Acute severe aortic insufficiency during cardiopulmonary bypass in a bicuspid aortic valve with unrecognized annular displacement and fibrous strands: a case report.

Background: Bicuspid aortic valve (BAV) with displacement of the attachment of the conjoined aortic leaflet and fibrous strands is a rare cardiac malformation. We report a case of BAV that presented as acute massive aortic regurgitation during cardiopulmonary bypass for a planned non-valve-related procedure and was successfully treated by emergency aortic valve replacement. Case summary: A 70-year-old man with triple vessel coronary disease and severe left ventricular systolic dysfunction underwent coronary bypass grafting and graft replacement of the ascending aorta. Acute aortic regurgitation occurred during ventricular fibrillation and after de-clamping of the aortic graft. Intra-operative findings included a fused BAV (right-left cusp fusion), very asymmetrical leaflet (commissure angle of the non-fused leaflet 135°), three aortic sinuses, and conjoined leaflets originating from the myocardium in the inter-ventricular septum. The aortic leaflets were resected and replaced with a prosthetic aortic valve at the attachment site of the conjoined leaflets. Post-operatively, no peri-valvular leaks were observed, and left ventricular function was improved. Discussion: Intra-operative acute massive aortic regurgitation may be caused by a morphologically abnormal aortic leaflet and root complex in patients with a BAV. The dilated aortic root, asymmetrical leaflet, and abnormal aortic leaflet insertion, with thick septal myocardium of the coronary aortic sinus, might have caused unstable leaflet co-aptation, leading to deformation of the aortic leaflets influenced by the change in myocardial tone and intra-operative change in the sinotubular junction. Familiarity with the classification of congenital BAV, and the anatomy of the normal and abnormal aortic root complex, is important.

[Anti-MBG crescentic glomerulonephritis with negative immunofluorescence: case report and literature review].

Anti-glomerular basement membrane (anti-GBM) antibody disease is a rapidly progressive glomerulonephritis characterized by (i) positivity to anti-GBM in serum reacting with a specific antigen present in type IV collagen at both the glomerular and alveolar levels (ii) presence of crescent on light microscopy and positivity to linear deposits of IgG and C3 on immunofluorescence. In the classic variant, the clinic is that of a nephro-pneumological syndrome but there are variants. Rarely, the glomerular damage is pauci-immune. We describe a case of a variant in which there is anti-MBG positivity in serum but negative immunofluorescence and offer a review of the literature and potential treatments.

A novel clinical-radiomic nomogram for the crescent status in IgA nephropathy.

Objective: We used machine-learning (ML) models based on ultrasound radiomics to construct a nomogram for noninvasive evaluation of the crescent status in immunoglobulin A (IgA) nephropathy. Methods: Patients with IgA nephropathy diagnosed by renal biopsy (n=567) were divided into training (n=398) and test cohorts (n=169). Ultrasound radiomic features were extracted from ultrasound images. After selecting the most significant features using univariate analysis and the least absolute shrinkage and selection operator algorithm, three ML algorithms were assessed for final radiomic model establishment. Next, clinical, ultrasound radiomic, and combined clinical-radiomic models were compared for their ability to detect IgA crescents. The diagnostic performance of the three models was evaluated using receiver operating characteristic curve analysis. Results: The average area under the curve (AUC) of the three ML radiomic models was 0.762. The logistic regression model performed best, with AUC values in the training and test cohorts of 0.838 and 0.81, respectively. Among the final models, the combined model based on clinical characteristics and the Rad score showed good discrimination, with AUC values in the training and test cohorts of 0.883 and 0.862, respectively. The decision curve analysis verified the clinical practicability of the combined nomogram. Conclusion: ML classifier based on ultrasound radiomics has a potential value for noninvasive diagnosis of IgA nephropathy with or without crescents. The nomogram constructed by combining ultrasound radiomic and clinical features can provide clinicians with more comprehensive and personalized image information, which is of great significance for selecting treatment strategies.

Streptococcal Infection-related Glomerulonephritis in an Elderly Diabetic Patient Complicated by Hemophagocytic Syndrome and Cytomegalovirus Nephritis.

