Pathological evaluation of renal complications in children following allogeneic hematopoietic stem cell transplantation: a retrospective cohort study.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematologic malignancies and non-malignant disorders, such as aplastic anemia, fanconi anemia, and certain immune deficiencies. Post-transplantation kidney injury is a common complication and involves a wide spectrum of structural abnormalities, including glomerular (MSPGN, mesangial proliferative glomerulonephritis; FSGS, focal segmental glomerulosclerosis; MPGN, membranoproliferative glomerulonephritis; MCD, minimal change disease), vascular (TMA, thrombotic microangiopathy), and/or tubulointerstitial (TIN, tubulointerstitial nephritis; ATI, acute tubular injury). Renal biopsy is the gold-standard examination for defining multiple etiologies of kidney impairment. Although kidney injury following HSCT has been studied, little is known about the effects of allo-HSCT on renal pathology in pediatric patients. METHODS: We retrospectively analyzed renal biopsy specimens from children with kidney injury after allo-HSCT and correlated results with clinical data in the last 10 years. RESULTS: Among 25 children (18 males and 7 females), three patients had proteinuria indicating nephrotic syndrome (24-hour urinary total protein/weight > 50 mg/kg/d), nine patients had severely reduced estimated glomerular filtration rate (eGFR < 30 ml/min/1.73 m2) and four patients received kidney replacement therapy (KRT). The main pathologies identified from kidney biopsies were MSPGN (n = 12), FSGS (n = 12), MPGN (n = 5), TMA (n = 4), MCD (n = 3), diffuse glomerular fibrosis (DGF, n = 2), ATI and TIN, in isolation or combined with other pathologies. The median follow-up time was 16.5 (0.5 ~ 68.0) months. Three patients died of recurrent malignancy and/or severe infection, one child developed to end-stage renal disease (ESRD), six patients (24%) had elevated serum creatinine (SCr > 100µmol/l) and nine patients (36%) still had proteinuria. CONCLUSIONS: This study evaluates histomorphologic findings from kidney biopsies of pediatric recipients following allo-HSCT. Detailed evaluation of renal biopsy samples is helpful to elucidate the nature of renal insult, and may potentially identify treatable disease processes.

Ameliorating role of microRNA-378 carried by umbilical cord mesenchymal stem cells-released extracellular vesicles in mesangial proliferative glomerulonephritis.

BACKGROUND: Mesenchymal stem cells (MSCs) and their released extracellular vesicles (Evs) have shown protective effects against kidney diseases. This study aims to study the functions of umbilical cord MSCs-released Evs (ucMSC-Evs) and their implicated molecules in mesangial proliferative glomerulonephritis (MsPGN). METHODS: A rat model of MsPGN was induced by anti-Thy-1.1, and rat mesangial cells (rMCs) HBZY-1 were treated with PDGF-BB/DD to mimic MsPGN condition in vitro. Rats and cells were treated with different doses of ucMSC-Evs, and then the pathological changes in renal tissues and proliferation of rMCs were determined. Differentially expressed microRNAs (miRNAs) after Evs treatment were screened by microarray analysis. The interactions among miR-378, PSMD14, and TGFBR1 were analyzed. Gain- and loss-of function studies of miR-378 and PSMD14 were performed to explore their effects on tissue hyperplasia and rMC proliferation and their interactions with the TGF-ß1/Smad2/3 signaling pathway. RESULTS: The ucMSC-Evs treatment ameliorated mesangial hyperplasia and fibrosis in rat renal tissues and suppressed the aberrant proliferation of rMCs in a dose-dependent manner. miR-378 was the most upregulated miRNA in tissues and cells after ucMSC-Evs treatment. miR-378 directly targeted PSMD14, and PSMD14 maintained the stability of TGFBR1 through deubiquitination modification, which led to TGF-ß1/Smad2/3 activation. Either miR-378 knockdown or PSMD14 overexpression diminished the protective functions of ucMSC-Evs by activating the TGF-ß1/Smad2/3 signaling pathway. CONCLUSION: UcMSC-Evs ameliorate pathological process in MsPGN through the delivery of miR-378, which suppresses PSMD14-mediated TGFBR1 stability and inactivates the TGF-ß1/Smad2/3 signaling pathway to reduce tissue hyperplasia and rMC proliferation. Video abstract.

