Intensive Blood Pressure Control and Cardiac Remodeling in Children With CKD

Systolic blood pressure control targeting office pressure at the 50^th percentile may be best for prevention of increased left ventricular mass in children with chronic kidney disease, according to findings published in The Lancet Child & Adolescent Health.

Researchers hypothesized that lower blood pressure would reduce adverse cardiac remodeling in children with chronic kidney disease. The primary outcome was mean annual difference in left ventricular mass index (LVMI) determined via echocardiography by a masked observer. Secondary outcomes included between-group differences in mean left ventricular wall thickness, renal function, and adverse effects. Primary and secondary outcomes were assessed in the intention-to-treat population.

The researchers conducted the open-label, parallel-group, multicenter, randomized, controlled HOT-KID (Hypertension Optimal Treatment in Children with Chronic Kidney Disease) trial from the end of October 2012 through the beginning of January 2017 in 14 clinics across England and Scotland. There were 124 children aged between 2 to 15 years (median 10.0 years of age [IQR, 6.8-12.6 years]) with stage 1 to 4 chronic kidney disease enrolled in the study. They were randomly assigned into the intensive treatment group (systolic target <40^th percentile; n=64) or to the standard treatment group (auscultatory office systolic blood pressure target between the 50th and 75th percentiles; n=60).

The children (44% girls; 86% White), were treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers as first-line agents, dose titrated every 2 to 4 weeks to achieve blood pressure target levels. Median follow-up was 38.7 months (IQR, 28.1-52.2 months). Kidney disease primary cause in these children was congenital anomalies of the kidney and urinary tract.  

There was lower blood pressure in the intensive treatment group vs the standard treatment group (mean systolic pressure lower by 4 mm Hg; P =.0012) but it was close to the 50^th percentile in both groups. The number of antihypertensive medications prescribed per patient was higher in the intensive treatment group than in the standard treatment group (mean difference, 0.50; 95% CI, 0.25-0.75; P <.0001). The decrease in heart rate in all patients was similar between study groups.  

Intensive vs standard treatment had similar annual reduction in LVMI (-1.9 g/m^2.7; 95% CI, -2.4 to -1.3 vs -1.2 g/m^2.7; 95% CI, -1.5 to 0.8), with a treatment effect of -0.7 g/m^2.7 (95% CI, -1.9 to 2.6 per year; P =.76) with mean values in both groups in the normal range at the end of follow-up. Intensive vs standard reduction in relative wall thickness was greater (-0.010; 95% CI, 0.015 to -0.006 vs -0.004; 95% CI, -0.008 to 0.001).

The risk difference for overall adverse events was 0.02 (95% CI, -0.15 to 0.19; P =.82 between treatment groups). The risk difference for serious adverse events was 0.07 (95% CI, -0.05 to 0.19; P =.25) between treatment groups. There was no greater association between intensive treatment or standard treatment regarding worse renal outcomes or greater adverse effects. Five percent of the study patients reached end-stage kidney disease during the study.

Study limitations include the small sample size and the open-label design. Also, maximum follow-up of 3 years is not generalizable to long-term outcomes and there are no adjustments made for multiple testing of relative wall thickness.

“These results suggest that cardiac remodeling in children with chronic kidney disease is related to blood pressure control and that a target office systolic blood pressure at the 50th percentile is close to the optimal target for preventing increased left ventricular mass,” the researchers wrote.