There has been a significant shift in epidemiology and renal outcomes of infection-related glomerulonephritis (IRGN) in recent years. The renal prognosis of IRGN is often poor in adults, especially in the elderly and diabetics. We herein report an elderly diabetic patient with IRGN due to streptococcal infection complicated by hemophagocytic syndrome and cytomegalovirus nephritis, which is uncommon among non-transplant patients. Infection control and steroids did not recover the patient's renal function. For elderly IRGN patients with diabetes, a further investigation of the most effective treatment for related renal outcomes is needed.

The Presence of ANCA in IgA Crescentic Nephropathy Does Not Lead to Worse Prognosis with Intensive Rescue Treatment.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The concomitant presence of both crescentic proliferation and anti-neutrophil cytoplasmic autoantibodies (ANCA) in this pathology represents a rare coincidence. However, it is not clear to what extent the presence of ANCA (IgA or IgG) in these patients could have any clinical significance. The aim of the current work is to describe the presence of ANCA (IgA or IgG) in patients with IgAN and crescentic proliferation and its possible clinical implications. METHODS: We retrospectively recruited all patients in our center with a histological diagnosis of IgAN with crescentic proliferation between January 2013 and December 2020. The main demographic and clinicopathologic data, fundamental histological characteristics, as well as the treatments implemented and main kidney outcomes, were collected and analyzed at a 6 and 12-month follow-up. RESULTS: Between January 2013 and December 2020, a total of 17 adults were diagnosed with concomitant crescentic proliferation through a kidney biopsy of IgAN. Five (29.4%) patients showed ANCA, three (60%) showed IgA-ANCA and two (40%) showed IgG-ANCA. All ANCA-positive patients had some degree of crescentic proliferation. At diagnosis, the mean age of patients was 48 years old (range: 27-75). Nine of them were women (52%) and the most common clinical presentation was hypertension (71%). At the time of biopsy, the mean serum creatinine and proteinuria were 2.2 mg/dL (DS 1.42) and 3.5 g/mgCr (DS 1.22), respectively, with no statistical differences between ANCA-positive and -negative patients. Histological analyses showed that 11 out of the 12 (91%) ANCA-negative IgAN patients displayed less than 25% cellular crescents, whereas 100% of ANCA-positive IgAN patients displayed more than 25% cellular crescents (p = 0.04). Notably, five (30%) patients displayed fibrinoid necrosis, with four of them (80%) being IgAN-ANCA-positive (p = 0.01). Only one ANCA-negative patient needed renal replacement therapy (RRT) upon admission (5%). The mean serum creatinine and proteinuria were 1.94 mg/dL (DS 1.71) and 1.45 g/gCr (DS 1.78), respectively, within 6 months of immunosuppressive therapy. At 12-month follow-up, the mean creatinine was 1.57 mg/dL (DS 1). Four (23.5%) patients needed RRT at the end of the follow-up and four (23.5%) patients died. CONCLUSIONS: Probably due to the limited number of IgAN-ANCA-positive and IgAN-ANCA-negative patients, no significant differences were found between the clinical and laboratory characteristics. IgAN-ANCA-negative patients seemed to display less extracapillary proliferation than IgAN-ANCA-positive patients, who tended to show significantly higher fibrinoid necrosis. There were no differences regarding renal prognosis and patient survival after aggressive immunosuppressive therapy within 6 and 12 months when comparing the two samples.

Clinical and pathological features of anti-glomerular basement membrane disease associated with membranous nephropathy: an observational study.

To investigate the clinical manifestations, pathological features, pathogenesis, treatment, and prognosis of anti-glomerular basement membrane (anti-GBM) disease with membranous nephropathy (MN). Seven patients with anti-GBM disease and concurrent MN were enrolled in this study. Control subjects included 13 patients with anti-GBM glomerulonephritis (GN) and 6 with anti-GBM disease and concurrent anti-neutrophil cytoplasmic antibodies-associated disease (anti-GBM + ANCA). Laboratory tests and pathological information were analyzed before immunosuppressive therapy or plasmapheresis administration. Prognosis was assessed in continuous follow-up. In the anti-GBM + MN group, 28.57% of patients exhibited acute kidney disease, lower than that in the anti-GBM GN group (84.62%, p = .022). None of the anti-GBM + MN or + ANCA patients exhibited hemoptysis, but 15.4% of anti-GBM GN patients did, with no significant difference (p = .720). Only 14.3% of anti-GBM + MN patients had crescentic GN. The proportion of necrosis averaged 29.0% in the anti-GBM + MN group. Survival curve analysis revealed that renal outcomes in the anti-GBM + MN group were better than those in the anti-GBM GN group (p = .019). Patients with both anti-GBM disease and MN showed atypical anti-GBM GN. They had a lower proportion of glomerular crescents and a better renal function prognosis than patients with classical anti-GBM GN. To improve renal recovery, early identification and treatment of anti-GBM disease associated with MN is needed.

