scholarly journals Infection-Related Glomerulonephritis

2021 ◽  
pp. 1-10
Author(s):  
Mazdak A. Khalighi ◽  
Anthony Chang
Keyword(s):  
Bacterial Infections ◽  
Alternative Pathway ◽  
Immunoglobulin A ◽  
Glomerular Injury ◽  
Diagnostic Challenge ◽  
Glomerular Diseases ◽  
Complement Component C3 ◽  
Duration Magnitude ◽  
Dense Deposits ◽  
Pathologic Findings

<b><i>Background:</i></b> There has been a long, storied relationship between various bacterial infections and glomerular injury, which is now encompassed under the term of infection-related glomerulonephritis (GN). The clinical and pathologic manifestations vary depending on the duration, magnitude, and underlying pathogen associated with the inciting infectious process. A brief and acute episode may lead to a self-limiting glomerular manifestation while a chronic or repetitive infection can result in persistent and irreversible injury. In this review, we will discuss the clinical and pathologic findings associated with the infection-related glomerulonephritides. <b><i>Summary:</i></b> An acute exudative GN with an influx of neutrophils is the most characteristic morphologic alteration associated with infection-related glomerular injury. The immunofluorescence staining pattern often reveals prominent complement component C3 deposition in both capillary walls and mesangial regions with or without accompanying immunoglobulin. Large subepithelial electron-dense deposits known as “humps” are the hallmark ultrastructural finding; however, these features can also be present in C3 glomerulopathies, which are often triggered by infections and may have similar underlying abnormalities in alternative pathway complement activation. In addition, other glomerular injuries can simultaneously be present along with infection-related GN, such as diabetic nephropathy, lupus nephritis, or immunoglobulin A nephropathy, constituting a true diagnostic challenge for the pathologist. <b><i>Key Messages:</i></b> Bacterial infection-related GN represents a spectrum of glomerular injury with variable clinical and pathologic presentations. The pathologic findings can show overlap with other glomerular diseases, and different forms of infection-related GN vary in terms of prognosis and treatment approach.

scholarly journals Characteristics of patients with coexisting DNAJB9-associated fibrillary glomerulonephritis and IgA nephropathy

2020 ◽  
Author(s):  
Samar M Said ◽  
Alejandro Best Rocha ◽  
Anthony M Valeri ◽  
Mohamad Sandid ◽  
Anhisekh Sinha Ray ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Immunoglobulin A ◽  
Renal Survival ◽  
Hepatitis C Infection ◽  
Clinicopathologic Characteristics ◽  
Fibrillary Glomerulonephritis ◽  
Kaplan Meier ◽  
Dense Deposits ◽  
End Stage

Abstract Background Coexistence of fibrillary glomerulonephritis (FGN) and immunoglobulin A (IgA) nephropathy (IgAN) in the same kidney biopsy (FGN–IgAN) is rare, and the clinicopathologic characteristics and outcome of this dual glomerulopathy are unknown. Methods In this study, 20 patients with FGN–IgAN were studied and their characteristics were compared with 40 FGN and 40 IgAN control patients. Results Concurrent IgAN was present in 1.8% of 847 consecutive FGN cases and was the second most common concurrent glomerulopathy after diabetic nephropathy. FGN–IgAN patients were overwhelmingly White (94%) and contrary to FGN patients were predominantly (60%) males. Compared with IgAN patients, FGN–IgAN patients were older, had higher proteinuria, a higher incidence of renal insufficiency, and a lower incidence of microhematuria and gross hematuria at diagnosis. Six (30%) patients had malignancy, autoimmune disease or hepatitis C infection, but none had a secondary cause of IgAN or clinical features of Henoch–Schonlein purpura. Histologically, all cases exhibited smudgy glomerular staining for immunoglobulin G and DnaJ homolog subfamily B member 9 (DNAJB9) with corresponding fibrillary deposits and granular mesangial staining for IgA with corresponding mesangial granular electron-dense deposits. On follow-up (median 27 months), 10 of 18 (56%) FGN–IgAN patients progressed to end-stage kidney disease (ESKD), including 5 who subsequently died. Serum creatinine at diagnosis was a poor predictor of renal survival. The proportion of patients reaching ESKD or died was higher in FGN–IgAN than in IgAN. The median Kaplan–Meier ESKD-free survival time was 44 months for FGN–IgAN, which was shorter than IgAN (unable to compute, P = 0.013) and FGN (107 months, P = 0.048). Conclusions FGN–IgAN is very rare, with clinical presentation and demographics closer to FGN than IgAN. Prognosis is guarded with a median renal survival of 3.6 years. The diagnosis of this dual glomerulopathy requires careful evaluation of immunofluorescence findings, and electron microscopy or DNAJB9 immunohistochemistry.

