Background: The presence of high blood pressure and proteinuria can predict disease progression in children with chronic kidney disease. Use of angiotensin-converting enzyme (ACE) inhibitors can delay renal disease progression in adults; yet the optimal blood pressure target for renal protection in children is unclear. Wühl and colleagues conducted a randomized controlled trial to evaluate the effectiveness of intensive blood pressure control and ACE inhibitor therapy on preventing the progression of renal disease in children.

The Study: The authors recruited patients three to 18 years of age with stages II to IV kidney disease, defined by a glomerular filtration rate (GFR) of 15 to 80 mL per minute per 1.73 m² of body surface area, and with hypertension. Patients were excluded if they had renal artery stenosis, other major illnesses, or if they had received a kidney transplant.

All patients received ramipril (Altace) in a dosage of 6 mg per day per square meter of body surface area, but were randomly assigned to intensive blood pressure control (target mean arterial pressure below the 50th percentile) or conventional control (target pressure between the 50th and 90th percentiles). Other antihypertensive agents, not including renin-angiotensin antagonists, could be added to achieve the target blood pressure. The primary outcome was the time needed for GFR to decline by 50 percent or until end-stage renal disease (GFR less than 10 mL per minute) appeared, with secondary outcomes including change in urinary protein excretion.

Results: A total of 385 patients were followed for five years. Fewer patients in the intensive control group progressed to the primary outcome than in the conventional control group (29.9 versus 41.7 percent, respectively; hazard ratio = 0.65). Median urinary protein excretion decreased during the first six months on ramipril, from 0.82 g to 0.36 g of protein per gram of creatinine, but excretion rates returned to baseline by 36 months, despite continued good blood pressure control.

Conclusion: The authors conclude that intensive blood pressure control with ramipril appreciably decreases the risk of renal failure in children with hypertension and chronic kidney disease. However, despite successful blood pressure control, proteinuria eventually returns to baseline levels.