The serum free triiodothyronine to free thyroxine ratio as a potential prognostic biomarker of chronic kidney disease in patients with glomerular crescents: A retrospective study.

Background: Crescent formation indicates severe glomerular pathology, and hypothyroidism usually predicts poor prognosis for severe diseases. However, the relationship between thyroid function and the progression of chronic kidney disease (CKD) is unclear. This study analysed the prognostic predictive value of the serum free triiodothyronine (FT3) to free thyroxine (FT4) ratio and its correlation with renal function in patients with CKD with crescent formation. Methods: This single-centre study included 162 CKD patients with glomerular crescents confirmed by renal pathology between March 2012 and December 2014. According to the first tertile (0.284) of FT3/FT4 ratio, the patients were divided into high and low FT3/FT4 ratio groups. Kaplan-Meier and Cox regression analyses were performed to evaluate the prognostic value of the FT3/FT4 ratio. Results: The age, haemoglobin, eGFR, urinary albumin-to-creatinine ratio, cardiac troponin T, N-terminal brain natriuretic peptide precursor, FT3, FT4, percentage of total crescents in non-globally sclerotic glomeruli, prevalences of hypertension, moderate to severe renal tubulopathy and crescentic nephritis, and proportion of patients receiving glucocorticoids and immunosuppressants were significantly different between high and low FT3/FT4 ratio groups (P < 0.05). Multivariate Cox regression analysis showed that when compared with patients with a high FT3/FT4 ratio (>0.284), those with intermediate and low FT3/FT4 ratios (≤0.284) had an increased risk of the long-term composite endpoint (P < 0.05 for various adjustment models). Conclusions: A low FT3/FT4 ratio is associated with increased mortality and worse outcome risk in CKD patients with crescent pathology.

Add-On Cyclic Angiotensin-(1-7) with Cyclophosphamide Arrests Progressive Kidney Disease in Rats with ANCA Associated Glomerulonephritis.

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.

Crescents, an Independent Risk Factor for the Progression of Type 2 Diabetic Kidney Disease.

CONTEXT: Crescents have been noticed in pathologic changes in patients with diabetic kidney disease (DKD). However, the clinical significance of crescents is still not well recognized. OBJECTIVE: The main objective was to investigate the association between crescents and the prognoses of type 2 DKD (T2DKD) patients, and, secondly, to analyze the relationship between crescents and clinicopathologic features. METHODS: A retrospective cohort study of 155 patients with T2DKD diagnosed by renal biopsy was carried out in a single center. Clinicopathologic features of patients with or without crescents were analyzed. Cox regression models and meta-analysis were used to determine the prognostic values of crescents for T2DKD. A nomogram was constructed to provide a simple estimation method of 1, 3, and 5-year renal survival for patients with T2DKD. RESULTS: Compared with T2DKD patients without crescents, patients with crescents had higher 24-hour proteinuria and serum creatinine levels, as well as more severe Kimmelstiel-Wilson (K-W) nodules, segmental sclerosis (SS), and mesangiolysis (all P < .05). Furthermore, the crescents were positively correlated with serum creatinine, 24-hour proteinuria, K-W nodules, SS, mesangiolysis, and complement 3 deposition. Multivariate Cox models showed that crescents were an independent prognostic risk factor for renal survival (hazard ratio [HR] 2.68, 95% CI 1.27-5.64). The meta-analyzed results of 4 studies on crescents in T2DKD confirmed that patients with crescents had a significantly higher HR for renal progression. CONCLUSION: Patients with crescents in T2DKD have more severe clinicopathologic changes and worse prognoses. The crescent can serve as an independent risk factor for T2DKD progression.

