Key Points
- To review the pathophysiological role of systemic and intrarenal angiotensin II in diabetic nephropathy and evaluate the therapeutic efficacy of renin–angiotensin system blockade.
- Synthesized molecular, cellular, and micropuncture studies examining intrarenal renin–angiotensin system activation, receptor signaling, and glucose-mediated renal injury.
- Reviewed clinical trial evidence and meta-analyses investigating angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and dual-blockade regimens.
- Intrarenal angiotensin II concentrations reach levels up to 1,000-fold higher than systemic blood, inducing glomerular hypertension, extracellular matrix accumulation, cellular hypertrophy, and transforming growth factor-β1 expression.
- Angiotensin-converting enzyme inhibitors and AT1 receptor blockers significantly reduce proteinuria and slow nephropathy progression independently of systemic blood pressure reduction.
- Dual blockade combining an angiotensin-converting enzyme inhibitor with an AT1 receptor blocker achieves greater reductions in microalbuminuria and urinary transforming growth factor-β1 than monotherapy alone.
Structured PICO
Does renin-angiotensin system blockade with ACEIs or ARBs slow the progression of diabetic nephropathy?
PPopulationPatients with diabetic nephropathy
IInterventionACE inhibitors (ACEIs) or Angiotensin II receptor blockers (ARBs), alone or in combination
CComparatorPlacebo or other antihypertensive drugs
OOutcomeProgression of diabetic nephropathy (reduction of proteinuria and lowering of arterial hypertension)surrogate
ACE inhibitors and ARBs are effective in slowing the progression of diabetic nephropathy, with combination therapy potentially indicated for patients with resistant hypertension or massive proteinuria.