Kidney Week

Abstract: FR-PO098

Urinary Symmetric Dimethylarginine Reflects Mild Renal Damage After Cisplatin Treatment in Rats

Session Information

• AKI: Tubules, Metabolism, New Models
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Hotta, Yuji, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Yuji Hotta,

• Naiki-Ito, Aya, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

Aya Naiki-Ito,

• Kitagawa, Ayae, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Ayae Kitagawa,

• Tomita, Natsumi, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Natsumi Tomita,

• Kondo, Masahiro, Nagoya City University Hospital, Nagoya, Japan

Masahiro Kondo,

• Kataoka, Tomoya, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

Tomoya Kataoka,

• Maeda, Yasuhiro, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Yasuhiro Maeda,

• Takahashi, Satoru, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

Satoru Takahashi,

• Kimura, Kazunori, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Kazunori Kimura,

Background

Serum symmetric dimethylarginine (SDMA) correlates with renal function, but the usefulness of measuring urinary SDMA levels is unclear. Here, we studied if urinary SDMA levels reflected mild nephropathy after cisplatin (CDDP) treatment that failed to increase serum creatinine (SCr) in rats.

Methods

[Single CDDP treatment] Eight-week-old male Wistar-ST rats were divided into control and CDDP groups, treated with saline and CDDP 1 mg/kg intraperitoneally, respectively. SCr, blood urea nitrogen (BUN), and urinary and serum SDMA levels were measured before and 5 days after treatment. SDMA was measured by ultra performance liquid chromatography-tandem mass spectrometry. Damage to proximal tubules (PTs) was evaluated by H&E staining. mRNA expression levels of organic anion transporter1 (Oat1) which transports SDMA were measured by real-time PCR. [Multiple CDDP treatment] We formed groups that were treated with saline and CDDP 1 mg/kg every 7 days (day 0, 7, 14, and 21) to study the effects of multiple CDDP treatment cycles. SCr, BUN and serum and urinary SDMA levels were measured at day 0 and day 5 in each cycle. Damage of PTs were studied 28 days after treatment. Statistical analysis was performed by Welch’s t-test.

Results

[Single CDDP treatment] SCr and BUN unchanged 5 days after treatment between control and CDDP groups. However, necrosis of PTs was partly observed in the CDDP group. Urinary SDMA levels in the CDDP group significantly increased on day 5 (P<0.01); serum SDMA levels did not change. mRNA expression levels of Oat1 unchanged between control and CDDP group. [Multiple CDDP treatment] SCr and BUN did not change even after 3 CDDP treatment cycles compared with control group. In CDDP group, heteromorphic regenerating endothelium was observed. Urinary SDMA in CDDP group was significantly increased compared with control group from day 5 until the endpoint (P<0.01).

Conclusion

Urinary SDMA levels reflect the mild damage of PTs after CDDP treatment, which SCr and BUN could not reflect. Thus, urinary SDMA may be a better biomarker than SCr and BUN.