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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2013  |  Volume : 24  |  Issue : 2  |  Page : 333-337
Crescentic glomerulonephritis developing in the course of idiopathic membranoproliferative glomerulonephritis


1 Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
2 Department of Nephrology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

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Date of Web Publication26-Mar-2013
 

   Abstract 

Membranoproliferative glomerulonephritis (MPGN) is a rare cause of the nephrotic syndrome in adults and children. Though small focal crescents may be seen in up to 10% of cases of MPGN, the presence of more than 50% crescents (crescentic MPGN) is rare. Very few cases of crescentic transformation of MPGN, documented by subsequent renal biopsies, have been described in the literature. A young female patient underwent kidney biopsy for the nephrotic-nephritic syndrome and was diagnosed as idiopathic MPGN. She was administered immunosuppressive therapy (steroids and cyclophosphamide), with which her renal functions stabilized. Six months later, she presented with features suggestive of rapidly progressive renal failure and underwent a second renal biopsy. The second biopsy showed crescentic glomerulonephritis with immune complex deposition, suggestive of MPGN. A final diagnosis of crescentic transformation of MPGN was made. Crescentic transformation of MPGN is a rare occurrence, but needs to be considered in a patient diagnosed as MPGN and presenting with rapidly progressive renal failure. The cause of such transformation remains to be elucidated.

How to cite this article:
Sharma A, Gupta R, Lal C, Agarwal SK, Dinda AK. Crescentic glomerulonephritis developing in the course of idiopathic membranoproliferative glomerulonephritis. Saudi J Kidney Dis Transpl 2013;24:333-7

How to cite this URL:
Sharma A, Gupta R, Lal C, Agarwal SK, Dinda AK. Crescentic glomerulonephritis developing in the course of idiopathic membranoproliferative glomerulonephritis. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Nov 22];24:333-7. Available from: http://www.sjkdt.org/text.asp?2013/24/2/333/109599

   Introduction Top


Membranoproliferative glomerulonephritis (MPGN) has been classified into types I, II, and III. [1] A review by D'Amico and Ferrario described six morphologic patterns of MPGN, the rarest being the crescentic form (with more than 50% crescents). [2] Small crescents involving

few glomeruli may be seen in about 10% of the biopsies of MPGN. [3] An extensive review of the literature revealed occasional reports of crescentic transformation of histologically diagnosed MPGN type I. [4],[5] Such transformation usually presents with rapid deterioration of renal function in a patient with a previous histologic diagnosis of MPGN. Though the exact cause of this event is not known as yet, a few cases have been reported in association with hepatitis B and C infection and urticarial vasculitis. [6],[7],[8] The renal survival in most of these patients has been poor, with progression to end-stage renal disease and need for renal transplantation. [3],[9]

We describe a patient with histologically documented MPGN type I who presented six months later with rapid deterioration of the renal function. A second renal biopsy showed features of crescentic GN, following which she was managed with aggressive immunosuppression. The patient required maintenance hemodialysis, but was lost to follow-up.


   Case Report Top


A 22-year-old female was referred to the nephrology outpatient department with generalized swelling of the body for two months. There was a recent history of an episode of gross hematuria and reduction in urine output. On evaluation at another hospital, she was detected to have proteinuria, microscopic hematuria, and renal dysfunction (serum creatinine 4.5 mg/dL). She was referred to our center for further evaluation and management. Physical examination was unremarkable except for mild hypertension [blood pressure (BP), 140/90 mm Hg], pallor, and pedal edema. Biochemical investigations revealed deranged renal function and anemia, with urine showing proteinuria and microscopic hematuria with active sediment. The investigations are tabulated in [Table 1]. Ultrasonography (USG) of the abdomen showed mildly enlarged kidneys (right kidney 13.8 × 5.4 cm, left 13.2 × 5.3 cm) with increased echogenicity.
Table 1: Biochemical investigations at first and second renal biopsies.

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A renal biopsy was performed and the patient was initiated on immunosuppression with intravenous methylprednisone and cyclophosphamide. With this therapy, her serum creatinine normalized to 1.0 mg/dL and she was discharged on maintenance dose of steroids and cyclophosphamide. However, she did not come for follow-up for the next three months.

Six months after her initial presentation, she came back with recent-onset anasarca, anorexia, vomiting, and abdominal distension. On eliciting the history, it was learnt that she had discontinued the immunosuppressive therapy due to financial constraints. During this time, proteinuria (spot 2+ to 3+) had persisted. At this admission, she was hypertensive (BP 160/100 mm Hg). Her investigations at second admission are tabulated in [Table 1]. USG of the abdomen showed normalsized kidneys with increased echogenicity.

