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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 6  |  Issue : 1  |  Page : 30-36

A clinicopathological study of membranoproliferative glomerulonephritis in the light of new evolving classification


1 Department of Pathology, TMSS Medical College, Bogura, Bangladesh
2 Sheikh Hasina National Institute of Burn and Plastic Surgery, Dhaka, Bangladesh
3 Department of Paediatric Nephrology, National Institute of Kidney Diseases and Urology, Dhaka, Bangladesh
4 Department of Paediatrics, TMSS Medical College, Bogura, Bangladesh
5 Department of ENT and HNS, TMSS Medical College, Bogura, Bangladesh

Date of Submission01-Sep-2021
Date of Acceptance23-Sep-2021
Date of Web Publication29-Dec-2021

Correspondence Address:
Dr. Asaduzzaman
Sheikh Hasina National Institute of Burn and Plastic Surgery, Dhaka
Bangladesh
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pnjb.pnjb_2_21

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  Abstract 

Background: Membranoproliferative glomerulonephritis (MPGN) is a progressive disease with poor prognosis. An emerging consensus on classification based on immunofluorescence findings separates MPGN into two groups: immune complex-mediated MPGN and complement-mediated MPGN. This study was undertaken to investigate the clinical, biochemical, and histopathological parameters in-between these two groups histologically diagnosed as MPGN previously. Materials and Methods: We conduct a retrospective cross-sectional study carried out at the Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period from June 2016 to December 2017. A total of 67 histologically diagnosed MPGN cases were enrolled in the study. Immunofluorescence evaluations were performed and correlated with retrospective clinical and biochemical data. Results: Immune complex-mediated MPGN and complement-mediated MPGN cannot be differentiated by histopathology. There were no significant differences between clinical (age, sex, clinical presentation) and biochemical (serum creatinine, C3 level, C4 level) parameters between immune complex-mediated MPGN and complement-mediated MPGN. Conclusion: Clinical and biochemical and histopathological parameters in-between these two groups of MPGN show no significant difference.

Keywords: Complement, dense deposit disease, immunofluorescence, membranoproliferative glomerulonephritis


How to cite this article:
Rahman DM, Asaduzzaman, Tahmina K, Selim A, Huq MM. A clinicopathological study of membranoproliferative glomerulonephritis in the light of new evolving classification. Paediatr Nephrol J Bangladesh 2021;6:30-6

How to cite this URL:
Rahman DM, Asaduzzaman, Tahmina K, Selim A, Huq MM. A clinicopathological study of membranoproliferative glomerulonephritis in the light of new evolving classification. Paediatr Nephrol J Bangladesh [serial online] 2021 [cited 2022 Jan 22];6:30-6. Available from: http://www.pnjb-online.org/text.asp?2021/6/1/30/334115




  Introduction Top


Membranoproliferative glomerulonephritis (MPGN) is the fourth most common cause of primary glomerulonephritis in Bangladeshi patients and the seventh most common cause of primary glomerulonephritis in Indian patients.[1],[2] MPGN refers to glomerular pathology in which there is thickening of the capillary wall together with mesangial expansion. MPGN, also called mesangiocapillary glomerulonephritis, is a lesion, not a disease. The lesion was first demarcated from other forms of glomerulonephritis in 1961–62 by Royer et al.[3]

MPGN accounts for up to 10% of cases of nephrotic syndrome in children and young adults.[4] Some patients present only with hematuria or proteinuria in the non-nephrotic range, but many others have a combined nephrotic and nephritic picture. MPGN is increasingly recognized to be associated with other systemic disorders and is known as secondary MPGN, but there is still a residue of cases of unknown etiology (primary MPGN).[4]

MPGN is a pattern of glomerular injury resulting from predominantly subendothelial and mesangial deposition of immune complexes and/or complement factors and their products. It is histologically defined on light microscopy (LM) by mesangial hypercellularity, endocapillary proliferation, and capillary wall remodeling with double contour formation, all of these changes resulting in a lobular accentuation of the glomerular tufts.[5]

Traditionally, primary MPGN has been further classified based on the findings of electron microscopy (EM) as MPGN type I (MPGN I), MPGN II, and MPGN III. MPGN I, which is the most common form, is characterized by subendothelial deposits, and MPGN III has both subepithelial and subendothelial deposits. MPGN II is characterized by dense deposits in the glomerular basement membrane (dense deposit disease [DDD]).

