Abstract: FR-PO674

Study of a Breakthrough Therapy Utilizing Alternative Actions of Vitamins A and D in a Murine Model of Minimal Change Nephrotic Syndrome

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Tsuji, Shoji, Department of Pediatrics, Kansai Medical University, Osaka, Japan
  • Kino, Jiro, Department of Pediatrics, Kansai Medical University, Osaka, Japan
  • Suruda, Chikushi, Department of Pediatrics, Kansai Medical University, Osaka, Japan
  • Kimata, Takahisa, Department of Pediatrics, Kansai Medical University, Osaka, Japan
  • Yamanouchi, Sohsaku, Department of Pediatrics, Kansai Medical University, Osaka, Japan
  • Kaneko, Kazunari, Department of Pediatrics, Kansai Medical University, Osaka, Japan
Background

The etiology of minimal change nephrotic syndrome (MCNS) remains unclear, although recent research suggests that regulatory T cell (Treg) malfunction and associated functional and structural podocyte abnormalities play a role. Steroids are shown to have high efficacy against MCNS, and are utilized to correct the above-stated podocyte abnormalities. However, long-term steroid treatment may induce various adverse effects.
In addition to their intrinsic vitamin functionality, vitamins A and D have recently demonstrated immunoregulatory functions, including effects on Treg differentiation and induction. Furthermore, they have been shown to restore damaged podocytes, directly [Okamura M, et al. Nephrol Dial Transplant 2009;24:3006]. The objective of this study was to investigate if vitamins A and D, which have fewer adverse effects, can correct the causes of MCNS in an animal model, and to search for a non-steroidal therapy for this syndrome.

Methods

Six-week-old MCNS model Wistar rats with puromycin aminonucleoside (PAN)-induced nephrosis were categorized into 4 treatment groups (n=3 per regimen): 1) VA Group received subcutaneous vitamin A 2.5 mg/kg dissolved in 1 mL dimethyl sulfoxide [DMSO]), 2) VD Group received intraperitoneal vitamin D 0.4 µg/kg dissolved in 0.2 mL phosphate-buffered saline [PBS]), 3) VAD Group received both the subcutaneous VA and intraperitoneal VD, 4) C (Control) Group received 0.2 mL subcutaneous DMSO and 0.2 mL intraperitoneal PBS. Starting two days pre-PAN administration, each regimen involved daily treatment for 12 days. Urinary protein excretion was measured and compared among the four groups. The Kruskal-Wallis Test was used for statistical analyses.

Results

Peak urinary protein excretion occurred at Day 9 post-PAN administration, when the median value was significantly lower in the VAD group than the C group (16.4 vs. 731.8 mg/kg/day; p=0.0144) and tended to be lower, although not significantly different, in the VAD group than the single-vitamin-treated rats (16.4 vs. 44.8 [VA] or 264.9 [VD] mg/kg/day.

Conclusion

Vitamins A and D exhibit an antiproteinuric effect with an additive action in MCNS model rats, and are potential therapeutic agents.