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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM ASIA - AFRICA  
Year : 2014  |  Volume : 25  |  Issue : 3  |  Page : 689-696
Clinicopathologic spectrum of crescentic glomerulonephritis: A hospital-based study


1 Department of Nephrology, Dialysis and Transplant Unit, SS Hospital, Institute of Medical Sciences, Varanasi, Uttar Pradesh, India
2 Department of Nephrology, Institute of Nephrology, S.S. Hospital, Banaras Hindu University, Varanasi, Uttar Pradesh, India
3 Department of Immunopathology, UGC Advanced Immunodiagnostic, Training and Research Center; Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

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Date of Web Publication9-May-2014
 

   Abstract 

Recent data regarding the clinical and histopathologic spectrum of crescentic glomerulonephritis (CSGN) among the Indian adult population is unknown. Our aim is to study the clinicopathological features and outcome of CSGN. It is a retrospective observational study from a tertiary care hospital in India over 3.5 years. Biopsy-proven cases of CSGN (i.e., >50% crescents in glomeruli) were included in the study. Cases with insufficient data were excluded. There were 34 cases of CSGN, accounting for an incidence of 5.5% among kidney biopsies. The mean age was 32.2 ± 16.09 years, with male to female ratio of 12:22. Clinical presentations of CSGN include rapidly progressive glomerulonephritis in 23 (67.7%), chronic renal failure (CRF) in seven (20.5%), nephrotic syndrome in two (5.8%) and acute nephritic syndrome in two (5.8%) patients. The immunological profile of CSGN showed MPO-ANCA in nine (26.4%), PR3-ANCA in one (2.9%), both PR3 and MPO-ANCA in one (2.9%), anti-GBM antibody in five (14.7%) and lupus nephritis in six (17.6%) patients. All the three antibodies were present in one patient. The percentage of glomeruli showing crescents were 100% in nine (26.4%) and ≥80% in seven (20.5%) patients. Type of crescents seen were cellular in 11 (32.3%) and fibrocellular in 22 (64.7%) patients and fibrous in one (2.9%) patient. Interstitial fibrosis was found in seven (20.5%) patients. Dialysis dependency was seen in 11 (32.3%) patients. After 3 months of follow-up, mortality was seen in three (8.8%), remission in eight (23.5%), CRF in 15 (44.1%) and ESRD in five (14.7%) patients. CSGN carries a poor prognosis. The disorder may have an insidious onset and a slowly progressive course. ANCA, anti-GBM-antibody and anti-dsDNA can coexist in CSGN.

How to cite this article:
Choudhury TA, Singh RG, Usha, Singh S, Singh TB, Rathore SS, Prabhakar. Clinicopathologic spectrum of crescentic glomerulonephritis: A hospital-based study. Saudi J Kidney Dis Transpl 2014;25:689-96

How to cite this URL:
Choudhury TA, Singh RG, Usha, Singh S, Singh TB, Rathore SS, Prabhakar. Clinicopathologic spectrum of crescentic glomerulonephritis: A hospital-based study. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2019 Oct 22];25:689-96. Available from: http://www.sjkdt.org/text.asp?2014/25/3/689/132241

   Introduction Top


Crescentic glomerulonephritis (CSGN) is a pathological condition that is characterized by involvement of glomeruli extensively (more than 50%) with crescents with or without accompanying glomerular tuft hypercellularity. The clinical hallmark of CSGN is rapidly progressive glomerulonephritis (RPGN). This manifests as progressive deterioration in renal function in days, or weeks or months rather than years. [1]

It has been reported that CSGN comprises 2-10% of the total number of kidney biopsies. [2],[3],[4] The primary diseases that subsequently develop CSGN show regional variation. [5] The clinical and epidemiological factors of CSGN and their histopathology and outcome in the Indian population are unclear. There is reported literature of CSGN in children in the region; however, data in adult patients are scarce and hence this study was planned for the same. The purpose of the study was to investigate the incidence, the underlying primary disease, clinical characteristics and their histological features in a population from Eastern India.


   Materials and Methods Top


This is a retrospective observational study. The study was conducted in the Department of Nephrology and Pathology, Institute of Medical Sciences, Banaras Hindu University from January 2008 to June 2011. The biopsy-proven cases of CSGN were included. Only those cases where >50% glomeruli showed crescents were included. Those cases of focal crescents are excluded from the study. Those cases who have insufficient data are also excluded. The details of hospital admission records were analyzed and patients were subsequently followed at the outpatient department.

Definitions used[6],[7]

Nephrotic-range proteinuria (NS) was defined as proteinuria >3.5 g/day with or without hypoalbuminemia.

