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


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.


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

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