| Abstract|| |
A series of 78 cases of glomerulonephritis (GN), in which renal biopsy revealed changes of GN associated with crescent formation, were reviewed. Renal pathology findings were correlated with clinical features including patient’s age, renal function, and serologic findings. In most of the cases (71.8%), the crescents were due to immune complex-mediated GN. This was followed by pauci-immune GN (20.5%) and anti-glomerular basement membrane antibody (GBM) GN (7.7%). The percentage of glomeruli with crescents was the highest in cases of anti-GBM disease (mean of 93.3%), followed by pauci-immune GBM (mean of 48.2%) and immune complex GN (30.9%). In cases with the pauci- immune GN, there were additional features of glomerular injury including fibrinoid necrosis, disruption of the GBM, and rupture of Bowman’s capsule. These changes were generally more pronounced in a subset of pauci-immune GN associated with serum elevation of antineutrophil cytoplasmic antibody (c-ANCA). In biopsies from patient with immune complex disease, systemic lupus erythematosus was the most common cause of crescentic GN.
|How to cite this article:|
Al-Hussain T, Asiri S, Amer S, Al Mana H, Akhtar M. Patterns of glomerulonephritis with crescents: Experience at a tertiary medical center in Saudi Arabia. Saudi J Kidney Dis Transpl 2017;28:532-7
|How to cite this URL:|
Al-Hussain T, Asiri S, Amer S, Al Mana H, Akhtar M. Patterns of glomerulonephritis with crescents: Experience at a tertiary medical center in Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Dec 5];28:532-7. Available from: http://www.sjkdt.org/text.asp?2017/28/3/532/206448
| Introduction|| |
Crescents are defined as the presence of two or more layers of cells in Bowman’s space. The presence of crescents in glomeruli is a marker of severe injury. Crescentic glomerulo- nephritis (CrGN) is a term used when >50% of the glomeruli have crescents. It is, however, not a specific disease but rather is a morphologic expression of severe glomerular injury that can be seen in different diseases and is clinically manifested by acute and rapid deterioration of the renal function. It is considered a critical pathological diagnosis requiring an aggressive immunosuppressive therapy.
On the basis of immunopathologic findings, CrGN can be classified into three major types: anti-glomerular basement membrane antibody (anti-GBM) glomerulonephritis (GN), pauci- immune GN (often ANCA-associated), and immune complex-mediated GN. The relative frequency of these subtypes of CrGN varies considerably depending on geographic locations and the age of patient populations.
Only two studies on CrGN have been published from Saudi Arabia, none of which included cases of anti-GBM GN. The aim of this study is to describe different patterns of GN with crescents encountered in Renal Pathology Service at King Faisal Specialist Hospital and Research Center. This we hope will provide a more representative and comprehensive picture of CrGN in this country.
| Methods|| |
This is a retrospective study, in which all renal biopsies with a diagnosis of GN with crescents from January 2003 to February 2014 were retrieved from the Department of Pathology and Laboratory Medicine at King Faisal Specialist Hospital and Research Center. All cases were originally studied by light microscopy, immunofluorescent microscopy, and electron microscopy. For light microscopy, in addition to hematoxylin and eosin stain, special stains including trichrome, periodic acid- Schiff, and Jones silver stains we used in all cases.
Different types of GN were compared for clinical (including patient’s age, renal function, and serology) and pathological features (including cellular crescents and fibrinoid necrosis). The pathology reports as well as glass slides and available electron microscopy photographs were reviewed. The clinical features and laboratory data were obtained from the hospital computer system (CERNER). The study has been approved by the Hospital Research Ethics Committee.
For statistical analysis data were analyzed using the Statistical Package for the Social Sciences version 20.0 for Windows (SPSS Inc., Chicago, IL). Means of continuous variables were compared the one-way ANOVA. Test of independence between categorical variables was done using Pearson’s Chi-square test. The type I error rate is set at 5%.
| Results|| |
A total of 78 cases of GN with crescents were identified among different age groups. Cases included anti-GBM GN (6 cases, 7.7%), pauci- immune GN (16 cases, 20.5%), and immune complex-mediated GN (56 cases, 71.8%). The mean age of the patients varied considerably with the type of GN [Table 1].
