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Ultrastructural Pathology Jan 2023Infection-related glomerulonephritis is well recognized in patients with ongoing infections. It can be missed, however, if the infection is unusual or undetected. We...
Infection-related glomerulonephritis is well recognized in patients with ongoing infections. It can be missed, however, if the infection is unusual or undetected. We present three cases where the renal biopsy findings prompted the identification or treatment of systemic infections.Case 1: A 84-year-old male presented with acute kidney injury (AKI) and IgA vasculitis on skin biopsy. A renal biopsy showed active glomerulonephritis with abundant neutrophils and predominantly mesangial immune complex deposits containing IgA. The findings prompted an infectious workup which was positive for COVID-19, suggesting exacerbation of IgA nephropathy by recent COVID-19 infection. Case 2: A 31-year-old female status post kidney transplant for granulomatosis with polyangiitis (GPA) had recent pregnancy with preterm delivery, disseminated herpes simplex virus (HSV) infection with HSV hepatitis, on urine culture, and AKI. A renal biopsy showed proliferative glomerulonephritis with subendothelial and mesangial immune complex deposits containing IgG and C3. The findings were most consistent with infection-related immune complex glomerulonephritis, most likely HSV-related. Case 3: A 78-year-old female presented with AKI, proteinuria, hematuria, and positive p-ANCA. Clinically, ANCA vasculitis was suspected, and renal biopsy did show focal, segmental, necrotizing glomerulonephritis. However, immunofluorescence and electron microscopy showed IgM-rich deposits in the mesangium. The unusual presentation prompted an infectious workup including a Bartonella antibody panel which showed very high titers, suggesting Bartonella endocarditis.Infection-related glomerulonephritis has a wide variety of presentations histologically and clinically. The three cases we present here emphasize the importance of recognizing these entities to help guide treatment and improve patient care.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Acute Kidney Injury; Antigen-Antibody Complex; Biopsy; COVID-19; Escherichia coli; Glomerulonephritis; Glomerulonephritis, IGA
PubMed: 36602913
DOI: 10.1080/01913123.2022.2164099 -
Frontiers in Immunology 2022Lupus nephritis (LN) is a severe renal disease caused by the massive deposition of the immune complexes (ICs) in renal tissue, acting as one of the significant organ... (Review)
Review
Lupus nephritis (LN) is a severe renal disease caused by the massive deposition of the immune complexes (ICs) in renal tissue, acting as one of the significant organ manifestations of systemic lupus erythematosus (SLE) and a substantial cause of death in clinical patients. As mesangium is one of the primary sites for IC deposition, mesangial cells (MCs) constantly undergo severe damage, resulting in excessive proliferation and increased extracellular matrix (ECM) production. In addition to playing a role in organizational structure, MCs are closely related to immunomodulation by phagocytosis, antigen-presenting function, and inflammatory effects, aberrantly participating in the tissue-resident immune responses and leading to immune-mediated renal lesions. Notably, such renal-resident immune responses drive a second wave of MC damage, accelerating the development of LN. This review summarized the damage mechanisms and the immune regulation of MCs in LN, facilitating the current drug research for exploring clinical treatment strategies.
Topics: Humans; Lupus Nephritis; Mesangial Cells; Lupus Erythematosus, Systemic; Kidney; Glomerular Mesangium
PubMed: 36591251
DOI: 10.3389/fimmu.2022.1063497 -
CEN Case Reports Aug 2023Granulocyte colony-stimulating factor (G-CSF) is commonly used to stimulate bone marrow production. G-CSF is usually safe but sometimes causes serious adverse effects...
Granulocyte colony-stimulating factor (G-CSF) is commonly used to stimulate bone marrow production. G-CSF is usually safe but sometimes causes serious adverse effects and, in rare cases, exacerbates glomerulonephritis. We report a case of immunoglobulin A (IgA) nephropathy that was aggravated by G-CSF. A 56-year-old Japanese man with no relevant medical history was admitted to our hospital as a donor of peripheral blood stem cells (PBSCs) for transplantation. To mobilize PBSCs, he received subcutaneous G-CSF (lenograstim), 500 μg for 4 days. Three days after the first dose of lenograstim, gross hematuria appeared, and after administration on the fourth day, renal dysfunction and nephrotic-range proteinuria were observed. Renal biopsy and light microscopic study revealed mild mesangial proliferation with expansion in association with the presence of cellular segmental crescents. Immunofluorescence study revealed diffuse, granular staining in the mesangium for IgA, complement component 3 (C3), and lambda light chains. We diagnosed highly active IgA nephropathy and initiated treatment with prednisolone and azathioprine. Three months later, renal function returned to normal. Screening for hidden chronic glomerulonephritis should be performed when G-CSF is administered, as in PBSC donors. Immunosuppressant therapy, such as prednisolone or azathioprine, is considered for exacerbations of highly active glomerulonephritis.
