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Anti-glomerular basement membrane (GBM) disease is a rare autoimmune condition characterized by the presence of positive anti-GBM autoantibodies, linear deposition of immunoglobulin G (IgG) along the GBM and severe kidney injury. In a limited number of cases, the association of anti-GBM disease with other glomerulonephritis has been reported. Herein, we present the case of a 66-year-old female patient with progressive worsen kidney function and decreased urine output. A renal biopsy revealed crescent glomerulonephritis with lineal IgG deposition along the GBM and mesangial IgA deposition, which supported the diagnosis of concurrent anti-GBM disease and IgA nephropathy (IgAN). In an extensive literature review, we identified a total of thirty-nine patients were reported anti-GBM disease combined with IgAN. The clinical characteristics of these patients demonstrate that the anti-GBM disease combined with IgAN tends to be milder with a more indolent course and a better prognosis than the classic anti-GBM disease, and its potential pathogenesis deserves to be further explored. [ABSTRACT FROM AUTHOR]

Anti-glomerular basement membrane (GBM) disease is a rare autoimmune condition characterized by the presence of positive anti-GBM autoantibodies, linear deposition of immunoglobulin G (IgG) along the GBM and severe kidney injury. In a limited number of cases, the association of anti-GBM disease with other glomerulonephritis has been reported. Herein, we present the case of a 66-year-old female patient with progressive worsen kidney function and decreased urine output. A renal biopsy revealed crescent glomerulonephritis with lineal IgG deposition along the GBM and mesangial IgA deposition, which supported the diagnosis of concurrent anti-GBM disease and IgA nephropathy (IgAN). In an extensive literature review, we identified a total of thirty-nine patients were reported anti-GBM disease combined with IgAN. The clinical characteristics of these patients demonstrate that the anti-GBM disease combined with IgAN tends to be milder with a more indolent course and a better prognosis than the classic anti-GBM disease, and its potential pathogenesis deserves to be further explored.

Background: Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune disorder that primarily affects the kidneys and, less commonly, the lungs. The rapid progression of glomerulonephritis is a hallmark of this disease, leading to significant renal damage if not treated promptly. Early diagnosis and treatment are critical to preventing irreversible kidney injury. Case Description: We report a case of a 45-year-old male who presented with 15 days of hematuria and 2 days of breathlessness. The patient had no history of hypertension or diabetes. Clinical examination revealed pallor, high blood pressure, and fine crepitations in bilateral lower lung fields. Laboratory investigations showed elevated serum creatinine, reduced hemoglobin, and significant proteinuria. Anti-GBM antibodies were markedly elevated, and a kidney biopsy confirmed the diagnosis of crescentic glomerulonephritis with a necrotizing pattern. The patient was treated with plasmapheresis, steroids, and cyclophosphamide, along with maintenance hemodialysis. Despite the aggressive nature of the disease, early intervention helped stabilize his renal function. Conclusion: This case highlights the importance of rapid diagnosis and prompt initiation of aggressive treatment in patients with anti-GBM disease presenting as rapidly progressive glomerulonephritis. Early intervention is key to preserving renal function and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Nephrotic range proteinuria in the setting of dual-positive anti-glomerular basement membrane (AGBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) is rare. Furthermore, using rituximab as a primary immunosuppressant along with steroids and plasmapheresis has not been widely studied. We present a case of dual AGBM and ANCA with nephrotic range proteinuria in a young female, where rituximab was used as a primary immunosuppressant with partial recovery. [ABSTRACT FROM AUTHOR]

Introduction. Pauci-immune crescentic glomerulonephritis (GN) is the most common cause of rapidly progressive GN in adults. The aim of this study was to determine the outcome of patients with pauci-immune crescentic GN and risk factors of the development of end-stage kidney disease (ESKD) in these patients. Methods. This case series study was carried on 120 patients with pauci-immune crescentic GN biopsied in our center betwen 1998 and 2016. Inclusion criteria were age > 16 years, at least one crescentic glomerulus, maximally 1+ deposition of immunoglobulins and complement components at fluorescent microscopy, and at least 6 months follow-up. The main outcomes were ESKD and death. Results. The study population included 120 patients with pauciimmune crescentic GN (mean age was 47 ± 17 years and 49.1% male). There was no significant difference in outcome between patients with diffuse or focal crescentic GN. Seventy-two patients (60%) developed ESKD and 31 patients (25.8%) died. The need for dialysis at admission, lower baseline hemoglobin and GFR and GFR at four months and high percentage of glomerulosclerosis and interstitial fibrosis had a significant relationship with low kidney survival (P < .05). The rate of ESKD was higher in patients who did not receive cyclophosphamide therapy, due to focal crescentic GN or high chronicity, compared to patients who received it (70.7 vs. 28.5%, P < .001). Conclusion. In our study, a high percentage of patients with pauciimmune crescentic GN developed ESKD. Low first GFR and high chronicity in biopsy were associated with lower kidney survival. Failure to administer cyclophosphamide in seemingly limited or advanced cases, together with late referral may have led to poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Relapses or new-onset IgA nephropathy (IgAN) have been documented in patients after vaccination against SARS-CoV-2; however, only one adult patient has been reported in whom pre-existing IgAN worsened during coronavirus disease 2019 (COVID-19). Case: We present the first pediatric case with biopsy-proven IgAN and genetically confirmed Alport syndrome, who developed end-stage kidney disease after an exacerbation of IgAN associated with COVID-19. The patient's basal serum creatinine was 0.7-0.9 mg/dL before infection. He had not been vaccinated against COVID-19. He was admitted to the hospital with edema, hypertension, an elevated serum creatinine of 4.7 mg/dL, and massive proteinuria. Three months before admission, he had been admitted to another hospital with COVID -19 and an elevated serum creatinine (1.9 mg/dL), but no biopsy had been performed at that time. The kidney biopsy revealed IgAN with 50% fibrocellular crescents with sclerosed glomeruli, tubular atrophy, and interstitial fibrosis. His serum creatinine did not decrease even after five administrations of pulse steroids, and hemodialysis was initiated. Conclusion: In conclusion, COVID -19 may pose a high risk for exacerbation of pre-existing glomerular disease. It is therefore necessary to closely monitor the kidney function of patients with underlying glomerulonephritis during and after COVID-19 and consider an early biopsy if serum creatinine does not return to baseline levels. In addition, this case report highlights the clinical importance of the co-occurence of IgAN and Alport syndrome. [ABSTRACT FROM AUTHOR]

Abstract Background Crescentic glomerulonephritis with syphilis infection is rare, and the mechanism underlying the formation of glomerular capillary wall damage-induced crescent has not been elucidated. Case presentation A 62-year-old Japanese male showed edema, eruption, and rapid deterioration of the renal function after an acute syphilis infection. A renal biopsy showed crescentic glomerulonephritis with C3 deposition in the glomerular capillary wall, and immunostaining for anti-Treponema pallidum antibody was weakly positive in some interstitium and one glomerulus. Electron microscopy revealed the presence of string-shaped structures in the glomerular capillary walls. After treatment with penicillin followed by prednisolone, the renal function and urinary abnormalities, including Treponema pallidum protein, disappeared. Conclusions Crescentic glomerulonephritis associated with syphilis showed a string-shaped deposition in the glomerular capillary and urinary Treponema pallidum protein excretion, and was effectively treated with penicillin and prednisolone.