Acute nephritic syndrome was defined as hematuria, RBC casts and proteinuria (<3.5 g/ day), which persist <3 months.

RPGN syndrome was defined as acute nephritic syndrome with acute deterioration in renal function, such as a two-fold increase in serum creatinine concentration or a decrease in creatinine clearance by 50%.

Chronic nephritic syndrome/CSGN was defined as proteinuria (1-3.5 g/day) and hematuria that persisted for more than three months.

Remission was defined as the level of serum creatinine <1.4 mg/dL and proteinuria of <0.4 g/day.

Partial remission was defined as serum creatinine decrease 50% if it is more than 2.3 mg/dL and proteinuria decrease 50% than that initially.

Histopathology


All renal biopsy specimens were processed for light microscopy at the histopathology section. Immunoflorescence and electron microscopy were not performed due to non-availability at our institute during the study period. Two pathologists reviewed the histopathologic findings. For light microscopy, renal tissue samples were fixed in 10% formaldehyde, embedded in paraffin and cut into thin sections. Sections were stained with hematoxylin and eosin, periodic acid-Schiff and Masson's trichome. AFOG stain was performed for immune deposits.

Serology

ANA, Anti-Ds DNA antibody, ANCA and Anti-GBM antibodies were measured by ELISA methods using Kits of Phoda Co.

Serum complements

The reference ranges for C3 and C4 were 72-156 mg/dL and 20-50 mg/dL, respectively. ASO titer >200 titer is considered positive.


   Statistical Analysis Top


The data were encoded using Microsoft Excel and analyzed using SPSS Software version 16.0. Descriptive statistics such as mean, standard deviation and proportions were computed for the different variables of interest. For determining relationships and correlation of variables, chi-square test, Fisher's exact test, Pearson's correlation and ANOVA were used in the analysis of appropriate variables. A P-value of less than 0.05 was considered significant.


   Results Top


Incidence of CSGN

There were 37 cases of CSGN, of which three cases were excluded due to insufficient data. The incidence of CSGN was 5.5% out of 670 non-transplant kidney biopsies performed during the period. The male to female ratio was 12:22. The mean age of presentation was 32.44 ± 15.9 (range: 12-72) years. Four (11.7%) patients were between 60 and 72 years and four (11.7%) patients were below 20 years. The clinical presentation and laboratory features are shown in [Table 1].
Table 1: Clinical and laboratory parameters of CSGN patients.

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The median time of presentation was 30 days (range: 10-365 days). The remarkable observation was that 20.5% of the patients presented as CRF and 38.2% of them had non-oliguric renal failure at presentation. Serum creatinine at presentation was ≥5.5 mg/dL in 13 (38.2%) patients, >3-5.4 mg/dL in 12 (35.3%) patients and <3 mg/dL in nine (26.4%) patients.

The immunological profile of CSGN is shown in [Table 2]. The remarkable observations were that four (11.7%) patients were positive for both ANCA and anti-GBM antibodies and two (5.8%) lupus nephritis patients were ANCA positive. One patient had both PR3 and MPO ANCA positivity. Anti-GBM antibody was positive in five (14.7%) patients and lupus nephritis was present in six (17.6%) patients. All the three antibodies were present in one patient. One case of each membranous nephropathy and post-streptococcal glomerulonephritis were associated with CSGN. In 15 (44.1%) cases, it was diagnosed as idiopathic CSGN.
Table 2: Immunopathologic characteristics of CSGN patients.

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Three of four double-positive (anti-GBM anti-body and ANCA) patients died, and the remaining patient showed partial remission. Both the patients of lupus nephritis with ANCA positivity were in CRF at last follow-up and showed partial remission [Table 4].

Follow-up data were not available for three patients. The median follow-up time was five months (range: 2-36 months). The outcome of patients is shown in [Table 3]. The median time for remission was 75 days (range: 25-150 days). The factors associated with worse outcome were dialysis dependency, anti-GBM and/or ANCA positivity and oligoanuria, as shown in [Table 4].
Table 3: Outcome and treatment of the CSGN patients.

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Table 4: Outcome analysis at the end of the third month from diagnosis.

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The causes of death were massive hemoptysis (1), sepsis with pneumonia (2) and intracranial and intramedullary hemorrhage (3). Median time for death was 15 days.


