Testing Android app release build variant

I have written many unit and instrumented tests for my Android app. So far, I only run these against the debug build variant. Is it necessary to run tests against the release build variant? What difference can there be that might give different results from testing? The main one that I can think of is when ProGuard is enabled, which I haven't done. What will ProGuard do that makes it necessary to run my test suite? What other issues should I be aware of that require testing the release build variant?