She was stabilized with two sessions of hemodialysis and a repeat kidney biopsy was performed in view of the rapidly deteriorating course.

Pathologic Findings

The first renal biopsy comprised ten glomeruli, all of which showed lobular accentuation and mesangial hypercellularity with matrix expansion [Figure 1]a. Peripheral capillary loops showed thickening of the glomerular basement membrane with partial and complete splits on silver-methenamine stain [Figure 1]b. There was focal tubular atrophy and interstitial fibrosis.
Figure 1. Photomicrographs from the first biopsy showing enlarged hypercellular glomeruli with lobular accentuation, mesangial cell proliferation, and thickened basement membrane (a, H&E ×200). Silvermethenamine stain showing mesangial cell interposition with "splits" of basement membrane (b, ×400). Immunofluorescence showing capillary wall granular staining for C3 (c, ×200). Electron micrograph demonstrating large sub-endothelial electron-dense deposits (d, ×2200).

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Immunofluorescence staining showed coarse granular capillary wall deposits of IgG, IgM, and C3 [Figure 1]c, while being negative for IgA and C1q. Electron microscopic examination of the renal biopsy tissue showed sub-endothelial [Figure 1]d and scattered mesangial electron-dense deposits. Focal mesangial interposition was noted. A final pathologic diagnosis of idiopathic MPGN type I was rendered.

The second renal biopsy showed nine glomeruli. All the glomeruli showed cellular to fibro-cellular crescents (100% crescents) with compression of the glomerular tuft [Figure 2]a-c. The compressed tuft showed focal neutronphil infiltration. There was diffuse interstitial fibrosis, tubular atrophy, and focal chronic interstitial inflammation. Immunofluorescence examination again showed capillary wall granular deposits of IgG, IgM, and C3, and absence of IgA and C1q deposits [Figure 2]d.
Figure 2. A panel of photomicrographs from the second biopsy showing interstitial edema, tubular atrophy, and interstitial fibrosis (a, H&E ×40). The glomeruli show cellular crescents with compression of glomerular tuft (b, H&E ×200), better highlighted on silver-methenamine stain (c, ×100). Immunofluorescence showing capillary wall granular staining for IgG in a glomerulus with crescent (d, ×200).

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Based on these findings, a diagnosis of crescentic transformation of MPGN was made.

Follow-up

Following the findings of the second renal biopsy, she was administered intravenous pulse of methylprednisone. Her hospital course was complicated by development of herpes zoster infection, for which immunosuppression was tapered. She was discharged on maintenance hemodialysis, but was lost to follow-up.


   Discussion Top


MPGN or mesangiocapillary glomerulonephritis (MCGN) is a rare cause of the nephrotic syndrome in adults as well as children. [10] Morphologically, MPGN is characterized by mesangial hypercellularity, mesangial matrix expansion, thickening of peripheral capillary loops by sub-endothelial and/or intramembranous immune complex deposits, and mesangial interposition with splitting of the basement membrane (tram track appearance). [2] MPGN, as a group, includes idiopathic cases and those associated with systemic and infectious disorders like systemic lupus erythematosus, cryoglobulinemia, cirrhosis, hepatitis B, malaria, and hematological malignancies. [10]

In a review by D'Amico and Ferrario, six morphologic variants of MPGN were described: classic, nodular, exudative, focal segmental MPGN, MPGN with massive deposits, and crescentic MPGN. [2] Nodular MPGN shows centrilobular sclerosis of the expanded mesangium and microaneurysms of glomerular capillaries. Exudative MPGN, in contrast to the classical MPGN, shows marked infiltration of inflammatory cells, mainly mononuclear cells. Focal segmental MPGN shows classical features, which however are restricted to segments of glomerular tuft. A small number of biopsies showed massive sub-endothelial deposits with mild mesangial proliferation. [2]

Crescents, especially small and focal, have been reported in about 10% of patients with MPGN. [3] Crescentic transformation of MPGN type I, documented by serial renal biopsies, has been reported in only rare case reports in the available literature. [4],[5],[9] McCoy et al, in 1975, reported a patient with crescentic transformation of MPGN with recurrence in the allograft. [4] Ahsan et al described a patient with MPGN type I which recurred in the allograft with rapid transformation to crescentic form. [9] A few cases of crescentic MPGN have been associated with hepatitis B, hepatitis C infection, and urticarial vasculitis. [6],[7],[8] The exact cause of this crescentic transformation in the course of MPGN is not yet known.

