Statin-induced proteinuria

In the past I've struggled to get my head around the question of the role of statins in CKD. On the one hand they appear to slow progression, and people with lots of proteinuria often show some reduction in this measure over time. However, the effects on urinary protein excretion are at best variable, and there's no doubt that in some patients proteinuria actually increases. Despite this, the beneficial effects on preservation of renal function seem pretty consistent.

This paper from Sydney, Australia clears up how, on the one hand, statins can increase proteinuria while still preserving renal function in the long run.
It all has to do with mevalonate. In order prevent the 200 or so steps in cholesterol synthesis, statins nip the process in the bud by inhibiting HMGcoA at the beginning of the mevalonate synthetic pathway. Mevalonate is a precursor of isoprenoid pyrophosphates, which are necessary for G-protein prenylation of proteins involved in receptor-mediated endocytosis of albumin in the proximal tubule. Hence, the more potent the statin, the more it inhibits this reuptake pathway, causing albuminuria. This is why albuminuria is more frequently seen with newer, more potent statins such as rosuvastatin. As this is effectively an artefactual finding, patients with heavy proteinuria at baseline may show a reduction over time via improved endothelial function in their renal vascular bed. Admit it, that's pretty interesting. Shut up, it is.