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Archives of Pathology & Laboratory... Jan 2024Galactose-deficient immunoglobulin A1 (Gd-IgA1) deposition in the renal mesangium plays a role in the pathogenesis of IgA nephropathy.
CONTEXT.—
Galactose-deficient immunoglobulin A1 (Gd-IgA1) deposition in the renal mesangium plays a role in the pathogenesis of IgA nephropathy.
OBJECTIVE.—
To assess the serum Gd-IgA1 level in biopsy-proven IgA nephropathy cases on diagnosis and 3 months post treatment and its relation with histologic Oxford classification.
DESIGN.—
In this hospital-based prospective cohort study, 40 cases and 20 controls were enrolled. Serum samples of biopsy-proven IgA nephropathy cases collected on the day of biopsy and 3 months post treatment were evaluated. Solid-phase ELISA (enzyme-linked immunosorbent assay) was performed for assessment of Gd-IgA1 level. All renal biopsies were scored by using Oxford Classification (C-MEST score). The association of serum Gd-IgA1 levels with other established prognostic parameters was assessed. To estimate the prognostic value of markers, logistic regression analysis and Kruskal-Wallis ANOVA (analysis of variance) were used.
RESULTS.—
Significant difference was observed in the serum Gd-IgA1 level values in the IgA nephropathy cases and healthy controls (P = .001) at baseline. However, no significant correlation between serum Gd-IgA1 levels at baseline and 3 months of follow-up (P = .31) or between baseline levels and age, proteinuria, hematuria, or estimated glomerular filtration rate was noted. There was no significant correlation between C-MEST score and serum Gd-IgA1 levels at baseline (P > .05); however, the distribution of Gd-IgA1 at 3 months was found to differ significantly between different grades of S score (P = .008).
CONCLUSIONS.—
Serum Gd-IgA1 levels may be of utility in predicting disease progression in IgA nephropathy cases. Measurement of serum Gd-IgA1 levels for the diagnosis and prognosis of IgA nephropathy may preclude the need for invasive renal biopsies.
PubMed: 38289288
DOI: 10.5858/arpa.2023-0190-OA -
Medical Science Monitor : International... Jan 2024The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874,... (Review)
Review
The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874, Eduard Henoch, a student of Schönlein, reported cases of children with purpura, abdominal pain, bloody diarrhea, and joint pain. IgA vasculitis, or Henoch-Schönlein purpura, is a systemic hypersensitivity vasculitis caused by the deposition of immune complexes in small blood vessels, including the renal glomeruli and mesangium. In the skin, the presentation is with non-thrombocytopenic purpura or urticaria. Worldwide, IgA nephropathy is the most common cause of primary glomerulonephritis. Detection of IgA deposition in small blood vessels and the renal glomeruli is diagnostic in most cases. This article aims to review the history, current classification, epidemiology, presentation, and diagnosis of IgA vasculitis and nephropathy, disease associations or trigger factors, including infections, vaccines, and therapeutic agents, and highlights some future approaches to improve diagnosis and clinical management.
Topics: Child; Humans; IgA Vasculitis; Immunoglobulin A; Glomerulonephritis, IGA; Vasculitis; Kidney Glomerulus; Hypersensitivity
PubMed: 38281080
DOI: 10.12659/MSM.943912 -
Cell Reports Feb 2024Recent regenerative studies using human pluripotent stem cells (hPSCs) have developed multiple kidney-lineage cells and organoids. However, to further form functional...
Recent regenerative studies using human pluripotent stem cells (hPSCs) have developed multiple kidney-lineage cells and organoids. However, to further form functional segments of the kidney, interactions of epithelial and interstitial cells are required. Here we describe a selective differentiation of renal interstitial progenitor-like cells (IPLCs) from human induced pluripotent stem cells (hiPSCs) by modifying our previous induction method for nephron progenitor cells (NPCs) and analyzing mouse embryonic interstitial progenitor cell (IPC) development. Our IPLCs combined with hiPSC-derived NPCs and nephric duct cells form nephrogenic niche- and mesangium-like structures in vitro. Furthermore, we successfully induce hiPSC-derived IPLCs to differentiate into mesangial and erythropoietin-producing cell lineages in vitro by screening differentiation-inducing factors and confirm that p38 MAPK, hypoxia, and VEGF signaling pathways are involved in the differentiation of mesangial-lineage cells. These findings indicate that our IPC-lineage induction method contributes to kidney regeneration and developmental research.