Focal segmental glomerulosclerosis in patients after Fontan operation: is this a Fontan-associated renal disease?

Despite acceptable survival for Fontan operation, there are concerns about late complications affecting the major organs. We herein present two cases of adults after Fontan operation who developed focal segmental glomerulosclerosis. These cases suggest that focal segmental glomerulosclerosis is owing to haemodynamic incompetence associated with Fontan operation, including congestion, hypoxia, and hyperviscosity, which may be called Fontan-associated renal disease.

Knockdown of Cxcl10 Inhibits Mesangial Cell Proliferation in Murine Habu Nephritis Via ERK Signaling.

BACKGROUND/AIMS: IFN-γ-inducible protein 10 (IP-10, CXCL10) has been widely demonstrated to be involved in chemotaxis, cell growth regulation and angiogenesis inhibition. It has been reported that CXCL10 expression is significantly increased in patients with MesPGN (Mesangial proliferative glomerulonephritis). However, the underlying mechanism of CXCL10 in MesPGN reminds unclear. METHODS: Wildtype (Cxcl10+/+) mice and Cxcl10-deficient (Cxcl10-/-) mice were used to generate a murine model of MesPGN. The histological changes in glomeruli were examined by PAS staining (Periodic Acid-Schiff staining), and cell proliferation was detected by PCNA immunohistochemistry staining. The expression of cell cycle regulatory proteins was analyzed by Western blotting and the effects of CXCL10 on primary mouse renal mesangial cells (MRMC) proliferation were detected using the EDU assay. Furthermore, the specific mechanisms by which CXCL10 affected mesangial cells were investigated in vitro using a specific inhibitor. RESULTS: Typical pathological phenotypes were observed in both mouse types, while the Cxcl10-/- mice had lighter accumulation of extracellular matrix, less cell proliferation and diminished up-regulation of cell cycle regulatory proteins compared to Cxcl10+/+ mice at day 7. Furthermore, we observed that CXCL10 inhibition resulted in less activation of ERK phosphorylation, and ERK pathway inhibition by a specific inhibitor, U0126, prevented CXCL10 induced MRMC proliferation and the activation of phosphorylated ERK. CONCLUSIONS: CXCL10 may aggravate mesangial proliferation in MesPGN by activating the ERK signaling pathway. These results provide a novel insight into the mechanism and potential therapy target of MesPGN.

Effect of Huaier On the Proliferation of Mesangial Cells in Anti-Thy-1 Nephritis.

BACKGROUND/AIMS: To determine whether an aqueous extract of Trametes robiniophila Murr. (Huaier) suppresses anti-Thy-1 mesangial proliferative glomerulonephritis (MsPGN) in vivo and platelet-derived growth factor (PDGF)-BB-induced mesangial cell proliferation in vitro. METHODS: Male Wistar rats were randomly categorized into 5 groups: Sham, Thy-1, and 3 Huaier-treated groups (low, medium, and high dose). Two weeks after treatment, urinary proteins were quantified and renal pathological changes were examined. MAX interactor 1 (Mxi-1) and proliferating cell nuclear antigen (PCNA) expression levels in isolated glomeruli, rat mesangial cell viability, cell-cycle distribution, and cell-cycle pathways were assessed. RESULTS: Huaier diminished the proliferative damages and urinary protein secretion in Thy-1 rats. PCNA was downregulated, whereas Mxi-1 was upregulated in the isolated glomeruli of Huaier-treated groups compared with the Thy-1 group. Huaier inhibited PDGF-BB- stimulated proliferation of rat mesangial cells in a time- and dose-dependent manner (50% inhibitory concentration = 6.19 mg/mL) and induced G2 cell-cycle arrest. Cell-cycle pathway proteins were downregulated, whereas Mxi-1 was upregulated in Huaier-treated mesangial cells compared with PDGF-BB-stimulated cells. CONCLUSION: Huaier reduces urinary protein excretion and relieves hyperplasia in mesangial cells in anti-Thy-1 MsPGN as well as inhibits PDGF-BB-stimulated proliferation and DNA synthesis of rat mesangial cells in vitro, suggesting its novel therapeutic potential in MsPGN.

