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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 51  |  Issue : 3  |  Page : 337-341
Mesangioproliferative glomerulonephritis: An important glomerulonephritis in nephrotic syndrome of young adult


1 UGC Advanced Immunodiagnostic Training and Research Center, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
3 Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

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   Abstract 

Mesangioproliferative glomerulonephritis (MesPGN) consists 10% of the total renal biopsy of glomerulonephritis. Aim of the present study was to find out clinicopathological changes in MesPGN and differences between diffuse and focal variety. MesPGN was seen mostly in young adults with mean age of 28.63 years for males and 26.3 years for females. Male predominance was noted (M:F ratio - 1.4:1). About 70.83% patient presented with edema feet, followed by hypertension (29.19%), fever (16.66%), oliguria, nausea and vomiting (10.41%). Urine analysis in 50 patients revealed that 70% patients presented with nephrotic-range proteinuria, 36% patients with microscopic hematuria and 56% patients with leukocyturia. Statistically, no significant difference was found in clinical features of diffuse and focal MesPGN. Microscopic comparison between diffuse and focal variety showed that significant increase of focal glomerular basement membrane thickening, focal endothelial cell proliferation, focal smooth muscle hyperplasia, hyaline sclerosis and vasculitis was more common in diffuse variety. In focal variety, Capillary loop congestion, periglomerulitis, cloudy swelling and vacuolar degeneration in tubules were significantly more as compared to diffuse variety. Details of the clinical features, special laboratory tests and histological details revealed that diffuse variety had systemic diseases, which included Wegner's granulomatosis, microscopic polyangitis, Henoch's schonlein purpura, systemic lupus erythematosus (two cases) and one case each of Kimura's disease, pyelonephritis and tuberculosis. Only one case of focal MesPGN showed tuberculosis. Thus, our study concludes that MesPGN is an important cause of nephrotic syndrome among young adults. Secondly, search for some other diseases should be made and thirdly, if biopsy shows focal mesangial cell proliferations in minimal change glomerulonephritis (MCGN), it should be diagnosed as focal MesPGN rather than MCGN because these cases show recurrences.

Keywords: Focal proliferative glomerulonephritis (GN), hematuria, mesangioproliferative GN, nephrotic syndrome

How to cite this article:
Usha, Kumar S, Singh R G, Tapas S, Prakash J, Garbyal R S. Mesangioproliferative glomerulonephritis: An important glomerulonephritis in nephrotic syndrome of young adult. Indian J Pathol Microbiol 2008;51:337-41

How to cite this URL:
Usha, Kumar S, Singh R G, Tapas S, Prakash J, Garbyal R S. Mesangioproliferative glomerulonephritis: An important glomerulonephritis in nephrotic syndrome of young adult. Indian J Pathol Microbiol [serial online] 2008 [cited 2020 Jun 2];51:337-41. Available from: http://www.ijpmonline.org/text.asp?2008/51/3/337/42506



   Introduction Top


The glomerular mesangium contains mesangial cells (MC) and extracellular matrix. It plays a crucial role in maintaining structure and function of glomerular capillary tuft. It is in direct contact with fenestrated endothelium. MC represent one-third of total number of glomerular cells. Mesangioproliferative glomerulonephritis (MesPGN) is characterized by proliferations of MC with increase in mesangial matrix and/or deposits in mesangial region. It is a heterogenous disease. It is seen in several conditions like IgA nephropathy, [1] Chronic obstructive pulmonary disease, [2] IgM nephropathy, [3] systemic lupus erythematosus (SLE), Alport's disease, postinfectious GN in resolving phase, complement nephropathy, [4] and Kimura's disease. [5] This glomerulonephritis is easily produced in experimental animal by immunizing with cationic DEAE dextran. [6]

Mesangial cell proliferation appears to play an important role in the pathogenesis of progressive glomerular abnormalities, leading to glomerulosclerosis. [7] Currently, several studies are available, which indicates that treatment with low protein diet, [8] heparin, [9] and neutralizing antibodies to platelet-derived growth factor [10] decrease extracellular matrix deposition and sclerotic changes.

Hence, the present study mainly aimed at finding the clinicopathological profile of MesPGN and the differences between diffuse and focal MesPGN.


