Abstract: TH-PO113

Plasma C4d Differentiates PLA2R Positive Membranous Nephropathy from Other Primary Glomerular Diseases

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Jiao, Congcong, The first hospital of China medical university, Shenyang, China
  • Kopp, Jeffrey B., NIDDK, NIH, Bethesda, Maryland, United States
  • Wang, Lining, Department of Nephrology, First Affiliated Hospital of China Medical University, Shenyang, P. R. China, Shenyang, China
  • Zhou, Hua, The first hospital of China medical university, Shenyang, China
  • Luan, Junjun, The first hospital of China medical university, Shenyang, China
  • Guo, Guangying, The first hospital of China medical university, Shenyang, China
  • Qu, Wei, China Medical University, Shenyang, China
  • Chen, Ying, China Medical University, Shenyang, China
  • Kong, Weiwei, The first hospital of China medical university, Shenyang, China
  • Zhang, Yani, The first hospital of China medical university, Shenyang, China
  • Fu, Jingqi, Chinese Medical University, Shenyang, China
  • Pi, Jingbo, Chinese Medical University, Shenyang, China
Background

Renal C4d staining is a potential diagnostic biomarker for immune complex-mediated glomerular diseases. Positive M-type phospholipase A2 receptor (PLA2R) staining on kidney biopsy is specific for primary membranous nephropathy (pMN) diagnosis. We aimed to assess whether plasma C4d can differentiate PLA2R positive MN from other primary glomerular diseases and to correlate plasma C4d level with renal PLA2R staining.

Methods

Plasma C4d levels were measured by ELISA in 16 healthy volunteers and 187 untreated patients with biopsy-proven glomerular diseases, including 80 PLA2R positive and 55 PLAR negative MN cases, 20 IgA nephropathy, 18 minimal change disease, and 14 focal segmental glomerulosclerosis cases. There were 123 nephrotic and 26 nephritic cases among subjects with primary glomerular diseases. PLA2R negative MN cases included atypical pMN (n=17), hepatitis B virus (HBV)-associated MN (n=23) and autoimmune-associated MN (n=15).

Results

Plasma C4d levels significantly increased in pMN compared with each of the other groups. C4d differentiated pMN from these three primary glomerular diseases either in nephrotic (AUC=0.7, p<0.001, n=111) or nephritic diseases (AUC=1.0, p<0.001, n=21). C4d also distinguished PLA2R positive MN from PLA2R negative MN (AUC=0.98, p<0.001, n=135). Interestingly, C4d was significantly decreased in autoimmune-associated MN compared with HBV-associated MN and PLA2R negative MN without identified primary causes. Plasma C4d was positively correlated with the extent of renal PLA2R staining (r=0.64, p<0.001, n=135).

Conclusion

Plasma C4d differentiates PLA2R positive MN from other primary glomerular diseases and correlated with renal PLA2R staining. Plasma C4d may serve as a supplementary biomarker, together with circulating PLA2R antibody, as a measurement panel for diagnosing pMN in patients with a contraindication to renal biopsy.

Funding

  • NIDDK Support