scholarly journals C5a and C5aR1 are key drivers of microvascular platelet aggregation in clinical entities spanning from aHUS to COVID-19

2021 ◽  
Author(s):  
Sistiana Aiello ◽  
Sara Gastoldi ◽  
Miriam Galbusera ◽  
Piero Luigi Ruggenenti ◽  
Valentina Portalupi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Thrombus Formation ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Uremic Syndrome

Unrestrained activation of the complement system till the terminal products, C5a and C5b-9, plays a pathogenetic role in acute and chronic inflammatory diseases. In endothelial cells, complement hyperactivation may translate into cell dysfunction, favoring thrombus formation. The aim of this study was to investigate the role of the C5a/C5aR1 axis as opposite to C5b-9 in inducing endothelial dysfunction and loss of anti-thrombogenic properties. In vitro and ex vivo assays with serum from patients with atypical hemolytic uremic syndrome (aHUS) -a prototype rare disease of complement-mediated microvascular thrombosis due to genetically determined alternative pathway dysregulation- and cultured microvascular endothelial cells, demonstrated that the C5a/C5aR1 axis is a key player of endothelial thromboresistance loss. C5a added to normal human serum, fully recapitulated the pro-thrombotic effects of aHUS serum. Mechanistic studies showed that C5a caused RalA-mediated exocytosis of vWF and P-selectin from Weibel-Palade bodies, which favored further vWF binding on the endothelium and platelet adhesion and aggregation. In patients with severe COVID-19 -who suffered from acute activation of complement triggered by SARS-CoV-2 infection- we found the same C5a-dependent pathogenic mechanisms. These results highlight C5a/C5aR1 as a common pro-thrombogenic effector spanning from genetic rare diseases to viral infections, and may have clinical implications. Selective C5a/C5aR1 blockade could have advantages over C5 inhibition, since the former preserves the formation of C5b-9 that is critical to control bacterial infections that often develop as comorbidities in severely ill patients. (Clinicaltrials.gov identifier NCT02464891)

scholarly journals Finding of pathological thrombomodulin gene variant in a patient with idiopathic nodular glomerulosclerosis and chronic thrombotic microangiopathy-like changes

2020 ◽  
Vol 8 ◽  
pp. 2050313X2094051
Author(s):  
Ramy Hanna ◽  
Jonathan E Zuckerman ◽  
Antoney Ferrey ◽  
Everado Arias Torres ◽  
Sam Tonthat ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Pathological Finding ◽  
Smoking History ◽  
Prior History ◽  
Diabetic Patients ◽  
Glomerular Injury ◽  
Nodular Glomerulosclerosis ◽  
Smoking Exposure ◽  
History Of ◽  
Idiopathic Nodular Glomerulosclerosis

Idiopathic nodular glomerulosclerosis is an unusual histopathological finding that has commonly been observed in male smokers with hypertension. It has remained an enigmatic condition and is best described as a diabetic pattern of glomerular injury seen in non-diabetic patients. It is also one of the few nicotine (smoking)-associated/smoking-associated patterns of renal injury. We present an even more unusual manifestation of this pathological finding in a 59-year-old Hispanic female who presented with chronic kidney disease approaching need for renal replacement therapy. The patient had idiopathic nodular glomerulosclerosis on kidney biopsy, despite no prior history of diabetes, nor smoking history, including no secondhand smoking exposure. The patient did have hypertension. The renal biopsy also showed evidence of chronic thrombotic-microangiopathic changes within arteries and arterioles. Genetic testing of the alternative pathway revealed an unusual and likely pathological variant of thrombomodulin supporting complement dysfunction as having a role in the presentation.