   Materials and Methods Top


Overall, 57 renal biopsies were diagnosed as MesPGN from January 1997 to October 2001. Cases were referred from OPD and indoors of General Medicine and Nephrology Unit of Sir Sunder Lal Hospital, BHU, Varanasi. Details of clinical features were recorded. Urine analysis, lipid profile, blood urea, blood sugar and hematological tests were done by standard methods. Kidney biopsies were fixed in 10% formalin. Paraffin blocks were prepared and sections were cut at 2- thickness and stained with hematoxylin and eosin stain (H and E stain), periodic acid-Schiff and acid fuschin orange G (AFOG) as described by Zollinger and Mihtasch. [11] AFOG stain was used to see deposits. Biopsies were classified as MesPGN when it showed mesangial cell proliferation in more than three cells per mesangial areas with or without mesangial matrix increase and deposition of immune complexes. It was classified as diffuse MesPGN when more than 50% glomeruli showed mesangial cell proliferation and focal when less than 50% glomeruli showed proliferation in only few segments.

Immunofluorescent study was not performed. Immune deposits were seen by AFOG stains as red color deposits, fibrin thrombi takes orange color and RBC takes yellow color in this stain. Sclerosed area, glomerular and tubular basement membrane (TBM) and mesangium appears blue in color.


   Results Top


Mesangioproliferative GN formed 10% of the total renal biopsies (57 cases out of 570). It included 37 cases of diffuse MesPGN [Figure 1] and 20 cases of focal MesPGN [Figure 2]. In the later group, majority of glomeruli had minimal change glomerulonephritis (MCGN) and only 25% glomeruli had focal segmental mesangial proliferation. About 68% of the cases were between 11 and 30 years of age. In focal variety, male predominance was higher (4:1) as compared to diffuse variety (1.46:1) [Table 1]. Mean age were 26.3 10.79 years for females and 28.63 13.08 years for males. Clinician provided clinical details in only 48 cases. Edema of face and feet were the most common manifestations seen in 70.83% cases followed by hypertension (29.17%), fever (14.58%), oliguria and vomiting (10.4%). The frequency of acute renal failure such as oliguria, vomiting and anorexia was more common in diffuse variety (13.33%) than focal (5.5%). Urinalysis in 50 patients revealed that 35 patients (70%) had nephrotic-range proteinuria, 28 patients (56%) had leukocyturia and 18 patients (36%) had microscopic hematuria.

Systemic manifestations, e.g., arthralgia, photosensitivity, purpura, ascites and amenorrhea, were seen in only diffuse MesPGN [Table 2]. Statically, no significant clinical differences were found between focal and diffuse variety.

Glomerulomegaly, focal glomerular basement membrane (GBM) thickening, necrosis, focal endothelial cell proliferation, crescent formation and hyalinized glomeruli were more common in diffuse variety; while in focal variety, severe congestion of capillary loops were noted in 50% cases. In diffuse variety, epithelioid non-caseating granuloma was seen in 8% cases. Two of the cases of granuloma had Wegner's granulomatosis while one had tuberculosis [Table 3].

Cloudy swelling and vacuolar degeneration were common in focal variety, whereas focal tubular necrosis, thickening of TBM, focal thyroidization and focal tubular atrophy were more common in diffuse variety. One-third cases of focal variety and diffuse variety had microscopic hematuria [Table 4] while 75% of diffuse and 70% of focal variety had focal mononuclear infiltration in interstitium. Four of these cases also had lymphoid follicles, two had lupus nephritis, one had associated pyelonephritis and one had tuberculosis; one case also showed eosinophilic abscess [Table 4]. Vascular changes were more severe in diffuse variety. Hyaline sclerosis, focal smooth muscle hyperplasia, vasculitis and perivasculitis were more common in diffuse variety [Table 5].

Statistical analysis of the morphological changes of glomerular, tubular interstitial and vascular lesions between the focal and the diffuse varieties showed that, in diffuse variety, only focal GBM thickening, focal endothelial cell proliferation and smooth muscle hyperplasia and hyaline sclerosis of blood were significantly increased as compared to focal variety. On the contrary, in focal variety, only glomerular capillary loop congestion, periglomerulitis and vacuolar degeneration in tubules were significantly more as compared to diffuse variety.

