Mesangial Proliferative Glomerulonephritis Research Articles

Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases. This study aimed to investigate the clinical significance of changes in interleukin-18 (IL-18) and neutrophil/lymphocyte ratio (NLR) in the pathogenesis of AAV and the impact of NLR on the prognosis of patients. The clinical data of 52 AAV patients (AAV group) who met the conditions of hospitalization, 30 patients with mild mesangial proliferative glomerulonephritis (disease controls), and 30 healthy volunteers (normal controls) in Nephrology Department of Liuzhou People's Hospital from May 2020 to August 2022 were selected. A total of 52 AAV patients were divided into active phase (>15 points) and remission phase (≤15 points) based on the Birmingham vasculitis activity score (BVAS). Serum IL-18 level was detected by enzyme-linked immunosorbent assay in three groups. Pearson product moment correlation analysis was performed to investigate the correlation between serum IL-18 levels and clinical laboratory indicators, and receiver operating characteristic (ROC) curve analysis was performed on serum IL-18, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and NLR in AAV patients. The levels of serum creatinine, parathyroid hormone, β2-microglobulin (β2-MG), ESR, CRP, and IL-18 in active stage of AAV were significantly higher than those in remission stage of AAV. Moreover, the serum IL-18 level of active AAV patients was significantly higher than that of disease control group (P < 0.05). The levels of eGFR, hemoglobin, and complement C3 were significantly lower than those during the remission (P < 0.05). Pearson product moment correlation analysis showed that serum IL-18 level in AAV patients was positively correlated with BVAS score and ESR level. The area under the curve of serum IL-18, NLR, CRP, ESR levels evaluated by ROC curve was 0.921, 0.899, 0.83, and 0.75, respectively. Kaplan-Meier survival curve showed that the cumulative survival rate of patients in low NLR group was significantly higher than that in high NLR group (68.36 vs 42.89%), with significant difference (Log-Rank = 6.745, P = 0.025 < 0.05). IL-18 may be adopted as one of the important biological markers to judge the disease of AAV, and the cumulative survival rate of patients with high NLR is low, which may be applied as an indicator to evaluate the poor prognosis of patients with AAV.

Pathological Factors Affecting the R2* Values of the Kidney in Blood Oxygenation Level-dependent MR Imaging: A Retrospective Study.

Despite the usefulness of blood oxygenation level-dependent (BOLD) MRI in assessing glomerulonephritis activity, its relationship with histological findings remains unclear. Because glomerulonephritis presents multiple complex injury patterns, analysis of each pattern is essential. We aimed to elucidate the relationship between the histological findings of the kidney and BOLD MRI findings in mesangial proliferative glomerulonephritis. Children under 16 years of age diagnosed with mesangial proliferative glomerulonephritis by kidney biopsy at our university hospital between January 2013 and September 2022 were included in this study. Cortical and medullary spin relaxation rate (R2*) values were measured using BOLD MRI at 3T within two weeks before and after the kidney biopsy. The R2* values, including the fluctuations with low-dose oxygen administration, were retrospectively examined in relation to the cortical (mesangial proliferation, endothelial cell proliferation, crescent, sclerosis, and fibrosis) and medullary findings (fibrosis). Sixteen times kidney biopsies were performed for glomerulonephritis during the study period, and one patient was excluded because of comorbidities; the remaining 14 patients included six boys with a mean age of 11.9 ± 3.5 years at the BOLD examination. None of the patients had medullary fibrosis. Among the kidney tissue parameters, only sclerosis showed a significant correlation with R2* values: medulla with R2* values under atmospheric pressure (r = 0.53, P < 0.05) and cortex with the rate of change in R2* values with low-dose oxygen administration (r = -0.57, P < 0.03). In the multiple regression analysis, only sclerosis was an independent contributor to the change in R2* values with oxygen administration in the cortex (regression coefficient -0.109, P < 0.05). Since the R2* values reflect histological changes in the kidney, BOLD MRI may facilitate the evaluation of mesangial proliferative glomerulonephritis, potentially reducing the patient burden.

Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Series From the French Nephropathology Group

Rationale & ObjectiveAtypical anti-glomerular basement membrane (GBM) nephritis is characterized by a bright linear immunoglobulin staining along the GBM by immunofluorescence without a diffuse crescentic glomerulonephritis nor serum anti-GBM antibodies by conventional ELISA. We characterized a series of patients with atypical anti-GBM disease. Study DesignCase series. Setting & ParticipantsPatients were identified by the French Nephropathology Group as having atypical anti-GBM nephritis between 2003 and 2022. FindingsAmong 38 potential cases, 25 were included. 14 (56%) were female and 23 (92%) had hematuria. Median [interquartile range (IQR)] serum creatinine at diagnosis was 150 [102-203] μmol/L and median [IQR] urine protein to creatinine ratio was 2.4 [1.3-5.2] g/g. 9 (36%) patients had endocapillary proliferative glomerulonephritis (GN), 4 (16%) had mesangial proliferative GN, 4 (16%) had membranoproliferative GN, 2 (8%) had pure and focal crescentic GN, 1 (4%) had focal segmental glomerulosclerosis, and 5 had glomeruli that were unremarkable on histopathology. Nine patients (36%) had crescents, involving a median of 9% of glomeruli. Bright linear staining for IgG was seen in 22 cases (88%) and for IgA in 3 cases (12%). The nine patients (38%) who had a monotypic staining pattern tended to be older with less proteinuria and rarely had crescents. Kidney survival rate at one year was 83% and did not appear to be associated with the light chain restriction. LimitationsRetrospective case series with a limited number of biopsies including electron microscopy. ConclusionsCompared to typical anti-GBM disease, atypical anti-GBM nephritis frequently presents with endocapillary or mesangial proliferative glomerulonephritis pattern and appears to have slower disease progression. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes.

[Clinical analysis of 10 patients with Fabry disease].

We aimed to analyze the clinical data of 10 patients (6 male and 4 female) with Fabry disease (FD). The mean age of the patients was (28.80±9.27) years. Seven patients had classical FD and three had delayed onset FD. Among the 10 patients, six had skin involvement and cutaneous angiokeratoma; five had hypohidrosis or anhidrosis; nine had intermittent neuralgia; and three had supraorbital ridge protrusion, forehead bulge, and lip thickening. Five patients had proteinuria, including one with chronic kidney disease stage 3 and one with chronic kidney disease stage 5. Cardiac involvement occurred in three patients, two had myocardial hypertrophy and one had valvular insufficiency. The activity of galactosidase decreased in seven patients (2.80-1.55 μmol·L-1·h-1). Plasma deacetyl-GL-3 was elevated in all 10 patients(3.12-120.00 ng/ml). Three patients underwent renal biopsy, wherein two cases of focal segmental glomerulosclerosis and one of mesangial proliferative glomerulonephritis was found. A large number of myeloid and zebra bodies were found in the podocytes in three patients, including a small number of myeloid and zebra bodies in the renal tubular epithelial cells in one patient with occasional zebra bodies in the renal interstitium. Nine patients had GLA gene mutations. One patient was c.102T>A, a de novo mutation. Four patients were treated with agalsidase α injection (0.2 mg/kg, intravenous infusion every 2 weeks), and their prognosis was good. FD has various clinical manifestations and multi-system involvement, which requires multidisciplinary cooperation. Detection of galactosidase activity, plasma globotriaosylsphingosine, and GLA gene mutation can help for accurate diagnosis.

Mutation of NPHS1, NPHS2, WT1, LAMB2, COL4A5 and other genes in children with idiopathic steroid resistant nephrotic syndrome