Background: A clinical syndrome manifested by features of glomerular disease in the urinalysis and by progressive loss of kidney function over a comparatively short period is called rapidly progressive glomerulonephritis (RPGN). RPGN is also called Crescentic glomerulonephritis(CrGN). Crescentic glomerulonephritis (CrGN) is defined as active crescents involving >50% of the total glomeruli. We have done this study to find out the major cause of RPGN in Nepal. Materials and Methods: This is a one-year prospective study done in the department of renal pathology at Pratham Pathology Private Limited over one year (1st November 2021-30th October 2022). Data of all patients were evaluated for the histopathological diagnosis. All cases of RPGN were included in the study. Evaluation of serological and demographic data, along with the number of active crescents was done. Results: A total of 182 cases of kidney biopsies were received for evaluation during one year (1st November 2021-30th October 2022) at Pratham Pathology Laboratory Private Limited, Kathmandu, Nepal. Out of it 18 cases (9.89%) were those of Crescentic glomerulonephritis. The most common cause of Crescentic glomerulonephritis encountered was Lupus Nephritis (7/18 cases). All cases of lupus presented with Crescentic glomerulonephritis were at stage IV. % of glomeruli with crescents ranged from 50-81.25% with mean involved glomeruli 60.61%. Conclusions: A total of 9.89% of the renal biopsies were presented with CrGN. Lupus nephritis was the most common cause of CrGN in Nepal.

Background: Crescentic glomerulonephritis with syphilis infection is rare, and the mechanism underlying the formation of glomerular capillary wall damage-induced crescent has not been elucidated. Case presentation: A 62-year-old Japanese male showed edema, eruption, and rapid deterioration of the renal function after an acute syphilis infection. A renal biopsy showed crescentic glomerulonephritis with C3 deposition in the glomerular capillary wall, and immunostaining for anti-Treponema pallidum antibody was weakly positive in some interstitium and one glomerulus. Electron microscopy revealed the presence of string-shaped structures in the glomerular capillary walls. After treatment with penicillin followed by prednisolone, the renal function and urinary abnormalities, including Treponema pallidum protein, disappeared. Conclusions: Crescentic glomerulonephritis associated with syphilis showed a string-shaped deposition in the glomerular capillary and urinary Treponema pallidum protein excretion, and was effectively treated with penicillin and prednisolone. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive analysis of infection-related glomerulonephritis (IRGN) in adults. The study analyzed 115 participants and found that the majority were male with an average age of 46. Skin infections were the most common source of infection, and Streptococcus pyogenes was the most prevalent infectious agent. Clinical symptoms included edema, oliguria, and hematuria. Histological evaluation revealed diffuse proliferative glomerulonephritis (DPGN) as the most common pattern. The study also highlighted the importance of kidney biopsy and electron microscopy in diagnosing and prognosticating IRGN in adults. [Extracted from the article]

Objective: To study the clinico-etiological spectrum and outcomes of children with rapidly progressive glomerulonephritis (RPGN). Methods: This retrospective cohort study evaluated patients <18 years with RPGN, over an 8-year period (2014–2022), for etiology and kidney outcomes. Results: Among 68 RPGN cases [median age 10 (7,12) years], 23 (33.8%) had lupus nephritis, 21 (30.9%) C3 glomerulopathy, and 15 (22.1%) infection-related glomerulonephritis (IRGN). At presen-tation, 18 (26.4%) patients had pulmonary edema, 20 (29.4%) had hypertensive emergency and 22 (32.4%) required dialysis. Median (IQR) follow-up duration was 24.5 (12,48) months. The median (IQR) admission eGFR was 19 (10.93, 38.60) mL/min/1.73 m2, which increased to 126 (102.7,142) mL/min/1.73m2 at the last follow-up. At the last follow-up, 39 (57.3%) and 13 (19.1%) patients attained complete and partial renal recovery, respectively; while 16 (23.5%) progressed to CKD stage 2 and beyond. The prevalence of end stage kidney disease (ESKD) was 7.3% at 1-year and 7.7% at the last follow-up. Factors predicting kidney survival were duration of symptoms prior to presentation ≥7 days, crescents ≥37.5%, and presence of fibrous crescents/segmental sclerosis. Conclusion: Lupus nephritis, was the commonest etiology of RPGN in children. Renal outcomes were determined by pre-admission symptoms, and percentage and stage of crescents. [ABSTRACT FROM AUTHOR]

Abstract Background Extra-capillary hypercellularity is a common finding in crescentic glomerulonephritis (GN) and focal segmental glomerulosclerosis (FSGS). In diabetic nephropathy (DN), extra-capillary hypercellularity is often observed as a finding of complications such as IgA nephropathy or microscopic polyangiitis superimposed on DN. However, in rare cases, epithelial cell proliferation may accompany DN. We experienced a case of nodular diabetic glomerulosclerosis with marked extra-capillary hypercellularity and revealed the origin of this atypical lesion using immunostainings. Case presentation A man in his 50 s was admitted to the hospital with nephrotic syndrome, and a renal biopsy was performed. Diffuse nodular lesions and extra-capillary hypercellularity were observed, but the results of serological examination or immunofluorescent assays did not implicate any other crescentic GN. Immunostaining for claudin-1 and nephrin was performed to identify the origin of the extra-capillary lesions. Given the clinical course and pathological findings, a diagnosis of DN-associated extra-capillary cell proliferation was made. Conclusions Extra-capillary hypercellularity, which resembles FSGS or crescentic GN, is a rare finding in DN and should therefore be treated with caution. In such cases, co-staining for claudin-1 and nephrin may facilitate the diagnosis of DN.

Nephrotic range proteinuria in the setting of dual-positive anti-glomerular basement membrane (AGBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) is rare. Furthermore, using rituximab as a primary immunosuppressant along with steroids and plasmapheresis has not been widely studied. We present a case of dual AGBM and ANCA with nephrotic range proteinuria in a young female, where rituximab was used as a primary immunosuppressant with partial recovery.

Background: Extra-capillary hypercellularity is a common finding in crescentic glomerulonephritis (GN) and focal segmental glomerulosclerosis (FSGS). In diabetic nephropathy (DN), extra-capillary hypercellularity is often observed as a finding of complications such as IgA nephropathy or microscopic polyangiitis superimposed on DN. However, in rare cases, epithelial cell proliferation may accompany DN. We experienced a case of nodular diabetic glomerulosclerosis with marked extra-capillary hypercellularity and revealed the origin of this atypical lesion using immunostainings. Case presentation: A man in his 50 s was admitted to the hospital with nephrotic syndrome, and a renal biopsy was performed. Diffuse nodular lesions and extra-capillary hypercellularity were observed, but the results of serological examination or immunofluorescent assays did not implicate any other crescentic GN. Immunostaining for claudin-1 and nephrin was performed to identify the origin of the extra-capillary lesions. Given the clinical course and pathological findings, a diagnosis of DN-associated extra-capillary cell proliferation was made. Conclusions: Extra-capillary hypercellularity, which resembles FSGS or crescentic GN, is a rare finding in DN and should therefore be treated with caution. In such cases, co-staining for claudin-1 and nephrin may facilitate the diagnosis of DN. [ABSTRACT FROM AUTHOR]

