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Table of Contents
COMMENTARY
Year : 2019  |  Volume : 13  |  Issue : 3  |  Page : 154-155

Transplantation in C3 glomerulopathy – Damned if you do, damned if you don't


Department of Nephrology, Care Hospitals, Hyderabad, Telangana, India

Date of Submission30-Jan-2019
Date of Decision05-May-2019
Date of Acceptance28-Aug-2019
Date of Web Publication17-Sep-2019

Correspondence Address:
Srikanth Gundlapalli
Department of Nephrology, Care Hospitals, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_4_19

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How to cite this article:
Gundlapalli S, Mondhe SD. Transplantation in C3 glomerulopathy – Damned if you do, damned if you don't. Indian J Transplant 2019;13:154-5

How to cite this URL:
Gundlapalli S, Mondhe SD. Transplantation in C3 glomerulopathy – Damned if you do, damned if you don't. Indian J Transplant [serial online] 2019 [cited 2019 Dec 11];13:154-5. Available from: http://www.ijtonline.in/text.asp?2019/13/3/154/266949



The traditional classification of membranoproliferative glomerulonephritis (MPGN) based on morphology has been replaced with a more scientifically acceptable etiopathological classification.[1] The newer classification identifies immunoglobulin associated- and complement-associated MPGN as the primary types. This led to better evaluation protocols for specific histopathological types and better prognostic predictions. The complement-mediated MPGN needs the workup of complement pathways, while the immunoglobulin-associated MPGN needs a workup for infections, autoimmune diseases, and monoclonal gammopathies. The complement-associated MPGN-C3 glomerulopathy has two distinct pathological subtypes: the C3GN and dense deposit disease. This morphometric distinction requires electron microscopy. Servais et al. first described the entity of C3GN characterized by C3 prevalence without intramembranous deposits.[2]

The pathogenesis similar to atypical hemolytic uremic syndrome (aHUS) involves specific complement protein deficiencies or antibodies against complement stabilizing components which leads to tick over in the alternate complement pathway. The similar pathophysiology of C3G and aHUS prompted the work on eculizumab for C3G. However, in contrast to aHUS, the response has been heterogeneous.[3] Complement activation with endothelial damage by complexes is the underlying pathogenic mechanism in aHUS, whereas deposition of the C3-cleaved products in the glomeruli is the problem in C3G. The upstream C3 cleaving is probably not interrupted by eculizumab which is C5 cleavage inhibitor, explaining the poor response to this form of therapy. Furthermore, the economic considerations limit the widespread use of this drug in the middle-income countries. Complement-mediated glomerulopathy is debilitating as it affects young adults, and the progression to end-stage kidney disease is much faster (29% reach end-stage renal disease in a mean follow-up of 28 months).[4] Poor survival outcomes of this young cohort on dialysis make transplant a necessary but risky option. The reported recurrence rate is as high as 50%–100%.[5]

The scientific evidence in the literature regarding the management of recurrent posttransplant C3G is scarce. Zand et al. reported a series of 14 patients with C3G recurrence.[6] A single patient in this series received plasmapheresis with partial response. McCaughan et al. reported promising response with eculizumab, but the economic and availability concerns can be a huge deterrent for this drug.[7] Pipeleers et al. reported the use of aggressive plasmapheresis immediate posttransplant followed by long-term maintenance twice monthly as a method to prevent recurrent C3G posttransplant.[8] Although newer and innovative therapies such as soluble complement receptor 1 which act as complement regulators have shown some promise in native disease, their role in posttransplant recurrence is unknown.

The rarity of disease and economic burden of management contributed to the lack of large scale studies in literature. The reference study[9] tried to look into the therapeutic option from a pathological standpoint which makes it unique. The workup for autoantibodies to complement pathway regulation and to assess the response of this set of population is a novel approach. The dramatic initial response to plasma exchange for patients with autoantibodies drives home the necessity of studies with etiopathological purview.



 
  References Top

1.
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. 1
    
2.
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. 2
    
3.
Welte T, Arnold F, Kappes J, Seidl M, Häffner K, Bergmann C, et al. Treating C3 glomerulopathy with eculizumab. BMC Nephrol 2018;19:7.  Back to cited text no. 3
    
4.
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. 4
    
5.
Braun MC, Stablein DM, Hamiwka LA, Bell L, Bartosh SM, Strife CF. Recurrence of membranoproliferative glomerulonephritis type II in renal allografts: The North American pediatric renal transplant cooperative study experience. J Am Soc Nephrol 2005;16:2225-33.  Back to cited text no. 5
    
6.
Zand L, Lorenz EC, Cosio FG, Fervenza FC, Nasr SH, Gandhi MJ, et al. Clinical findings, pathology, and outcomes of C3GN after kidney transplantation. J Am Soc Nephrol 2014;25:1110-7.  Back to cited text no. 6
    
7.
McCaughan JA, O'Rourke DM, Courtney AE. Recurrent dense deposit disease after renal transplantation: An emerging role for complementary therapies. Am J Transplant 2012;12:1046-51.  Back to cited text no. 7
    
8.
Pipeleers L, Sennesael J, Massart A, Geers C, Goodship T, Stordeur P, et al. Successful use of plasma exchange to prevent recurrence of C3 glomerulonephritis after kidney transplantation: A case report. Transplantation 2012;94(10S):1050.  Back to cited text no. 8
    
9.
Kumar A, Bharati J, Nada R, Singh S, Sharma A, Gupta KL, et al. Utility of plasma exchange in early recurrent C3 glomerulopathy. Indian J Transplant 2019;13:122-6.  Back to cited text no. 9
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