Background: Many children with idiopathic steroid resistant nephrotic syndrome have been reported worldwide due to mutation of NPHS1, NPHS2, WT1 and LAMB2 genes. This study aimed to determine the frequency of mutation of NPHS1, NPHS2, WT1, LAMB2, COL4A5 and other genes and their association with renal histopathological patterns of idiopathic steroid resistant nephrotic syndrome patients. Methods: This cross-sectional study was conducted on 25 patients with idiopathic steroid resistant nephrotic aged 1-17 years in the Department of Paediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Bangladesh, from July 2017 to June 2018. Next Generation Sequencing and mutation analysis were performed after DNA extraction from patients' venous blood lymphocytes. Histopathological study of renal tissue was done among 17 patients. Results:  A little more than half (56%) of the patients were male. The mean age at the initial attack of nephrotic syndrome was 94.2 months. They mostly had minimal change disease (41%) and IgA nephropathy (12%). One subject had the NPHS2 gene mutation, histopathologically diffuse mesangial proliferative glomerulonephritis, and clinically stage-4 chronic kidney disease. Another subject had the COL4A5 gene mutation and focal segmental glomerulosclerosis.  Both were male and had no familial renal disease, consanguinity, or hematuria. Conclusion: Children with idiopathic steroid resistant nephrotic syndrome showed NPHS2 and COL4A5 gene mutations. Histopathologically, they showed diffuse mesangial proliferative glomerulonephritis and focal segmental glomerulosclerosis.

ERK1/2-dependent activity of SOX9 is required for sublytic C5b-9-induced expression of FGF1, PDGFα, and TGF-β1 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-β1) 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-β1 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-β1 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-β1, and ameliorated glomerular injury in rat Thy-1N. Overall, these findings suggest that expression of FGF1, PDGFα, and TGF-β1 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.

Pediatric Mesangial Proliferative Glomerulonephritis Has Increased the Platelet Thrombus Formation Potentials under High-Shear Flow Condition

Introduction: Blood coagulation is associated with glomerulonephritis (GN) pathophysiology. Using whole-blood-based rotational thromboelastometry, we recently reported that the degree of hypercoagulability in pediatric patients with immunoglobulin A nephropathy (IgAN), a GN, might be associated with pathological severity. To further clarify the coagulation status of mesangial proliferative GN (MesPGN), we assessed the platelet thrombus formation (PTF) under high-shear flow using a microchip-based flow chamber system (T-TAS^®). Methods: Thirty-four pediatric patients definitively diagnosed with MesPGN by renal biopsy at Nara Medical University Hospital between 2015 and 2022 were enrolled, and 29 patients (case group; median age, 8.0 years) were assessed. Microchips coated with collagen (PL-chip) were used to assess PTF at high-shear in whole blood. The times to increase by 10 and 30 kPa (T₁₀ and T₃₀) from baseline were calculated and compared with those of the pediatric controls. Changes in the parameters during the treatment course and the relationship between pathological severity and the parameters were evaluated. Results: T₁₀ and T₃₀ parameters in the PL-chip were significantly shorter, and the area under the curves were greater in the case group than those in the control group (both p < 0.05). Each parameter was enhanced during the 3-week treatment but improved after the end of treatment. No significant relationship was observed between pathological severity and these parameters. Little PTF difference was observed between IgAN and Henoch-Schönlein purpura nephritis. Conclusions: Pediatric MesPGN increased the potential for PTF under high-shear flow conditions.

Immuno-Nanoparticles Developed Using Dexamethasone and Captopril Co-Loaded PLGA Improve Glomerulonephritis Through Modulating Macrophage Polarization

The purpose of this study was to prepare liposome-coated poly(lactic-co-glycolic acid) co-loaded with dexamethasone (DXMS, D) and captopril (CAP, C) loading with PLGA nanoparticles (P) and modified polyethylene glycol and integrin α8 antibody on the surface of nanoparticles to obtain double-drug-loaded core–shell immunoliposome composite nanoparticles (DCPI), and then studied the loading Kidney targeting, anti-inflammatory effects and effects on macrophage differentiation of drug nanoparticles. In vitro cell experiments showed that DCPI could reduce the secretion of M2 macrophage-specific cytokines and the RNA expression levels of markers, and promote M2 macrophages toward unpolarized macrophages differentiation. In vivo experiments showed that DCPI had significant renal targeting, normalized renal index, serum creatinine, and blood urea nitrogen levels in mice with mesangial proliferative glomerulonephritis, and reduced inflammatory cytokines in the kidney’s secretion, and decreased RNA expression of M1 and M2 macrophage markers in kidneys. In conclusion, kidney-targeted DCPI nanoparticles can effectively regulate the polarization of macrophages, play an “anti-inflammatory/anti-fibrotic” therapeutic effect, and be a target for glomerulonephritis. Treatment provides new strategies and evidence.

