
PubMed: 35806283
DOI: 10.3390/ijms23137276 -
Cureus Sep 2022Nephrotic syndrome is a condition characterized by damage to podocytes that results in significant proteinuria, edema, hyperlipidemia, and hypercoagulability. Infections... (Review)
Review
Nephrotic syndrome is a condition characterized by damage to podocytes that results in significant proteinuria, edema, hyperlipidemia, and hypercoagulability. Infections and malignancies are frequently associated with nephrotic syndrome. The COVID-19 virus has been associated with several atypical presentations of upper respiratory infections and acute kidney injury. Considering that COVID-19 causes systemic inflammatory changes, it seems plausible that it may also lead to nephrotic syndrome. This study aimed to investigate if an association between COVID-19 and the different types of nephrotic syndromes exists. Data were extracted into a spreadsheet. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS, IBM Corp., Armonk, NY, USA). We performed a systematic search of PubMed/Medline and Embase databases using both medical subject headings (MeSH) and regular keywords associated with COVID-19 and nephrotic syndrome, including different types of nephrotic syndromes. The search was performed on 17th December 2021. We included case reports and case series about adult patients who developed findings suggestive of nephrotic syndrome shortly after infection or vaccination. We excluded cases involving children, pregnant women, articles written in languages other than English, and those that were not retrievable. The relevance and quality of identified articles were assessed. We included 32 articles in the study, primarily case reports and case series. In our study, COVID-19 and the COVID-19 vaccine have been associated with the development of nephrotic syndrome, primarily a collapsing form of focal segmental glomerulosclerosis, although other forms have been observed as well. There was little consistency in patient histories, clinical presentations, clinical courses, or treatment regimens, although it appeared that most cases eventually resolved. More cases need to be reported and analyzed before more definitive conclusions can be reached. In conclusion, nephrotic syndrome is a possible complication of both COVID-19 infection and the COVD-19 vaccine and should be considered in patients exhibiting sudden onset edemas or deterioration in kidney function. While the majority of cases respond to standard treatment, clearer guidelines will need to be developed once more data is available.
PubMed: 36312654
DOI: 10.7759/cureus.29613 -
Pediatric Nephrology (Berlin, Germany) Jun 2021Calcineurin inhibitor (CNI) use in genetic steroid-resistant nephrotic syndrome (SRNS) is controversial as response rate is reported to be lower than non-genetic disease... (Review)
Review
BACKGROUND
Calcineurin inhibitor (CNI) use in genetic steroid-resistant nephrotic syndrome (SRNS) is controversial as response rate is reported to be lower than non-genetic disease and no plausible mechanism of action is known.
METHODS
We reviewed PubMed for publications on CNI use in hereditary SRNS to determine (1) CNI response rate; (2) impact of response on renal outcome; and (3) clinical and molecular predictors of response. Variant pathogenicity was assessed according to American College of Medical Genetics criteria and patients were assigned to 1 of 4 categories based on estimated genotype contribution to phenotype. Cases with non-existing phenotype-to-genotype contribution were excluded. Subgroup analysis was performed for the possible and confirmed genetic cases.
RESULTS
Data of 178 genetic SRNS cases from 22 studies were analyzed; 35% responded (fully or partially) to CNI with minimal change being the commonest biopsy pattern among responders. Full responders had superior kidney survival compared with partial and non-responders (log-rank test χ = 10.7; P < 0.01). WT1 variant carriers were most likely to respond to CNI compared with any other mutation [OR 4.7 (2.0-11.3); P < 0.01].
CONCLUSIONS
These findings support the current recommendation for using CNI as first-line treatment for children with SRNS whilst genetic analyses are pending. This would allow assessment of treatment response even in cases later established as genetic ensuring that benefits on kidney function are balanced with treatment toxicity.
Topics: Calcineurin Inhibitors; Child; Humans; Kidney; Mutation; Nephrotic Syndrome; Podocytes
PubMed: 32651716
DOI: 10.1007/s00467-020-04695-0 -
Journal of Ethnopharmacology Dec 2021Tripterygium wilfordii Hook F (TwHF) has been clinically applied in the treatment of Diabetic Kidney Diseases (DKD). A large number of animal experiments focused on the... (Meta-Analysis)
Meta-Analysis
ETHNOPHARMACOLOGICAL RELEVANCE
Tripterygium wilfordii Hook F (TwHF) has been clinically applied in the treatment of Diabetic Kidney Diseases (DKD). A large number of animal experiments focused on the TwHF treatment of DKD were conducted every year, but the evidence for these preclinical studies is unclear.