|Table 1: Frequency of different types of glomerulonephritis with crescents correlated with age and sex.|
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In all cases, crescents were characterized by cellular proliferation occupying Bowman space [Figure 1]. In cases with anti-GBM GN, the mean patient age was 47.5 years (19–70) with four male and two female patients [Table 1]. All patients presented with acute renal failure with hematuria, proteinuria (0.22–3.0 g/day), and high creatinine (567–789 pmol/L). Microscopically, the biopsies contained 4–35 glome- ruli with a mean of 18.8 glomeruli. A mean of 93.3% of the glomeruli in the biopsies revealed crescents [Table 2]. In all cases, >50% of the glomeruli were involved by crescents. All cases had strong linear GBM staining with antiserum specific for immunoglobulin G by immunofluorescence study [Figure 2].
|Table 2: Frequency of different morphologic features of glomerulonephritis (GN) with crescents on renal biopsy.|
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|Figure 1: A representative glomerulus from a biopsy in a patient with crescentic glomerulonephritis. Bowman's space is occupied by several layers of proliferating epithelial cells forming a crescent (Trichrome stain).|
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|Figure 2: Linear staining pattern along glomerular basement membrane for IgG in a biopsy from patient with anti-GBM disease (Immunofluorescent microscopy).|
IgG: Immunoglobulin G, anti-GBM: Antiglomerular basement membrane antibody.
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In patients with pauci-immune GN, the age of the patients ranged from 14 to 66 years with a mean of 35.9 years; five of the patients were males and 11 were females [Table 1]. Most of the patients presented with acute renal failure with hematuria, proteinuria (0.57–3.33 g/day), and high creatinine (101–1831 pmol/L). Eleven of sixteen patients had available serology including five patients with positive PR3- ANCA, four patients with positive MPO- ANCA, and two patients with negative ANCA titer. Microscopically, the biopsies revealed 10–42 glomeruli with a mean of 21.2 glo- meruli. The mean percentage of glomeruli involved by crescents was 48.2% and 50% of the biopsies revealed >50% crescents [Table 2]. In many of these biopsies in addition there was evidence of fibrinoid necrosis, and occasionally, rupture of the glomerular capillaries and Bowman’s capsule [Figure 3]. On immuno- fluorescent microscopy, all biopsies manifested no or only minimal staining for immunoglobulins and complements [Figure 4].
|Figure 3: A glomerulus from a biopsy in a patient with pauci-immune glomerulonephritis. There is extensive destruction of the glomerular basement membrane as well as the Bowman's capsule (Jones Silver stain).|
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|Figure 4: Immunofluorescent microscopic pattern in a biopsy with pauci-immune glomerulonephritis showing lack of staining for IgG (similar pattern for IgA, IgM, C3, and C1q) Patient had elevated levels of C-ANCA.|
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In cases with immune complex-mediated GN, the mean patient age was 25.8 years with a range of 2–69 years. Of these patients, 19 were male and 37 were female with a ratio of 1:2 [Table 1]. All patients had hematuria, protei- nuria (0.59–12.5 g/day), and high creatinine up to 1402 pmol/L. Microscopically, the biopsies had a mean of 22 glomeruli (range 2–59), and the mean percentage of glomeruli with crescents was 30.9% (12 had >50% crescents) [Table 2]. By immunofluorescence study, all biopsies had moderate-to-strong granular staining for one or more immunoglobulins and/or complements [Figure 5]. These findings correlated with variable amount of immune complex type electron dense deposits within the glomeruli as demonstrated by electron microscopy [Figure 6]. Cases with immune complex- mediated GN included lupus nephritis (48.2%), postinfectious GN (12.5%), membranoprolife- rative GN (type 1) (10.7%), IgA nephropathy (7.1%), proliferative GN (5.4%), and others (16.1%).
|Figure 5: Immunofluorescent microscopic pattern of staining for IgG in a patient with immune complex-mediated glomerulonephritis due to systemic lupus erythematosus.|
IgG: Immunoglobulin G.