IgA nephropathy in a girl with mitochondrial disease.

Mitochondrial renal disease is one of the important causes of end-stage renal disease in children and its incidence may be underestimated. We here describe the case of a 13-year-old girl who was diagnosed with mitochondrial disease (MD) accompanied by IgA nephropathy (IgAN). She presented with persistent proteinuria, short stature, and hearing defect, and her younger sister had the same symptoms. Renal biopsy indicated mild focal segmental mesangial proliferation with dominant mesangial IgA deposition on immunofluorescence. Electron microscopy showed marked proliferation of abnormal mitochondria in the proximal tubular cells. Enzyme activity of the mitochondrial respiratory chain complex I and IV in cultured skin fibroblasts was significantly decreased. This case indicated the possible co-occurrence of IgAN and MD. Underlying MD should be considered in patients with urine abnormalities, especially in those with multiple organ involvement.

Assessment of the effect of mesangial hypercellularity in childhood nephropathies to the clinical and laboratory findings.

AIM: To assess the relationship between mesangial hypercellularity in various childhood nephropathies and clinical and laboratory parameters. METHODS AND PATIENTS: The reports of the renal biopsies were evaluated retrospectively. The patients with diagnosis of IgA nephropathy (isolated and Henoch-Schönlein nephritis), IgM nephropathy, or isolated mesangial proliferative glomerulonephritis were included. Each nephropathy group was divided into two subgroups according to the severity of mesangial hypercellularity as mild and severe. The biochemical data and histopathological findings of the patients were recorded. RESULTS: When the groups were compared, it was found that the patients with IgA nephropathy had hematuria (p = 0.043) and the patients with IgM nephropathy had nephrotic syndrome more frequently than the other patients (p = 0.01). No difference was detected between the groups regarding the severity of mesangial hypercellularity. On the other hand, when the groups were evaluated within themselves, no significant association was detected between the severity of mesangial hypercellularity and clinical and laboratory parameters. It was determined that the renal biopsy was performed earlier in patients with Henoch-Schönlein nephritis compared to the other cases (p = 0.004). Compared to the isolated IgA nephropathy group, it was found that the number of cases with severe mesangial hypercellularity was higher and the level of proteinuria was more prominent in patients with Henoch-Schönlein nephritis. Additionally, when the patients with Henoch-Schönlein nephritis were evaluated, the degree of proteinuria was found to be higher in patients with severe mesangial hypercellularity compared to those of showing mild mesangial hypercellularity (p = 0.002). CONCLUSION: It was observed that there is no direct relation between the severity of mesangial hypercellularity and clinical and laboratory findings in various childhood nephropathies. However, when Henoch-Schönlein nephritis is compared with IgA nephropathy, it was found that the severity of mesangial hypercellularity was higher in cases with Henoch-Schönlein nephritis and the level of proteinuria was more prominent in those cases. However, no difference was detected in glomerular filtration rates and biochemical data with regard to the level of mesangial hypercellularity.

Pediatric Bilateral Hypoplastic Kidney Complicated With C1q Nephropathy: A Case Report.