Topics: Male; Humans; Middle Aged; Glomerulonephritis, IGA; Azathioprine; Lenograstim; Glomerulonephritis; Granulocyte Colony-Stimulating Factor; Prednisolone; Immunoglobulin A
PubMed: 36508113
DOI: 10.1007/s13730-022-00764-5 -
Journal of Nephrology Apr 2023IgA nephropathy (IgAN) is one of the most common glomerulonephritides. The disease is characterized by haematuria, proteinuria, deposition of galactose-deficient IgA1... (Review)
Review
IgA nephropathy (IgAN) is one of the most common glomerulonephritides. The disease is characterized by haematuria, proteinuria, deposition of galactose-deficient IgA1 in the glomerular mesangium and mesangial hypercellularity, further leading to extracellular matrix expansion. Kidney biopsy is the gold standard for IgAN diagnosis. Due to the invasiveness of renal biopsy, there is an unmet need for noninvasive biomarkers to diagnose and estimate the severity of IgAN. Understanding the role of RNA molecules as genetic markers to target diseases may allow developing therapeutic and diagnostic markers. In this review we have focused on intrarenal, extrarenal and extracellular noncoding RNAs involved in the progression of IgAN. This narrative review summarizes the pathogenesis of IgAN along with the correlation of noncoding RNA molecules such as microRNAs, small interfering RNAs, circular RNAs and long non-coding RNAs that play an important role in regulating gene expression, and that represent another type of regulation affecting the expression of specific glycosyltranferases, a key element contributing to the development of IgAN.
Topics: Humans; Glomerulonephritis, IGA; Immunoglobulin A; Glomerular Mesangium; RNA, Untranslated
PubMed: 36495425
DOI: 10.1007/s40620-022-01498-4 -
Frontiers in Cell and Developmental... 2022IgA Nephropathy (IgAN) is the commonest primary glomerular disease around the world and represents a significant cause of end-stage renal disease. IgAN is characterized... (Review)
Review
IgA Nephropathy (IgAN) is the commonest primary glomerular disease around the world and represents a significant cause of end-stage renal disease. IgAN is characterized by mesangial deposition of IgA-immune complexes and mesangial expansion. The pathophysiological process includes an abnormally glycosylated IgA1, which is an antigenic target. Autoantibodies specifically recognize galactose-deficient IgA1 forming immune complexes that are amplified in size by the soluble IgA Fc receptor CD89 leading to deposition in the mesangium through interaction with non-classical IgA receptors. The local production of cytokines promotes local inflammation and complement system activation, besides the stimulation of mesangial proliferation. The spectrum of clinical manifestations is quite variable from asymptomatic microscopic hematuria to rapidly progressive glomerulonephritis. Despite all the advances, the pathophysiology of the disease is still not fully elucidated. The mucosal immune system is quoted to be a factor in triggering IgAN and a "gut-kidney axis" is proposed in its development. Furthermore, many recent studies have demonstrated that food intake interferes directly with disease prognosis. In this review, we will discuss how mucosal immunity, microbiota, and nutritional status could be interfering directly with the activation of intrinsic pathways of the mesangial cells, directly resulting in changes in their function, inflammation and development of IgAN.
PubMed: 36467425
DOI: 10.3389/fcell.2022.993716 -
American Journal of Physiology. Renal... Jan 2023Although mesangial cell-glomerular basement membrane (GBM) connections play a key role in maintaining the glomerular capillary loop structure, information remains...
