How can ACE inhibitors and ARBS cause kidney dysfunction while being protective in diabetic nephropathy?
ACE inhibitors and ARBs exert their effects by blocking the RAAS pathway. The pharmacodynamic effects of these agents are achieved by inhibiting the vasoconstrictive effect of angiotensin II at the efferent arteriole in the glomerulus.
RAAS blockade at the glomerular structure of the nephron reduces glomerular capillary pressure, which is associated with reduced proteinuria, an important surrogate outcome for kidney function.
As a result of the reduced filtration fraction associated with this hemodynamic change, an increase in the baseline serum creatinine concentration prior to drug initiation of 30% is generally determined acceptable. However, this increased in the serum creatinine has been associated with an increased risk of adverse outcomes long term. Increases in creatinine beyond this are suggestive of atherosclerotic kidney artery stenosis and should be further evaluated.