Progressive kidney dysfunction is often observed in children with bilateral hypoplastic kidneys. While glomerulopathy can exacerbate hypoplastic kidney progression, only IgA nephropathy and post-streptococcal acute glomerulonephritis have been noted in such cases. Herein, we present a case of a four-year-old female patient with bilateral hypoplastic kidney, kidney dysfunction, and significant proteinuria (urinary protein/creatinine ratio > 1 g/gCr), prompting referral owing to persistent hematuria since two years of age. Enalapril was initiated; however, urinary findings exhibited no improvement despite stable symptoms and kidney function. Subsequently, a kidney biopsy was performed at six years of age, and C1q nephropathy was diagnosed. Given the presence of only mild mesangial proliferation, steroids were not administered; enalapril treatment was continued. By seven years of age, the patient's hematuria had resolved, and proteinuria levels had decreased. On the latest follow-up at 12 years of age, kidney function was preserved with only mild proteinuria. This case report highlights the favorable prognosis of asymptomatic C1q nephropathy characterized by mild mesangial proliferation, even in patients with hypoplastic kidneys, renal dysfunction, and significant proteinuria. It emphasizes the significance of timely pathological evaluation for guiding appropriate interventions in such patients.

Changes in renal function and morphological variations of kidney diseases in rheumatoid arthritis patients.

Objective: Rheumatoid nephropathy is one of the most severe extra-articular manifestations of rheumatoid arthritis (RA) associated with a very unfavorable prognosis. This study aimed to identify changes in renal function and morphological variations of kidney diseases in RA patients. Methods: The study enrolled patients (126 patients) between 18 and 55 years of age with a confirmed active RA of more than 12 months. Each patient underwent the following range of laboratory and instrumental research methods: general clinical analysis of blood and urine, performing urinalysis according to Nechiporenko method; determining daily proteinuria; determining the blood content of glucose, urea, creatinine, uric acid, total bilirubin, liver transaminase level, ionogram, lipidogram, and coagulogram; determining the blood content of rheumatoid factor, anti-streptolysin O, and C-reactive protein; and X-ray of the joints of hands and feet. Renal function was examined by estimating glomerular filtration rate, tubular reabsorption index, and renal functional reserve. For studying the morphological changes in the kidneys under ultrasound examination, renal biopsy was performed in 31 patients with RA with urinary syndrome (proteinuria more than 0.3 g per day and hematuria). Results: Nephropathy in RA is characterized by impaired renal function and manifested by an increased blood creatinine and a decrease in glomerular filtration rate and renal functional reserve. Among morphological variations of nephropathy at RA, mesangial proliferative glomerulonephritis prevails, accounting for 48.4% of patients. Other disorders include the secondary amyloidosis (29.0% of patients), tubulointerstitial nephritis (16.1%), membranous glomerulonephritis (3.2%), and focal-segmental glomerulosclerosis (3.2%). Conclusion: Kidney damage is a common systemic manifestation of RA with a long and active course, a major nephropathy trigger.

ERK1/2-dependent activity of SOX9 is required for sublytic C5b-9-induced expression of FGF1, PDGFα, and TGF-ß1 in rat Thy-1 nephritis.

Mesangial proliferative glomerulonephritis (MsPGN) and its related rat model Thy-1 nephritis (Thy-1N) are associated with C5b-9 deposition and are characterized by proliferation of glomerular mesangial cell (GMC) and expansion of extracellular matrix (ECM) expansion, alongside overexpression of multiple growth factors. Although fibroblast growth factor 1 (FGF1), platelet-derived growth factor alpha (PDGFα), and transforming growth factor beta 1 (TGF-ß1) are well known for their proproliferative and profibrotic roles, the molecular mechanisms responsible for regulating the expression of these growth factors have not been thoroughly elucidated. In this study, we found that sublytic C5b-9 induction of sex-determining region Y-box 9 (SOX9) transactivated FGF1, PDGFα, and TGF-ß1 genes in GMCs, resulting in a significant increase in their mRNA and protein levels. Besides, sublytic C5b-9 induction of activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylated SOX9 at serine 181 and serine 64, which enhanced SOX9's ability to transactivate FGF1, PDGFα, and TGF-ß1 genes in GMCs. Furthermore, we demonstrated that inhibiting ERK1/2 activation or silencing either ERK1/2 or SOX9 gene led to reduced SOX9 phosphorylation, decreased generation of FGF1, PDGFα, and TGF-ß1, and ameliorated glomerular injury in rat Thy-1N. Overall, these findings suggest that expression of FGF1, PDGFα, and TGF-ß1 is promoted by ERK1/2-mediated phosphorylation of SOX9, which may provide a valuable insight into the pathogenesis of MsPGN and offer a potential target for the development of novel treatment strategies for MsPGN.