Anti-glomerular Basement Membrane Glomerulonephritis: A Study in Real Life.

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a severe entity with few therapeutic options including plasma exchange and immunosuppressive agents. The aim of this study was to analyze the clinical and pathological features that predict the evolution of end-stage kidney disease (ESKD) and the kidney survival in a cohort of patients with anti-GBM disease with renal involvement in real life. Methods: A retrospective multicentre observational study including 72 patients from 18 nephrology departments with biopsy-proven anti-GBM disease from 1999 to 2019 was performed. Progression to ESKD in relation to clinical and histological variables was evaluated. Results: Creatinine at admission was 8.6 (± 4) mg/dL and 61 patients (84.7%) required dialysis. Sixty-five patients (90.3%) underwent plasma exchange. Twenty-two patients (30.6%) presented pulmonary hemorrhage. Kidney survival was worse in patients with creatinine levels > 4.7 mg/dL (3 vs. 44% p < 0.01) and in patients with > 50% crescents (6 vs. 49%; p = 0.03). Dialysis dependence at admission and creatinine levels > 4.7 mg/dL remained independent significant predictors of ESKD in the multivariable analysis [HR (hazard ratio) 3.13 (1.25-7.84); HR 3 (1.01-9.14); p < 0.01]. The discrimination value for a creatinine level > 4.7 mg/dL and 50.5% crescents had an area under the curve (AUC) of 0.9 (95% CI 0.82-0.97; p < 0.001) and 0.77 (95% CI 0.56-0.98; p = 0.008), respectively. Kidney survival at 1 and 2 years was 13.5 and 11%, respectively. Patient survival at 5 years was 81%. Conclusion: In real life, patients with severe anti-GBM disease (creatinine > 4.7 mg/dL and > 50% crescents) remained with devastating renal prognosis despite plasma exchange and immunosuppressive treatment. New therapies for the treatment of this rare renal disease are urgently needed.

Rare Case of Renal Limited Dual Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: Double Trouble!

Dual anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) characterized by the presence of both anti-proteinase-3 (PR3-ANCA) and anti-myeloperoxidase (MPO-ANCA) antibodies is a rare clinical entity. Only few cases have been reported previously, most of which were associated with infections, drugs, autoimmune diseases and malignancies. Herein, we describe a young woman who presented with rapidly progressive glomerulonephritis with hypocomplementemia and markedly elevated anti-PR3 and anti-MPO titres. Meticulous work-up ruled out all possible secondary causes. Renal biopsy showed the presence of focal fibrocellular crescents with focal mesangial hypercellularity. Immunofluorescence and electron microscopy showed pauci-immune deposits. The patient was treated with an induction regimen comprising oral prednisolone and cyclophosphamide. She attained both clinical and serological remission at 3 months and is currently on an azathioprine-based maintenance regimen. We have extensively reviewed all previous cases of dual AAV and have formulated an approach to diagnose and treat this rare entity. LEARNING POINTS: Dual anti-neutrophil cytoplasmic antibody-associated vasculitis characterized by both PR3-ANCA and MPO-ANCA antibodies is a rare clinical entity.Prior to treating with immunosuppression, we need to rule out secondary aetiologies such as drugs, certain infections, autoimmune diseases and haematological malignancies.Atypical presentations such as hypocomplementemia, other serological abnormalities like positive ANA, cryoglobulins, anti-histone antibody and histology showing mesangial hypercellularity, interstitial inflammation and lack of pauci-immunity, may create a diagnostic dilemma.

Crescents and IgA Nephropathy: A Delicate Marriage.

IgA nephropathy (IgAN) is a progressive disease with great variability in the clinical course. Among the clinical and pathologic features contributing to variable outcomes, the presence of crescents has attracted particular interest as a distinct pathological feature associated with severity. Several uncontrolled observations have led to the general thought that the presence and extent of crescents was a prognostic indicator associated with poor outcomes. However, KDIGO 2021 guidelines concluded that either the presence or the relative number of crescents should not be used to determine the progression of IgAN nor should they suggest the choice of immunosuppression. Our aim is to report and discuss recent data on the debated issue of the value of active (cellular and fibrocellular) crescents in the pathogenesis and clinical progression of IgAN, their predictive value, and the impact of immunosuppression on renal function. We conclude that the value of crescents should not be disregarded, although this feature does not have an independent predictive value for progression in IgAN, particularly when considering immunosuppressed patients. An integrated overall evaluation of crescents with other active MEST scores, clinical data, and novel biomarkers must be considered in achieving a personalized therapeutic approach to IgAN patients.