scholarly journals Comparative analysis of the tonsillar microbiota in IgA nephropathy and other glomerular diseases

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ji In Park ◽  
Tae-Yoon Kim ◽  
Bumjo Oh ◽  
Hyunjeong Cho ◽  
Ji Eun Kim ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Upper Airway ◽  
Illumina Miseq ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Principal Coordinates Analysis ◽  
Glomerular Diseases ◽  
Principal Coordinates ◽  
Airway Infections ◽  
Repeated Events

Abstract Immunoglobulin A nephropathy (IgAN) involves repeated events of gross haematuria with concurrent upper airway infections. The mucosal immune system, especially the tonsil, is considered the initial site of inflammation, although the role of the tonsillar microbiota has not been established in IgAN. In this study, we compared the tonsillar microbiota of patients with IgAN (n = 21) and other glomerular diseases (n = 36) as well as, healthy controls (n = 23) from three medical centres in Korea. The microbiota was analysed from tonsil swabs using the Illumina MiSeq system based on 16S rRNA gene. Tonsillar bacterial diversity was higher in IgAN than in other glomerular diseases, although it did not differ from that of healthy controls. Principal coordinates analysis revealed differences between the tonsillar microbiota of IgAN and both healthy and disease controls. The proportions of Rahnella, Ruminococcus_g2, and Clostridium_g21 were significantly higher in patients with IgAN than in healthy controls (corrected p < 0.05). The relative abundances of several taxa were correlated with the estimated glomerular filtration rate, blood urea nitrogen, haemoglobin, and serum albumin levels. Based on our findings, tonsillar microbiota may be associated with clinical features and possible immunologic pathogenesis of IgAN.

scholarly journals Evaluation of Tryptic Podocin Peptide in Urine Sediment Using LC-MS-MRM Method as a Potential Biomarker of Glomerular Injury in Dogs with Clinical Signs of Renal and Cardiac Disorders

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3088 ◽  
Author(s):  
Barbara Szczepankiewicz ◽  
Remigiusz Bąchor ◽  
Robert Pasławski ◽  
Natalia Siwińska ◽  
Urszula Pasławska ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Cardiorenal Syndrome ◽  
Specific Protein ◽  
Glomerular Injury ◽  
Model Peptide ◽  
Diagnostic Challenge ◽  
Urine Sediment ◽  
Heart Insufficiency ◽  
Potential Biomarker ◽  
Potential Applicability

The early asymptomatic stage of glomerular injury is a diagnostic challenge in the course of renal and extra-renal disease, e.g., heart insufficiency. It was found that podocin, a podocyte-specific protein present in the urine, may serve as a biomarker in the diagnosis of glomerular disease in humans and animals including glomerulonephritis, glomerulosclerosis, amyloidosis, or nephropathy. Therefore, there is a need of development of the sensitive and straightforward method of urinary podocin identification. In this work, we report our extended research under the glomerular injury investigation in dogs by application of clinical examination and LC-MS-MRM method in the identification of canine podocin in urine samples. The LC-MS-MRM method is based on the identification of podocin tryptic peptide with the 218H-AAEILAATPAAVQLR-OH232 sequence. The model peptide was characterized by the highest ionization efficiency of all the proposed model podocin tryptic peptides in a canine urine sediment according to the LC-MS/MS analysis. The obtained results revealed the presence of the model peptide in 40.9% of dogs with MMVD (active glomerular injury secondary to heart disease = cardiorenal syndrome-CRS) and 33.3% dogs with chronic kidney disease. The potential applicability of the developed methodology in the analysis of podocin in canine urine sediments was confirmed.