BackgroundCrescentic glomerulonephritis (CrGN) is a relatively rare but severe condition in childhood with the clinical feature of rapidly progressive glomerulonephritis (RPGN). The aim of this study is to investigate the clinicopathological features and prognosis of CrGN in children.MethodsWe retrospectively analyzed the clinical and laboratory data, renal pathological results, treatment, and outcome of 147 CrGN in two Chinese pediatric nephrology centers.ResultsAmong the 147 children, there were 22 cases of type I (15.0%), 69 cases of type II (46.9%), and 56 cases of type III (38.1%). The mean percentages of crescents in CrGN I, II, and III were 85.3%, 68.7%, and 73.6%, respectively. The children with type I CrGN presented with more severe clinical manifestations and pathological lesions. The 3-month cumulative renal survival rates of types I, II, and III CrGN were 66.3%, 93.6%, and 75.6%, respectively. The 1-year cumulative renal survival rates of types I, II, and III CrGN were 56.9%, 85.3%, and 73.1%, respectively, and the 5-year cumulative renal survival rates of types I, II, and III CrGN were 33.8%, 73.5%, and 47.1%, respectively. The Kappa Consistency Test between the 3-month and 1-year total renal survival (82.1% vs. 74.7%) of the children was 0.683 (P

A 48-year-old male patient presented with dialysis dependent renal failure with biopsy showing crescentic glomerulonephritis and Positron emission tomography–computed tomography (PET-CT scan) revealing features of pericardial, pulmonary tuberculosis with positive urinary GeneXpert test for tuberculosis bacilli. Clinicians should keep in mind the atypical presentations of tuberculosis while managing rapidly progressive renal failure especially in tropical countries with high prevalence of tuberculosis.

The risk of progression to end-stage kidney disease (ESKD) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and glomerulonephritis (AAV-GN) remains high. At 5 years of follow-up, 14–25% of patients will evolve to ESKD, suggesting that kidney survival is not optimized in patients with AAV. The addition of plasma exchange (PLEX) to standard remission induction has been the standard of care, particularly in patients with severe renal disease. However, there is still some debate regarding which patients benefit from PLEX. A recently published meta-analysis concluded that the addition of PLEX to standard remission induction in AAV probably reduced the risk of ESKD at 12 months and that PLEX was associated with an estimated absolute risk reduction for ESKD at 12 months of 16.0% for those at high risk or with a serum creatinine >5.7 mg/dl (high certainty of important effects). These findings were interpreted as supportive of offering PLEX to patients with AAV and a high risk of progression to ESKD or requiring dialysis and are making their way into societies recommendations. However, the results of the analysis can be debated. We provide an overview on the meta-analysis as an attempt to guide the audience through how the data were generated, to comment on our interpretation of the results and to explain why we feel uncertainty remains. In addition, we would like to provide insights in two questions that we believe are very relevant to consider when addressing the role of PLEX: the role of kidney biopsy findings in the decision making of whom might benefit from PLEX and the impact of novel treatments (i.e. complement factor 5a inhibitors) in avoiding progression to ESKD at 12 months. The treatment of patients with severe AAV-GN is complex and further studies that include only patients at high risk of progression to ESKD are needed. [ABSTRACT FROM AUTHOR]

Glomerular parietal epithelial cells (PECs) have been increasingly recognized to have crucial functions. Lineage tracking in animal models showed the expression of a podocyte phenotype by PECs during normal glomerular growth and after acute podocyte injury, suggesting a reparative role of PECs. Conversely, activated PECs are speculated to be pathogenic and comprise extracapillary proliferation in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CrescGN). The reparative and pathogenic roles of PECs seem to represent two sides of PEC behavior directed by the local milieu and mediators. Recent studies suggest microRNA-193a (miR193a) is involved in the pathogenesis of FSGS and CrescGN. In a mouse model of primary FSGS, the induction of miR193a caused the downregulation of Wilms' tumor protein, leading to the dedifferentiation of podocytes. On the other hand, the inhibition of miR193a resulted in reduced crescent lesions in a mouse model of CrescGN. Interestingly, in vitro studies report that the downregulation of miR193a induces trans-differentiation of PECs into a podocyte phenotype. This narrative review highlights the critical role of PEC behavior in health and during disease and its modulation by miR193a. [ABSTRACT FROM AUTHOR]

The discovery of tissue-resident memory T cells (TRM cells) reinterpreted the potential of human tissue-specific immunity. Following T cell receptor (TCR) activation and clonal expansion, effector T cells migrate to peripheral tissues where they remain long-term and differentiate to TRM cells after antigen clearance. This allows for prompt immunological responses upon antigen re-encounter. In addition to their protective properties in acute infections, recent studies have revealed that TRM cells might lead to aggravation of autoimmune diseases, such as lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN). These diseases present as proliferative and crescentic glomerulonephritis (cGN), which is a life-threatening condition leading to end-stage renal disease (ESRD) if left untreated. A better understanding of renal TRM cells might lead to identifying new therapeutic targets for relapsing autoimmune diseases of the kidney. In this review, we summarize the current knowledge of renal TRM cells and discuss their potential pathophysiological roles in renal autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aims to evaluate the clinical and histopathological profile in children with crescentic glomerulonephritis (CGN) and determine the predictors of renal outcome. Methods: In this retrospective study, we reviewed all native kidney biopsies performed in patients <18 years over 9 years (2011-2019). Individuals with ≥20% crescents with follow-up for at least 1 year were enrolled. Results: This study included 34 patients. The most common variety was immune-complex glomerulonephritis (GN) (type II CGN) (n=21; 62%), including patients with Henoch- Schonlein purpura (n=6), lupus nephritis (n=6), post-infectious GN (n=3), C3GN (n=3), and dense deposit disease (n=3). The second most common was pauci-immune GN (type III CGN; n=12; 35%) followed by anti-glomerular basement membrane disease (type I CGN; n=1; 3%). Hypertension (88%), hematuria (84.2%), and oliguria (64%) were the most common presenting features. The outcome predictors for poor renal survival were the presence of oliguria (HR-5.11, P=0.035), severe hypertension (HR-11.51, P=0.019), estimated glomerular filtration rate <15 mL/min/1.73 m2 at presentation (HR-5.05, P=0.007), percentage of crescents (HR-10.66, P=0.001), presence of fibrous crescents (HR-6.34, P=0.001), and interstitial fibrosis and tubular atrophy (HR-8.88, P=0.0046). The overall outcome of the study revealed complete recovery (n=12), partial recovery (n=6), chronic kidney disease (n=3), and end-stage renal disease (n=13). The renal survival in patients with ≥50% crescents was poor (P=0.037) as compared to subjects with <50% crescents. Conclusion: Renal survival can be predicted by the severity of presenting features and histopathological markers. Two-thirds of patients had type II CGN with renal survival outcomes similar to type III CGN. The percentage of crescents is the most important predictor of renal survival. [ABSTRACT FROM AUTHOR]

Crescent glomerulonephritis (CreGN) is the most dangerous glomerulonephritis and always leads to end stage renal disease (ESRD). The immunological mechanism plays an important role in its pathogenesis and prognosis. Recently, the role of the gut and intestinal microbiota in a variety of kidney diseases including CreGN has been disclosed. The “gut-kidney axis” will directly affect the immune response in the kidney and subsequent pathophysiology through the intestinal microbiota and gut-derived immune cells.

