Update - not that I have any expectation of you, but thought you might be curious - seems to be an issue with the itch desktop client! Or possibly MacOS security? idk
Can't save games that I've installed via the client, but if I download and manually install (and override system security for each game to allow me to actually launch them) I can save... interesting... and bothersome, but hey, love a successful workaround.
Oh and it seems RenPy may indeed also be involved, as I have MDRG installed thru the client and it saves fine.