   Discussion Top


This is a retrospective study of 34 patients of CSGN, where the incidence of CSGN was 5.5% of kidney biopsies. The incidence of CSGN varies with geographic location and policies of kidney biopsies. The incidence of CSGN was 1.75% in a study from China. [8] However, studies from Western Europe and North America (2-10%) and South Africa (3.8%) showed a near-similar incidence. [2],[3],[4],[5] Gupta et al [9] found an incidence of 2.65% of kidney biopsies, but the study included both pediatric and adult patients. The difference with the present study may be due to the differing patient cohorts and policies of kidney biopsies. CSGN occurs in all ages. The mean age of presentation in our study was 32.44 ± 15.9 years, with a predominance of female sex (male to female ratio 0.54). Gupta et al [9] from India also observed younger age of presentation of CSGN (27.6 + 17.1 years). However, the study population included 26% of the pediatric group. There was a female predominance in immune complex-mediated CSGN. [9] The female predominance is due to the higher prevalence of immune complex diseases.

Thirty percent of the patients of CSGN present with chronic renal failure. [8] Although the most common presentation of CSGN was RPGN (67.7%) in the present study, a number of patients of CSGN presented with CRF-CGN (17.6%) and nephrotic syndrome (6.0%). Although statistically not significant, they had better outcome. This is in contrast with the dictum "CSGN is the pathologic entity for clinical syndrome RPGN." These patients had an insidious onset of disease and slowly progressive course that led to late presentation. Health awareness as well as the economic status of our patients may be the contributory factor. Among patients of CRF presentation, 71.4% remained in CRF and 28.6% showed remission, and none progressed to ESRD or had mortality till three months (P-value 0.28). However, patients who presented with RPGN had a higher mortality or ESRD [Table 4]. Because of an insidious onset and slow progression, these groups of patients are often diagnosed too late and, by that time, irreversible histopathological changes occur and potential immunosuppressive therapy remains questionable.

While considering the etiology of CSGN, the present study revealed that idiopathic (44.1%) is the most common variety, followed by ANCA-associated (23.5%) and lupus nephritis (11.7%). Vasculitis is the most common form in western countries. [2],[3],[4] Data from a study in China demonstrated that lupus nephritis was the most common etiology, followed by IgA nephropathy and vasculitis. [8] Progression to ESRD or mortality was lower among patients of unknown etiology than known etiology (statistically not significant). Prospective studies with large number of patients required to substantiate the findings.

Four patients (13.3%) in our study had both Anti-GBM antibodies and were ANCA positive. Three had MPO-ANCA and one patient had PR3-ANCA. They had worse outcome; three of them died and one progressed to CRF (P-value 0.00). Levy et al (2004) reported that 82% of patients (n = 27) of double-positive had MPO-ANCA. Our study revealed 75% MPO-ANCA and 25% PR3-ANCA double-positive patients. The study also demonstrated poor outcome in double-positive patients. [10]

The overall frequency of ANCA in Goodpasture's disease is 30%, [11] whereas patients with ANCA-associated vasculitis develop anti-glomerular basement antibodies in <5% of the cases. [12] Usually, both antibodies occur together at the time of clinical presentation. Concomitant ANCA positivity in patients of anti-GBM disease affects the prognosis, whereas some authors describe an unfavorable outcome for those patients with double positivity [12],[13] and others disagree. [14],[15],[16] A study from the Netherlands showed that patient and renal survival is different in double-positive patients (statistically not significant) than positivity of either. Renal survival at one year was 65%, 10% and 15% in ANCA, double-positive and anti-GBM-positive patients, respectively. [16] Renal failure was lower in ANCA-positive patients compared with double-positive or anti-GBM-positive patients (5.0, 10.3 and 9.6 mg/dL, respectively; P = 0.01). Levy et al [12] analyzed 27 patients with CSGN and double-positivity for anti-GBM antibodies and ANCAs (mostly MPO-ANCA), and described patient and renal survival rates of 52% and 26%, respectively, at one year. Sixty-eight percent of patients were dialysis dependent at presentation, and none of them recovered renal function, despite immunosuppression with or without plasma exchange.

Although patients with CSGN and double-positivity for anti-GBM antibodies and ANCAs may have a poor prognosis when presenting with severe disease, behaving more like anti-GBM disease than vasculitis, recovery from severe renal failure may be rare. They are the candidates for aggressive immunosuppressive therapy with plasma exchange, which can improve renal outcome.