scholarly journals A Case of Essential Thrombocythemia and IgA Nephropathy with Literature Review of the Concurrence

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Shoja Rahimian ◽  
Timothy Johnson ◽  
Ronald Herb
Keyword(s):  
Renal Function ◽  
Literature Review ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Immunoglobulin A ◽  
Glomerular Disease ◽  
Common Finding ◽  
Glomerular Diseases ◽  
Pathological Review ◽  
History Of

Myeloproliferative neoplasms such as essential thrombocythemia (ET) have been associated with glomerular disease on rare instances. A case of ET associated with immunoglobulin A nephropathy (IgAN) is described in a 57-year-old man with a history of hypertension. Progressively worsening renal function was noted in the patient along with unexplained mild thrombocytosis. Pathological review of renal biopsy identified IgAN concurrently with newly diagnosed JAK2-mutated ET. The patient was started on aspirin therapy and closely monitored for his renal function. A literature review of the association of ET and renal disease revealed nine cases of ET associated with IgAN, focal segmental glomerulosclerosis, and fibrillary glomerulonephritis. Comparison of the pathological features of the renal biopsies within the cases noted mesangial proliferation as a common finding, which has been described to be potentiated by platelet-derived growth factor (PDGF). This commonality may represent a link between ET and glomerular disease which deserves further attention in future cases. Improved management of such cases depends on the recognition of the combined occurrence of ET and glomerular diseases and uncovering the shared pathogenesis between platelets and glomeruli.

scholarly journals Estrogen-related receptor-α mediates puromycin aminonucleoside-induced mesangial cell apoptosis and inflammatory injury

2019 ◽  
Vol 316 (5) ◽  
pp. F906-F913 ◽  
Author(s):  
Wei Gong ◽  
Jiayu Song ◽  
Xi Chen ◽  
Shuzhen Li ◽  
Jing Yu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Caspase 3 ◽  
Mesangial Cells ◽  
Orphan Nuclear Receptor ◽  
Glomerular Injury ◽  
Apoptotic Response ◽  
Puromycin Aminonucleoside ◽  
Glomerular Diseases ◽  
Estrogen Related Receptor

Glomerular diseases are the leading cause of chronic kidney disease, and mesangial cells (MCs) have been demonstrated to be involved in the pathogenesis. Puromycin aminonucleoside (PAN) is a nephrotoxic drug that induces glomerular injury with elusive mechanisms. The present study was undertaken to investigate the role of PAN in MC apoptosis, as well as the underlying mechanism. Here we found that PAN induced MC apoptosis accompanied by declined cell viability and enhanced inflammatory response. The apoptosis was further evidenced by increments of apoptosis regulator BAX (BAX) and caspase-3 expression. In line with the apoptotic response in MCs following PAN treatment, we also found a remarkable induction of estrogen-related receptor-α (ERRα), an orphan nuclear receptor, at both mRNA and protein levels. Interestingly, ERRα silencing by an siRNA approach resulted in an attenuation of the apoptosis and inflammatory response caused by PAN. More importantly, overexpression of ERRα in MCs significantly triggered MC apoptosis in line with increased BAX and caspase-3 expression. In PAN-treated MCs, ERRα overexpression further aggravated PAN-induced apoptosis. In agreement with the in vitro study, we also observed increased ERRα expression in line with enhanced apoptotic response in renal cortex from PAN-treated rats. These data suggest a detrimental effect of ERRα on PAN-induced MC apoptosis and inflammatory response, which could help us to better understand the pathogenic mechanism of MC injury in PAN nephropathy.

scholarly journals Complement component C3 fixes selectively to the major outer membrane protein (MOMP) of Legionella pneumophila and mediates phagocytosis of liposome-MOMP complexes by human monocytes.