Although mesangial cell-glomerular basement membrane (GBM) connections play a key role in maintaining the glomerular capillary loop structure, information remains limited about how these connections are formed during glomerulogenesis. We have previously shown that weakened podocyte-GBM interactions owing to tensin 2 () deficiency lead to abnormal GBM maturation during postnatal glomerulogenesis. Here, we investigated whether abnormal GBM maturation affected mesangial cell-GBM connections and mesangial cell differentiation. Histological analysis of the outer cortical glomeruli in -deficient mice revealed that GBM materials overproduced by stressed immature podocytes accumulated in the mesangium and interrupted the formation of mesangial cell-GBM connections, resulting in fewer capillary loops compared with that of normal glomeruli. In addition, expression of α-smooth muscle actin, an immature mesangial cell marker, persisted in mesangial cells of -deficient outer cortical glomeruli even after glomerulogenesis was completed, resulting in mesangial expansion. Furthermore, analysis of mouse primary mesangial cells revealed that mesangial cell differentiation depended on the type of extracellular matrix components to which the cells adhered, suggesting the participation of mesangial cell-GBM connections in mesangial cell differentiation. These findings suggest that abnormal GBM maturation affects mesangial cell differentiation by impairing mesangial cell-GBM connections. Mesangial cell-glomerular basement membrane (GBM) connections play an important role in maintaining the structural integrity of the glomerular tuft. However, information remains scarce about how GBM maturation affects the formation of these connections during glomerular development. Here, we show that abnormal GBM maturation due to tensin 2 deficiency affects mesangial cell differentiation by impairing mesangial cell-GBM connections during postnatal glomerulogenesis.
Topics: Mice; Animals; Glomerular Basement Membrane; Basement Membrane; Tensins; Glomerular Mesangium; Podocytes; Cell Differentiation
PubMed: 36417276
DOI: 10.1152/ajprenal.00192.2022 -
Heliyon Nov 2022Calcium-calmodulin-dependent protein kinase II (CaMKII) is upregulated in diabetes mellitus (DM), leading to the overproduction of collagen in the myocardium. We...
Calcium-calmodulin-dependent protein kinase II (CaMKII) is upregulated in diabetes mellitus (DM), leading to the overproduction of collagen in the myocardium. We hypothesized that CaMKII plays a role in the development of diabetic nephropathy (DN). Streptozotocin (STZ) injection into FVB wild-type mice led to mild mesangial matrix expansion, reproducing an essential feature of early human DN. Mesangial matrix measurements were performed on trichrome-stained paraffin sections using a trainable segmentation method based on WEKA (Waikato Environment for Knowledge Analysis) Image J-Fiji plugin (TWS plugin), and the electron micrographs of the whole glomeruli stitched from individual 4800x partial glomerular images. Both methods demonstrated that the statistically significant mesangial matrix expansion seen in the diabetic mice was prevented by chronic pretreatment with KN-93, a small molecule CaMKII inhibitor. This study indicates a role for CaMKII in the development of mesangial alterations in diabetes and suggests a possible new therapeutic target.
PubMed: 36411910
DOI: 10.1016/j.heliyon.2022.e11653 -
Journal of Nephrology Apr 2023Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease caused by pathogenic mutations in the APOE gene. Collagen type III glomerulopathy (CG) is a... (Review)
Review
Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease caused by pathogenic mutations in the APOE gene. Collagen type III glomerulopathy (CG) is a sporadic condition in adults characterized by abnormal accumulation of type III collagen in the subendothelial space and mesangium of the glomerulus. We report the first case of both LPG and CG in a 21-year-old male. A search of the literature found no confirmed reports of these two concomitant nephropathies. The patient presented with hypertension, proteinuria, hematuria and hyperlipidemia. Renal pathology showed lipid vacuoles in the enlarged glomerular capillary loops and type III collagen in the segmental mesangial area and on the inner side of the glomerular basement membrane by electron microscopy. Whole-exome sequencing revealed a heterozygous mutation (c.127C>T; p. Arg43Cys) in exon 3 of the APOE gene, known as the APOE-Kyoto of LPG. In addition, two heterozygous COL4A4 mutations (c.4715C>T in exon 47 and c.5065 T>C in exon 48) were observed, the first one was suspected pathogenic and the other one was uncertain significant. There is no special treatment for these diseases. The patient was treated with lipid-lowering agents, renin-angiotensin-aldosterone system inhibition and tripterygium glycosides. The patient received double-filtration plasmapheresis and immunoadsorption therapy when renal function deteriorated dramatically. Immunoadsorption was beneficial for this patient.
