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Year : 2017  |  Volume : 60  |  Issue : 2  |  Page : 290-291
Crescentic C3 glomerulopathy with acquired partial lipodystrophy: An unusual cause of rapidly progressive renal failure


1 Wellcome Trust Research Laboratory, Division of GI Sciences, Central Electron Microscopy Unit, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India

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Date of Web Publication19-Jun-2017
 

How to cite this article:
Matthai SM, Jacob S, Palak R, Jagdish K, Varughese S, Tamilarasi V. Crescentic C3 glomerulopathy with acquired partial lipodystrophy: An unusual cause of rapidly progressive renal failure. Indian J Pathol Microbiol 2017;60:290-1

How to cite this URL:
Matthai SM, Jacob S, Palak R, Jagdish K, Varughese S, Tamilarasi V. Crescentic C3 glomerulopathy with acquired partial lipodystrophy: An unusual cause of rapidly progressive renal failure. Indian J Pathol Microbiol [serial online] 2017 [cited 2022 Jan 20];60:290-1. Available from: https://www.ijpmonline.org/text.asp?2017/60/2/290/208401


Complement component C3 glomerulopathy (C3GP) is a recently defined entity characterized by predominant glomerular C3 fragment deposition with absent or scanty immunoglobulin deposition due to abnormal control of complement activation, deposition, or degradation.[1] C3GP is subcategorized morphologically into dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) based on electron microscopic (EM) findings. DDD previously called membranoproliferative glomerulonephritis Type II refers to cases with hyperosmiophilic, dense transformation of glomerular basement membranes (GBM) on EM [2] and other cases of C3GP without the pathognomonic ultrastructural findings are designated C3GN. DDD has an estimated prevalence of 2–3/million population [3] and traditionally presents with nephritic-nephrotic syndrome in children or young adults.[4] We describe a rare case of DDD with crescentic glomerulonephritis, presenting as rapidly progressive renal failure (RPRF) in an adult female patient, associated with acquired partial lipodystrophy (Barraquer Simons' or Dunnigan-Koeberling syndrome).[5]

A 26-year-old female presented with RPRF. She had prominent loss of subcutaneous adipose tissue around cheeks suggestive of acquired partial lipodystrophy [Figure 1]a. Investigations showed proteinuria (3.5 g/400 ml urine/day) with active urine sediments (red blood cell 19, white blood cell 63/HPF), serum creatinine 6.64 mg/dL, low complement component C3 (16.9 mg/dL [normal range >90]) and normal C4 (28 mg/dL). ANA, DsDNA, ASO, and ADNaseB levels were within normal limits. Serology for hepatitis viruses and HIV was negative. Renal biopsy showed cellular and fibrocellular crescents in 8 of 10 glomeruli with mesangial expansion, proliferation, and thickened capillary walls [Figure 1]b,[Figure 1]c,[Figure 1]d. Immunofluorescence showed isolated coarsely granular deposits of only C3. EM showed dense transformation of GBMs in all glomeruli due to hyperosmiophilic, ribbon-like intramembranous deposits [Figure 2]a and [Figure 2]b and similar deposits in tubular basement membranes [Figure 2]c confirming the diagnosis of DDD/C3GP with crescentic glomerulonephritis.
Figure 1: (a) Acquired partial lipodystrophy of face. (b) Crescentic glomerulonephritis with marked thickening of capillary walls and narrowed capillary lumina (H and E, ×200). (c) Fibrocellular crescent with mesangial proliferation and narrowed capillary lumina (H and E, ×400). (d) Fibrocellular crescent and glomerular capillary wall thickening due to deposits (PAS, ×400)

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Figure 2: (a) Dense, osmiophilic, ribbon like transformation of glomerular basement membranes in dense deposit disease, transmission electron microscopy (×1700). (b) Ischemic collapse of glomerular tuft with dense deposit disease, transmission electron microscopy (×2550). (c) Tubular basement membrane dense deposits, transmission electron microscopy (×1700)

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She received steroids and plasmapheresis. On the last follow-up at 3 months, she was dialysis dependent.