The discovery of tissue-resident memory T cells (TRM cells) reinterpreted the potential of human tissue-specific immunity. Following T cell receptor (TCR) activation and clonal expansion, effector T cells migrate to peripheral tissues where they remain long-term and differentiate to TRM cells after antigen clearance. This allows for prompt immunological responses upon antigen re-encounter. In addition to their protective properties in acute infections, recent studies have revealed that TRM cells might lead to aggravation of autoimmune diseases, such as lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN). These diseases present as proliferative and crescentic glomerulonephritis (cGN), which is a life-threatening condition leading to end-stage renal disease (ESRD) if left untreated. A better understanding of renal TRM cells might lead to identifying new therapeutic targets for relapsing autoimmune diseases of the kidney. In this review, we summarize the current knowledge of renal TRM cells and discuss their potential pathophysiological roles in renal autoimmune diseases.

Non-resolving inflammation plays a critical role during the transition from renal injury towards end-stage renal disease. The glucocorticoid-inducible protein annexin A1 has been shown to function as key regulator in the resolution phase of inflammation, but its role in immune-mediated crescentic glomerulonephritis has not been studied so far. Methods: Acute crescentic glomerulonephritis was induced in annexin A1- deficient and wildtype mice using a sheep serum against rat glomerular basement membrane constituents. Animals were sacrificed at d5 and d10 after nephritis induction. Renal leukocyte abundance was studied by immunofluorescence and flow cytometry. Alterations in gene expression were determined by RNA-Seq and gene ontology analysis. Renal levels of eicosanoids and related lipid products were measured using lipid mass spectrometry. Results: Histological analysis revealed an increased number of sclerotic glomeruli and aggravated tubulointerstitial damage in the kidneys of annexin A1-deficient mice compared to the wildtype controls. Flow cytometry analysis confirmed an increased number of CD45+ leukocytes and neutrophil granulocytes in the absence of annexin A1. Lipid mass spectrometry showed elevated levels of prostaglandins PGE2 and PGD2 and reduced levels of antiinflammatory epoxydocosapentaenoic acid regioisomers. RNA-Seq with subsequent gene ontology analysis revealed induction of gene products related to leukocyte activation and chemotaxis as well as regulation of cytokine production and secretion. Conclusion: Intrinsic annexin A1 reduces proinflammatory signals and infiltration of neutrophil granulocytes and thereby protects the kidney during crescentic glomerulonephritis. The annexin A1 signaling cascade may therefore provide novel targets for the treatment of inflammatory kidney disease. [ABSTRACT FROM AUTHOR]

While angiotensin-converting enzyme (ACE) regulates blood pressure by producing angiotensin II as part of the renin-angiotensin system, we recently reported that elevated ACE in neutrophils promotes an effective immune response and increases resistance to infection. Here, we investigate if such neutrophils protect against renal injury in immune complex (IC)-mediated crescentic glomerulonephritis (GN) through complement. Nephrotoxic serum nephritis (NTN) was induced in wild-type and NeuACE mice that overexpress ACE in neutrophils. Glomerular injury of NTN in NeuACE mice was attenuated with much less proteinuria, milder histological injury, and reduced IC deposits, but presented with more glomerular neutrophils in the early stage of the disease. There were no significant defects in T and B cell functions in NeuACE mice. NeuACE neutrophils exhibited enhanced IC uptake with elevated surface expression of FccRII/III and complement receptor CR1/2. IC uptake in neutrophils was enhanced by NeuACE serum containing elevated complement C3b. Given no significant complement activation by ACE, this suggests that neutrophil ACE indirectly preactivates C3 and that the C3b-CR1/2 axis and elevated FccRII/III play a central role in IC elimination by neutrophils, resulting in reduced glomerular injury. The present study identified a novel renoprotective role of ACE in glomerulonephritis; elevated neutrophilic ACE promotes elimination of locally formed ICs in glomeruli via C3b-CR1/2 and FccRII/III, ameliorating glomerular injury. [ABSTRACT FROM AUTHOR]

Crescentic glomerulonephritis (GN) is a feature of severe glomerular injury. Anti-GBM disease, immune-complex mediated glomerulonephritis, and ANCA-associated vasculitis are the main causes of crescentic GN. Alport syndrome is a progressive form of hereditary nephritis presenting with hematuria and progression to proteinuria and renal failure. Herein we present a 16-year-old male with rapidly progressive glomerulonephritis syndrome, sensory-neural hearing loss, and a family history of hematuria and proteinuria in his mother and aunt. Light microscopic examination shows cellular crescent in glomeruli. In an electron microscopy study, GBM changes compatible with Alport syndrome were identified. Alport syndrome rarely can be presented as crescentic GN. Electron microscopy is necessary for the diagnosis of this type of pauci-immune crescentic glomerulonephritis. [ABSTRACT FROM AUTHOR]

Non-resolving inflammation plays a critical role during the transition from renal injury towards end-stage renal disease. The glucocorticoid-inducible protein annexin A1 has been shown to function as key regulator in the resolution phase of inflammation, but its role in immune-mediated crescentic glomerulonephritis has not been studied so far.Methods: Acute crescentic glomerulonephritis was induced in annexin A1-deficient and wildtype mice using a sheep serum against rat glomerular basement membrane constituents. Animals were sacrificed at d5 and d10 after nephritis induction. Renal leukocyte abundance was studied by immunofluorescence and flow cytometry. Alterations in gene expression were determined by RNA-Seq and gene ontology analysis. Renal levels of eicosanoids and related lipid products were measured using lipid mass spectrometry.Results: Histological analysis revealed an increased number of sclerotic glomeruli and aggravated tubulointerstitial damage in the kidneys of annexin A1-deficient mice compared to the wildtype controls. Flow cytometry analysis confirmed an increased number of CD45+ leukocytes and neutrophil granulocytes in the absence of annexin A1. Lipid mass spectrometry showed elevated levels of prostaglandins PGE2 and PGD2 and reduced levels of antiinflammatory epoxydocosapentaenoic acid regioisomers. RNA-Seq with subsequent gene ontology analysis revealed induction of gene products related to leukocyte activation and chemotaxis as well as regulation of cytokine production and secretion.Conclusion: Intrinsic annexin A1 reduces proinflammatory signals and infiltration of neutrophil granulocytes and thereby protects the kidney during crescentic glomerulonephritis. The annexin A1 signaling cascade may therefore provide novel targets for the treatment of inflammatory kidney disease.

A recent article described a thickening of the glomerular basement membrane (GBM) along with changes in the expression of key components of the extracellular matrix in 6‐month‐old NPHS2‐Cre transgenic mice, which express the Cre recombinase specifically in podocytes. This transgenic line has been widely used to characterize the implication of candidate genes in glomerular diseases in younger mice. Using a different mouse strain (C57BL/6J) than the previous report (129S6/SvEvTac), we sought to characterize 3‐ and 6‐month‐old NPHS2‐Cre+/− mice in control and pathological conditions. At baseline, there was no difference in renal function and histology between control and NPHS2‐Cre+/− mice. Notably, GBM thickness evaluated by transmission electron microscopy was similar between the two groups. We then induced an immune‐mediated severe glomerular insult, the anti‐glomerular basement membrane glomerulonephritis model (anti‐GBM‐GN) in 3‐month‐old control and NPHS2‐Cre+/− mice. NPHS2‐Cre+/− mice exhibited the same alterations in renal function and structure as control mice. In summary, our study strongly suggests that NPHS2‐Cre+/− transgenic mice on a C57BL/6J background can be safely used for podocyte‐specific gene inactivation in control conditions and in the anti‐GBM‐GN model. [ABSTRACT FROM AUTHOR]