It is proposed that MPGN may be classified into two major groups based on immunofluorescence (IF) findings: immunoglobulin (Ig)-mediated and complement-mediated (C3G) MPGN [Figure 1]. If the IF studies show predominantly C3 and are negative or show no significant staining for Ig’s, this is called complement-mediated MPGN, also known as C3 glomerulopathy. If Ig’s are present on IF studies, it is considered as Ig-mediated MPGN.[6],[7],[8],[9]
Figure 1: New evolving classification system of membranoproliferative glomerulonephritis[6],[7]

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This study was on MPGN cases to explore clinical and biochemical and histopathological parameters inbetween these two groups in Bangladeshi perspective.


  Materials and Methods Top


We collected retrospective clinical data on patients diagnosed with MPGN, based on renal biopsy findings at the Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU). This cross-sectional study enrolled 67 diagnosed cases of MPGN during the period from June 2016 to December 2017. A total of 36 male patients and 31 female patients were included in the study. Cases diagnosed as lupus nephritis, post-streptococcal glomerulonephritis, IgA nephropathy, and C1q nephropathy were excluded from the study due to different prognosis.

All recorded clinical and biochemical information of the selected cases was retrieved from the departmental archive. Clinical and biochemical tests were done in the respective department applying appropriate methods. Clinical data including patient’s age, sex, clinical presentation (nephrotic syndrome/nephriric syndrome/nephrito-nephrotic/rapidly progressing glomerulonephritis/acute kidney injury), and results of laboratory investigation such as serum creatinine, hematuria, and urinary total protein (UTP) were measured.

Routine hematoxylin and eosin (H and E), PAS, and Jones methenamine silver-stained sections of the renal biopsy sample were examined by two experienced pathologists in the department of pathology, BSMMU. Sections were examined for changes in four components: glomeruli, tubules, interstitium, and blood vessels. Cryostat sections were examined by a fluorescence microscope for antibody deposition in the renal tissue.


  Result Top


In all of the 67 cases of this study, two samples of renal tissue were obtained from each patient. Informed written consent was taken from the patient/attendant. In each case, relevant clinical history with special attention to age, sex, and clinical presentation was recorded. Relevant biochemical parameters, renal function tests like serum creatinine, 24-h urinary protein (UTP), serum C3 level, and serum C4 level, were recorded. LM was done for the final diagnosis. Findings were correlated with clinical and biochemical data prior to a definitive diagnosis. Then IF study was done and the final diagnosis was made.

Age distribution of the patients

The mean age of immune complex-mediated MPGN was 35.71 ± 11.76 and complement-mediated MPGN was 35.87 ± 14.98. The mean age difference was not statistically significant (P > 0.05) between the two groups. [Figure 2] shows the age distribution of the patients. It reveals that most of the cases of immune complex-mediated MPGN belong to the age group 30–39. On the contrary, most of the patients of complement-mediated MPGN belong to the age group 40–49 [Figure 2].
Figure 2: Age distribution of the patients

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Sex distribution of patients

Sex distributions of the patients of immune complex-mediated MPGN and complement-mediated MPGN were evaluated. In the case of immune complex-mediated MPGN, number of male patients was 31 (53%) and female patients were 28 (47%). In the case of complement-mediated MPGN, number of the male patients was 5 (62%) and female patients was 3 (38%) [Figure 3].
Figure 3: Composite bar diagram showing sex distribution of immune complex-mediated MPGN and complement-mediated MPGN

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Presentations of cases

Nephrotic syndrome is the most common presentation (58%) in cases of immune complex-mediated MPGN as compared with complement-mediated MPGN (37.5%). Nephritic syndrome is the most common presentation (50%) in cases of complement-mediated MPGN as compared with immune complex-mediated MPGN (27%).These differences are not statistically significant (P > 0.05) between the two groups [Figure 4].
Figure 4: Composite bar diagram showing presentations of immune complex mediated MPGN and complement mediated MPGN

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Serum creatinine level

The mean creatinine value of immune complex-mediated glomerulonephritis was 1.56 mg/dL and in the case of complement-mediated glomerulonephritis it was 1.33 mg/dL. This difference was not statistically significant (P > 0.05) between these two groups [Table 1].
Table 1: Mean serum creatinine value and range of creatinine

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C3 level

Serum C3 level decreased in 62% cases and was normal in 38% of cases of immune complex-mediated MPGN. On the contrary, serum C3 level decreased in 57% of cases and was normal in 43% of cases of complement-mediated MPGN. These differences were not statistically significant (P > 0.05) [Figure 5].
Figure 5: Bar diagram showing C3 level in two groups of MPGN