[Genetic analysis of a patient with Alport syndrome due to compound heterozygous variants of COL4A4 gene].

To analyze the clinical phenotype and genetic characteristics of a patient with Alport syndrome. A patient with Alport syndrome who had visited the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the patient were collected. High-throughput sequencing was carried out to detect potential variant of the COL4A3, COL4A4 and COL4A5 genes, and Sanger sequencing was carried out for verification of candidate variants in the family. The main clinical manifestations of the patient included hematuria, proteinuria, and impaired hearing. Audiometric testing suggested symmetrical cochlear sensory neural hearing loss on both sides. Renal biopsy revealed mild mesangial proliferative glomerulonephritis. Genetic testing revealed that the patient has harbored compound heterozygous variants of the COL4A4 gene, namely c.940G>A (p.Gly314Ser) and c.3773G>A (p.Gly1258Asp), which were respectively inherited from her father and mother. Neither variant has been reported before, and were predicted to be pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. The c.940G>A (p.Gly314Ser) and c.3773G>A (p.Gly1258Asp) compound heterozygous variants of the COL4A4 gene probably underlay the Alport syndrome in this patient. Above finding has enriched the mutational spectrum of the COL4A4 gene.

CCL22 and Leptin associated with steroid resistance in childhood idiopathic nephrotic syndrome.

Previous studies have indicated a decrease in T regulatory cells (Tregs) among patients with steroid-resistant nephrotic syndrome. CCL22 and Leptin influenced the immune function of Tregs through their respective pathways. This study aimed to compare patients with steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) in terms of CCL22 and Leptin levels. This prospective study included 117 children diagnosed with idiopathic nephrotic syndrome (INS). Peripheral blood samples were collected before initiating steroid therapy, and serum levels of CCL22 and Leptin were measured. Patients were categorized into three groups based on their response to steroid treatment. Renal biopsies were recommended for all children diagnosed with INS, with higher acceptance rates in glucocorticoid resistance patients. Based on the response to steroid treatment, 117 children were divided as groups of SSNS (82 cases), frequent relapse nephrotic syndrome (FRNS) (10 cases), and SRNS (25 cases). A total of 41 patients underwent kidney biopsy, 11 cases (13.4%) in SSNS, 7 cases (70.0%) in FRNS and 24 cases (96.0%) in SRNS. 30 cases were minimal change disease (MCD), 9 cases were mesangial proliferative glomerulonephritis (MsPGN) and 3 cases were focal segmental glomerulosclerosis (FSGS). The levels of Leptin were significantly higher in SR patients (1208.1 ± 1044.1 pg/ml) compared to SS patients (515.4 ± 676.9 pg/ml) and controls (507.9 ± 479.8 pg/ml), regardless of the pathological type. CCL22 levels were significantly elevated in SRNS (92.2 ± 157.0 pg/ml), but the difference seemed to be attributed to the specific type of pathology, such as Minimal change disease (MCD) (127.4 ± 206.7 pg/ml) and focal segmental glomerulosclerosis (FSGS) (114.8 ± 22.0 pg/ml). For SRNS prediction, the AUC of Leptin, CCL22, and the joint prediction index were 0.764, 0.640, and 0.806, respectively. Serum levels of CCL22 and Leptin, detected prior to steroid therapy, were associated with steroid resistance in childhood INS.

Histological Patterns of Steroid Resistant Nephrotic Syndrome in Bulgarian Children: a Single Centre Study

