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Analysis of clinicopathologic features and prognosis of IgA nephropathy patients with H factor deposition in renal tissue

YANG Meng, XIE Jing-yuan, OUYANG Yan, ZHANG Xiao-yan, PAN Xiao-xia, XU Jing, WANG Zhao-hui, WANG Wei-ming, CHEN Nan   

  1. Department of Nephrology, Ruijin Hospital, Institute of Nephrology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025， China
  • Online:2016-08-29 Published:2016-08-31
  • Supported by:

    National Key Basic Research Program of China，2012CB517604；National Natural Science Foundation of China，81370015, 81570598；Shanghai Municipal Education Commission—GaoFeng Clinical Medicine Grant Support，20152207；Foundation of Shanghai Municipal Science and Technology Committee，14430721000；National Key Construction of Clinical Specialty and Construction Fund of Shanghai Municipal Public Health Bureau

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Abstract:

Objective · To investigate the association between clinicopathologic features of H factor (CFH) deposition in renal tissue of patients with IgA nephropathy (IgAN) and the prognosis. Methods · The primary IgAN patients who were confirmed by renal biopsy and were followed for at least 1 year by the Department of Nephrology at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine were enrolled. CFH deposition in renal tissue was detected by immunohistochemistry. Serum CFH level was measured by Enzyme Linked Immunosorbent Assay (ELISA). The baseline clinical data, pathological data, and prognosis were recorded. The end point of the study was defined as a decrease in eGFR by 30% or eGFR<15 mL/(min · 1.73 m2) or receiving renal replacement therapy. Results · A total of 283 patients with IgAN were recruited. Renal pathological examinations revealed that 198 (70%) of them had CFH deposition in renal tissue. Patients with positive CFH deposition had higher urine protein excretion and serum uric acid levels and renal pathology showed severer mesangial proliferation, segmental sclerosis, and interstitial fibrosis. The association between CFH deposition in renal tissue and serum CFH deposition was not significant. Kaplan-Meier analysis found that the progression-free time was significantly shorter in patients with positive CFH deposition than in patients without CFH deposition [(59.90±1.87) months vs (65.10±1.78) months, P=0.01]. Multivariate Cox regression analysis showed that CFH deposition was still an independent risk factor for IgAN progression after adjustment of baseline eGFR, hemoglobin, systolic blood pressure, and serum albumin (HR=2.54, 95% CI: 1.04-6.17). Conclusion · Patients with positive CFH deposition have severer clinical manifestations and poorer prognosis as compared with patients without CFH deposition, suggesting the local activation of alternative complement pathway rather than systemic activation can promote the progression of IgAN.

Key words: IgA nephropathy, complement alternative pathway, complement factor H, disease progression