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Serum C4 level

Serum C4 level decreased in 28% cases and was normal in 72% of cases of immune complex-mediated MPGN. On the contrary, it decreased in 50% cases and was normal in 50% cases of complement-mediated MPGN. These differences were not statistically significant (P > 0.05) [Figure 6].
Figure 6: Bar diagram showing C4 level in two groups of MPGN

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Crescent formation

Crescent formation is observed in two cases (3%) of immune complex-mediated MPGN and one case of complement-mediated MPGN (12.5%) [Figure 7].
Figure 7: Bar diagram showing proportion of crescent formation between two groups of MPGN

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Hematuria

Hematuria was present in 69% of cases of immune complex-mediated MPGN. On the contrary, hematuria was present in 75% cases of complement-mediated MPGN. These differences are not statistically significant (P > 0.05).


  Discussion Top


The traditional classification of MPGN is confusing. It is not based on disease pathogenesis and the types are overlapping. A new classification system of MPGN based on IF finding has been proposed. It helps to identify the underlying causes of MPGN and to provide guidance for more individualized treatment. This cross-sectional study was carried out to find out the clinical biochemical and histopathological and parameters in-between these two groups of MPGN.

A total of 67 MPGN cases were included in this cross-sectional study. Two samples of renal tissue were obtained from each patient. Clinical information, all papers, and written consent were taken from the patient/attendant. Specimens for LM were preserved in 10% formalin. All clinical information was recorded in a predesigned proforma before doing histopathology. Clinical data were collected with special attention to patient’s age, sex, clinical presentation, and results of laboratory investigation. Parameters relevant to this study such as urinary albumin, UTP, urinary RBCs, serum C3 level, and serum C4 level were also recorded. We categorized 59 cases (88%) as immune complex-mediated MPGN and 8 cases (12%) as complement-mediated MPGN out of 67 cases.

There were no significant differences (P > 0.05) between the mean age of immune complex-mediated MPGN cases and complement-mediated MPGN (C3 glomerulopathy) cases. The mean age of immune complex-mediated MPGN cases was 35.71 and in complement-mediated MPGN (C3 glomerulopathy) cases it was 35.87. The study conducted by Servis et al.[10] showed that the mean age of presentation of C3 glomerulonephritis was 30.3 (standard deviation [SD] ± 19.3). In this study, it was also found that proportion of C3 glomerulopathy was higher in pediatric patients. This study results show that 1 out of 5 pediatric patients have C3 glomerulopathy (20%). This finding is comparable with the study conducted by Giedraite et al.[11] on pediatric patients. They diagnosed 8 out of 23 pediatric MPGN cases as C3 glomerulopathy which was approximately 34% of total MPGN cases.

Most of the patients of this study with both immune complex-mediated and complement-mediated MPGN are male. The study conducted by Walker et al.[12] also revealed no significant sex difference.

At presentation, almost all patients had proteinurea and most of the patients had hematuria. Nephrotic syndrome was present in 57% of patients of immune complex-mediated MPGN and 37% patients of complement-mediated MPGN. These differences were not statistically significant (P > 0.05). The study conducted by Servis et al.[10] showed that 38% of patients with DDD had nephrotic syndrome at presentation as compared with 65% of patients with MPGN type I.

Hematuria was present in 75% of cases of complement-mediated MPGN and 69% cases of immune complex-mediated MPGN. The study conducted by Nasr et al.[13] showed that 87% of patients of DDD had hematuria on presentation [Figure 8].
Figure 8: Bar diagram showing proportion of hematuria between two groups of MPGN

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Nephritic syndrome was present in 27% of patients of immune complex-mediated MPGN and 50% patients of complement-mediated MPGN in this study. These differences were not statistically significant (P > 0.05). The study conducted by Mathur et al.[14] showed that 50% of patients with a complement-mediated MPGN of their study cases had nephritic syndrome and 50% of patients had nephrotic syndrome at presentation.

There was no significant difference between mean serum creatinine levels in-between immune complex-mediated MPGN and complement-mediated MPGN in our study (P > 0.05). Mean serum creatinine value in immune complex-mediated glomerulonephritis was 1.56 mg/dL. It was slightly lower in the case of complement-mediated glomerulonephritis (1.33 mg/dL). Mean serum creatinine was 2.2 mg/dL in the study conducted by Nasr et al.,[13] on 32 patients diagnosed as DDD.

