Poor Allograft Outcome in Indian Patients with Post-transplant C3 Glomerulopathy

Overview

Journal Clin Kidney J

Publisher Oxford University Press

Specialty Nephrology

Date 2021 Feb 10

PMID 33564431

Citations 4

Authors

Ashwani Kumar

Raja Ramachandran

Amit Rawat

Reena Das

Charan S Rayat

Deepesh B Kenwar

Ashish Sharma

Krishan L Gupta

Ritambhra Nada

Affiliations

Soon will be listed here.

Abstract

Background: Complement 3 glomerulopathy (C3G) results from dysfunction of the alternative complement pathway (ACP). No data are available on post-transplant C3G in South Asia.

Methods: In this study, renal allograft biopsies of C3G patients performed from 2012 to 2017 were analysed for ACP functional assay (APFA), serum complement levels, complement factor H (CFH), complement factor B (CFB) and autoantibodies to CFH and CFB. Limited genetic screening for / genes was carried out. All study patients were also followed up.

Results: A total of 21 cases of C3G were included, of which 11 had native C3G disease (that is, recurrent C3G). Of these 11 recurrent cases, 7 presented with allograft dysfunction and 4 with proteinuria and renal dysfunction. Early post-transplant recurrence (<1 month) was noted in six patients, whereas recurrence in five patients occurred within 8-17 months of transplant. Biopsies showed mild focal mesangial expansion with or without endocapillary proliferation and thrombotic microangiopathy. Rejection was also noted in six patients. APFA/C3 levels were low in all cases. Serum CFH levels were low [dense deposit disease (DDD), 44%; C3 glomerulonephritis (C3GN), 25%], whereas CFB levels were normal. Autoantibodies to CFH, CFB and C3 nephritic factor were present in 11, 0 and 44% of DDD cases, respectively, and in 17, 17 and 33% of C3GN cases, respectively. Genetic analysis revealed only non-pathogenic gene variants (93%). No novel mutation was found. At follow-up (140 months), stable graft was noted in 28% of cases, progressive renal failure in 19%, graft loss in 34%, and 19% of patients died.

Conclusion: Post-transplant C3G can present with graft dysfunction and/or proteinuria. Subtle histological findings demand careful interpretation of immunofluorescence results. Autoantibodies to complement pathway regulatory proteins are common, and no novel mutation has been found from limited genetic workup. Clinical outcome is poor.

Citing Articles

Outcome of Patients Transplanted for C3 Glomerulopathy and Primary Immune Complex-Mediated Membranoproliferative Glomerulonephritis.

Halfon M, Taffe P, Bucher C, Haidar F, Huynh-Do U, Mani L Kidney Int Rep. 2025; 10(1):75-86.

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Childhood onset C3 glomerulopathy: recurrence after kidney transplantation-a case series.

Borovitz Y, Landau D, Dagan A, Alfandari H, Haskin O, Levi S Front Pediatr. 2024; 12:1460525.

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C3 Glomerulopathy Recurs Early after Kidney Transplantation in Serial Biopsies Performed within the First 2 Years after Transplantation.

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Prognosis is still poor in patients with posttransplant C3 glomerulopathy despite eculizumab use.

Mirioglu S, Hocaoglu R, Velioglu A, Ozluk Y, Dirim A, Oruc A Clin Kidney J. 2024; 17(7):sfae190.

PMID: 39021814 PMC: 11252667. DOI: 10.1093/ckj/sfae190.

C3 glomerulopathy: Understanding an ultra-rare complement-mediated renal disease.

Heiderscheit A, Hauer J, Smith R Am J Med Genet C Semin Med Genet. 2022; 190(3):344-357.

PMID: 35734939 PMC: 9613507. DOI: 10.1002/ajmg.c.31986.

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