Hypertension and proteinuria are risk factors for faster progression of kidney disease. Pharmacologic control of hypertension reduces urine protein excretion and slows progression of the disease. Recent guidelines included in the seventh report of the Joint National Committee for the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) recommend decreasing blood pressure goals in patients with decreased renal function to less than 130/80 mm Hg. Although lower blood pressure levels might confer added protection, excessively low blood pressure may be associated with increased cardiovascular disease risk. Jafar and associates reviewed the relationship between blood pressure and urine protein excretion with kidney disease by performing a meta-analysis of data from the angiotensin-converting enzyme (ACE) Inhibition in Progressive Renal Disease (AIPRD) database. The database lists 1,860 nondiabetic patients enrolled in randomized, controlled trials of the effect of ACE inhibitors on kidney disease progression.
All patients had been randomized to blood pressure medication groups with or without ACE inhibitors. Five ACE inhibitors were used in the treatment group, and both groups were treated to achieve a blood pressure target of 140/90 mm Hg. The primary end point was kidney disease progression, which was defined as a doubling in serum creatinine concentration or development of kidney failure. The lowest risk for disease progression was at current systolic blood pressure levels of 110 to 129 mm Hg. Current urine protein excretion of less than 2,000 mg per 24 hours (2 g per day) was associated with the lowest risk for disease progression. After adjustment for these variables, the risk of disease progression was lower in patients receiving ACE inhibitors.
The authors conclude that there is a strong relationship between higher systolic blood pressure and urine protein excretion and kidney disease progression risk in nondiabetic patients receiving antihypertensive therapy, with or without ACE inhibitors. Lowest disease progression risk was noted in patients with systolic blood pressures of 110 to 129 mm Hg, although this relationship was weaker in patients with a urinary protein excretion of less than 1,000 mg per 24 hours (1 g per day). Antihypertensive regimens that include ACE inhibitors appear to slow kidney disease progression in nondiabetic patients.
In an accompanying editorial, Mulrow and Townsend agree that measurement of urine protein is essential, as well as reduction of systolic blood pressure to 110 to 130 mg Hg (using the lower number as a goal for patients with a protein excretion rate greater than 2,000 mg per 24 hours). Combining ACE inhibitors with an angiotensin- receptor blocker appears to have additional clinical benefit to that of ACE inhibitor therapy alone.