The renal prognosis in previously reported cases of crescentic transformation has been variable; some patients responded to aggressive immunosuppression and plasmapharesis, while others progressed to end-stage renal disease requiring transplantation. [4],[7] In our patient, no secondary cause of MPGN was found on extensive investigations. Crescentic transformation was noted six months after the initial biopsy diagnosis of MPGN. We hypothesize that this crescentic transformation occurred due to the withdrawal of immunosuppressive therapy. The response to immunosuppressive therapy in MPGN has been a subject of controversy. Many published studies did not find improvement in the clinical course though uncontrolled studies have shown benefit of steroids and cytotoxic agents. [11] In our patient, initial aggressive immunosuppression had a good response with stabilization of renal functions. The pathogenesis of crescentic transformation with rapid deterioration of renal functions on discontinuation of therapy is not amply clear. It may be explained by the activation of complement pathway by immune complexes, leading to immune activation and consequent inflammatory reaction.

In conclusion, crescentic transformation of idiopathic MPGN is an extremely uncommon phenomenon. This case is being reported due to the rarity of such transformation in idiopathic MPGN. Also, the need of continued immunosuppressive therapy in these patients, long after the initial response, is emphasized and it is important to be aware of this potential complication in untreated or partially treated patients of MPGN.


   Acknowledgments Top


Dr. Alok Sharma and Dr. Ruchika Gupta wish to acknowledge CSIR, Delhi, for research grant support as Senior Research Associate.

 
   References Top

1.Jackson EC, McAdams J, Strife F, Forristal J, Welch TR, West CD. Differences between membranoproliferative glomerulonephritis types I and III in clinical presentation, glomerular morphology and complement perturbation. Am J Kidney Dis 1987;2:115-20.  Back to cited text no. 1
    
2.D'Amico G, Ferrario F. Mesangiocapillary glomerulonephritis. J Am Soc Nephrol 1992;2: S159-66.   Back to cited text no. 2
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3.Kim Y, Michael AF, Fish AJ. Idiopathic membranoproliferative glomerulonephritis. In: Brenner B, Stein J, eds. Nephrotic Syndrome. New York: Churchill Livingstone 1982. p. 237.   Back to cited text no. 3
    
4.McCoy R, Clapp J, Seigler HF. Membranoproliferative glomerulonephritis: Progression from the pure form to the crescentic form with recurrence after transplantation. Am J Med 1975;59:288-92.  Back to cited text no. 4
[PUBMED]    
5.Korzets Z, Bernheim J, Bernheim J. Rapidly progressive glomerulonephritis (crescentic glo-merulonephritis) in the course of type I idiopathic membranoproliferative glomerulonephritis. Am J Kidney Dis 1987;10:56-61.   Back to cited text no. 5
[PUBMED]    
6.Ahmed MS, Wong CF, Shawki H, Kapoor N, Pandya BK. Rapidly deteriorating renal function with membranoproliferative glomerulonephritis type I associated with hepatitis C treated successfully with steroids and antiviral therapy: A case report and review of literature. Clin Nephrol 2008;69:298-301.  Back to cited text no. 6
[PUBMED]    
7.Enriquez R, Sirvent AE, Amorós F, Pérez M, Matarredona J, Reyes A. Crescentic membranoproliferative glomerulonephritis and hypo-complementemic urticarial vasculitis. J Nephrol 2005;18:318-22.  Back to cited text no. 7
    
8.Li PK, Lai FM, Ho SS, Wong KC, Lui SF, Lai KN. Acute renal failure in hepatitis B virus-related membranous nephropathy with mesangiocapillary transition and crescentic transformation. Am J Kidney Dis 1992;19:76-80.   Back to cited text no. 8
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9.Ahsan N, Manning EC, Dabbs DJ, Gifford RR, Yang HC. Recurrent type I membranoproliferative glomerulonephritis after renal transplantation and protective role of cyclosporine in acute crescentic transformation. Clin Transplant 1997;11:9-14.   Back to cited text no. 9
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10.Zhou XJ, Silva FG. Membranoproliferative glomerulonephritis. In: Hepinstall's Pathology of the Kidney. Jennette JC, Olson JL, Schwartz MM, Silva FG, eds. 6 th ed, Philadelphia: Lippincott Williams and Wilkins; 2007. p. 301.   Back to cited text no. 10
    
11.Yanagihara T, Hayakawa M, Yoshida J, et al. Long-term follow-up of diffuse membranoproliferative glomerulonephritis type I. Pediatr Nephrol 2005;20:585-90.  Back to cited text no. 11
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Correspondence Address:
Amit K Dinda
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029
India
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DOI: 10.4103/1319-2442.109599

PMID: 23538361

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    Abstract
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