Discussion
anaemia, chronic kidney disease, Concentric remodelling, cardiac remodelling, left ventricular hypertrophy
ANAEMIA, ADVERSE EFFECT, PRESSURE AREA, BLOOD, LEFT VENTRICULAR HYPERTROPHY
To our knowledge, the HOT-KID study provides the first evidence from a randomised controlled trial on the effects of differing blood pressure targets on cardiac remodelling. The main findings of the HOT-KID study are that, in an intention-to-treat analysis, allocation to an office systolic blood pressure target lower than the 40th percentile versus a target higher than the 50th percentile did not result in a significant reduction in LVMI over the course of several years and that the 95% CIs for change in mean LVMI excluded the effect size we specified as clinically significant: a change of greater than 3·1 g/mIn the context of a near-normal left ventricular mass in the majority of participants and a low prevalence of left ventricular hypertrophy, a change in LVMI is unlikely. In contrast to LVMI, relative wall thickness was elevated in the majority of children, reflecting a tendency to concentric remodelling. Concentric remodelling is a recognised feature of hypertension-mediated organ damage in clinical practice guidelinesSome children in the intensive treatment group did not reach a blood pressure lower than the 40th percentile, and the majority of children in the standard treatment group had blood pressure that was close to the 50th percentile. As a result, the blood pressure difference between the two groups was modest. This finding might be explained by the tendency of physicians, patients, and their families to be conservative when considering up-titrating or down-titrating therapy, leading to convergence of achieved blood pressure in the two groups. This convergence of achieved blood pressure is in keeping with trials of similar design. In the ESCAPE study, for example, target blood pressure in the two groups of the trial was 24 h mean arterial pressure between the 50th and 95th percentile and lower than the 50th percentile, and the blood pressure difference between the groups ranged between 2·7 mm Hg and 3·9 mm Hg in different study years.The degree to which cardiac remodelling in children with chronic kidney disease is driven by blood pressure or by other chronic kidney disease-specific factors, including anaemia and increased concentrations of phosphate and parathyroid hormone, has been debated.In the children with left ventricular hypertrophy or abnormal geometry, this regressed in both groups. This finding suggests that there is no benefit in targeting a systolic blood pressure to lower than the 40th percentile. However, several factors point to a blood pressure close to the 50th percentile rather than the 75th percentile as being beneficial. Blood pressure in the standard treatment group was much closer to the lower rather than higher end of the 50th–75th percentile target. This combined with the finding of a blood pressure dependence of cardiac remodelling even with a narrow range suggests that the reverse remodelling seen in the standard treatment group would have been attenuated had the majority of children had blood pressure in the upper range of the 50th–75th percentile. Thus, a target of the 50th percentile would seem close to the optimal for preventing cardiac remodelling. In practical terms, any definition of a target requires an upper limit above which treatment is up-titrated. In our study, there was no adverse effect on safety or renal outcomes of targeting to lower than the 40th percentile. Therefore, until data from larger-scale randomised controlled trials of office blood pressure are available, we suggest targeting to an office systolic blood pressure lower than the 50th percentile with up-titration of treatment at the 50th percentile.Our trial focused on the use of office auscultatory blood pressure measurement rather than ambulatory blood pressure measurement. Auscultatory blood pressure was chosen because we have previously found it to be a sensitive predictor of left ventricular hypertrophy.In conclusion, within the constraints of a small open-label trial, the HOT-KID trial suggests that cardiac remodelling 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.