Nephrotic syndrome is the most frequent glomerular disease in childhood. Steroid resistant nephrotic syndrome (SRNS) represents about 20% of children with nephrotic syndrome. SRNS is one of the leading indications for performing renal biopsy in children. The objective of this retrospective study is to determine the histological patterns of SRNS in Bulgarian children and to compare them with the worldwide findings. The study included 49 patients with SRNS. All biopsies were performed at the Department of Pediatric Nephrology and Dialysis, University Children's Hospital, Sofia, Bulgaria between January 2004 and January 2020. The renal biopsies were examined histologically and with immunohistochemistry at the Pathology Department, Military Medical Academy, Sofia and Medical University – Sofia, Bulgaria. Twenty-eight boys (57.1%) and 21 girls (42.9%) were included in the study. The age at diagnosis ranged from 8 months to 212 months (17 years and 8 months) with a mean of 94 months (7 years and 10 months). Generalized edema was the most common presentation – 55.1%, followed by microhaematuria – 53.1% of cases. Histological examination revealed several different forms: Focal segmental glomerulosclerosis (FSGS) in 30.6% (n=15), Mesangial proliferative glomerulonephritis (MesPGN) in 14.3% (n=7), Membranous glomerulonephritis (MGN) in 12.2% (n=6), IgM nephropathy in 12.2% (n=6), Membranoproliferative glomerulonephritis (MPGN) type I in 8.2% (n=4), C3 glomerulopathy 8.2% (n=4), Minimal change disease (MCD) in 4.1% (n=2), IgA glomerulonephritis in 4.1% (n=2), Diffuse mesangial sclerosis (DMS) in 4.1\% (n=2) and C1q nephropathy in 2.0% (n=1). Although SRNS in Bulgarian children might represent a broad spectrum of glomerular diseases it could be attributed in approximately two/third of patients to four of them – FSGS, MesPGN, MGN, and IgM nephropathy.

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.

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.

Classification of Glomerular Pathology Images in Children Using Convolutional Neural Networks with Improved SE-ResNet Module.

Classification of glomerular pathology based on histology sections is the key to diagnose the type and degree of kidney diseases. To address problems in the classification of glomerular lesions in children, a deep learning-based complete glomerular classification framework was designed to detect and classify glomerular pathology. A neural network integrating Resnet and Senet (RS-INet) was proposed and a glomerular classification algorithm implemented to achieve high-precision classification of glomerular pathology. SE-Resnet was applied with improvement by transforming the convolutional layer of the original Resnet residual block into a convolutional block with smaller parameters as well as reduced network parameters on the premise of ensuring network performance. Experimental results showed that our algorithm had the best performance in differentiating mesangial proliferative glomerulonephritis (MsPGN), crescent glomerulonephritis (CGN), and glomerulosclerosis (GS) from normal glomerulus (Normal) compared with other classification algorithms. The accuracy rates were 0.960, 0.940, 0.937, and 0.968, respectively. This suggests that the classification algorithm proposed in the present study is able to identify glomerular lesions with a higher precision, and distinguish similar glomerular pathologies from each other.

Status of Hepatitis B Virus Surface Antigen (HBsAg) Deposition in Renal Tissue among Glomerulonephritis Patients

Background: Hepatitis B virus (HBV) related glomerulonephritis (GN) may be found in HBV seropositive as well as seronegative patients. HBV may present in the renal tissue of such patients. Objective: The purpose of the present study was to assess status of HBsAg deposition in renal tissue among glomerulonephritis patients. Methodology: This cross-sectional study was conducted in the Department of Nephrology at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh during the period of July 2015 to June 2016. All diagnosed GN patients both HBV seropositive and seronegative aged more than 18 years of both sexes admitted in the department of Nephrology BSMMU were taken as the study population. Serological tests both HBsAg and anti-HBc (total) were done to identify the HBV seropositive and seronegative individuals by ELISA technique and Chemiluminescense Method respectively. Renal biopsy was done percutaneously through a posterior approach. Immunohistochemistry and one core were preserved in normal saline for direct immunofluorescence (DIF). Both test tubes were sent to find out histological features and presence of HBsAg in renal biopsy tissue in Pathology Department of Bangabandhu Sheikh Mujib Medical University, Dhaka. Results: HBsAg antigen in renal tissue was found in 2 patients among 7 patients who were seropositive for both HBsAg and Anti-HBc antibody (total), 2 patients among 8 patients who were HBsAg seronegative but Anti-HBc (total) seropositive, 2 patients among 38 patients who were seronegative for both HBsAg and Anti-HBc (total). There were no patients in this study who was HBsAg seropositive but Anti HBc (total) seronegative. Total 11.3% (6 patients) of renal biopsy specimens were found to have HBsAg deposits which included 3 cases of Membranoproliferative GN and one of each of Membranous nephropathy, Mesangial proliferative GN and IgA nephropathy. Conclusion: The high rate of HBsAg deposits has been found in renal tissue among GN patients. Bangladesh Journal of Medical Microbiology, January 2022;16(1):14-18