Topics: Humans; Animals; Mice; Induced Pluripotent Stem Cells; Kidney; Cell Lineage; Regeneration; Erythropoietin
PubMed: 38237600
DOI: 10.1016/j.celrep.2023.113602 -
AME Case Reports 2024Mesenteric cystic lymphatic malformation (LM) is a rare congenital benign malformation in adults, and its location in the mesentery of the sigmoid colon is even rarer.
BACKGROUND
Mesenteric cystic lymphatic malformation (LM) is a rare congenital benign malformation in adults, and its location in the mesentery of the sigmoid colon is even rarer.
CASE DESCRIPTION
We describe a rare case of LM of the mesentery in a 49-year-old woman. The patient was inadvertently identified during a physical examination 1 month earlier. Transvaginal ultrasound and magnetic resonance imaging (MRI) revealed the presence of an intrapelvic mass posterior to the uterus and right anterior to the sigmoid colon. According to the results of the ultrasound, the mass showed hypoechoic solid features with a blood flow signal, and MRI showed that the internal enhancement of the mass was uneven. According to its imaging characteristics, it was preliminarily speculated as a stromal tumor. The patient underwent laparoscopic fenestration and drainage of a sigmoid mesocolic cyst. The patient underwent laparoscopic fenestration and drainage of the sigmoid mesocolic cyst. The pathological diagnosis was cystic lymphangioma of the sigmoid mesangium. After the operation, the patient recovered well without any complications. No recurrence was observed during the 3-month follow-up.
CONCLUSIONS
LM is a challenging and rare disease, and its diagnosis is difficult. However, the combination of imaging examination and endoscopic ultrasound (EUS) technology can significantly improve the accurate diagnosis rate of the disease. Complete resection is the best choice for definite diagnosis and prevention of recurrence. It has been proved that laparoscopic surgery is a safe and feasible method for the treatment of this disease.
PubMed: 38234359
DOI: 10.21037/acr-23-143 -
Aging Jan 2024Immunoglobulin A nephropathy (IgAN), one type of glomerulonephritis, displays the accumulation of glycosylated IgA in the mesangium. Studies have demonstrated that both... (Review)
Review
Immunoglobulin A nephropathy (IgAN), one type of glomerulonephritis, displays the accumulation of glycosylated IgA in the mesangium. Studies have demonstrated that both genetics and epigenetics play a pivotal role in the occurrence and progression of IgAN. Post-translational modification (PTM) has been revealed to critically participate in IgAN development and progression because PTM dysregulation results in impaired degradation of proteins that regulate IgAN pathogenesis. A growing number of studies identify that PTMs, including sialylation, o-glycosylation, galactosylation, phosphorylation, ubiquitination and deubiquitination, modulate the initiation and progression of IgAN. Hence, in this review, we discuss the functions and mechanisms of PTMs in regulation of IgAN. Moreover, we outline numerous compounds that govern PTMs and attenuate IgAN progression. Targeting PTMs might be a useful strategy to ameliorate IgAN.
Topics: Humans; Glomerulonephritis, IGA; Glycosylation; Phosphorylation; Protein Processing, Post-Translational
PubMed: 38175721
DOI: 10.18632/aging.205406 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Nov 2023To investigate the role of histone deacetylase 6 (HDAC6) in podocyte injury in diabetic kidney disease (DKD) in mice.
OBJECTIVE
To investigate the role of histone deacetylase 6 (HDAC6) in podocyte injury in diabetic kidney disease (DKD) in mice.
METHODS
1) The 8-week-old male CD-1 mice were selected to construct the model of DKD with streptozocin (STZ). After the model was established, the mice were intraperitoneally injected with HDAC6 inhibitor CAY10603 (5mg/kg/daily) or same volume vehicle as control. The mice were divided into four groups, control (CTL)+vehicle (Veh) (=5), CLT+CAY10603 (=3), STZ+Veh (=9), and STZ+CAY10603 (=7). Mice in STZ+Veh and STZ+CAY10603 groups developed DKD, while mice in the CTL+Veh and CTL+CAY10603 groups were served as normal controls. The therapeutic effect was evaluated through urine albumin-to-creatinine ratio (uACR) and renal pathology after the 2-week treatment with CAY10603. 2) Human podocytes were cultured and were divided into four groups as follows: CTL, transforming growth factor-β (TGFβ), TGFβ+CAY10603 (250 nmol/L), and TGFβ+CAY10603 (500 nmol/L) groups. The control group did not receive any treatment, the last three groups were given 36-h TGFβ treatment at 5 ng/µL, with or without CAY10603 as indicated for an additional 12 h. Western blot was performed to determine the inhibitory effect of CAY10603 on NLRP3 inflammasome. 3) 6 knockout (KO) mice were generated and used to create STZ-induced model of DKD. The mice were divided into four groups: C57BL/6J wild type (WT) (=6), 6 KO (=6), WT+STZ (=10), and 6 KO+STZ (=9). Samples were collected 16 weeks after successful modeling and changes in uACR and renal pathology were evaluated accordingly.