Interestingly, in diffuse variety, 11 out of 57 cases (19.21%) had distinct diseases. Clinical features and laboratory findings revealed that Wegner's granulomatosis was seen in two cases, microscopic polyarteritis nodosa in four cases, SLE in two cases; tuberculosis, polyarteritis nodosa, Kimura's disease and pyelonephritis were seen in one case each, while in focal variety, one case had tuberculosis and perivasculitis. AFOG stain revealed deposit in mesangium in 50% cases in both varieties.

One case of Kimura's disease had subcutaneous nodule in neck region and proteinuria. Lymphoid biopsy showed germinal cell hyperplasia, vascular proliferation and eosinophilic abscess. Kidney had MesPGN, lymphoid tissue and eosinophilic abscess.


   Discussion Top


In the present study, MesPGN consisted 10% of total biopsies of glomerulonephritis. Mostly it was seen in second and third decades of life. Males were 2.5 times more affected than females. Nephrotic-range proteinuria was seen in 70% cases and microscopic hematuria was seen in one-third cases; leukocyturia was present in more than 35% patients.

Mesangioproliferative GN is not an uncommon entity. [12] Glassocke et al . also reported MesPGN is in 10-20% of biopsies of glomerulonephritis. They also reported it in older children and young adults with male predominance, presenting as insidious onset of proteinuria, hematuria and hypertension in one-third cases.

Little et al . [3] analyzed MesPGN in detail and found that 7.2% of total of this GN had segmental IgM nephropathy. They also found it in SLE, Vasculitis, focal segmental glomerulosclerosis (FSGS) and Alport's syndrome. Mean age in their series was 26.5 years. Contrary to our study, in their study, only 41% patients presented with nephrotic syndrome, 26% with asymptomatic proteinuria, 18% with gross hematuria and 15% with isolated hematuria. Approximately 82% patients were steroid-dependent and 7.4% had poor prognosis. MesPGN with eosinophilia is very well described in the literature. [5]

In our study, 70% patients were presented with nephrotic-range of proteinuria. Most of the cases were clinically suspected as MCGN and some cases were suspected as FSGS and mesangiocapillary GN.

Approximately 20% of renal biopsies from patients with nephrotic syndrome may have some degree of mesangial cell proliferation in some patients of minimal change disease. [13],[14] MesPGN is also associated with FSGS and IgM nephropathy.

Significance of IgM nephropathy is not clear. Some authors say that it is a distinct entity while some believe that it is the early stage of FSGS. [15],[16] Another uncommon disorder called as CIq nephropathy is also seen in young adults between 15 and 30 years. This also has male predominance with male to female ratio of 1.8:1, manifests as edema in 50%, hypertension in 40% and hematuria in 30% case. This entity does not respond to steroid. [12] CIq nephropathy also has focal segmental mesangial proliferation [17] and it may show spontaneous improvement [18] hence may mimic MCGN.

Whether it is a diffuse or focal variety, most of the cases of MesPGN were either steroid-dependent or steroid-resistant.

Lower frequency of glomerular hyalinization, GBM necrosis, crescent formation, focal tubular necrosis, thyroidization of tubules and vascular changes suggest that focal variety is less severe than diffuse MesPGN.

Although we did not carry out immunofluorescent study to see IgA, IgM, or other deposits, AFOG stain revealed deposit in mesangium in 50% cases; similarly, other workers [12] also noted deposit in only 50% cases.

Follow-up study was not available because most of the patients did not visit laboratory, but presence of hyalinized glomeruli and tubular atrophy in 21% and 17.5% cases, respectively, suggest that disease is progressive.

Hence, from our study, we conclude that MesPGN is a very common GN in nephrotic syndrome of young adults. Therefore, it should be included in the causes of Nephrotic Syndrome of young adults. Secondly, focal MesPGN terminology should also be described in literature and pathologists should mention it when it is seen with minimal change and FSGS, so that clinician can plan treatment accordingly.


   Acknowledgments Top


The authors are thankful to UGC Advanced Immunodiagnostic Training and Research Centre, Institute of Medical Sciences, BHU, for its financial support and Mr Ram Ujagir Singh, Mr Saroj Kumar and Mr Nakhroo Ram for their technical support.

