AUA 2018: Cyclophilin D Participates in the Promotion of Kidney Stone Formation via Oxidative Stress

San Francisco, CA USA ( Yasuhiko Ito, MD and colleagues experimented with Cyclophilin D -deficient mice to correlate its influence on inflammation, oxidative stress, and mitochondrial damage. CypD was specifically knocked out as it controls mitochondrial permeability transition (MPT), which causes mitochondrial collapse. The team induced kidney stones in control (n=6) and CypD-deficient mice (n=6) by intraperitoneal injections of 80mg/kg glyoxylic acid for 6 days and analyzed the kidneys on day 12.

Comparing CypD-deficient mice with wild type mice, they measured oxidative stress using immunohistochemical staining of superoxide dimutase (SOD) and malondialdehyde (MDA). The team also gauged inflammation by quantitative reverse transcriptase polymerase chain reaction of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Mitochondria was observed with transmission scanning microscopy (TEM). They compared formation of renal crystal deposits using polarized light microscopy.

They report differences in both oxidative stress (significantly lower in CypD-/- than in CypD+/+) and stone formation ratio, with CypD-/- mice at 0.05% and CypD+/+ at 0.22%. However, the team reports no significant differences in MCP-1, IL-6, and TNF-α (p=0.604, 0.356, and 0.549, respectively). From the TEM images of the mitochondria, they observed that the comparative rupturing of mitochondria in CypD-deficient mice were less prevalent.

Although there may be potential side effects in the human body of downregulating CypD, medication to suppress CypD could have implications in preventing the formation of renal stones by decreasing inflammation and oxidative stress.

Presenter(s): Yasuhiko Ito, MD

Co-Authors: Maarten Hulshof, André Vis, Koos Zwinderman, Jos Twisk, Karl Delaere, Jeroen van Moorselaar, Paul Verhagen, George van Andel

Written by: Victoria Lee, MD, Clinical Fellow, Department of Urology, University of California-Irvine at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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