RESULTS
After 2 weeks of treatment, mice in the STZ+CAY10603 group exhibited reduction in uACR (<0.05) and inhibition of glomerular mesangium expansion (<0.05) compared with those of the mice in the STZ+Veh group. There was no statistically significant difference in the indicators between the CTL+Veh group and the CTL+CAY10603 group. cultured podocytes, compared with the control group, NLRP3 inflammasome activation was seen in the TGFβ group. CAY10603 treatment significantly inhibited the activation of NLRP3 in the dosage-dependent manner (<0.05). Compared with those of the WT group, the WT+STZ group showed increased uACR (<0.05), obvious glomerulosclerosis and loss of podocytes numbers. Compared with those of the WT+STZ group, the 6 KO+STZ group showed effectively reduction of uACR (<0.05) and improvement in the renal pathological changes in mice. There was no significant difference in these aspects between the WT and 6 KO groups.
CONCLUSION
Inhibition of HDAC6 alleviates proteinuria and podocyte injury in the mouse model of DKD by suppressing the activation of NLRP3 inflammasome.
Topics: Animals; Humans; Male; Mice; Diabetes Mellitus; Diabetic Nephropathies; Histone Deacetylase 6; Inflammasomes; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Podocytes; Transforming Growth Factor beta
PubMed: 38162083
DOI: 10.12182/20231160207 -
Lupus Science & Medicine Dec 2023This study aimed to investigate the clinical significance of exostosin 1 (EXT1) in confirmed and suspected lupus membranous nephropathy (LMN).
OBJECTIVE
This study aimed to investigate the clinical significance of exostosin 1 (EXT1) in confirmed and suspected lupus membranous nephropathy (LMN).
METHODS
EXT1 was detected in 67 renal tissues of M-type phospholipase A2 receptor (PLA2R)-negative and ANA-positive membranous nephropathy by immunohistochemistry, and cases were divided into confirmed LMN and suspected LMN. The clinicopathological data were compared among the above groups, as well as EXT1-positive group and EXT1-negative group.
RESULTS
Twenty-two cases (73.3%) of confirmed LMN and six cases (16.2%) of suspected LMN exhibited EXT1 expression on the glomerular basement membrane and/or mesangium area, showing a significant difference (p<0.001). Concurrently, lupus nephritis (LN) of pure class V demonstrated a lower frequency of EXT1 positivity compared with mixed class V LN in the confirmed LMN group (31.8% vs 68.2%, p=0.007). EXT1-positive patients in the confirmed and suspected LMN group showed significant differences in some clinicopathological data comparing with EXT1-negative patients (p<0.05). Follow-up data revealed that a greater proportion of patients in the EXT1-positive group achieved complete remission post-treatment (p<0.05). Cox regression analysis showed that EXT1 positivity was significantly correlated with complete remission across the entire study cohort (HR 5.647; 95% CI, 1.323 to 12.048; p=0.019). Kaplan-Meier analysis indicated that the EXT1-positive group had a higher rate of accumulated nephrotic remission compared with the EXT1-negative group in the whole study cohort (p=0.028).
CONCLUSIONS
The EXT1-positive group exhibited a higher active index and a more favourable renal outcome than the EXT1-negative group. It would be better to recognise suspected LMN with EXT1 positivity as a potential autoimmune disease and maintain close follow-up due to its similarities with confirmed LMN.
Topics: Humans; Clinical Relevance; Glomerulonephritis, Membranous; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis
PubMed: 38154829
DOI: 10.1136/lupus-2023-001051 -
Cureus Oct 2023Fibrillary glomerulonephritis (FGN) is a rare immune-mediated glomerular disease traditionally characterized by the presence of amyloid-like, randomly aligned,...
