Lower blood pressure targets in childhood chronic kidney disease

We read with interest the editorial commentary by Subhash and colleagues (1) and thank them for their thoughts on our study: “Intensive compared with less intensive blood pressure control to prevent adverse cardiac remodelling in children with chronic kidney disease (HOT-KID): a parallel-group, open-label, multicentre, randomised, controlled trial” (2).

In the Hypertension Optimal Treatment in Children with Chronic Kidney Disease (HOT-KID) trial, the median age of all participants was 10.0 years [interquartile range (IQR), 6.8–12.6 years], who were followed up for a median of 38.7 months (IQR, 28.1–52.2 months). Nearly 2/3^rd of the participants had congenital anomalies of the kidney and urinary tract, and chronic kidney disease (CKD) was thus lifelong in them. The supervised reduction of office systolic blood pressure (BP) in children with CKD [aged 2–15 years with stage 1–4 CKD, i.e., an estimated glomerular filtration rate (eGFR) higher than 15 mL/min per 1.73 m²] was associated with a reduction in left ventricular hypertrophy (LVH) and indexed LVM (LVMI) in both trial arms, with the mean annual reduction in LVMI (per year, g/m^2.7) similar for intensive and standard treatments {−1.9 g/m^2.7 [95% confidence interval (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=0.76}. Although on an intention to treat analysis, the trial did not show any significant effect on the primary outcome of LVMI between groups, it provided support for a BP target lower than the 50th percentile for preventing progression of adverse ventricular remodelling with no increase in treatment related side effects (2). It is important to note that trial results were likely influenced by the mean BP in trial participants at baseline, 107/63 mmHg, corresponding to mean BP z-score 0.55/0.06 and therefore mean BP levels between 50^th–75^th percentile; most had LVMI in the normal range with only 9 of 124 (7.3%) participants with LVH. At baseline, 2/3^rd of participants were already receiving anti-hypertensive therapy, although there was no difference in the initial BP value and baseline echocardiographic measurements between those on antihypertensives and those without antihypertensive medication (2).

We agree with the authors that further studies in different stages of CKD and looking at interactions with haemoglobin and secondary hyperparathyroidism are required. So, whilst we did not show a benefit of intensive BP reduction in those with mild-moderate CKD, the situation could be different in those with more advanced disease, especially when complicated by anaemia and clinically relevant secondary hyperparathyroidism. As traditional and non-traditional cardiovascular risk factors are highly prevalent in children with CKD, the impact of these on hypertension and cardiac health should also be considered in future studies (3).

A key issue in the management of children with CKD relates to the implementation of reliable BP measurement tools so that clinically relevant adverse cardiovascular outcomes can be reduced. The HOT-KID trial introduced first evidence from a randomised, controlled trial for manual auscultatory office BP measured in a standardised manner (2). These data provide a useful construct when considering future work evaluating children with CKD, including studies to define the best methodology for serial monitoring currently recommended in this population (4), with available BP measurement methods and other emergent BP techniques in the future. Treatment protocols with improved BP monitoring and achievement of BP targets in clinical practice require evaluating. There remains an urgent need to establish the optimum mode of BP measurement for long-term follow-up in children with CKD, which is applicable across different health models and acceptable to both patients and health professionals.

In addition to the future research directions discussed by Subhash and colleagues (1), we would highlight additional questions when managing childhood CKD. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers are all known to have an effect on cardiac remodelling independent of BP. We are currently unable to distinguish between effects of BP versus combined effects of BP and the drugs used to attain BP control in childhood CKD. Further, longer-term studies evaluating cardiac health markers extending to adulthood in those with childhood-onset CKD are needed.

Over the course of the HOT-KID trial, a modest separation in BP of average 4/4 mmHg (lower office BP in the intensive trial arm) was achieved, and was similar to the BP separation achieved between trial arms in the only other intervention trial, the Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CKD in Pediatric Patients (ESCAPE) trial (5). Together, these intervention studies in children with CKD demonstrate, (I) that relatively ‘small’ changes in BP have a significant impact on the evaluated kidney and heart outcomes; (II) those with better outcomes were on more antihypertensive medications; and (III) that at least in the trial scenario, there was no increase in side effects (2,5).

Overall, there are persuasive trial data supporting lower BP targets, know-how that lower BP reduces rate of progression of kidney dysfunction and regresses adverse left ventricular remodelling in childhood CKD. This should help clinicians to develop and adapt clinical care models to improve achieved BP control in children with CKD—an objective that still remains a challenge for most children.

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Provenance and Peer Review: This article was commissioned by the editorial office, Translational Pediatrics. The article has undergone external peer review.

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-9/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-9/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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ReferencesOther Section

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1. Subhash S, Satariano M, Doshi K, et al. Hypertension monitoring on cardiac health outcomes. Transl Pediatr 2024;13:518-24. [Crossref] [PubMed]
2. Sinha MD, Gu H, Douiri A, et al. Intensive compared with less intensive blood pressure control to prevent adverse cardiac remodelling in children with chronic kidney disease (HOT-KID): a parallel-group, open-label, multicentre, randomised, controlled trial. Lancet Child Adolesc Health 2023;7:26-36. [Crossref] [PubMed]
3. Brady TM, Roem J, Cox C, et al. Adiposity, Sex, and Cardiovascular Disease Risk in Children With CKD: A Longitudinal Study of Youth Enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Am J Kidney Dis 2020;76:166-73. [Crossref] [PubMed]
4. Levin A, Ahmed SB, Carrero JJ, et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int 2024;105:684-701. [Crossref] [PubMed]
5. ESCAPE Trial Group. Strict blood-pressure control and progression of renal failure in children. N Engl J Med 2009;361:1639-50. [Crossref] [PubMed]