Clinicopathological characteristics, risk factors and renal outcome in IgA nephropathy with crescents.

BACKGROUND/AIMS: The aim of the study was to investigate the clinicopathological characteristics, risk factors and renal outcome in IgA nephropathy (IgAN) patients with crescents. METHODS: Four hundred and fifty-eight biopsy-proven primary IgAN patients included between January 2010 and October 2021 for a retrospective analysis were divided into three groups according to crescent score of the updated Oxford classification: C0 group (n = 255), C1 group (n = 187) and C2 group (n = 16). The clinicopathological features and renal outcomes were recorded. In univariate and multivariate models, the association between crescents and renal outcome and C2-associated clinical factors were analyzed. RESULTS: Patients with a higher proportion of crescents presented worse clinical characteristics with regard to kidney function, proteinuria, hematuria, hemoglobin, uric acid, cholesterol, and serum albumin, while global glomerulosclerosis, segmental adhesion, tuft necrosis, segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1/2), and lymphocyte and monocyte infiltration were more severe. By multivariate logistic regression analysis, eGFR (OR 0.981, 95% CI 0.964-0.999, P = 0.039), proteinuria (OR 1.655, 95% CI 1.180-2.321, P = 0.004), and hematuria (OR 4.752, 95% CI 1.426-15.835, P = 0.011) were significantly associated with C2. C2 was significantly associated with poorer renal survival even in patients receiving immunosuppressive therapy. Nevertheless, only eGFR at baseline, rather than crescents, was an independent predictor for renal survival in multivariate Cox analyses. CONCLUSION: IgAN patients with crescents presented more severe clinical and pathological features. Renal function, proteinuria and hematuria contributed to identifying patients with crescents. Crescents were associated with poorer renal survival, even in patients receiving immunosuppressive therapy, but it was not an independent predictor.

Rapidly progressive IgA nephropathy: clinicopathological characteristics and outcomes assessed according to the revised definition of the KDIGO 2021 Guideline.

BACKGROUND: Rapidly progressive immunoglobulin A nephropathy (RPIgAN) is a severe clinical phenotype of IgAN associated with a poor outcome. The recently published Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Guideline for the Management of Glomerular Diseases has proposed a new definition for RPIgAN that is based simply on a ≥50% decline in the estimated glomerular filtration rate (eGFR) over ≤3 months. METHODS: In 1677 IgAN patients followed at a single centre in China, we evaluated the utility of this new definition to identify the highest-risk IgAN patients who might be suitable for combination immunosuppressive therapy. RESULTS: The proportion of a ≥50% decline in eGFR over ≤3 months was 5.2%. The majority of these patients had reversible causes, with only 2.3% (39/1677) meeting the KDIGO 2021 criteria for RPIgAN. These patients had a significantly higher risk for end-stage kidney disease (ESKD) than non-RPIgAN patients (logrank P < 0.001). RPIgAN was an independent risk factor for ESKD [hazard ratio 3.99 (95% confidence interval 2.25-7.09); P <0.001]. A minority of the RPIgAN patients (25.6%) had ≥50% crescents. There was no significant difference in the risk for ESKD between patients in the RPIgAN group with ≥50% crescents and ˂50% crescents (logrank P = 0.27). Patients with RPIgAN and ≥50% crescents had a higher risk for ESKD than patients with non-RPIgAN and ≥50% crescents (logrank P = 0.04). CONCLUSIONS: These data support the validity of the KDIGO 2021 definition but require independent validation in other non-Chinese cohorts.

The effectiveness and safety of corticosteroid therapy for IgA nephropathy with crescents: a prospective, randomized, controlled study.

