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Abstract: SA-PO638

Urine Aquaporin-2 Messenger RNA Predicts Global Glomerulosclerosis and Renal Outcome in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Kikuchi, Masao, University of Miyazaki, Kiyotake, MIYAZAKI, Japan
  • Fukuda, Akihiro, Oita University, Yufu, Japan
  • Minakawa, Akihiro, Miyazaki university, Miyazaki, Japan
  • Sato, Yuji, University of Miyazaki Hospital, Miyazaki, Japan
  • Fujimoto, Shouichi, University of Miyazaki, Kiyotake, MIYAZAKI, Japan
Background

Despite substantial progress in the treatment for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), the prognosis of patients with AAV has not sufficiently improved. The poor prognosis is not only caused by the activity of AAV but also caused by adverse events due to the therapeutic agents. Avoiding excessive immunosuppression can lead to an improvement in the prognosis. Useful and noninvasive predictor for renal outcome is needed. We recently announced that urine aquaporin 2 (U-AQP2), which is a water channel localized in the renal collecting ducts, mRNA predicts the renal outcome in AAV at the 56th ERA-EDTA Congress in Budapest, 2019. Here, we examined the association between U-AQP2 mRNA and renal biopsy tissue.

Methods

We enrolled 33 patients with AAV diagnosed at Miyazaki University Hospital from January 2009 to March 2016. Their U-AQP2 mRNA levels at the onset of AAV were evaluated by real-time polymerase chain reaction, and normalized by urine creatinine concentration. We divided them into two groups (High U-AQP-2 group (n=7) and Low U-AQP-2 group (n=26)) based on mean value of U-AQP2 mRNA and performed Kaplan-Meier analysis to assess renal survival in two groups. We also examined the renal biopsy tissues of each group.

Results

High U-AQP2 group showed poorer renal prognosis than Low U-AQP2 group (p<0.001). In analysis of renal biopsy tissue, the percentage of global glomerulosclerosis in High U-AQP2 group was significantly higher than in Low U-AQP2 group (32.9 % vs. 16.8 %, p=0.02). The percentage of crescentic lesions in High AQP2 group was not significantly different from Low AQP2 group (39.8 % vs. 33.3 %, p=0.44). The degree of tubulointerstitial lesion in High AQP2 group was also not significantly different from Low AQP2 group. Urinary NAG concentration, which is an indicator of tubular injury, did not change between the two groups.

Conclusion

This result could suggest severe glomerular damage caused by AAV affects distal nephron. U-AQP2 mRNA may be able to detect deep lesions that are difficult to diagnose in kidney biopsy tissue. U-AQP2 could predict irreversible damage by AAV.