In this study, there was one patient with positive ANA, anti-dsDNA, ANCA and anti-GBM positivity and one patient with ANCA and anti-dsDNA positivity. The former patient showed partial remission and progressed to CRF, while the patient improved later and is presently without dialysis [Table 4]. The role of triple positivity is uncertain. Approximately 20% of patients with SLE have ANCA positivity by immunoflorescence, mainly with a p-ANCA pattern. [17] A study on 566 patients with SLE from multiple centers in Europe found ANCA positivity by immunoflorescence in 16.4% of patients, including 15.4% p-ANCA and 1% c-ANCA. [18] Histologically, they are characterized by prominent necrosis and crescent formation in the absence of significant endocapillary proliferation or subendothelial deposits. [19],[20] It has been suggested that abnormalities in both humoral and cell-mediated immunity are involved in lupus nephritis patients positive for MPO-ANCA. [21] These cases represent the coexistence of LN with ANCA-associated necrotizing and crescentic GN. In the setting of LN with ANCA-associated GN, aggressive immunosuppressive therapy is warranted. [22] The precise role of ANCA in the pathologic course of crescentic lupus nephritis remains unclear. [23] Another patient had both PR3 and MPO-ANCA positive. The clinical significance of both types of ANCA positivity in the same patient is uncertain. The patient was a middle aged female who has shown improvement with cytotoxic regimen. There are case reports of sequential presence of both MPO and PR3 ANCA in the same patient. [24]

The present study revealed that fibrocellular crescents were the most common type of crescents, followed by cellular crescents. The higher prevalence of fibrocellular (65%) crescents and interstitial fibrosis (20.5%) portend to poor outcome of CSGN in the study.

The present study revealed a mortality rate of 9.9% among patients of CSGN. The median time of death was 15 days. The mortality within the first year was 13.9% in a study by Mark et al (2004) in patients of small vessel vasculitis. [25] Marjan et al reported a mortality of 20% within the first year of diagnosis. [26] The present study accounted for a mortality up to three months after diagnosis, and three (9%) patients had no follow-up data that may explain low mortality. Further, prolonged follow-up is necessary to document mortality outcome. Follow-up at three months revealed a remission rate of 23.5%. There is no uniform definition of remissions in CSGN. Again, remission differs among the type of etiology of CSGN. The remission rate is lowest in anti-GBM disease. It is demanded that the remission rate be 80-90% among patients of CSGN. A comparative low rate of remission in this study is an audit of presentation at advanced renal failure, slowly progresssive disease in few patients, low socio-economic status and poor education.


   Limitations of the Study Top


  1. Retrospective study
  2. Lack of immunoflorescence
  3. Lack of long-term follow-up
  4. Small number of patients in the study.



   Conclusion Top


CSGN carries poor prognosis. Majority of our patients reported in advanced stages of renal failure, which has a strong bearing on outcome. CSGN can have an insidious and slowly progressive course. Early recognition and timely intervention are required to prevent progression to CRF or ESRD. Anti-dsDNA, anti-GBM antibody and ANCA can coexist in CSGN.

 
   References Top

1.Glassock RJ, Cohen AH, Adler AG. Rapidly progressive glomerulonephritis. In Brenner Rector's The Kidney, Vol. II, 5 th ed. Philadelphia: W.B. Saunders Company; 1996. p. 1402-11.  Back to cited text no. 1
    
2.Peteersson EE, Saunedlin B, Heigl Z. Incidence and outcome of pauciimmune necrotizing and crescentic glomerulonephritis in adults. Clin Nephrol 1995;43:141-9.  Back to cited text no. 2
    
3.Jennette JC, Falk RJ. Antineutrophil Cytoplasmic autoantibodies and associated diseases: A review. Am J Kid Dis 1990;15:517-25.  Back to cited text no. 3
    
4.Andrassy K, Kuster S, Waldherr R, Ritz E. Rapidly progressive glomerulonephritis, analysis of prevalence and clinical course. Nephron 1991;59:206-12.  Back to cited text no. 4
    
5.Zent R,Van Zyl Smit R, Duffield M, Cassidy MJ. Crescentic Glomerulonephritis at Goote Shuur Hospital, South Africa, not a benign disease. Clin Nephrol 1994;42:22-9.  Back to cited text no. 5
    
6.Zhou TF, Zhao MH, Zou WZ, Liu G, Wang H; The changing spectrum of primary glomerular diseases within 15 years: A survey of 3331 patients in a single Chinese centre; Nephrol Dial Transplant 2009;24:870-6.  Back to cited text no. 6
    
7.Tang Z, Wang Z, Zhang HT, et al; Clinical features and renal outcome in lupus patients with diffiuse crescentic glomerulonephritis (abstract), Rheumatol Int 2009;30:45-9.  Back to cited text no. 7
    
8.Tang Z, Wu Y, Wang Q, et al. Clinical spectrum of diffuse cresscenteric Glomerulonephritis in Chinese patients. Chin Med J 2003;116: 1737-40.  Back to cited text no. 8
    