Background. Kidney involvement related to infective endocarditis (IE) may present with different clinical findings. The most common histopathological finding of renal involvement is a combination of proliferative and exudative glomerulonephritis. However, severe acute kidney injury (AKI) induced by crescentic glomerulonephritis (CGN) is extremely rare in children with IE. To date, only 4 pediatric cases with IE-induced CGN had been reported. We present a 14-year old girl with IE-induced CGN. Case. A 14-year old girl with fever, macroscopic hematuria, oliguria, and acute kidney injury (AKI) was admitted to our clinic. The medical history revealed that the patient had undergone several cardiac interventions due to truncus arteriosus type 1, and she recovered from IE-induced glomerulonephritis following antibiotherapy six months ago. During admission, the patient was diagnosed with IE according to one major (positive imaging finding) and three minor (fever, predisposing cardiac disease, and immunological criterion) criteria. Immediate antibiotic treatment was initiated. A kidney biopsy was performed, which showed crescentic glomerulonephritis (CGN with crescents, >50%). Daily pulse steroid (3 days), monthly pulse cyclophosphamide (6 doses), and oral steroid (2 mg/kg/day) therapy were initiated with gradual dose tapering. The patient underwent 12 hemodialysis sessions until the 38th day of the treatment. She was discharged on the 45th day of treatment with normal kidney function tests and negative acute phase reactants. Treatment was maintained with mycophenolate mofetil (MMF) after a 6-month course of cyclophosphamide. MMF was discontinued in the 12th month. At the 18thmonth follow-up visit the patient had mild proteinuria, and was on ramipril therapy. Conclusions. The occurrence of CGN should be considered in children with predisposing cardiac disease, who develop hematuria, proteinuria, and severe AKI. Although antibiotic therapy alone is often sufficient in this immune complex GN induced by infection, early initiation of additional immunosuppressive therapy in the presence of CGN may be beneficial for long term preservation of kidney functions. [ABSTRACT FROM AUTHOR]

Rapidly progressive crescentic glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA-GN) is a major cause of renal failure. Current immunosuppressive therapies are associated with severe side effects, intensifying the need for new therapeutic strategies. The activation of Mas receptor/Angiotensin-(1-7) axis exerted renoprotection in chronic kidney disease. Here, we investigated the effect of adding the lanthionine-stabilized cyclic form of angiotensin-1-7 [cAng-(1-7)] to cyclophosphamide in a rat model of ANCA-GN. At the onset of proteinuria, Wistar Kyoto rats with ANCA-GN received vehicle or a single bolus of cyclophosphamide, with or without daily cAng-(1-7). Treatment with cAng-(1-7) plus cyclophosphamide reduced proteinuria by 85% vs. vehicle, and by 60% vs. cyclophosphamide, and dramatically limited glomerular crescents to less than 10%. The addition of cAng-(1-7) to cyclophosphamide protected against glomerular inflammation and endothelial rarefaction and restored the normal distribution of parietal epithelial cells. Ultrastructural analysis revealed a preserved GBM, glomerular endothelium and podocyte structure, demonstrating that combination therapy provided an additional layer of renoprotection. This study demonstrates that adding cAng-(1-7) to a partially effective dose of cyclophosphamide arrests the progression of renal disease in rats with ANCA-GN, suggesting that cAng-(1-7) could be a novel clinical approach for sparing immunosuppressants. [ABSTRACT FROM AUTHOR]

Abstract Background Crescentic glomerulonephritis is a disease characterized by severe glomerular injuries that is classified into five different pathological types. Patients with type V disease have pauci-immune crescentic glomerulonephritis (PICGN) that is negative for anti-neutrophil cytoplasmic autoantibodies (ANCAs). There are limited clinical data on the manifestations, treatment, and prognosis of type V crescentic glomerulonephritis, especially in children. Case presentation A 13-year-old girl who had an intermittent fever for more than 10 months was admitted to our hospital. She had no gross hematuria, oliguria, edema, or hypertension, but further tests indicated a decreased glomerular filtration rate, hematuria, proteinuria, and an elevated level of IL-6. The antinuclear antibody spectrum test was positive at 1:1000, and the ANCA and anti-glomerular basement membrane antibody tests were negative. A renal biopsy confirmed the diagnosis of ANCA-negative PICGN. We administered methylprednisolone pulse therapy with intravenous cyclophosphamide and oral mycophenolate mofetil. At the 3-month follow-up, her urine protein level was significantly lower, and her serum creatinine level was in the normal range. Conclusions Fever may be an extrarenal manifestation of ANCA-negative PICGN, and IL-6 may play a role in the pathogenesis of this disease. Early methylprednisolone pulse therapy with an immunosuppressant may reduce symptoms and improve prognosis.

Abstract A recent article described a thickening of the glomerular basement membrane (GBM) along with changes in the expression of key components of the extracellular matrix in 6‐month‐old NPHS2‐Cre transgenic mice, which express the Cre recombinase specifically in podocytes. This transgenic line has been widely used to characterize the implication of candidate genes in glomerular diseases in younger mice. Using a different mouse strain (C57BL/6J) than the previous report (129S6/SvEvTac), we sought to characterize 3‐ and 6‐month‐old NPHS2‐Cre+/− mice in control and pathological conditions. At baseline, there was no difference in renal function and histology between control and NPHS2‐Cre+/− mice. Notably, GBM thickness evaluated by transmission electron microscopy was similar between the two groups. We then induced an immune‐mediated severe glomerular insult, the anti‐glomerular basement membrane glomerulonephritis model (anti‐GBM‐GN) in 3‐month‐old control and NPHS2‐Cre+/− mice. NPHS2‐Cre+/− mice exhibited the same alterations in renal function and structure as control mice. In summary, our study strongly suggests that NPHS2‐Cre+/− transgenic mice on a C57BL/6J background can be safely used for podocyte‐specific gene inactivation in control conditions and in the anti‐GBM‐GN model.

Introduction: antineutrophil cytoplasmic antibodies (ANCA) associated Glomerulonephritis (GN) is rare but a life-threatening disease especially, particularly in patients with advanced renal failure at presentation. This study aims to evaluate the epidemiological, clinical and histopathological features of renal involvement and investigate factors associated with ESRD. Methods: patients with renal biopsy-proven ANCA associated glomerulonephritis were included retrospectively over a thirty years period. The renal survival, defined as time to reach ESRD, was evaluated based on clinical parameters, histopathological classification as well as the renal risk score. Results: a total of 65 patients with crescentic GN were included in the study. The mean age was 47.9 years ± 22.4 years (range: 18-78) with an M/F sex ratio at 1.13. Hematuria, proteinuria and oliguria were found in respectively 100%, 81.5% and 56.2% of cases. Sixty patients (92.3%) had renal failure at presentation, and 30 patients (46%) required initial hemodialysis (HD) therapy. The pattern of glomerular injury was categorized as mixed in 43.7% of cases, sclerotic in 34.3%, crescentic in 16.6%, and focal class in 6%. Regarding renal risk score, patients were classified in the category low risk, intermediate risk and high risk with respectively 16.9%, 44.6% and 38.4%. All patients received corticosteroids and immunosuppressive treatment. Complete, partial remission and relapses were noted in respectively 15.3%, 18% and 72% of cases. Factors associated with ESRD were serum creatinine level >500 μmol/l (P=0,0016), CRP level >60 mg/l (P = 0,0013), interstitial fibrosis (P=0,0009) and glomerulosclerosis> 10% of total glomeruli (P=0,001). The survival rate was 89%, 60.9% and 32.8% at respectively 1, 5 and 10 years. Death occurred in 10 cases (15%) caused mostly by infections (40%). Initial serum creatinine level>140 µmol/l (P=0,02), alveolar hemorrhage (P=0.001) and infections (P=0,0001) were associated with mortality. Conclusion: in our cohort of ANCA GN, confirms the data showing improved patient survival but constantly high relapse risk. In addition, we observed that ANCA GN classification was predictive, as the risk of progressing to ESRD increased with the ascending category of focal, crescentic, mixed and sclerotic GN. [ABSTRACT FROM AUTHOR]

