Research in context
chronic kidney disease, kidney disease, slower kidney disease, ventricular remodelling, adverse cardiac events, adverse ventricular remodelling, cardiac remodelling, left ventricular hypertrophy
KIDNEY DISEASE, ADVERSE EVENTS, EVENTS, PROGRESSION, CHRONIC KIDNEY DISEASE, BLOOD, LEFT VENTRICULAR HYPERTROPHY

Current recommendations regarding the management of blood pressure in children with chronic kidney disease are heavily based on data from a single trial, the Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of Chronic Kidney Disease in Pediatric Patients (ESCAPE) trial, with slower kidney disease progression in those with lower blood pressure targets (24 h ambulatory mean arterial pressure <50th percentile). However, recommended targets when using office-based blood pressure measurement are not based on as robust evidence and are higher (auscultatory systolic blood pressure target <90th percentile). Children with chronic kidney disease are predisposed to the development of left ventricular hypertrophy, which is associated with adverse clinical outcomes in early adulthood, but the optimal blood pressure to prevent adverse ventricular remodelling leading to left ventricular hypertrophy is uncertain. Effects of lower compared with higher blood pressure control were studied in a subset of children in the ESCAPE trial with no effect seen on left ventricular mass index (LVMI), but not all participants who underwent randomisation were studied.
To our knowledge, HOT-KID is the first randomised controlled trial to examine the effect of different levels of blood pressure control on left ventricular remodelling in children with chronic kidney disease. On an intention-to-treat basis, the trial showed no significant effect of intensive office blood pressure reduction (target <40th percentile) compared with standard reduction (target 50th–75th percentile) on the primary outcome: LVMI. However, probably because of better-than-expected blood pressure control on entry to the study, left ventricular hypertrophy was present in only a small proportion of the participants, and LVMI was within the normal range. In contrast to LVMI, relative wall thickening, a measure of remodelling that might precede left ventricular hypertrophy and is itself related to adverse outcomes, was elevated at baseline and was significantly reduced by intensive compared with standard blood pressure reduction. This was despite the blood pressure in the standard treatment group being close to the 50th percentile.
Although the HOT-KID trial has limitations, as it is a small, open-label trial, it supports the concept that a blood pressure target lower than the 50th percentile is close to the optimal for preventing progression of adverse ventricular remodelling. In combination with results of the ESCAPE study, a blood pressure threshold of lower than 50th percentile can be recommended as likely to prevent both progression of kidney disease and adverse ventricular remodelling. A remaining challenge is to clarify the best method of monitoring blood pressure in children and the equivalence of blood pressure thresholds.Definitive evidence to determine the optimal blood pressure target in children to reduce adverse events requires follow-up in sufficiently large numbers over many years to obtain data on clinical events. Such an undertaking is not regarded as feasible currently. In children with chronic kidney disease, the strong association of cardiac remodelling—left ventricular hypertrophy in particular—with adverse cardiac events later in adulthood has led to a focus on cardiac remodelling as a surrogate outcome in this population.Our previous work using auscultatory office blood pressure highlighted that left ventricular hypertrophy was closely associated with blood pressure and was less likely to occur in patients with blood pressure lower than the 50th percentile.