Renal Disease in Inborn Errors of Immunity: a Case Series

Renal disease is an underappreciated complication of inborn errors of immunity (IEIs). Chronic kidney disease (CKD) is associated with significant morbidity and mortality in the general population; however, clinical experience with CKD in IEIs is limited. We examined the age of onset, progression, and outcomes of CKD in 4 adult IEI patients seen at our centre. Immunologic diagnoses for all patients were made clinically and with the support of genetic testing. Renal biopsy pathology reports, age at symptom onset and diagnosis of IEI, age at diagnosis of CKD, serum creatinine levels, and measures of proteinuria were assessed.We reviewed the charts of four patients with IEIs and CKD. The IEI diagnoses were: 1) STAT3 loss-of-function (Job syndrome), 2) common variable immunodeficiency (CVID) with compound heterozygous TNFRSF13B (TACI) variants, 3) CVID with negative whole exome sequencing (WES), and 4) combined immunodeficiency with negative WES. All patients received renal biopsy-confirmed diagnoses of CKD. Biopsies were performed between adolescence and adulthood (mean age 27.25 years, range 18–35), on average 18.5 years after their initial symptoms of an underlying IEI (range 13–24 years). The histopathological diagnoses respectively were 1) immune complex-mediated mesangial proliferative and membranous glomerulonephritis, 2) interstitial nephritis with glomerulosclerosis and interstitial fibrosis with lymphocytic infiltration likely from lymphoma, 3) granulomatous infiltration from underlying CVID, and 4) lupus nephritis predominantly with proteinuria. In all cases, despite treatment, renal disease was non-reversible. One patient required renal transplantation, and one patient became dialysis dependent. For two patients, renal function stabilized but did not revert to pre-disease levels. Renal disease is a potentially serious comorbidity that can develop in IEIs, predisposing to further infections and impairing quality of life. Practitioners caring for people with IEIs should be aware that CKD can affect young adults and may present several years from IEI symptom onset. Monitoring for renal disease and prompt referral to a nephrologist for potential treatment should be pursued, as recognizing CKD in its early stages may help prevent or slow progression.

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

BackgroundAllogeneic 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.MethodsWe retrospectively analyzed renal biopsy specimens from children with kidney injury after allo-HSCT and correlated results with clinical data in the last 10 years.ResultsAmong 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.ConclusionsThis 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.

The role of glomerular lesions in the prognosis of patients with acute kidney injury during hemorrhagic fever with renal syndrome

Objective This study aimed to explore the role of glomerular lesions in patients who suffered from acute kidney injury (AKI) during hemorrhagic fever with renal syndrome (HFRS). Methods The study comprised 66 patients with AKI during HFRS treated at the National Clinical Research Center of Kidney Diseases of China, Jinling Hospital, from January 2014 to December 2018. According to the kidney pathological findings, the 66 patients were divided into two groups: the tubulointerstitial injury group (HFRS-TI group, n = 43) and the tubulointerstitial injury with glomerular lesions group (HFRS-GL group, n = 23). The clinical and pathological characteristics of the 66 patients were analyzed. Results There were 9 cases of IgA nephropathy, 1 case of membranous nephropathy, 2 cases of diabetic nephropathy, and 11 cases of mesangial proliferative glomerulonephritis in the HFRS-GL group. There were more males in the HFRS-GL group than in the HFRS-TI group (92.3% vs. 69.8%, p < .05). A higher proportion of interstitial fibrosis (56.5% vs. 27.9%, p < .05) and more immunoglobulin and complement depositions (p < .001) were observed in the HFRS-GL group than in the HFRS-TI group. Rates of remission of AKI were lower in the HFRS-GL group than in the HFRS-TI group (73.9% vs. 95.3%, p < .05). The presence of glomerular lesions (HR = 5.636, 95% CI = 1.121–28.329, p = .036) and moderate tubulointerstitial injury (HR = 3.598, 95% CI = 1.278–10.125, p = .015) were found to be independent risk factors for kidney prognosis. Conclusions Patients with AKI during HFRS can have glomerular lesions or glomerulonephritis. Patients with AKI during HFRS who have glomerular lesions or moderate renal tubulointerstitial injury proven by kidney biopsy have a relatively poor kidney prognosis. A kidney biopsy can help determine long-term prognosis in patients with AKI during HFRS.