BACKGROUND: Pozzi protocol (methylprednisolone intravenous infusion in 1st-3rd-5th months and oral steroid for 6 months) has been thought to be the classic therapy for IgA nephropathy (IgAN) patients with proteinuria> 1.0 g/24 h. There is no consensus on the treatments for IgAN with active pathological changes, especially for IgAN patients with crescents proportion < 50%. This study aimed to evaluate the effectiveness and safety of the treatment protocol of methylprednisolone intravenous infusion at the 1st-2nd-3rd months for IgAN patients with crescents. METHODS: In this prospective, randomized, controlled, non-blind study, 68 IgAN patients with crescents proportion < 50% were divided into the 1-2-3 group receiving 0.25 g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd months, and oral prednisone 0.5 mg/kg/d on consecutive days for 6 months and the 1-3-5 group with the same intravenous methylprednisolone treatment in the 1st-3rd-5th months, and the same oral prednisone. The primary outcome measure was remission of proteinuria (complete or partial); while the secondary outcome measures were deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine levels, or a 25% decline from baseline eGFR levels). RESULTS: There was no significant difference in incidence of crescents (median 14.66% vs. 11.45%, p = 0.143) between the 1-2-3 and 1-3-5 groups. From month 1 to month 6, there was a decreasing trend in the levels of urine protein and serum creatinine and an increasing trend in eGFR in both groups. The mean period of remission in the 1-2-3 group seemed shorter. Overall, there were 55 (80.89%) patients meeting remission. The rates of remission in the 1-2-3 group and 1-3-5 group were 85.3 and 76.47%, respectively (P = 0.644). The 1-2-3 group had lower creatinine and higher eGFR than the 1-3-5 group, but the difference was not significant. The complication rate was 11.11 and 15.79% in the two groups, respectively. There was no significant difference in the complications between groups. CONCLUSIONS: Both the 1st-3rd-5th and 1st-2nd-3rd protocols can effectively alleviate proteinuria and protect renal function in IgAN patients with crescents but the 1st-2nd-3rd protocol seemed to have better effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02160132 , Registered June 10, 2014.

Anti-Phospholipase A2 Receptor in Nonlupus Patients with Membranous Nephropathy and Crescents.

Introduction: Anti-phospholipase A2 receptor (PLA2R) is detected in approximately 70% of biopsies of "primary" membranous nephropathy (MN). Crescents in MN in nonlupus patients suggest additional injury, such as antineutrophil cytoplasmic antibody (ANCA) or anti-glomerular basement membrane (anti-GBM)-associated glomerulonephritis and are postulated to reflect injury by a mechanism that unmasks cryptic epitopes leading to the second autoantibody. Methods: We studied PLA2R staining in nonlupus patients with MN and crescents. Native renal biopsies in 16 nonlupus patients with MN and crescents were stained for PLA2R. Results: The patients included 5 women and 11 men, with mean age 61 years and elevated serum creatinine (mean 4.68 mg/dL). Hematuria and proteinuria (mean 4.97 g/day) were documented in 13 patients. Two patients had positive serum anti-GBM antibody. Nine of 11 patients tested for ANCA were positive, with p-ANCA (n = 4), c-ANCA (n = 2), or both (n = 1), with 2 not specified. On average, 27% of glomeruli had crescents. One patient had an initial biopsy with MN, 4 years later had MN with crescent, and 7 years later had rebiopsy with persistent MN with crescents. One patient had ANCA-associated vasculitis, and 5 years later had MN and crescent. The remaining 14 patients had concurrent diagnoses of MN and crescents. PLA2R was positive in 5 cases, 3 with ANCA positivity, 2 with unknown ANCA status, and none with anti-GBM disease. The patient with initial MN preceding crescent was PLA2R positive; the patient with initial ANCA-associated vasculitis preceding MN was PLA2R negative. Conclusions: Most patients (64%) presented with concomitant MN and crescents, with rare occurrence of an initial disease process followed later by the second injury. PLA2R was positive in 31% of patients, suggesting most are secondary MN. Further study to determine the cryptic epitopes may shed light on the triggering mechanisms for these rare but unlikely coincidental glomerular injuries.

Glomerulonephritis with Crescents in Polyomavirus Nephropathy.

