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Kidney Week

Abstract: TH-PO963

Therapeutic Effect of siRNA-CD40 on AKI Caused by Reversible Obstructive Nephropathy in Mice

Session Information

Category: Pathology and Lab Medicine

  • 1501 Pathology and Lab Medicine: Basic

Authors

  • Guiteras, Roser, IDIBELL, Hospitalet de Llobregat, Spain
  • Barros, Alonso Narváez, IDIBELL, Hospitalet de Llobregat, Spain
  • Sola, Anna, IDIBELL, Hospitalet de Llobregat, Spain
  • Manonelles, Anna, Hospital Universitari de Bellvitge, Barcelona, Spain
  • Torras, Joan, Hospital Universitari de Bellvitge, Barcelona, Spain
  • Cruzado, Josep M., Hospital Universitari de Bellvitge, Barcelona, Spain
Background

The costimulatory CD40-CD40L pathway plays a role in kidney inflammation. We have previously reported that renal CD40 upregulation precedes cellular interstitial infiltrate and fibrosis in the unilateral ureteral obstruction (UUO) model. Here we sought to evaluate whether the administration of siRNA anti-CD40 has a therapeutic effect in a reversible UUO mice model (rUUO).

Methods

Eight week-old C57BL6J male mice were divided into four groups: wild type (n=6); rUUO-Sham (n=8); rUUO+siRNA Scrambled, a non-specific siRNA (n=6), and rUUO+siRNA anti-CD40, specific siRNA anti-CD40 (n=8). Ureteral clamping was performed on 8 week-old C57BL6J male mice. At day 3 after surgery, the ureteral clamp was removed and nephrectomy of the contralateral kidney was performed. Immediately, PBS, siRNA SC (50µg) or anti-CD40 (50µg) was administrated via the tail vein. Mice were killed 48h hours after. Blood samples at days 0, 3, 4 and 5 were collected for creatinine analysis. Histology and kidney mRNA expression were performed.

Results

The administration of siRNA anti-CD40 was associated with a significant reduction of renal CD40 mRNA expression (Table 1). siRNA anti-CD40 reduced significantly the severity of acute renal failure associated with UUO (Figure 1). Pathologic analysis showed reduction of tubular dilation, F4/80 macrophage infiltration and interstitial fibrosis in animals treated with CD40-siRNA (Table 1). Furthermore, kidney mRNA gene expression analysis showed significantly lower levels of pro-inflammatory cytokines such IL-2 and CCL-2 and pro-fibrotic TGFβ-1 in CD40-siRNA mice.

Conclusion

The administration of siRNA-CD40 therapy at the time of ureter clamp removal in the UUO model reduces the severity of the acute kidney injury and promotes kidney repair.