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Kidney Week

Abstract: TH-PO366

Renoprotective Effects of Phosphodiesterase 5 Inhibitor in Models of CKD with Hypertension and Nephrotic Syndrome

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Hotta, Yuji, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan
  • Tomita, Natsumi, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan
  • Naiki-Ito, Aya, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
  • Yoshikawa, Mayu, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan
  • Kataoka, Tomoya, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
  • Takahashi, Satoru, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
  • Kimura, Kazunori, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan
Background

Phosphodiesterase (PDE) 5 inhibitor has a renoprotective effect. PDE5 expression in glomeruli is confirmed, but its role has been unclear. In this study, we assessed the effects of tadalafil (Tad), a PDE5 inhibitor, using two renal dysfunction models, chronic kidney disease (CKD) with hypertension and nephrotic syndrome.

Methods

1) CKD model. We used Dahl salt-sensitive rats with hypertension and CKD induced by a high-salt diet. The rats were divided into normal salt, high salt, and Tad 1- and 10-mg/kg treatment groups. After 8 weeks of treatment, we analyzed kidney function, blood pressure, and histopathological changes. 2) Nephrotic syndrome model. A nephrotic syndrome model was created with Wistar-ST rats by adriamycin (ADR) injection. The rats were divided into control, ADR, and ADR+Tad 10 mg/kg groups. After 2 or 4 weeks of treatment, urinary protein and serum albumin levels were evaluated.

Results

1) CKD model. High-salt diet induced kidney dysfunction and severe hypertension. Tad 10 mg/kg treatment prevented increases in serum creatinine (SCr) and urinary protein levels and hypertension (Fig. 1). Tad 1 mg/kg treatment significantly prevented the increase in SCr and urinary protein levels, but not hypertension. Histopathological analysis revealed that Tad treatment attenuated glomerular injury. 2) Nephrotic syndrome model. ADR injection induced high urinary protein level and low serum albumin level. Tad treatment attenuated proteinuria at 2 and 4 weeks and reduction of serum albumin level at 4 weeks.

Conclusion

This study suggests that Tad treatment is effective for both CKD and nephrotic syndrome. The improvement might be induced by the effects against glomerular impairment, particularly podocyte injury.


Fig. 1 SCr (A) and urinary protein to creatinine ratio (B) in CKD model. NS, normal salt; HS, high salt; TL, HS+tadalafil (1 mg/kg/day); TH, HS+tadalafil (10 mg/kg/day; n=5–7). *P<0.05; **P<0.01, versus NS; #P<0.05; ##P<0.01, versus HS.