The Effect and Mechanism of Fufang Banbianlian Injection in the Treatment of Mesangial Proliferative Glomerulonephritis.

OBJECTIVE: Mesangial proliferative glomerulonephritis (MsPGN) is an important cause of chronic kidney disease. Abnormal proliferation of mesangial cells and immune-inflammatory response are its important pathological manifestations. Currently, there is no ideal treatment for this disease. Fufang Banbianlian Injection (FBI) has anti-inflammatory, antioxidant, and immuneenhancing effects, and is mostly used for the treatment of bronchitis, pneumonia, and respiratory tract infections in children. METHODS: A rat model of MsPGN was established and treated with FBI. The efficacy was tested through pathological experiments and urine protein quantification. Network pharmacology methods were used to predict the signaling pathways and key proteins that exert the efficacy of FBI, and were screened through molecular docking experiments. The active substances that work were verified through cell experiments. RESULTS: The results confirmed that intervention with FBI can inhibit the proliferation of glomerular cells and reduce the infiltration of macrophages, thereby reducing the pathological damage of rats with mesangial proliferative nephritis; it has been found to have an obvious therapeutic effect. Molecular docking results have shown kaempferol (Kae), the main component of FBI, to have a good affinity for key targets. The results of in vitro verification experiments showed that FBI and its active ingredient Kae may play a therapeutic role by regulating the NF-κB signaling pathway in mesangial cells, inhibiting its activation and the secretion of proinflammatory cytokines. CONCLUSION: Through network pharmacology, molecular docking, and experimental verification, it was confirmed that FBI and its active ingredient Kae can reduce the molecular mechanism of pathological damage of MsPGN by regulating the NF-κB signaling pathway and providing potential therapeutic drugs for the treatment of this disease.

Differential expression profile of urinary exosomal microRNAs in patients with mesangial proliferative glomerulonephritis.

OBJECTIVE: To investigate the differential expression profile of urinary exosomal microRNA (miRNA) in patients with mesangial proliferative glomerulonephritis (MsPGN) and healthy controls and their potential role in the pathogenesis of MsPGN. METHODS: Urine specimens were collected from five MsPGN patients and five healthy controls, and differentially expressed miRNAs were screened using high-throughput sequencing technology. The sequenced urinary exosomal miRNAs were further investigated by quantitative real-time polymerase chain reaction (qRT-PCR) in a validation cohort (16 MsPGN patients and 16 healthy controls). Correlation and receiver operating characteristic (ROC) curve analyses were used to determine the association between clinical features and miRNA expression in MsPGN. Finally, fluorescence in situ hybridization was performed to detect miRNA expression in the renal tissues of MsPGN patients. RESULTS: Five differentially expressed miRNAs (miR-125b-2-3p, miR-205-5p, let-7b-3p, miR-1262, and miR-548o-3p) were identified by qRT-PCR. The expression of these miRNAs correlated with ACR, 24hUpro, mAlb, UA, and combined yielded a ROC curve area of 0.916 in discriminating MsPGN patients from the controls. In addition, the expression of miR-205-5p, let-7b-3p, miR-1262, and miR-548o-3p was elevated in the MsPGN patient group, and miR-125b-2-3p was decreased in the MsPGN patient group. CONCLUSIONS: Differential expression of urinary exosomal miRNAs may pose a risk of MsPGN and help distinguish MsPGN patients from controls. Certain miRNA expressions may be associated with disease progression, contributing to the epigenetic understanding of the pathophysiology of MsPGN.

The therapeutic effect of Shenhua tablet against mesangial cell proliferation and renal inflammation in mesangial proliferative glomerulonephritis.

