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Abstract: SA-PO451

Urine Biomarker Potential for Assessment of Disease Activity in Pediatric Nephrotic Syndrome

Session Information

  • Pediatric Nephrology - II
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1600 Pediatric Nephrology

Authors

  • Hama, Taketsugu, Wakayama Medical University, Wakayama, Japan
  • Tanaka, Yu, Wakayama Medical University, Wakayama, Japan
  • Sato, Masashi, Wakayama Medical University, Wakayama, Japan
  • Mukaiyama, Hironobu, Wakayama Medical University, Wakayama, Japan
  • Shima, Yuko, Wakayama Medical University, Wakayama, Japan
  • Nakanishi, Koichi, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
  • Yoshikawa, Norishige, Wakayama Medical University, Wakayama, Japan
  • Suzuki, Hiroyuki, Wakayama Medical University, Wakayama, Japan
Background

Biomarkers are considered to be a powerful tool of diagnosis and assessment of disease activity. Currently, proteinuria is the standard means of diagnosis of nephrotic syndrome (NS). Other non-invasive biomarkers are desired, especially those that may provide better understanding of NS activity than proteinuria.

Methods

We extracted urine RNA and using real-time PCR, examined the expression levels of various biomarkers. Expression levels were then compared between NS and other diseases. We also investigated the correlation between biomarkers and the conditions of disease across four stages; pre-treatment proteinuria (stage 1), proteinuria during treatment (stage 2), remission during treatment (stage 3) and post-treatment remission (stage 4). At our hospital, 117 RNA samples were taken from 104 consecutive patients with various kidney diseases (30 nephrotic syndrome, 27 IgAN, 15 isolated hematuria, 7 isolated proteinuria, 25 others). Across the four stages, the 30 NS patients provided 46 RNA samples (stage 1 = 7, stage 2 = 8, stage 3 = 12, stage 4 = 19).

Results

Using biomarkers, we could diagnose NS and observe its activity across the four stages. Pediatric NS samples showed significantly higher levels of liver fatty acid-binding protein (FABP-1) (p<0.01), megalin (p<0.01), cubilin (p<0.01) and lower level of podocin (p<0.01) compared to the other diseases. In NS samples only, FABP-1, cubilin and kidney injury molecule-1 (KIM-1) expression levels correlated positively with urine protein volume, whereas podocin correlated negatively. FABP-1 expression was around double and podocin expression was approximately 75% lower in relapse than in remission (Table 1). In stage 2, cubilin expression doubled. In stage 3, KIM-1 expression increased 170%.

Conclusion

Urine RNA expressions reveal clues to the pathophysiology of NS. Urine biomarkers other than proteinuria can be considered an effective non-invasive tool to understand disease activity in pediatric NS.

Table 1. Urine RNA relative expression
 FABP-1KIM-1cubilinIL-18NGALmegalinpodocinThy1HSPG2
Pre-treatment proteinuria [stage 1, n=7]1.01.01.01.01.01.01.01.01.0
Proteinuria during treatment [stage 2, n=8]1.30.91.81.51.61.71.01.53.5
Remission during treatment [stage 3, n=12]0.41.70.92.32.01.43.71.83.6
Post-treatment remission [stage 4, n=19]0.50.50.92.83.60.86.31.52.7

Funding

  • Government Support - Non-U.S.