Topics: Male; Adult; Humans; Young Adult; Collagen Type III; Kidney Diseases; Kidney; Kidney Glomerulus
PubMed: 36370330
DOI: 10.1007/s40620-022-01491-x -
Molecules (Basel, Switzerland) Oct 2022Diabetes mellitus (DM) is a group of metabolic disorders, the characteristics of which include chronic hyperglycemia owing to defects in insulin function, insulin... (Review)
Review
Diabetes mellitus (DM) is a group of metabolic disorders, the characteristics of which include chronic hyperglycemia owing to defects in insulin function, insulin secretion, or both. Inflammation plays a crucial role in DM pathogenesis and innate immunity in the development of microvascular complications of diabetes. In addition, hyperglycemia and DM mediate a proinflammatory microenvironment that can result in various microvascular complications, including diabetic nephropathy (DNP), diabetic neuropathy (DN), and diabetic retinopathy (DR). DNP is a major cause of end-stage renal disease. DNP can lead to albuminuria, decreased filtration, mesangium expansion, thickening of the basement membrane, and eventually renal failure. Furthermore, inflammatory cells can accumulate in the interstitium and glomeruli to deteriorate DNP. DN is another most prevalent microvascular complication of DM and the main cause of high mortality, disability, and a poor quality of life. DNs have a wide range of clinical manifestations because of the types of fiber dysfunctions and complex structures of the peripheral nervous system. DR is also a microvascular and multifactorial disease, as well as a major cause of visual impairment globally. Pathogenesis of DR is yet to be fully revealed, however, numerous studies have already confirmed the role of inflammation in the onset and advancement of DR. Despite evidence, and better knowledge regarding the pathogenesis of these microvascular complications of diabetes, there is still a deficiency of effective therapies. Bioactive compounds are mainly derived from plants, and these molecules have promising therapeutic potential. In this review, evidence and molecular mechanisms regarding the role of inflammation in various microvascular complications of diabetes including DNP, DN, and DR, have been summarized. The therapeutic potential of several bioactive compounds derived from plants in the treatment of these microvascular complications of diabetes has also been discussed.
Topics: Humans; Diabetes Mellitus, Type 2; Quality of Life; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Inflammation; Anti-Inflammatory Agents; Hyperglycemia
PubMed: 36364178
DOI: 10.3390/molecules27217352 -
Kidney International Feb 2023IgA nephropathy (IgAN) is the most common glomerulonephritis, characterized by the presence of predominant IgA deposits in the mesangium. Deposition of pathogenic IgA in...
IgA nephropathy (IgAN) is the most common glomerulonephritis, characterized by the presence of predominant IgA deposits in the mesangium. Deposition of pathogenic IgA in kidney tissue is a fundamental initiating process that has not been fully studied. Here, we employed optical imaging to directly visualize kidney deposition of IgA with optimized spatial and temporal resolution in BALB/c nude mice. Real-time fluorescence imaging revealed that IgA isolated from patients with IgAN preferentially accumulated in the kidneys, compared with IgA purified from healthy individuals. There was no difference in the distribution of either IgA preparation by the liver. Photoacoustic computed tomography dynamically demonstrated and quantified the enhanced retention of pathological IgA in the kidney cortex. Photoacoustic microscopy tracked IgA deposition in the glomeruli with a resolution down to three microns in a mouse model. Notably, longitudinal fluorescent imaging revealed that galactose-deficient IgA (Gd-IgA), which was elevated in the circulation of patients with IgAN, persisted in the kidney for longer than two weeks, and stable deposition of Gd-IgA induced kidney impairment, including albuminuria and mesangial proliferation. Thus, our study highlights that the aberrant kidney depositional kinetics of Gd-IgA is involved in the pathogenesis of IgAN. Hence, cross-scale optical imaging has potential applications in assessing immune-mediated kidney diseases and uncovering underlying mechanisms of disease.
Topics: Animals; Mice; Glomerulonephritis, IGA; Galactose; Mice, Nude; Immunoglobulin A; Optical Imaging
PubMed: 36341730
DOI: 10.1016/j.kint.2022.08.038