Clinical Trial
Intensive Blood Pressure Control Improves Renal Survival in Pediatric Kidney Disease Patients

Otto Mehls, MD;
Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, Heidelberg University

Similarly to adults, children with kidney disease commonly face progression to renal failure once a threshold of renal impairment is reached. A 2-year study of children up to age 18 found that blood pressure (BP) and proteinuria correlate with progression of chronic renal failure (CRF). (1) This, too, is similar to adult nephropathies where BP levels are closely associated with progressive renal failure. Studies in adults have suggested renoprotective effects of rigorous BP control, especially with renin-angiotensin system antagonists.

Because pediatric data in this area are lacking, investigators convened the multicenter Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of Chronic Renal Failure in Pediatric Patients or ESCAPE trial to evaluate efficacy of fixed-dose ACE inhibition in children with chronic kidney disease (CKD) stages II through IV as well as evaluate whether intensified BP control confers renoprotective effects in this population.

Investigators enrolled 385 patients ages 3 to 18 years with a glomerular filtration rate (GFR) between 15 and 80 ml/min/1.73 m2 and a 24-hour mean arterial pressure (MAP) >50th percentile. After a washout period, all patients were treated with the ACE-inhibitor ramipril 6 mg/m2 and additionally randomized to conventional (24-hour MAP 50th-95th percentile; n = 196) or intensified blood pressure control (24-hour MAP <50 percentile; n = 189).

Patients were followed for 5 years, which included bimonthly assessment of renal function and proteinuria, 24-hour ambulatory BP monitoring every 6 months, and an annual echocardiography. The primary endpoint was a composite renal survival endpoint (cumulative loss of GFR >50 % or GFR <10 ml/min/1.73m² or need for renal replacement therapy).

Both BP and proteinuria dropped after treatment with ramipril, but proteinuria rose again during treatment, nearly reaching the baseline level after 36 months. Nevertheless, significantly fewer patients in the intensified therapy arm reached the composite primary endpoint compared to those receiving conventional BP control therapy (15.5% vs. 26.9%; p = 0.01).

Figure 1

Figure 2

Renal survival did vary significantly depending on specific variables. For instance, there was significantly greater survival among patients with lower-stage kidney disease than those in more advanced stages (Figure 1); likewise, patients younger than 10 years experienced greater survival rates than did those 10-16 years old (p < 0.001). Patients with lower achieved blood pressure (</=50th percentile) enjoyed higher survival rates as well (p < 0.01), although when stratified into three levels (<50th percentile, 50th-95th percentile, >95th percentile), there was little difference between the first two groups while the latter demonstrated a significant reduction in survival, starting at approximately the second year of follow-up (p < 0.0001). Increasing level of proteinuria also proved to significantly impact survival (p < 0.005) (Figure 2).

Another variable influencing survival was the patient’s underlying disease. Intensive therapy appeared to provide greater renoprotection in patients with glomerulopathies (p = 0.0034) than those with hypodysplastic diseases, although those with the latter disorders still benefited significantly with intensive therapy (p = 0.0442).

According to Prof. Otto Mehls, Heidelberg University, Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, Heidelberg University (Germany), the ESCAPE trial suggests that children can gain substantial benefit in terms of a slower progression towards renal failure with the addition of intensive BP control added to an ACE inhibitor. The intervention reduces the relative risk of losing 50% GFR or attaining end-stage renal disease by 40% or an absolute risk reduction of 11% (84.5% vs. 73.2% renal survival) compared to less intensive therapy. However, he cautioned, the ongoing proteinuria observed in this trial remains a risk factor for progressive renal failure despite improved BP control. Consequently, additional therapeutic strategies may be needed for children receiving long-term ACE inhibition.

References:

1. Wingen AM, Fabian-Bach C, Schaefer F, Mehls O. Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood. Lancet. 1997;49:1117–23.

<< back