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Abstract: TH-PO1003

Genetic Polymorphism in C3 Is Associated with CKD Progression in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Ibrahim, Sara T., faculty of medicine Alexandria university,Egypt, Alexandria, Egypt
  • Chinnadurai, Rajkumar, Salford Royal Hospital NHS Trust, Salford, United Kingdom
  • Ali, Ibrahim, Salford Royal Hospital NHS Trust, Salford, United Kingdom
  • Elgohary, Iman Ezzat, faculty of medicine Alexandria university,Egypt, Alexandria, Egypt
  • Adam, Ahmed G., faculty of medicine Alexandria university,Egypt, Alexandria, Egypt
  • Kalra, Philip A., Salford Royal Hospital NHS Trust, Salford, United Kingdom
Background

A single nucleotide polymorphism (SNP) in complement factors can harmfully affect their activity. The commonest SNP in C3 is R102G, causing two allotypic variants: C3 fast (C3F) and C3 slow (C3S). C3F has been shown to be prevalent in CKD, especialy IgA nephropathy but no study has explored its role in CKD progression.

Methods

Delta (Δ) eGFR (±ml/min/1.73m2/yr) for 2038 patients in the Salford Kidney Study (SKS) was calculated by linear regression, with ≤-3ml/min/1.73m2/yr defined as rapid progressors (RP) and those between -0.5 and +1ml/min/1.73m2/yr labelled stable progressors (SP). All patients had ≥2-years follow-up and eGFR-time graphs were analysed to ensure no AKI episodes contributed to CKD progression. We also studied all biopsy-proven GN patients in SKS regardeless of their ΔeGFR.
R102G was analyzed by real-time PCR. The association between C3F and progression (ESRD or ≥40% decline in eGFR) was analysed using Cox regression.

Results

There were 255 SP and 259 RP with median delta eGFR (0.07 vs. -4.7 ml/min/1.73m2/yr). There was no significant difference in C3 allele frequency between the two groups as a whole: C3F 27% in RP vs. 24.3% in SP p = 0.32. In the subgroups analysis there were 37 patients with IgA nephropathy (21 RP and 16 SP), in this group there was a significantly higher frequency of C3F in RP (38.6% vs. 9.4% in SP; p<0.001).
In the GN group there were 269 patients, containing 114 IgA nephropathy patients. Cox regression showed strong and independent association between C3F and progression only in the IgA nephropathy with HR =1.9 (95% CI 1.1 – 3.1; p 0.018) for C3FS, increasing further for C3FF to HR =2.8 (95% CI 1.2 – 6.2; p 0.014).

Conclusion

C3 SNP; R102G; is associated with CKD progression in patients with IgA nephropathy but not in other causes of CKD.

Funding

  • Government Support - Non-U.S.