AIM OF THE STUDY
This study aims to evaluate the efficacy of TwHF on diabetic nephropathy through a stematic reviews and meta-analysis of animal models, and whether it has an effect on improving kidney pathology, renal function indicators and blood sugar levels, it also summarizes the use of TwHF for treatment the underlying mechanism of DKD.
MATERIALS AND METHODS
We systematically searched studies from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang database from inception to May 2020. Chinese studies from the list of Chinese Core Journals would be included. SYRCLE's risk of bias tool for animal studies was applied to assess the methodological quality of studies. A meta-analysis was performed by using RevMan 5.3.
RESULTS
Out of 429 records identified in the initial search, 32 studies were selected. The results indicated that, compared with control group, TwHF treatment improved 24 h urine protein (24 h-UP) level (SMD - 4.21, 95% CI - 5.38 to - 3.04, P < 0.001), serum creatinine (Scr) (MD - 14.97, 95% CI - 20.42 to - 9.53, P < 0.001), blood urea nitrogen (BUN) (MD - 4.07, 95% CI - 5.49 to - 2.66, P < 0.001), blood glucose (Glu) (MD - 2.40, 95% CI - 4.304 to - 0.49, P = 0.01), Triglyceride (TG) (MD - 1.57, 95% CI - 2.06 to - 1.08, P < 0.001), and Cholesterol (TC) (MD - 1.49, 95% CI - 2.23 to - 0.75 P < 0.001); and increased the level of albumin (Alb) (MD 3.40, 95% CI 1.69 to 5.11, P < 0.001) and weight (MD 30.89, 95% CI 24.35 to 37.42, P < 0.001). There were no statistical difference on Alanine aminotransferase (ALT) (MD 3.00, 95% CI - 7.80 to 13.81, P = 0.59) and Aspartate aminotransferase (AST) (MD 0.77, 95% CI -15.05 to 16.60, P = 0.92) after TwHF. Meta regression analysis showed that the DKD model induced by different methods (type I/II), the dose of Tripterygium wilfordii and the intervention time were not the reasons for the heterogeneity of 24 h-UP, Alb, Glu, Scr, and BUN (p > 0.05).
CONCLUSIONS
TwHF is an effective and safe to treat DKD, which can protect the kidneys through anti-inflammation, improving oxidative stress and podocyte damage, and inhibiting mesangial cell proliferation and extracellular matrix proliferation.
Topics: Animals; Diabetic Nephropathies; Phytotherapy; Tripterygium
PubMed: 34419607
DOI: 10.1016/j.jep.2021.114536 -
Clinical Kidney Journal Dec 2020Patients heterozygous for or mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes...
BACKGROUND
Patients heterozygous for or mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes (TBMs), to autosomal dominant Alport syndrome (ADAS) and end-stage renal disease (ESRD). Many patients are mentioned in the literature under the descriptive diagnosis of TBM nephropathy (TBMN), in which case it actually describes a histological finding that represents the carriers of autosomal recessive Alport syndrome (ARAS), a severe glomerulopathy, as most patients reach ESRD at a mean age of 25 years.
METHODS
We performed a systematic literature review for patients with heterozygous / mutations with the aim of recording the spectrum and frequency of pathological features. We searched three databases (PubMed, Embase and Scopus) using the keywords 'Autosomal Dominant Alport Syndrome' OR 'Thin Basement Membrane Disease' OR 'Thin Basement Membrane Nephropathy'. We identified 48 publications reporting on 777 patients from 258 families.
RESULTS
In total, 29% of the patients developed chronic kidney disease (CKD) and 15.1% reached ESRD at a mean age of 52.8 years. Extrarenal features and typical Alport syndrome (AS) findings had a low prevalence in patients as follows: hearing loss, 16%; ocular lesions, 3%; basement membrane thickening, 18.4%; and podocyte foot process effacement, 6.9%. Data for 76 patients from 54 families emphasize extensive inter- and intrafamilial heterogeneity, with age at onset of ESRD ranging between 21 and 84 years (mean 52.8).
CONCLUSIONS
The analysis enabled a comparison of the clinical course of patients with typical ARAS or X-linked AS with those with heterozygous mutations diagnosed with TBMN or ADAS. Despite the consequence of a potential ascertainment bias, an important outcome is that TBM poses a global high risk of developing severe CKD, over a long follow-up, with a variable spectrum of other findings. The results are useful to practicing nephrologists for better evaluation of patients.
PubMed: 33391746
DOI: 10.1093/ckj/sfz176