1990 ◽  
Vol 172 (4) ◽  
pp. 1201-1210 ◽  
Author(s):  
C Bellinger-Kawahara ◽  
M A Horwitz
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Legionella Pneumophila ◽  
Alternative Pathway ◽  
Major Outer Membrane Protein ◽  
Complement Component ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Monocytes ◽  
Complement Component C3

Legionella pneumophila is a facultative intracellular bacterial pathogen that parasitizes human monocytes and alveolar macrophages. Previous studies from this laboratory have shown that monocyte complement receptors CR1 and CR3 and complement component C3 in serum mediate L. pneumophila phagocytosis. In this study, we have explored C3 fixation to L. pneumophila. We developed a whole-cell enzyme-linked immunosorbent assay (ELISA) to measure C3 fixation to the bacterial surface. By this assay, C3 fixes to L. pneumophila that are opsonized in fresh nonimmune serum, and C3 fixation takes place via the alternative pathway of complement activation. Immunoblot analysis of opsonized L. pneumophila indicated that C3 fixes selectively to specific acceptor molecules of L. pneumophila. Consistent with this, when nitrocellulose blots of whole L. pneumophila or bacterial components are incubated in fresh nonimmune serum, C3 fixes exclusively to the major outer membrane protein (MOMP) of L. pneumophila, a porin; C3 does not fix to L. pneumophila LPS on these blots. To further explore the role of MOMP in C3 fixation and phagocytosis, we reconstituted purified MOMP into liposomes. By the ELISA, MOMP-liposomes, but not plain liposomes lacking MOMP, avidly fix C3. Consistent with a dominant role for MOMP in C3 fixation, MOMP-liposomes form a C3 complex of the same apparent molecular weight as whole L. pneumophila in nonimmune serum. Opsonized radioiodinated MOMP-liposomes avidly adhere to monocytes, and adherence is dose dependent upon serum. By electron microscopy, opsonized MOMP-liposomes are efficiently phagocytized by human monocytes, and phagocytosis takes place by a conventional appearing form of phagocytosis. This study demonstrates that C3 fixes selectively to the MOMP of L. pneumophila, and that, in the presence of nonimmune serum, MOMP can mediate phagocytosis of liposomes and, potentially, phagocytosis of intact L. pneumophila by human monocytes.

scholarly journals MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yingjin Qiao ◽  
Anna-Lena Berg ◽  
Pei Wang ◽  
Yan Ge ◽  
Songxia Quan ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Protective Effect ◽  
Dominant Negative ◽  
Melanocortin Receptor ◽  
Hair Color ◽  
Glomerular Injury ◽  
Glomerular Diseases ◽  
Red Hair ◽  
Filtration Barrier

Abstract Melanocortin therapy by using adrenocorticotropic hormone (ACTH) or non-steroidogenic melanocortin peptides attenuates proteinuria and glomerular injury in experimental glomerular diseases and induces remission of nephrotic syndrome in patients with diverse glomerulopathies, even those resistant to steroids. The underlying mechanism remains elusive, but the role of melanocortin 1 receptor (MC1R) has been implicated and was examined here. Four patients with congenital red hair color and nephrotic syndrome caused by idiopathic membranous nephropathy or focal segmental glomerulosclerosis were confirmed by gene sequencing to bear dominant-negative MC1R mutations. Despite prior corticosteroid resistance, all patients responded to ACTH monotherapy and ultimately achieved clinical remission, inferring a steroidogenic-independent and MC1R-dispensable anti-proteinuric effect of melanocortin signaling. In confirmatory animal studies, the protective effect of [Nle4, D-Phe7]-α-melanocyte stimulating hormone (NDP-MSH), a potent non-steroidogenic pan-melanocortin receptor agonist, on the lipopolysaccharide elicited podocytopathy was completely preserved in MC1R-null mice, marked by reduced albuminuria and diminished histologic signs of podocyte injury. Moreover, in complementary in vitro studies, NDP-MSH attenuated the lipopolysaccharide elicited apoptosis, hypermotility and impairment of filtration barrier function equally in primary podocytes derived from MC1R-null and wild-type mice. Collectively, our findings suggest that melanocortin therapy confers a proteinuria reducing and podoprotective effect in proteinuric glomerulopathies via MC1R-independent mechanisms.

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