In a recent study of clinicopathological features of C3GP by Terence Cook et al., patients with DDD were found to be younger, more likely to have low serum C3 levels, and more likely to have crescentic GN than patients with C3GN.[1] However, in the largest study from India to date, none of the biopsies diagnosed with DDD had crescentic glomerulonephritis.[2] Our patient was 26-year-old, presenting with RPRF and renal biopsy demonstrated crescentic GN by light microscopy and ultrastructural examination revealed DDD. This being the first case of DDD with crescentic GN and acquired partial lipodystrophy reported from the Indian population may be reflective of existing ethnic diversity within India.

Acquired partial lipodystrophy (Barraquer Simons' or Dunnigan-Koeberling syndrome) in which subcutaneous fat is lost from the face and upper body, has a well-established association with DDD [3] and was present in this patient also. It often predates the onset of renal clinical manifestations of DDD. Other reported associations include ocular drusen,[4] monoclonal gammopathy in older patients [5] and increased risk of diabetes mellitus type I in families with DDD. We investigated our patient for these associations also which yielded negative results.

The presence of C3 in the absence of immunoglobulins in C3GP suggests activation of complement by antibody-independent pathways, typically the alternative pathway, and many patients have evidence of genetic or acquired alternative pathway dysregulation. The absence of Complement factor B from glomerular tissue on laser microdissection is consistent with alternate pathway C3 convertase formation leading to excessive C3 activation in the fluid phase, with subsequent deposition of C3 breakdown products.

RPRF defined as decline in renal function of >50% over days to weeks, almost always presents to a nephrologist as a clinical emergency. Accurate diagnosis of etiology by renal biopsy is crucial in management and prognostication of patients with RPRF. The diagnosis of DDD rests on EM, and it may be worthwhile to include ultrastructural examination of renal biopsies in such scenarios for accurate subcategorization.

It is important to diagnose and segregate patients of C3GP from other glomerular diseases with similar morphological patterns as targets for therapy are different. Immune complex-mediated disease needs targeting primary infection, relevant autoantibodies, or clonal light chains according to the diagnosis. In C3GP, plasmapheresis for removal of autoantibodies and use of ecluzimab targeted against C5 component are the only potential available therapies. Variants of C3GP are also important from renal transplantation perspective as rate of recurrences are variable with different subtypes of C3GP.

This case highlights an unusual presentation of a rare disease along with its uncommon clinical associations. A comprehensive renal biopsy examination inclusive of EM is essential for diagnosis and contributes to patient management and prognostication.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Medjeral-Thomas NR, O'Shaughnessy MM, O'Regan JA, Traynor C, Flanagan M, Wong L, et al. C3 glomerulopathy: Clinicopathologic features and predictors of outcome. Clin J Am Soc Nephrol 2014;9:46-53.  Back to cited text no. 1
    
2.
Viswanathan GK, Nada R, Kumar A, Ramachandran R, Rayat CS, Jha V, et al. Clinico-pathologic spectrum of C3 glomerulopathy-an Indian experience. Diagn Pathol 2015;10:6.  Back to cited text no. 2
[PUBMED]    
3.
Williams DG, Scopes JW, Peters DK. Hypocomplementaemic membranoproliferative glomerulonephritis and nephrotic syndrome associated with partial lipodystrophy of the face and trunk. Proc R Soc Med 1972;65:591.  Back to cited text no. 3
[PUBMED]    
4.
Duvall-Young J, MacDonald MK, McKechnie NM. Fundus changes in (type II) mesangiocapillary glomerulonephritis simulating drusen: A histopathological report. Br J Ophthalmol 1989;73:297-302.  Back to cited text no. 4
[PUBMED]    
5.
Sethi S, Sukov WR, Zhang Y, Fervenza FC, Lager DJ, Miller DV, et al. Dense deposit disease associated with monoclonal gammopathy of undetermined significance. Am J Kidney Dis 2010;56:977-82.  Back to cited text no. 5
[PUBMED]    

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Correspondence Address:
Smita Mary Matthai
Asst.Professor of Pathology, Central Electron Microscopy Unit, Christian Medical College, Vellore - 632 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.208401

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