Fibrillary glomerulonephritis (FGN) is a rare immune-mediated glomerular disease traditionally characterized by the presence of amyloid-like, randomly aligned, fibrillary deposits in the capillary wall, measuring approximately 20 nm in diameter and composed of polyclonal IgG. FGN is usually a primary disease with no pathognomonic clinical or laboratory findings. More than that, on light microscopic evaluation, it can receive various histological patterns, rendering its diagnosis indistinguishable. However, the identification by immunohistochemistry of a novel biomarker, DNA-J heat-shock protein family member B9 (DNAJB9), has created a new era in FGN diagnosis even in the absence of electron microscopy. Typically, most patients manifest various degrees of renal insufficiency, hypertension, microscopic hematuria, proteinuria, and occasionally frank nephrotic syndrome. The prognosis is usually severe and progression to end-stage kidney disease (ESKD) is the rule, given that no specific treatment is available until now, despite the fact that in small studies rituximab-based therapy seems to alleviate the severity and improve the disease progression. Herein, we report the case of a 63-year-old Caucasian man presenting with uncontrolled hypertension, headache, shortness of breath, and lower limb edema. Diagnostic evaluation revealed mild deterioration of kidney function, nephrotic range proteinuria, and faint IgGκ monoclonal bands in serum and urine immunofixation. After negative meticulous investigation for secondary nephrotic syndrome causes, the patient underwent a kidney biopsy. Biopsy sample showed two glomeruli with mesangial expansion and thickened glomerular basement membrane (GBM) on light microscopy, a pattern masquerading as membranous nephropathy stage III-IV, while IgG and C3 were 1-2+ on GBM and mesangium in immunofluorescence. Thickened GBM with fibrils on electron microscopy were found, while DNAJB9 in immunohistochemistry was positive, confirming FGN. Once diagnosis of FGN was made, a combination of steroids with rituximab was initiated while the patient was receiving the standard anti-hypertensive therapy, simultaneously with a sodium-glucose cotransporter-2 (SGLT2) inhibitor. The 12-month follow-up showed approximately 85% decrease in proteinuria alongside stabilization of kidney function and blood pressure normalization. Hence, in this article, we aim to highlight that DNAJB9-associated FGN may mimic membranous glomerulopathy stage III-IV on light microscopy, especially when a small kidney sample with extensive involvement by fibrils of GBM is examined. Moreover, we underscore the fact that ultramicroscopic examination is of crucial importance in the differential diagnosis of glomerular deposition diseases and that DNAJB9 identification on immunohistochemistry consists of a revolutionary and robust biomarker in FGN diagnosis.
PubMed: 37899889
DOI: 10.7759/cureus.47862 -
Cureus Sep 2023IgA vasculitis and IgA nephropathy are characterized by IgA deposition in blood vessels and glomerular mesangium, respectively. The former is far more common in the...
IgA vasculitis and IgA nephropathy are characterized by IgA deposition in blood vessels and glomerular mesangium, respectively. The former is far more common in the pediatric population, while the latter presents more often in adulthood. A consensus regarding whether these two conditions are manifestations of the same disease that occurs on a spectrum has not yet been reached, and, to our knowledge, no clinical trials to address this question have been conducted. Here, we describe a 27-year-old patient who presented to the emergency department multiple times before being diagnosed with IgA vasculitis with no identifiable trigger and soon after developed IgA nephropathy. This case highlights the importance of ruling out these conditions, especially IgA vasculitis, in adults presenting with a petechial rash, but also the need for studies that investigate whether and how these conditions are related so that patients can be appropriately diagnosed and treated as efficiently as possible.
PubMed: 37868543
DOI: 10.7759/cureus.45639 -
Advanced Science (Weinheim,... Nov 2023The function of the glomerulus depends on the complex cell-cell/matrix interactions and replication of this in vitro would aid biological understanding in both health...
The function of the glomerulus depends on the complex cell-cell/matrix interactions and replication of this in vitro would aid biological understanding in both health and disease. Previous models do not fully reflect all cell types and interactions present as they overlook mesangial cells within their 3D matrix. Herein, the development of a microphysiological system that contains all resident renal cell types in an anatomically relevant manner is presented. A detailed transcriptomic analysis of the contributing biology of each cell type, as well as functionally appropriate albumin retention in the system, is demonstrated. The important role of mesangial cells is shown in promoting the health and maturity of the other cell types. Additionally, a comparison of the incremental advances that each individual cell type brings to the phenotype of the others demonstrates that glomerular cells in simple 2D culture exhibit a state more reflective of the dysfunction observed in human disease than previously recognized. This in vitro model will expand the capability to investigate glomerular biology in a more translatable manner by the inclusion of the important mesangial cell compartment.
Topics: Humans; Glomerular Mesangium; Microphysiological Systems; Kidney; Phenotype
PubMed: 37867234
DOI: 10.1002/advs.202303131