Polyomavirus nephropathy (PVN) is a known complication of renal transplantation due to the reactivation of latent BK virus (BKV) infection. Viral replication is usually confined to tubules. However, in severe viremia and late stages of PVN, it can involve glomerular parietal epithelial cells. Glomerular involvement by BKV can cause crescent formation and may lead to graft failure. We describe a relatively rare case of PVN with glomerular involvement and crescent formation in a 52-year-old male who had undergone a transplant 16 months ago. Despite the stoppage of immunosuppression, graft failure occurred eventually. Interestingly, we observed the intense positivity for IgG and c4d in the Bowman capsule on immunofluorescence. Observation of such positivity along Bowman capsule in renal biopsies with a limited number of glomeruli should alert pathologists to do a vigilant search of BKV inclusion and perform immunohistochemistry for SV 40 large T antigen.

IgA Nephropathy with Crescents: A Single-Center Experience.

INTRODUCTION: The presence of crescents in IgA nephropathy (IgAN) has been associated with a poor prognosis. We assess the prognosis of crescents in our patients with IgAN. METHODS: IgAN was diagnosed in 73 patients biopsied at Rush University Medical Center from 1992 to 2020, and crescents were seen in 26 (36%). Clinical, laboratory and histologic features at biopsy, and treatment and outcome (end-stage kidney disease, ESKD) were collected retrospectively. Data are presented as mean ± SD and a p value of <0.05 was significant. RESULTS: There was no difference in hypertension, SCr, or eGFR in patients with crescents compared to those without crescents but patients with crescents had higher UPro/Cr ratio (2.8 ± 2.7 vs. 1.7 ± 1.7 g/g, p 0.04). The percentage of glomeruli with global and segmental sclerosis (32 ± 25% vs. 38 ± 28%, p 0.35) and the proportion of interstitial fibrosis and tubular atrophy (22 ± 20% vs. 22 ± 22%, p 0.76) were similar. Only 19% of patients with crescents had lesions involving ≥25% of glomeruli. A larger proportion of patients with crescents were treated with immunosuppressive agents (70% vs. 21%, p 0.0005). After 8.4 ± 7 years of follow-up, ESKD (19% vs. 23%, p 0.77) and renal survival at 10 years (80% vs. 74%, p 0.99) were similar in patients with and without crescents. CONCLUSION: The presence of crescents in IgAN was not associated with an increased risk of progression to ESKD. This may be a result of the fact that the majority of our patients had crescents involving <25% of glomeruli and received aggressive treatment with immunosuppressive agents.

Crescents in primary glomerulonephritis: a pattern of injury with dissimilar actors. A pathophysiologic perspective.

Cellular crescents are defined as two or more layers of proliferating cells in Bowman's space and are a hallmark of inflammatory active glomerulonephritis and a histologic marker of severe glomerular injury. In general, the percentage of glomeruli that exhibit crescents correlates with the severity of kidney failure and other clinical manifestations of nephritic syndrome. In general, a predominance of active crescents is associated with rapidly progressive glomerulonephritis and a poor outcome. The duration and potential reversibility of the underlying disease correspond with the relative predominance of cellular or fibrous components in the crescents, the initial location of the immunologic insult inside the glomerulus, and the sort of involved cells and inflammatory mediators. However, the presence of active crescents may not have the same degree of significance in the different types of glomerulopathies. The pathophysiology of parietal cell proliferation may have dissimilar origins, underscoring the fact that the resultant crescents are a non-specific morphological pattern of glomerular injury with different implications in clinical prognosis in the scope of glomerular diseases.

A Rare Case of Type 4 Rapidly Progressive Glomerulonephritis (Atypical) with Mesangial IgA Deposits: A Case Report.

Rapidly progressive glomerulonephritis can result from glomerular deposition of anti-GBM antibody, immune complexes, or may involve pauci-immune mechanisms. The coexistence of IgA nephropathy, anti-GBM, and anti-neutrophilic cytoplasmic antibodies is unheard of, and the pathogenic role of these antibodies in IgA nephropathy or vice versa remains unclear. Herein, we describe a case of a patient with type 4 rapidly progressive glomerulonephritis who was found to have significant mesangial IgA deposits. The prognosis of this remains unclear but our patient responded well to cytotoxic therapy and plasmapheresis and achieved remission by 6 months. The findings suggest an overlap syndrome of IgA nephropathy-associated type 4 crescentic glomerulonephritis that resembles the former histologically and the latter in its potential to respond to aggressive therapy if detected relatively early in its course.