9.Gupta R, Singh L, Sharma A, Bagga A, Agarwal SK, Dinda AK. Crescentic glomerulonephritis: A clinical and histomorphological analysis of 46 cases. Indian J Pathol Microbiol 2011;54:495-500.  Back to cited text no. 9
    
10.Levy JB, Hammad T, Coulthart A, Dougan T, Pusey CD. Clinical features and outcome of patients with both ANCA and Anti-GBM antibodies. Kidney Int 2004;66:1535-40.  Back to cited text no. 10
    
11.Jayne DR, Marshall PD, Jones SJ, Lockwood CM. Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis. Kidney Int 1990;37:965-70.  Back to cited text no. 11
    
12.Levy JB, Hammad T, Coulthard A, Dougan T, Pusey CD. Clinical features and outcome of patients with both ANCA and anti-GBM antibodies. Kidney Int 2004;66:1535-40.  Back to cited text no. 12
    
13.Donoghue DJ, Short CD, Brenchley PE, Lawler W, Ballardie FW. Sequential development of systemic vasculitis with anti-neutrophil cytoplasmic antibodies complicating anti-glomerular basement membrane disease. Clin Nephrol 1989;32:251-5.  Back to cited text no. 13
    
14.Bosch X, Mirapeix E, Font J, et al. Prognostic implication of anti-neutrophil cytoplasmic autoantibodies with myeloperoxidase specificity in anti-glomerular basement membrane disease. Clin Nephrol 1991;36:107-13.  Back to cited text no. 14
    
15.Yang G, Tang Z, Chen Y, et al. Antineutrophil cytoplasmic antibodies in Chinese patients with anti-GBM crescentic glomerulonephritis. Clin Nephrol 2005;63:423-8.  Back to cited text no. 15
    
16.Rutgers A, Slot M, Paassen PV, Vriesman PV, Heeringa P, Tervaert JW. Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentic glomerulonephritis. Am J Kidney Dis. 2005; 46:253-62.  Back to cited text no. 16
    
17.Sen D, Isenberg DA. Antineutrophil cytoplasmic autoantibodies in systemic lupus erythematosus. Lupus 2003;12:651-8.  Back to cited text no. 17
    
18.Galeazzi M, Morozzi G, Sebastiani GD, et al. Anti-neutrophil cytoplasmic antibodies in 566 European patients with systemic lupus erythematosus: Prevalence, clinical associations and correlation with other autoantibodies. European Concerted Action on the Immunogenetics of SLE. Clin Exp Rheumatol 1998;16:541-6.  Back to cited text no. 18
    
19.Hill GS, Delahousse M, Nochy D, Bariety J. Class IV-S versus class IV-G lupus nephritis: Clinical and morphologic differences suggesting different pathogenesis. Kidney Int 2005;68: 2288-97.  Back to cited text no. 19
    
20.Mittal B, Hurwitz S, Rennke H, Singh AK. New subcategories of class IV lupus nephritis: Are there clinical, histologic, and outcome differences? Am J Kidney Dis 2004;44:1050-9.  Back to cited text no. 20
    
21.Marshall S, Dressler R, D' Agati. Membranous lupus naphritis and Antineutrophil Cytoplasmic Antibody associated Segmental nectotizing and crescentic glomerulonephritis; Am J Kidney Dis 1997;29:119-27.  Back to cited text no. 21
    
22.Nasr SH, D'Agati VD, Park HR, et al. Necrotizing and crescentic lupus nephritis with anti-neutrophil cytoplasmic antibody seropositivity. Clin J Am Soc Nephrol 2008;3:682-90.  Back to cited text no. 22
    
23.Yu F, Tan Y, Liu G, Wang SX, Zou WZ, Zhao MH. Clinicopathological characteristics and outcomes of patients with crescentic lupus nephritis Crescentic lupus nephritis. Kidney Int 2009;76:307-17.   Back to cited text no. 23
    
24.Verburgh CA, Bruijn JA, Daha MR, van Es LA. Sequential development of anti-GBM nephritis and ANCA-associated pauci-immune glomerulonephritis. Am J Kidney Dis 1999; 34:344-8.  Back to cited text no. 24
    
25.Little MA, Nazar L, Farrington K. Outcome in glomerulonephritis due to systemic small vessel vasculitis: Effect of functional status and non-vasculitic comorbidity. Nephrol Dial Transplant 2004;19:356-64.  Back to cited text no. 25
    
26.Slot MC, Tervaert JW, Franssen CF, Stegeman CA. Renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement. Kidney Int 2003;63:670-7.  Back to cited text no. 26
    

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Correspondence Address:
Dr. Tauhidul Alam Choudhury
Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP
India
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DOI: 10.4103/1319-2442.132241

PMID: 24821180

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