Exploring the Protective Effect of the Ethanolic Extract of Rosa laevigata Michx. Fruit on Rats with Mesangial Proliferative Glomerulonephritis Based on NLRP3 Inflammasome Pathway

Objective: To investigate the effect of the ethanolic extract of Rosa laevigata Michx. fruit on rats with mesangial proliferative glomerulonephritis based on the NLRP3 inflammasome pathway. Methods: Thirty Wistar rats were divided into three groups, a blank control group, a diabetic nephropathy (DN) model group, and an ethanolic extract intervention group, according to the random number table method, with 10 rats in each group. One day before the experiment, basic feeding was initiated for all the rats; the changes in activity and weight of each group of rats were observed and recorded after 7 d, and a rat model of renal function injury was established after 1 d. Results: Compared with the control group, the model group had significantly higher kidney/body ratio, 24 h urine protein, serum creatinine (SCr), blood urea nitrogen (BUN), glomerular mesangial cell (GMC) count, and extracellular matrix (ECM) positive area ratio (P &lt; 0.05); the same indicators were  significantly lower in the intervention group than in the model group (P &lt; 0.05). The NLRP3 inflammasome pathway in renal intrinsic cells was activated in the intervention group. The overactivation of NLRP3 inflammasome is known to promote interleukin (IL)-1? release, which was inhibited in the intervention group. Conclusion: The ethanolic extract of Rosa laevigata Michx. fruit has a protective effect on renal intrinsic cells and may be related to NLRP3 inflammasome pathway, suggesting that the fruit of Rosa laevigata Michx. has a potential role in protecting renal intrinsic cells from inflammatory damage. NLRP3 inflammasomes are involved in the development of various chronic inflammatory diseases, such as acute and chronic glomerulonephritis and renal fibrosis.

Egyptian pediatric clinical practice adapted guidelines: evidence-based [2] steroid-resistant nephrotic syndrome (SRNS) 2022

BackgroundNephrotic syndrome is one of the most common chronic kidney diseases in children. Steroid sensitive type (SSNS) constitutes about 85–90%, whereas steroid-resistant type (SRNS) only 15–20% (Mickinney et al. Pediatr Nephrol 16:1040-1044, 2001). While MCD is the most common histopathology in SS type, children with SRNS have MCD, mesangial proliferative glomerulonephritis, or focal and segmental glomerulosclerosis (FSGS) (International Study Kidney Disease in children, Kidney Int 20;765-771, 1981). SRNS is defined as those who do not show remission after 6 weeks and standard dose of oral steroids ± 3 IV MPD doses (Trautmann et al. Pediatr Nephrol 35:1529-1561, 2020).ObjectivesThese national adapted guidelines aim to frame evidence-based recommendations adopted or adapted from the IPNA 2020, KDIGO 2021, and Japanese 2014 de novo guidelines for diagnosis and management of nephrotic children to be presented in two manuscripts: (1) steroid sensitive (SSNS) and (2) steroid-resistant nephrotic syndrome (SRNS).MethodologyFormulation of key questions was followed with a review of literature guided by our appraised guidelines using AGREE plus appraisal tool. Virtual monthly meetings all through the year 2021 were activated  for reviewing and validation of final adaptation evidence-based draft, considering all comments of external reviewers including KDIGO assigned reviewer.DiscussionRationale behind the selection of adopted statements and tailoring of others to suit our local facilities, expertise, and our local disease profile was discussed in the text with reasons.ConclusionThe provided guidelines aim to optimize patient care and outcome and suggest research areas lacking validated research recommendations.