 
   References Top

1.John M, Lam M, Latham B, Saker B, French MA. Nephrotic syndrome in a patient with IgA deficiency-associated mesangio-proliferative glomerulonephritis. Pathology 2000;32:56-8.  Back to cited text no. 1    
2.Das Gupta DJ, Garg ID, Kaushal SS, Chauhan S, Sharma A, Goyal A. Mesangioproliferative glomerulonephritis in chronic obstructive pulmonary disease. J Indian Med Assoc 1998;96:338-40.  Back to cited text no. 2    
3.Little MA, Dorman A, Gill D, Walshe JJ. Mesangioproliferative glomerulonephritis with IgM deposition: Clinical characteristic and outcome. Ren Fail 2000;22:445-57.  Back to cited text no. 3    
4.Power DA, d' Apice AJ, Seymour AE. In clinical immunolgoy. In : Bradley J, Mccluskey J, editors. 1st ed. Oxford University; 1997. p. 289-90.  Back to cited text no. 4    
5.Whelan TV, Maher JF, Kragel P, Dysart N, Dannenhoffer R, Prager L. Nephrotic syndrome associated with Kimura's disease. Am J Kidney Dis 1988;11:1349-51.  Back to cited text no. 5    
6.Burg M, Grone H, Koch K, Floege J. Cationic dextran induces mesangioproliferative nephritis in rats independent of glomerular IgA deposition. Nephrol Dial Transplant 1997;12:1856-62.  Back to cited text no. 6    
7.Haas CS, Schocklmann HO, Lang S, Kralewski M, Sterzel RB. Regulatory mechanisms in glomerular mesangial cell proliferation. J Nephrol 1999;12:405-15.  Back to cited text no. 7    
8.Fukui M, Nakamura T, Ebihara I, Nagaoka I, Tomino Y, Koide H. Low protein diet attenuates increased gene expressions of platelet derived growth factor and transforming growth factor β in experimental glomerulosclerosis. J Lab Clin Med 1993;121:224-34.  Back to cited text no. 8    
9.Floege J, Eng E, Yound BA, Couser WG, Johnson RJ. Heparin suppresses mesangial cell proliferation and matrix expansion in experimental glomerulonephritis. Kidney Int 1993;43:369-80.  Back to cited text no. 9    
10.Johnson RJ, Raines EW, Floege J, Yoshimura A, Pritzl P, Alpers C, et al . Inhibition of mesangial cell proliferations and matrix expansion in glomerulonephritis in the rat by antibody to platelet derived growth factor. J Exp Med 1992;175:1413-6.  Back to cited text no. 10    
11.Zollinger HU, Mihatsch MJ. Renal pathology in biopsy. 1 st ed. New York: Springer-Verlag, Berlin Heidelberg; 1978. p. 10-1.  Back to cited text no. 11    
12.Falk RJ, Jennette JC, Nachman PH. Primary glomerular disease in the kidney. In: Brenner BM, editor. 7th ed. Vol. 1. Saunder's Co; 2004. p. 1313-4.  Back to cited text no. 12    
13.Waldherr R, Gubler ME, Levy M, Broyer M, Habib R. The significance of pure diffuse mesangial proliferation in idiopathic nephrotic syndrome. Clin Nephrol 1978;10:171-9.  Back to cited text no. 13    
14.Ordonez NG, Rosai J. Urinary tract. In surgical pathology. In : Rosai J, editor. Mosby; 2004. p. 1170-1.  Back to cited text no. 14    
15.Al-Eisa A, Carter JE, Lirenman DS, Magil AB. Childhood IgM nephropathy: Comparison with minimal change disease. Nephron 1996;72;37-43.  Back to cited text no. 15    
16.Alxopoulos E, Papagianni A, Stangou M, Pantzaki A, Papadimitriou M. Adult onset idiopathic nephrotic syndrome associated with pure mesangial hypercellularity. Nephrol Dial Transplat 2000;15:981-7.  Back to cited text no. 16    
17.Appel GB, Radhkrishnan J, Agati VD. Secondary glomerular disease. In the kidney. In : Brenner BM, editor. 7th ed. Saunder Co; 2004. p. 1382-447.  Back to cited text no. 17    
18.Nishida M, Kawakatsu H, Komatsu H, Ishiwari K, Tamai M, Sawada T. Spontaneous improvement in a case of C1q nephropathy. Am J Kidney Dis 2000;35:E22.  Back to cited text no. 18    

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Correspondence Address:
Usha
UGC Advanced Immunodiagnostic Training and Research Center, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.42506

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    Figures

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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