Rapidly progressive glomerulonephritis (RPGN) is a rare syndrome which is marked by a sudden rise in serum creatinine and the presence of crescents on renal biopsy. If appropriate and timely treatment is not instituted, as many as 90% of affected patients may develop End Stage Renal Disease (ESRD). There is only limited access to renal replacement therapy in many low resource countries, thus it is important that awareness of this entity is raised. We narrate the clinical course of two children who were admitted with rising serum creatinine, hypertension and haematuria and who were subsequently diagnosed with crescentic glomerulonephritis on biopsy. Despite having received immunosuppressive therapy, both children had a poor renal outcome, perhaps due to delays in institution of appropriate treatment. It is imperative that all clinicians who manage children are made aware of this clinical syndrome so that timely referrals to nephrology are done. This will help to improve renal outcomes. [ABSTRACT FROM AUTHOR]

Glomerular diseases are one of the most challenging entities in terms of diagnosis and management, especially when associated with systemic illnesses such as malignant disorders. Herein, a case of crescentic glomerulonephritis (CrGN) associated with polycythaemia vera (PV) in a 50-year-old female is described. She presented with bilateral pedal oedema, splenomegaly, renal dysfunction and severe proteinuria. On evaluation, we found PV and CrGN. Renal involvement in PV is rare and generally considered as a manifestation of hypervolemia or high-viscosity-induced renal hyper-perfusion and hyper-filtration. This is a unique case of immunologically-mediated renal disease in PV. [ABSTRACT FROM AUTHOR]

We describe five cases of severe necrotizing vasculitis following the RNA-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including four relapsing anti neutrophil cytoplasmic antibodies (ANCA) vasculitis, 27 days (1–60) after vaccination and one patient with quiescent chronic hepatitis B and de novo polyarteritis nodosa (PAN) 21 days after vaccination. Ten other cases were reported to the French national pharmacovigilance database: six patients with ANCA-associated vasculitis and four patients with PAN (first symptoms 19 days on average after vaccination). Five of these 10 patients developed kidney dysfunction. In conclusion, coronavirus disease 2019 (COVID-19) vaccines can be associated with de novo or recurrent ANCA vasculitis or PAN. Attention should be paid to patients with known ANCA vasculitis or patients with a history of hepatitis B infection. [ABSTRACT FROM AUTHOR]

Crescentic glomerulonephritis (CGN) results from a diverse set of diseases associated with immune dysregulation and the breakdown of self-tolerance to a wide range of autoantigens, some known and some that remain unknown. Experimental data demonstrate that neutrophils have an important role in the pathogenesis of CGN. Upon activation, neutrophils generate reactive oxygen species, release serine proteases and form neutrophil extracellular traps (NETs), all of which can induce direct tissue damage. In addition, serine proteases such as myeloperoxidase and proteinase 3, presented on NETs, can be processed and recognized as autoantigens, leading to the generation and maintenance of autoimmune responses in susceptible individuals. The basis of the specificity of autoimmune responses in different patients to NET proteins is unclear, but relates at least in part to differences in human leucocyte antigen expression. Conditions associated with CGN are often characterized by aberrant neutrophil activation and NETosis and, in some, impaired NET degradation. Targeting neutrophil degranulation and NETosis is now possible using a variety of novel compounds and may provide a promising therapeutic alternative to glucocorticoid use, which has been a mainstay of management in CGN for decades and is associated with significant adverse effects. In this review, we discuss the evidence supporting the role of neutrophils in the development of CGN and the pathways identified in neutrophil degranulation and NETosis that may translate to novel therapeutic applications. [ABSTRACT FROM AUTHOR]

Introduction: Immunohistochemical staining of Ki-67, CD68 and Bcl-2 have been studied in glomerulonephritis. We aimed to assess these immunohistochemical staining features, hemodialysis initiation and 60 month mortality rates in crescentic glomerulonephritis.Methods: In this retrospective study, patients, with a previous diagnosis of crescentic glomerulonephritis were divided into two groups: Hemodialysis Initiated and Not Initiated groups. Kidney biopsy specimens'Ki-67, CD68 and Bcl-2 staining scores were defined as below 5% "0", 5-10% "+1", 11- 20% "+2", over 20% "+3". Patients demographic, laboratory data, status of hemodialysis initiation, and mortality were obtained from medical records and immunohistochemical staining scores were compared between groups. Estimated glomerular filtration rates (eGFR) were assessed at 0, 6, and 12 months, except patients' ongoing hemodialysis. Results: A total of 56 patients were diagnosed as crescentic glomerulonephritis. Pauci-immune crescentic glomerulonephritis (58.9%) was the most common etiology. Hemodialysis was initiated in 36 patients. Mean age, baseline creatinine, urea, C-reactive protein levels were significantly higher and, hemoglobin and proteinuria levels were significantly lower in the Hemodialysis Initiated group. Immunohistochemical staining scores were not significantly different between groups. In Hemodialysis Initiated group, 8.33% of patients were recovered from hemodialysis. Mortality rates were 44,4% and 10% in patients in the group of hemodialysis initiated and not initiated group respectively. When we combine the hemodialysis not initiated patients and patients recovered from hemodialysis; median eGFR at baseline, 6th and 12th month were 32.9, 43.9, and 58.0 mL/min/1.73m², respectively (p=0.016). Conclusion: Hemodialysis initiation was associated with high mortality. Degree of immunohistochemical staining was similar in both groups. Increment in eGFR was documented in first year in patients, other than the ones on still on hemodialysis. [ABSTRACT FROM AUTHOR]

Background. Crescentic glomerulonephritis (CGN) is a rapidly progressive and rare cause of glomerulonephritis in childhood. The aim of this study is to evaluate demographic data of children with crescentic glomerulonephritis, to classify the etiologies and to investigate the correlation between the severity of kidney disease and the expression of CD163+ macrophages. Methods. Between the years 2000 and 2016 in a single center, patients under 18 years of age with kidney biopsies containing crescents were included in the study. A total of 88 children were enrolled. The expression of CD163 in kidney tissues was detected by immunohistochemistry in 61 patients. Clinical features and outcome were collected from their medical records. Results. The most common etiology was Henoch-Schönlein purpura (HSP) nephritis/Immunglobulin A vasculitis (26.1%), followed by lupus nephritis (22.7%) and idiopathic crescentic glomerulonephritis (18.2%). CD163 positive cell counts in patients with GFR levels less and more than 60 ml/min/1.73 m2 at their last visit were 7.6±6.6 cells vs. 2.0±3.0 cells (p=0.057) per one glomerulus and 52.2±18.2 cells/hpf vs. 33.3±10.0 cells/hpf (p <0.05) in tubulointerstitium, respectively. Tubulointerstitital CD163+ cells were also found to be higher in patients with end stage kidney disease than complete and partial responders (68 cells/hpf vs 39 cells/hpf, p<0.05). Conclusions. CD163 positive cell counts, particularly in tubulointerstitial areas, have been associated with poor prognosis of CGN. [ABSTRACT FROM AUTHOR]