Serum C3 level decreased in 62% cases and was normal in 38% cases of immune complex-mediated MPGN in our study. On the contrary, serum C3 level decreased in 57% of cases and was normal in 43% of cases of complement-mediated MPGN. These differences were not statistically significant (P > 0.05). The study conducted by Pavinic and Miglinas showed that 40% of the C3GN patients had low C3 levels in the circulation, and 46% of patients of MPGN type I showed low C3 level.[15]


  Conclusion Top


Recognizable clinical and pathologic spectrum of MPGN has evolved considerably since its first description more than a half-century ago. Then MPGN was largely a pediatric disorder and was believed to be mostly idiopathic (or primary) in character. Now it is seen throughout a broad span of ages. In fact, in many areas of the world, MPGN tends to be a disorder seen more commonly in older adults and mostly of a secondary origin. Recently, a new classification system based on pathological IF findings has been proposed to replace the traditional clinical classification system in order to better identify the underlying causes of MPGN and to provide guidance for more individualized treatment. This latest classification can only be done by IF study as this study shows that there were no significant differences between clinical biochemical and histopathological differences exist between these two groups.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hossain MT, Begum M, Rahman AN, Kamal M Immune deposits in glomerular diseases and their clinical, histopathological and immunopathological correlation. Bangladesh J Pathol 2011;26:14-9.  Back to cited text no. 1
    
2.
Narasimhan B, Chacko B, John GT, Korula A, Kirubakaran MG, Jacob CK Characterization of kidney lesions in Indian adults: Towards a renal biopsy registry. J Nephrol 2006;19:205-10.  Back to cited text no. 2
    
3.
Royer P, Habib R, Vermeil G, Mathieu H, Alizon M. Prolonged glomerulonephritis in children. Apropos of 4 anatomical aspects revealed by renal biopsy. Ann Pediatr1962;9:173-87.  Back to cited text no. 3
    
4.
Kumar V, Abbas AK, Aster JC Robbins & Cotran Pathologic Basis of Disease: South Asia Edition, Professional edition e-book. Philadelphia, PA: Elsevier Health Sciences; 2015.  Back to cited text no. 4
    
5.
Jennette JC, Olson LJ, Schwartz MM, et al(ed). Heptinstall’s Pathology of the Kidney. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.  Back to cited text no. 5
    
6.
Bomback AS, Appel GB Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol 2012;8:634-42.  Back to cited text no. 6
    
7.
Sethi S, Fervenza FC Membranoproliferative glomerulonephritis: Pathogenetic heterogeneity and proposal for a new classification. Semin Nephrol 2011;31:341-8.  Back to cited text no. 7
    
8.
Pickering MC, D’Agati VD, Nester CM, Smith RJ, Haas M, Appel GB, et al. C3 glomerulopathy: Consensus report. Kidney Int 2013;84:1079-89.  Back to cited text no. 8
    
9.
Rabasco-Ruiz C, Huerta-Arroyo A, Caro-Espada J, Gutiérrez-Martínez E, Praga-Terente M C3 glomerulopathies: A new perspective on glomerular diseases. Nefrologia 2013;33:164-70.  Back to cited text no. 9
    
10.
Servais A, Frémeaux-Bacchi V, Lequintrec M, Salomon R, Blouin J, Knebelmann B, et al. Primary glomerulonephritis with isolated C3 deposits: A new entity which shares common genetic risk factors with haemolytic uraemic syndrome. J Med Genet 2007;44:193-9.  Back to cited text no. 10
    
11.
Giedraite N, Besusparis J, Masalskiene J, Cerkauskiene R, Jankauskiene A New classification of paediatric membranoproliferative glomerulonephritis cases in Lithuania. Pediatr Nephrol 2015 pg. 301.  Back to cited text no. 11
    
12.
Walker PD, Ferrario F, Joh K, Bonsib SM Dense deposit disease is not a membranoproliferative glomerulonephritis. Mod Pathol 2007;20:605-16.  Back to cited text no. 12
    
13.
Nasr SH, Valeri AM, Appel GB, Sherwinter J, Stokes MB, Said SM, et al. Dense deposit disease: Clinicopathologic study of 32 pediatric and adult patients. Clin J Am Soc Nephrol 2009;4:22-32.  Back to cited text no. 13
    
14.
Mathur M, Sharma S, Prasad D, Garsa R, Singh AP, Kumar R, et al. Incidence and profile of C3 glomerulopathy: A single center study. Indian J Nephrol 2015;25:8-11.  Back to cited text no. 14
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15.
Pavinic J, Miglinas M The incidence of possible causes of membranoproliferative glomerulonephritis: A single-center experience. Hippokratia 2015;19:314-8.  Back to cited text no. 15
    


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