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Updated: Nov 18, 2025
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
Poor allograft outcome in Indian patients with post-transplant C3 glomerulopathy
Ashwani Kumar1, Raja Ramachandran2, Amit Rawat3
1Department of Histopathology, PGIMER, Chandigarh, India.
Insights
Post-transplant complement 3 glomerulopathy (C3G) in South Asia often presents with graft dysfunction. This study found low complement levels and common autoantibodies, with a poor clinical outcome for kidney transplant recipients.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- Complement 3 glomerulopathy (C3G) arises from alternative complement pathway (ACP) dysfunction.
- Limited data exists on C3G following kidney transplantation in South Asia.
Purpose of the Study:
- To investigate the characteristics and outcomes of post-transplant C3G in South Asia.
- To analyze complement pathway markers and genetic factors in recurrent C3G.
Main Methods:
- Analysis of renal allograft biopsies from 2012-2017 for ACP functional assay (APFA), complement levels, and autoantibodies.
- Limited genetic screening for CFH/CFHR5 genes.
- Patient follow-up for clinical outcomes.
Main Results:
- Eleven of 21 C3G cases showed recurrence, presenting with allograft dysfunction or proteinuria.
- Low APFA/C3 levels and low serum complement factor H (CFH) were observed.
- Autoantibodies to complement regulatory proteins were common; only non-pathogenic CFH gene variants were found.
Conclusions:
- Post-transplant C3G can manifest as graft dysfunction or proteinuria with subtle histological findings.
- Autoantibodies are prevalent, and no novel mutations were identified in this cohort.
- The clinical outcome for these patients is generally poor, with high rates of graft loss and mortality.
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 CFH/CFHR5 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 CFH 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.
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