DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20184886

C4d deposition in native kidney disease and its correlation with proteinuria and serum urea/creatinine

Sant Pandey, Sucheta Yadav, Suresh Babu, Ashutosh Kumar, Bhupendra P. Singh, Anupam Wakhlu, Atin Singhai, S. K. Sonkar, Vishal Pooniya

Abstract


Background: C4d is a well-known biomarker of the complement cascade. It is derived from cleavage of the labile thioester bond of C4b. This cleavage provides C4d a covalent bond which helps C4d to anchor to nearby cells where immune complexes are deposited. Antibodies dissociate naturally because of relatively weak hydrostatic and Van der Waals forces between antigens and antibodies, whereas covalent bond of C4d has a much longer half-life. For this reason, C4d serves as a footprint of complement activation.

Methods: This was a retrospective and prospective cross-sectional study, done at our tertiary care hospital.

Results: Authors evaluated 50 cases and 10 controls to adjudge the significance of C4d deposits in native renal diseases. Majority of the patients (44%) were in the age group of 10-20 years followed by 20% in the age group of 31-40 years. 62% of study population were male. Majority of patients were diagnosed with FSGS (16%), followed by membranous nephropathy (14%), lupus nephropathy (14%) and IgA nephropathy (12%). There was correlation of intensity expression of glomerular C4d deposits with presenting 24 hours urinary protein level at the time of biopsy (p value=0.027) but no correlation with urea/creatinine.

Conclusions: All patients diagnosed with membranous nephropathy, IgA nephropathy and hypertensive nephropathy showed glomerular C4d deposits, and also diagnosed with IgA nephropathy, post infectious glomerulonephritis, lupus nephritis, minimal change disease, acute/chronic tubulointerstitial nephritis, diabetic nephropathy, hypertensive nephropathy showed tubular C4d deposits. All patients diagnosed with diabetic nephropathy and hypertensive nephropathy showed arterial C4d deposits.


Keywords


Chronic kidney disease, Focal segmental glomerular sclerosis, IgAN-IgA nephropathy, Lupus nephritis

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References


Xing GQ, Chen M, Liu G, Zheng X, Jie E, Zhao MH. Differential deposition of C4d and MBL in glomeruli of patients with ANCA-negative pauci-immune crescentic glomerulonephritis. J Clinical Immunol. 2010 Jan 1;30(1):144-56.

Espinosa-Hernández M, Ortega-Salas R, López-Andreu M, Gómez-Carrasco JM, Pérez-Sáez MJ, Pérez-Seoane C, et al. C4d as a diagnostic tool in membranous nephropathy. Nefrologia. 2012 May 14;32(3):295-9.

Maeng YI, Kim MK, Park JB, Cho CH, Oh HK, Park KK. Glomerular and tubular C4d deposition in IGA nephropathy: relation with histopathology and with albuminuria. Int J Clin Exp Pathol. 2013;6(5):904.

Kim MK, Maeng YI, Lee SJ, Lee IH, Bae J, Kang YN, et al. Pathogenesis and significance of glomerular C4d deposition in lupus nephritis: activation of classical and lectin pathways. Inter J Clin Exp Pathol. 2013;6(10):2157.

Nasri H, Ahmadi A, Rafieian-kopaei M, Bashardoust B, Nasri P, Mubarak M. Association of glomerular C4d deposition with various demographic data in IgA nephropathy patients; a preliminary study. J Nephropathol. 2015 Jan;4(1):19.

Espinosa M, Ortega R, Sánchez M, Segarra A, Salcedo MT, González F, et al. Association of C4d deposition with clinical outcomes in IgA nephropathy. Clin J Am Society Nephrol. 2014 Feb 27:CJN-09710913.

Fabiano RC, de Almeida Araújo S, Bambirra EA, Oliveira EA, e Silva AC, Pinheiro SV. Mesangial C4d deposition may predict progression of kidney disease in pediatric patients with IgA nephropathy. Pediatric Nephrol. 2017 Jul 1;32(7):1211-20.

Sepe V, Albrizio P, Canton AD. C4d Glomerular Deposits and Disease Progression in Native Idiopathic Membranous Nephropathy. J Nephrol Ther. 2015;5(212):2161-0959.

Daram SR, Yalamanchili P, Salinas-Madrigal L, Bastani B. Patterns of C4d staining in patients with lupus nephritis. J Appl Res Clin Exp Ther. 2006;6(2):176.

Val-Bernal JF, Garijo MF, Val D, Rodrigo E, Arias M. C4d immunohistochemical staining is a sensitive method to confirm immune-reactant deposition in formalin-fixed paraffin-embedded tissue in membranous glomerulo-nephritis. Histol Hi. 2011;26(10):1391.

Trnuma Y Ohi H, Hatono M. Accelerated decay of the cel bound C4b2a complex by serum of patients with membranoproliferative glomerulonephritis and acute poststreptococcal glomerulonephritis. Clin Immunol Immunopathol. 1992;62(3):270-6.

Freneaux-Bacchi V, Weiss L, Demouchy C, May A, Palomera S, Kazatichkine MD. Hypocomlementaemia of poststreptococcal acute glomerulonephritis is associated with C3 nephritis factor (C3NeF) IgG autoantibody activity. Nephrol Dialysis Trans. 1994;9(12):1747-50.

Bose BM, Pothen L, Parameswaran JK Poothiode U. Clinicopthological comparative study of C4d positive and negative cases og IgA nephropathy. Immunopathologia Persa. 2016 Sep 19;3(1).

Van Es LA, De Heer E, Vleming LJ, Van Der Wal A, Mallat M, Bajema I, et al. GMP-17-positive T-lymphocytes in renal tubules predict progression in early stages of IgA nephropathy. Kidney international. 2008;73(12):1426-33.