Introduction: Antiglomerular basement membrane disease manifests as rapidly progressive glomerulonephritis and alveolar hemorrhage. It encompasses 10–15% of crescentic glomerulonephritis and is associated with poor outcome. In this study, we have elaborated on the clinical details, morphological features, and outcome of anti-GBM glomerulonephritis. Materials and Methods: All the consecutive biopsy-proven cases of anti-GBM glomerulonephritis over a period of 4½ years were analyzed, retrospectively. Results: Sixteen cases were diagnosed as anti-GBM glomerulonephritis during the study period. Twelve patients presented with rapidly progressive renal failure of which four patients required hemodialysis at the time of presentation. Goodpasture's syndrome was noted in two patients. Thirteen cases were positive for circulating anti-GBM antibodies and two patients showed double positivity for both anti-GBM antibodies and ANCA. Fifteen biopsies revealed crescentic glomerulonephritis with linear deposition of IgG along the glomerular basement membrane in all the 16 cases. Conclusion: Renal biopsy analysis is important in the diagnosis of Anti GBM nephritis. Morphology is an important predictor of disease progression.

Crescentic glomerulonephritis (CrGN) is characterized by the presence of crescents in more than 50% of glomeruli. This study aims to identify the etiology and clinicopathological features and outcomes of CrGN. In this observational study, 80 biopsy-proven CrGN were included. Patients’ demographic profile, clinical parameters, treatments, and outcomes were collected and analyzed. The mean age in our study population was 40.86 ± 16.5 years. Type II CrGN was the most common type of CrGN. Female predominance was observed in type I and type II CrGN. The highest percentage of glomeruli with crescents was seen in type I (87 ± 15.2%, P = 0.04), followed by type III and type II. At the last follow-up, mean estimated glomerular filtration rate was 25.8 ± 11.41 mL/min/1.73 m2 and was significantly lower in type I CrGN (11.6 ± 4.8 mL/min/1.73 m2 P = 0.001). The overall 5-year renal survival rate was 55% and was highest in type II (69.4%), followed by type III and type I (27.3%) CrGN (P = 0.0299). In our study, oliguria at the time of presentation, percentage of crescents, glomerular sclerosis, and moderate/severe IFTA were associated with poor renal outcomes. In conclusion, CrGN was seen in 5.7% of kidney biopsies in our study. Type II CrGN was the most common type of CrGN followed by type III CrGN. Renal survival was poor in type I CrGN patients compared to type II and type III CrGN. Also, oliguria, crescents, glomerular sclerosis, and moderate/severe IFTA were associated with poor renal outcomes.

Bartonella endocarditis is often an elusive diagnosis, usually derived from evaluating multiple laboratory tests and assessment of presenting symptoms. Herein we describe a case of Bartonella henselae native mitral valve endocarditis with an initial presentation of volume overload and renal failure. The Bartonella organism is tedious to isolate from culture medium, causing most diagnoses to be delayed. Due to the destructive nature of B. henselae endocarditis, the need for rapid identification remains prudent. This therefore creates an opportunity for Next Generation Sequencing (NGS) to be used. We further summarize the varied presentations that may be associated with B. henselae endocarditis, and hope that this will heighten the clinicians’ awareness of this entity when presented with acute onset renal failure and culture negative vegetations.

Glomerular parietal epithelial cells (PECs) have been increasingly recognized to have crucial functions. Lineage tracking in animal models showed the expression of a podocyte phenotype by PECs during normal glomerular growth and after acute podocyte injury, suggesting a reparative role of PECs. Conversely, activated PECs are speculated to be pathogenic and comprise extracapillary proliferation in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CrescGN). The reparative and pathogenic roles of PECs seem to represent two sides of PEC behavior directed by the local milieu and mediators. Recent studies suggest microRNA-193a (miR193a) is involved in the pathogenesis of FSGS and CrescGN. In a mouse model of primary FSGS, the induction of miR193a caused the downregulation of Wilms’ tumor protein, leading to the dedifferentiation of podocytes. On the other hand, the inhibition of miR193a resulted in reduced crescent lesions in a mouse model of CrescGN. Interestingly, in vitro studies report that the downregulation of miR193a induces trans-differentiation of PECs into a podocyte phenotype. This narrative review highlights the critical role of PEC behavior in health and during disease and its modulation by miR193a.

Chronic kidney disease (CKD) leads to significant morbidity and mortality worldwide. Glomerulonephritis (GN) is the second leading cause of CKD resulting in end stage renal failure. The most severe and rapidly progressive type of GN is characterized by glomerular crescent formation. The current therapies for crescentic GN, which consist of broad immunosuppressive drugs, are partially effective, non-specific, toxic and cause many serious side effects including infections, cancer, and cardiovascular problems. Therefore, new and safer therapies are needed. Human amniotic epithelial cells (hAECs) are a type of stem cell which are isolated from the placenta after birth. They represent an attractive and novel therapeutic option for the treatment of various inflammatory conditions owing to their unique and selective immunosuppressive ability, as well as their excellent safety profile and clinical applicability. In this review, we will discuss the immunopathogenesis of crescentic GN, issues with currently available treatments and how hAECs offer potential to become a new and harmless treatment option for this condition. [ABSTRACT FROM AUTHOR]

Introduction: Syphilis is a sexually transmitted disease caused by the bacterium Treponema Pallidum and has a diverse clinical presentation, including nephropathies, the most common of which is membranous nephropathy. Crescentic glomerulonephritis is not typically considered to be a manifestation of Syphilis associated renal disease. Case presentation: Here we describe an unusual case of crescentic glomerulonephritis associated with secondary syphilis resulting in a rapidly progressing glomerulonephritis presentation requiring hemodialysis. The patient was treated with Penicillin G and intravenous solumedrol. The patient’s kidney function recovered and several months after presentation the patient was asymptomatic off hemodialysis with a serum creatinine of 1.54 mg/dL. Discussion/conclusion: Secondary syphilis rarely presents with rapidly progressive glomerulonephritis. This report is only the third such case reported to date of a diffuse necrotizing/crescentic glomerulonephritis resulting from a syphilis infection. As syphilis is on the rise, this report highlights an important differential diagnostic consideration for any necrotizing/crescentic glomerulonephritis.

Chronic kidney disease (CKD) leads to significant morbidity and mortality worldwide. Glomerulonephritis (GN) is the second leading cause of CKD resulting in end stage renal failure. The most severe and rapidly progressive type of GN is characterized by glomerular crescent formation. The current therapies for crescentic GN, which consist of broad immunosuppressive drugs, are partially effective, non-specific, toxic and cause many serious side effects including infections, cancer, and cardiovascular problems. Therefore, new and safer therapies are needed. Human amniotic epithelial cells (hAECs) are a type of stem cell which are isolated from the placenta after birth. They represent an attractive and novel therapeutic option for the treatment of various inflammatory conditions owing to their unique and selective immunosuppressive ability, as well as their excellent safety profile and clinical applicability. In this review, we will discuss the immunopathogenesis of crescentic GN, issues with currently available treatments and how hAECs offer potential to become a new and harmless treatment option for this condition.