Shenhua tablet (SH), a formulation of traditional Chinese medicine, exerts renoprotective effect on chronic kidney diseases, and it has been found to restrain inflammation, but the mechanism is still unclear. Here, we explored the potential renoprotection of SH in mesangial proliferative glomerulonephritis (MsPGN) rat model induced by anti-Thy1 antibody. Administration of SH reduced urinary albumin/creatinine ratio (UACR) and significantly attenuated mesangial cell proliferation and renal inflammation. Notably, SH protected rats against renal inflammation, which was associated with decreasing macrophage infiltration and promoting macrophage anti-inflammatory activity. Network analysis combined with arrays identified the Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway as the main pathways of SH could target inflammation. Furthermore, it was confirmed that mesangial cell proliferation, which response to inflammation, were alleviated by ASS1 expression enhanced after SH administration both in vivo and in vitro. Collectively, SH has the beneficial on relieving the progression of MsPGN to alleviate inflammation and mesangial proliferation by inhibiting STAT3 phosphorylation and maintains the expression level of ASS1, might be an effective strategy for treating MsPGN.

Overlap of Thrombotic Microangiopathy and Mesangial Proliferative Glomerulonephritis Caused by Combination Therapy with Atezolizumab and Bevacizumab.

Vascular endothelial growth factor inhibitors and checkpoint inhibitors are effective treatments for solid tumors. These new classes of anti-cancer agents frequently cause kidney-related side effects. Although their anti-cancer effects may be enhanced when used in combination, the severity of their kidney-related side effects is unknown. We herein report the first case of thrombotic microangiopathy and mesangial proliferative glomerulonephritis caused by combined treatment with atezolizumab and bevacizumab in a 74-year-old man with hepatocellular carcinoma. The combination therapy was discontinued and replaced with intravenous methylprednisolone followed by oral prednisolone. Subsequently, the urinary protein excretion levels declined.

SOCS1 Peptidomimetic Alleviates Glomerular Inflammation in MsPGN by Inhibiting Macrophage M1 Polarization.

Mesangial proliferative glomerulonephritis (MsPGN), the most common pathological change in primary glomerulonephritis, is characterized by increased macrophage infiltration into glomeruli, which results in proinflammatory cytokine release. Macrophage infiltration and differentiation are induced by the Janus kinase 2 and signal transducer and activator of the transcription 1 (JAK2/STAT1) pathway. As a suppressor of cytokine signaling 1 (SOCS1) downregulates the immune response by inhibiting the JAK2/STAT1 pathway, we investigated whether a peptide mimicking the SOCS1 kinase inhibitor region, namely, SOCS1 peptidomimetic, protects against nephropathy. Glomerular JAK2/STAT1 pathway activation was synchronized with kidney injury in an MsPGN rat model. Rats treated with the SOCS1 peptidomimetic exhibited reduced pathological glomerular changes and lessened macrophage recruitment. Moreover, in vivo, the phosphorylation of the JAK2/STAT1 pathway was downregulated in infiltrated macrophages of glomeruli. In vitro, the SOCS1 peptidomimetic inhibited macrophage M1 polarization by suppressing JAK2/STAT1 activation. In conclusion, our study demonstrated that the SOCS1 peptidomimetic plays a protective role against pathologic glomerular changes in MsPGN by reducing macrophage infiltration and inhibiting macrophage polarizing to the M1 phenotype. SOCS1 peptidomimetic, therefore, presents a feasible therapeutic strategy to alleviate renal inflammation in MsPGN.

Baicalin Reduces Renal Inflammation in Mesangial Proliferative Glomerulonephritis through Activation of Nrf2/ARE and PI3K/AKT Pathways.

