Abstract: TH-PO097

Glomerular FHR5 Associates with Severity in IgA Nephropathy

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Medjeral-Thomas, Nicholas R., Imperial College London, London, LONDON, United Kingdom
  • Constantinou, Nicholas, Imperial College London, London, LONDON, United Kingdom
  • Lomax-Browne, Hannah J., Imperial College London, London, LONDON, United Kingdom
  • Cook, H. Terence, Imperial College London, London, LONDON, United Kingdom
  • Pickering, Matthew C., Imperial College London, London, LONDON, United Kingdom
Background

Serum factor H-related protein 5 (FHR5) levels are higher in IgA nephropathy (IgN) patients than healthy controls and correlate with histological severity. We hypothesised that glomerular FHR5 deposition would associate with IgAN severity.

Methods

37 IgAN patients had stored tissue available from diagnostic renal biopsy and were categorised as progressive (n=19) or stable (n=18) disease. Immunohistochemistry protocols to detect complement C3c/C3b/iC3b, C3d, C4d, C5b9, factor H (fH) and FHR5 were developed and glomerular staining intensity graded on a scale: 0 (absent), 0.5 (minimal), 1, 2 or 3.

Results

Glomerular FHR5 deposition was present in 31 and absent in 6 patients. All cases with FHR5 staining showed glomerular C3 staining. A greater proportion of progressive than stable patients had detectable glomerular FHR5 (18/19 progressive and 13/18 stable patients, p=0.09). Of the 6 patients with absent FHR5, 5 (83%) had stable IgAN. We next sub-divided our cohort into those with negative(0)/minimal(0.5) glomerular FHR5 staining (FHR5-) and those with staining intensity scores of 1-3 (FHR5+). Features of IgAN severity were more common in the FHR5+ cohort (Table). After median 51 months follow up (range 13-296 months), four of the FHR5+ but none of the FHR5- patients reached end stage renal failure (p<0.0001). A greater proportion of the FHR5+ cohort showed glomerular complement deposition (Table) with a positive correlation between FHR5 staining and C3c/C3b/iC3b (r=0.57, p<0.0001), C3d (r=0.74, p<0.0001), and C5b9 (r=0.68, p<0.0001).

Conclusion

We conclude that glomerular FHR5 associates with disease severity and glomerular complement activation and represents a novel IgAN biomarker.

Clinical featureFHR5+(n=24), medianFHR5– (n=13), medianDifference of medians95% CIp value
eGFR (ml/min per 1.73m2)6389-26-50.2 to -3.20.03
UPCR (mg/mmol)15559962 to 1230.04
Serum C3 (g/L)1.131.37-0.24-0.46 to -0.050.02
Histology featureFHR5+, proportionFHR5–, proportionOdds Ratio95% CIp value
Mesangial hypercellularity18/243/13101.9 to 39.70.005
Tubular atrophy12/242/135.50.97 to 27.80.07
Cellular Crescents12/242/135.50.97 to 27.80.07
C3c/C3b/iC3b24/2411/13  0.11
C3d17/203/12173.0 to 77.60.002
C4d15/224/134.81.1 to 17.00.04
C5b920/213/1066.76.5 to 743<0.0001
fH3/224/12  0.21