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|Figure 6: Electron micrograph featuring part of the glomerulus in a biopsy from patient with lupus nephritis. There are variably sized electron dense deposits within subepithelial, subendothelial, and intramesangial location.|
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| Discussion|| |
Cellular crescents are defined as a multi- layered accumulation of proliferating cells in Bowman’s space and represent a severe form of glomerular injury which requires immediate appropriate treatment. Several types of glome- rular disease can be accompanied by cellular crescents including anti-GBM disease, ANCA- related glomerular disease, and immune complex-mediated glomerulopathy among others. Cellular crescents occlude the urinary outlet and obstruct the flow of the glomerular filtrate, seriously affecting the function of the nephrons, which if the condition remains unresolved may quickly undergo degeneration. By blocking the urinary space, the crescent probably also serves to prevent excessive loss of blood and plasma proteins from severely damaged glomerular capillaries. Crescent formation most frequently occurs in necrotizing and highly inflammatory forms of GN. This would suggest that it is the inflammatory component that accounts for crescent formation. Glome- rular tuft necrosis in these cases may involve injury to the endothelium, GBM, and podo- cytes. Accumulating evidence suggests that plasma leakage provides mitogenic stimuli that drive parietal epithelial hyperplasia and crescent formation. Parietal epithelial cells (PEC) normally exist in an environment devoid of plasma exposure. The rupture of glomerular capillaries in crescentic disease markedly increases the plasma concentration inside Bowman’s space. Several plasma components could potentially account for the PEC hyper- plasia, but currently available evidence seems to implicate fibrinogen activation as the most important factor.
The current study showed that the most common cause of CrGN in both adults and children is immune complex-mediated GN. Jennette and others, however, reported that the most common cause of crescentic GN in adult is pauci-immune GN, whereas in children, the most common cause is immune complex- mediated GN.,, In a recent study, Chen et al reported that the most frequent type of CrGN in China is lupus nephritis followed by pauci- immune crescentic GN. In that study, a majority of patients with pauci-immune GN had MPO-ANCA or PR3-ANCA detectable by enzyme-linked immunosorbent assay. In our study, five patients had positive PR3-ANCA, four patients had positive MPO-ANCA, and two patients had negative ANCA titer. Comparison of these three groups revealed that biopsies from patients with C-ANCA elevation tended to have a higher percentage of glome- ruli with crescents and were more likely to reveal more severe glomerular injury as indicated by more frequent presence of necrosis [Table 3]. This difference is not statistically significant probably due to a small number of cases in each group. Interestingly, Jennette reported similar findings.
|Table 3: Comparison of pathologic and clinical features of pauci-immune glomerulonephritis with available ANCA serology (11 cases).|
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Anti-GBM GN represents the most aggressive form of GN with a higher percentage of glomeruli with crescents. In our series, one female patient with MPO-ANCA positive and 23.1% crescent had concurrent Anti-GBM antibodies. This is a well-recognized concurrence which may occur in less than one-third of the patients and MPO-ANCA is much more than PR3-ANCA. Patients with both Anti- GBM and ANCA have a less extensive crescent formation. Another interesting fin- ding is that in biopsies from patients with AntiGBM disease, most a much higher proportion of glomeruli revealed crescents (mean of 93%) as compared to pauci-immune GN (48.2%) and immune-complex-mediated GN (30.9%) [Table 2].
Only two studies on CrGN have been previously published from Saudi Arabia. None of these included cases of anti-GBM GN which represent 7.7% in our series. Oudah et al reported 72 renal biopsies with CrGN in adult patients (over the age of 18 years). These included lupus nephritis (49.3%), pauci- immune GN (26.5%), postinfectious GN (6.3%), and other immune complex-mediated GN (19%). As in the current study, the most common type of crescentic immune complex- mediated GN was lupus nephritis. Another study of CrGN from Saudi Arabia reported 37 children (below the age of 18 years). Lupus nephritis was the most common cause of CrGN representing 54.1% of the patients.
An inherent weakness of this study is the small number of cases that were available in each group precluding reliable statistical analysis. The strength of this study, however, is that in all cases, the renal biopsies were examined by light microscopy, immunofluore- scence microscopy as well as electron microscopy.
| Conclusions|| |
In this study, most of the cases of GN with crescents were due to immune complex- mediated GN (71.8%), followed by pauci- immune GN (20.5%) and anti-GBM GN (7.7%). Patients with anti-GBM GN were older and had a higher percentage of glomeruli with crescents. Patients with immune complex- mediated GN were younger and had lesser percentage of crescents in comparison to anti- GBM GN. Immune complex-mediated GN was the most frequent type of CrGN representing 71.8% of all the cases. Lupus nephritis was the most common cause of immune complex-mediated CrGN.
| Acknowledgment|| |
The authors would like to thank Dr. Mohamed Shoukri for doing statistical analysis.
Conflict of interest: None declared.
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Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, MBC-10, P. O. Box 3354, Riyadh 11211
Kingdom of Saudi Arabia
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3]