OBJECTIVE: Mesangial proliferative glomerulonephritis (MPGN) is a prevalent form of primary glomerulonephritis, distinguished by the proliferation of mesangial cells and the accompanying inflammatory response. Baicalin, the active ingredient in the Scutellaria baicalensis Georgi plant, has been observed to have a protective effect on the kidneys. However, its specific impact on MPGN has yet to be studied widely. Hence, this study aimed to investigate the effect on MPGN and the underlying mechanisms of Baicalin. METHODS: Thirty-six Sprague-Dawley (SD) rats, aged 6 to 8 weeks, were randomly allocated into different subgroups: control, model, benazepril, and three baicalin subgroups (low, medium, and high dose), each consisting of six rats. The concentrations of 24-hour urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), triglycerides (TG), total cholesterol (TC), interleukins (IL-1α, IL-2, IL-10), and interferon-γ (IFN-γ) were measured with biochemistry. The pathological alterations in the renal tissue were examined using Hematoxylin and Eosin (HE) along with Periodic Acid-Schiff (PAS) staining. Concurrently, the extent of apoptosis was evaluated using TdT-mediated dUTP nick end labeling (TUNEL) staining. In vitro, mesangial cells were exposed to 30 µg/mL lipopolysaccharide for 24 h, with or without varying concentrations of baicalin (10, 20, 40 µM). MTT assay was applied to estimate cell activity, flow cytometry to evaluate the cell cycle, and 5-ethynyl-2-deoxyuridine (EdU) detection to measure cell proliferation. IL-1α, IL-2, IL-10, and IFN-γ concentrations in the cell supernatant were assayed with biochemistry. Furthermore, the expression of apoptosis-related proteins, concluding BCL2-Associated X (Bax), Bcl-2, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1, NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway-related proteins (Nrf2 and HO-1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway-related proteins (p-PI3K, PI3K, p-AKT, and AKT) in both the renal tissue and cell supernatant were measured. RESULTS: Baicalin treatment significantly reduced the 24-hour urinary protein, serum levels of BUN, SCr, TG, TC, IL-1α, IL-2, IL-10, and IFN-γ in vivo experiments. Baicalin treatment also improved the pathological condition of renal tissue and decreased the occurrence of apoptosis. In vitro, findings confirmed that baicalin inhabits the proliferation of mesangial cells triggered by Lipopolysaccharide (LPS), induces a G1 phase cell cycle arrest, and reduces the concentrations of IL-1α, IL-2, IL-10, and IFN-γ. Baicalin also decreased the ratios of p-PI3K/PI3K and p-AKT/AKT while enhancing the levels of Nrf2 and HO-1 in both renal tissue and cell supernatant. CONCLUSIONS: Baicalin can mitigate MPGN by impeding the proliferation and inflammation of mesangial cells by activating Nrf2/ARE and PI3K/AKT pathways.

Albiflorin ameliorates mesangial proliferative glomerulonephritis by PI3K/AKT/NF-κB pathway.

Background: The most common type of glomerulonephritis in China is mesangial proliferative glomerulonephritis (MPGN) featured with mesangial cell overproliferation and inflammation, as well as fibrosis. Albiflorin (AF) is an effective composition extracted from Paeonia Alba Radix and has been administrated for various diseases. Nevertheless, there is no research reporting the effect of AF on MPGN.Purpose: Our work aims to probe into the role and possible mechanism of AF on MPGN.Research Design: We investigated the effects of AF on mesangial cell overproliferation, inflammation, and fibrosis in vitro and in vivo and identified the related signaling pathways.Study Sample: human mesangial cells (HMCs) and male Sprague Dawley (SD) rats.Data Analysis: SPSS 18.0 was used to analyze the data.Results: AF attenuated the proliferation and inflammation both in vitro and in vivo. In detail, AF decreased the ki67 expression in lipopolysaccharides (LPS)-treated HMCs and MPGN rats, and the mRNA expression or contents of inflammatory cytokines were reduced after AF treatment. The fibrosis of LPS-treated HMCs and MPGN rats was also reduced by AF. Moreover, AF effectively restrained 24 h urinary protein, improved kidney function, and mitigated dyslipidemia and pathological injury of MPGN rats. Additionally, we found that the protective effects of AF were accompanied by the blocking of PI3K/AKT/NF-κB pathway, and the inhibitory effects of AF on MPGN were reversed by insulin-like growth factor (IGF-1), the PI3K agonist.Conclusions: AF alleviates MPGN via restraining mesangial cell overproliferation, inflammation, and fibrosis via PI3K/AKT/NF-κB signaling.

