Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetic nephropathy (DN). Intensive treatment requires blockade of the renin-angiotensin system (RAS) by either angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), which reduce blood pressure and proteinuria. Combining the two therapies has shown greater benefits than either drug alone to reduce progression of DN.
Although treatment goals are more likely to be achieved with the combination, this requires close monitoring of serum creatinine and potassium which invariably rise on such therapy.
DN occurs in 30-40% of all diabetic patients and has become the leading cause of ESRD in the western world. The most important risk factors for progression of nephropathy in patients with diabetes both before and during antihypertensive treatments are elevated systemic BP and albuminuria. These are also predictors of poor renal and cardiovascular outcome in patients with diabetes. Initial reduction in albuminuria after blockade of RAS predicts an attenuated rate of decline in GFR. Hence, albuminuria may serve as a surrogate end point for monitoring treatment efficacy and prognosis in DN.
The RAS plays a central role in the initiation and progression of diabetic and non-diabetic nephropathies and blockade of the RAS is now recommended as the first-line therapy in diabetic patients with elevated urinary albumin excretion (figure 1). Several clinical studies have shown similar effects with ACE inhibitors or ARBs in reducing albuminuria, retarding progressive loss in renal function and improvements in survival above and beyond any such effects attributable to reduction in BP alone. Blockade of RAS by either ACE inhibitors or ARBs slows but does not completely arrest the progression of renal disease toward ESRD. Since these agents act at different sites on the RAS, they may have additive effects that result in even greater reno-protection when used in combination and have been effective in diabetic patients with microalbuminuria and macroalbuminuria.
The renin-angiotensin system.