Background: Crescentic glomerulonephritis is a disease characterized by severe glomerular injuries that is classified into five different pathological types. Patients with type V disease have pauci-immune crescentic glomerulonephritis (PICGN) that is negative for anti-neutrophil cytoplasmic autoantibodies (ANCAs). There are limited clinical data on the manifestations, treatment, and prognosis of type V crescentic glomerulonephritis, especially in children.Case Presentation: A 13-year-old girl who had an intermittent fever for more than 10 months was admitted to our hospital. She had no gross hematuria, oliguria, edema, or hypertension, but further tests indicated a decreased glomerular filtration rate, hematuria, proteinuria, and an elevated level of IL-6. The antinuclear antibody spectrum test was positive at 1:1000, and the ANCA and anti-glomerular basement membrane antibody tests were negative. A renal biopsy confirmed the diagnosis of ANCA-negative PICGN. We administered methylprednisolone pulse therapy with intravenous cyclophosphamide and oral mycophenolate mofetil. At the 3-month follow-up, her urine protein level was significantly lower, and her serum creatinine level was in the normal range.Conclusions: Fever may be an extrarenal manifestation of ANCA-negative PICGN, and IL-6 may play a role in the pathogenesis of this disease. Early methylprednisolone pulse therapy with an immunosuppressant may reduce symptoms and improve prognosis. [ABSTRACT FROM AUTHOR]

Background. The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase survival. Potential biomarkers for relapses are ANCA and B cells, but their predictive value is a matter of debate. Therefore this study investigated how ANCA and B-cell status related to relapses in AAV patients treated with rituximab (RTX) as remission induction (RI). Methods. This single-centre cohort study identified 110 ANCA-positive AAV patients treated with RTX between 2006 and 2018. Serial ANCA, CD19+ B-cell status and relapses were assessed >2 years. Results. Patients (31/110) relapsed within 2 years after RTX RI treatment. Patients who achieved and maintained PR3-ANCA negativity (n  = 29) had few relapses (3%), while persistent proteinase 3 (PR3)-ANCA positivity (n  = 49) and reappearance of PR3-ANCAs (n  = 10) associated significantly with more relapses (37%, P = 0.002 and 50%, P = 0.002). Patients with incomplete B-cell depletion (n  = 11) had significantly more relapses (54%) as compared with patients with B-cell depletion [ n  = 76 (26%), P = 0.02]. Also, patients with repopulation of B cells (n  = 58) had significantly more relapses (41%) as compared with patients without B-cell repopulation [ n  = 27 (15%), P = 0.03]. Overall, the absence of PR3- or myeloperoxidase (MPO)-ANCA positivity was highly predictive for remaining relapse-free. In PR3-ANCA-positive patients, 96% of the relapses occurred with persistent or reappearance of PR3-ANCAs and 81% with B-cell repopulation. In MPO-ANCA-positive patients, all relapses were restricted to patients with persistent MPO-ANCAs and B-cell repopulation. Conclusions. Upon RI treatment with RTX in AAV patients, ANCA and B-cell status were predictive of the majority of relapses and specifically their absence strongly predicted a relapse-free status. Therefore the implementation of ANCA and B-cell monitoring could guide therapeutic decision-making to prevent relapses in AAV patients treated with RTX. [ABSTRACT FROM AUTHOR]

Anti–glomerular basement membrane (GBM) nephritis is characterized by circulating anti-GBM antibodies and crescentic glomerulonephritis (GN) with deposition of IgG along the GBM. In a limited number of cases, glomerular immune complexes have been identified in anti-GBM nephritis. A 38-year-old female presented azotemia, hematuria, and proteinuria without any pulmonary symptoms. A renal biopsy showed crescentic GN with linear IgG deposition along the GBM and mesangial IgA deposition. The patient was diagnosed as concurrent anti-GBM nephritis and IgA nephropathy. Therapies with pulse methylprednisolone and cyclophosphamide administration were effective. Concurrent cases of both anti-GBM nephritis and IgA nephropathy are rare among cases of anti-GBM diseases with deposition of immune complexes. This rare case of concurrent anti-GBM nephritis and IgA nephropathy with literature review is noteworthy.

Lupus nephritis (LN) is the secondary glomerulonephritis (GN) involved in systemic lupus erythematosus (SLE) and a typical immune complex-type GN. Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease characterized by systemic vasculitis and pauci-immune-type crescentic glomerulonephritis (CrGN) with ANCA production. Human AAV causes death due to lung haemorrhage and end-stage renal disease, for which renal replacement therapies are necessary. The SLE/AAV overlap syndrome was recently reported in humans. The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse is a unique model of human AAV showing production of myeloperoxidase (MPO)-ANCA. We previously discovered seven disease susceptibility quantitative trait loci (QTL) derived from SCG/Kj mice by linkage analysis. To investigate the individual functions of each QTL, and to identify AAV susceptibility genes, we introduced them into a B6/lpr background to establish SCG/Kj interval congenic mice (SICM). B6/lpr.C1scg mice, a type of SICM, exhibited the production of autoantibodies, including MPO-ANCA. The GN in B6/lpr.C1scg mice was not pauci-immune type: deposition of immunoglobulins and complement components was observed in nephritic glomeruli, similar to that in LN. The incidence of GN in female B6/lpr.C1scg mice was 100%. Granulocyte infiltration was also observed in the glomerular tuft and crescents. B6/lpr.C1scg mice also displayed vasculitis in multiple organs, most frequently the lung and kidney. Vasculitis was characterized by the infiltration of mononuclear cells to vascular walls followed by granulocyte infiltration, resembling human lupus vasculitis. The incidence of lung vasculitis was over 90% in male and female B6/lpr.C1scg mice. Blood MPO-ANCA levels were significantly associated with histopathological disease phenotypes. MPO deposition was observed in nephritic glomeruli, and granulocytes infiltrated into inflamed vessels and glomeruli. These observations suggest that the activation of granulocytes and local MPO release contribute to the pathogenesis of GN and vasculitis. As a monocongenic mouse, B6/lpr.C1scg mice show the association between murine chromosome 1 segment and autoimmunity. This strain can be used as a model of the SLE/AAV overlap syndrome, and will be useful for elucidating the mechanism of ANCA generation and the pathogenesis of CrGN and vasculitis, as well as in the search for genetic factors related to AAV.

Abstract Background The nature of immunoglobulin M (IgM) nephropathy has been controversial for a long time, but it is now considered an independent disease like immunoglobulin A nephropathy. IgM nephropathy has been known to have various clinical manifestations ranging from asymptomatic hematuria and/or proteinuria to nephrotic syndrome. Recently, one case of IgM nephropathy manifesting as crescentic glomerulonephritis (GN) was reported in a child. Case presentation We experienced a case of IgM nephropathy that manifested clinically as nephritic and nephrotic syndrome with pathologically confirmed crescentic GN in a 30-year-old woman. We administered a calcineurin inhibitor and corticosteroids to treat the ongoing nephrotic syndrome after remission of crescentic GN. As a result, her proteinuria was significantly reduced and edema improved. Conclusions We described a case of IgM nephropathy in an adult patient who initially developed crescentic GN with nephritic and nephrotic syndrome. This case report could contribute to a deeper understanding of IgM nephropathy.