A case of systemic sarcoidosis with mesangial proliferative glomerulonephritis showing predominant deposition of IgG in the mesangial region.

A 37-year-old African-British man was referred to our hospital for detailed examination because of persistent fever, swelling and pain in both ankle joints, and blurred vision for two months. Inguinal lymph node biopsy showed a large number of epithelioid granulomas without necrosis. Granulomatous anterior uveitis, nephropathy, high serum angiotensin-converting enzyme activity, and high serum-soluble interleukin-2 receptor were observed, and the diagnosis of systemic sarcoidosis was made. His serum creatinine was 1.4 mg/dL and hematuria, leukocyturia, and urine protein were also seen. The renal biopsy finding was mesangial proliferative glomerulonephritis, with no findings of granuloma formation or tubular interstitial nephritis. Immunofluorescence staining showed deposition of IgG, C3, and C1q in the mesangial region. IgG3 was dominant in subclass staining. There was no monoclonality on kappa and lambda staining. Electron microscopy showed predominant deposition in the mesangial region with some subepithelial and endothelial deposition. His hematuria and leukocyturia disappeared with steroid therapy, suggesting sarcoidosis-related nephropathy. A case of systemic sarcoidosis with mesangial proliferative glomerulonephritis showing predominant deposition of IgG in the mesangial region is presented. No cases of such histological findings have been reported so far, and it is necessary to analyze further cases to clarify the pathogenic significance of the renal biopsy findings observed in this case.

A case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) that responded favorably to steroid therapy.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) generally has a poor prognosis and the consensus is that it needs to be treated with clone-directed therapy. However, the prognosis of PGNMID is heterogenous and some cases have been successfully treated using other therapeutic strategies. We herein report a case of PGNMID that responded favorably to steroids without clone-directed therapy. An 18-year-old woman was referred to a nephrologist with proteinuria detected in an annual health check-up. Over a 3-year period, the concentration of creatinine (Cr) increased from 0.76 to 1.00 mg/dL and proteinuria from 0.35 to 1.9 g/g Cr. Monoclonal gammopathies were not detected in her serum or urine. Based on the findings of kidney biopsy at the age of 21 years, the patient was diagnosed with proliferative glomerulonephritis with monoclonal IgG1-kappa deposits. The histological feature was mesangial proliferative glomerulonephritis with advanced glomerulosclerosis, which is a rare presentation of PGNMID. Intravenous methylprednisolone pulse therapy was initiated, followed by oral prednisolone at a dose of 30 mg daily. One year later, a second kidney biopsy revealed a significant decrease in mesangial deposits of IgG1-kappa. Prednisolone was gradually tapered and discontinued 2 years after the first kidney biopsy. At the time of prednisolone withdrawal, urinalysis showed proteinuria of 0.2 g/g Cr without hematuria. Kidney function remained stable throughout the treatment period.

Warfarin-Related Nephropathy Manifested as Diffuse Mesangial Proliferative Glomerulonephritis.

Warfarin is associated with anticoagulant-related nephropathy (ARN), one of the potential side effects. This is evidenced by a progressively increasing number of detected cases of deterioration in the kidney function even in patients with normal baseline function (GFR {glomerular filtration rate}) in addition to the chronic kidney disease (CKD) patients who are already vulnerable to ARN. There has been a clinical correlation in a rapid decline of kidney function and international normalized ratio (INR) levels of greater than three. ARN is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. We want to emphasize the importance of monitoring kidney function regularly and adjusting the appropriate doses of warfarin. We present a case of a 57-year-old female who was on warfarin for the mechanical aortic valve, presented with acute kidney injury and supratherapeutic INR. Her renal biopsy showed diffuse mesangial proliferative glomerulonephritis.