Think that because the testosterone replacement therapy given to the rats was orally administered it could have caused the kidney damage? Would injections have avoided this problem? I'd imagine it's the alkylation/methylation used to make the steroids orally available that made them toxic. Anyone with more knowledge have an opinion?
I don't have a lot of knowledge on the subject but I'll chime in. I would say, like you said, the fact that it was given orally and that I'm sure the rats didn't know to increase their water consumption. With an oral steroid and low-normal water intake, kidney damage wouldn't surprise me at all.
It's more likely that the proteinuria was a result of the elevated blood pressure. The elevated BP if over significant time or acutely elevated can cause glomerulonephritis/sclerosis. Toxicity from drugs usually results in a interstitial nephritis or acute tubular necrosis more so than a glomerular or basement membrane issues. NSAIDS are some of the worst drugs on the kidneys. Again, it's likely the hypertension is to blame.
I have monitored my kidney function in regard to glomerular filtration rate, creatinine, BUN, urinalysis and electrolytes while on numerous orals and have only noticed an elevated GFR and slightly elevated creatinine which is due to increased muscle mass compared to the average individual.
Your correct, proteinuria can be a serious sign of kidney failure(nephrotic syndrome). Most cases of proteinuria are asymptomatic. I think you'd be surprised of how many people with HTN actually have proteinuria if a urinalysis was done.
Most people with HTN are undiagnosed or are controlled to some degree with ACE inhibitors or angiotensin receptor blockers, unlike these rats.
Regardless of protein in diet, it usually is not dietary protein excreted in urine and tends to be mainly plasma albumins.
The only way to tell truly if these rats suffered prerenal(HTN) vs. renal(toxicity) is to evaluate BUN/creatine ratio, urinalysis cast type, FENa and urine sodium and osmolality. Studies like this cause more unnecessary concern than good, there are way too many variables to be considered.
I'm really surprised this thread got such great discussion going. Completely unexpected, but really cool. I love posts like these because it makes me want to do some research to further my understanding. I didn't even think it would be that complex (read ignorance). I guess I'm a nerd, but this thread just made my day.