Hypertension (defined as SBP and DBP ≥95th percentile for age, height and sex) is highly prevalent in CYP on dialysis (154-156). However, lack of BP measurement standardisation for CYP on dialysis makes interpretation of values difficult. Details regarding standardisation of BP measurement are available from clinical practice guidelines (157, 158). Although there is lack of data demonstrating an association between hypertension in CYP on dialysis and increased incidence of CV events or mortality, several studies have reported correlation with proxy markers of CV morbidity, such as LVH and carotid intima media thickness (cIMT) (8, 159-161). Improved BP control in children on haemodialysis, with BP maintained <90th percentile, has been demonstrated to reduce left ventricular mass (LVM) (160). As such, echocardiography should be conducted at regular intervals to screen for serial morphological changes.
Current evidence for the management of BP in CYP with CKD not on dialysis is to lower MAP to ≤50th percentile to slow CKD progression (158, 162) and to reverse adverse cardiac remodelling (163). For patients on dialysis, particularly those with residual urine output, targeting BP to this level increases the risk of extreme BP variability and IDH. IDH is defined by the Paediatric Continuous Renal Replacement Therapy (PCRRT) working group as SBP <5th percentile for age along with the presence of clinical symptoms (164). As for adults, episodes of IDH in CYP affect dialysis adequacy, increase the risk of myocardial stunning, and may lead to long-term adverse clinical outcomes (164, 165). For this reason, targeting BP to ≤50th percentile in CYP on dialysis is not generally recommended. Consensus recommendations for minimising the risk of IDH in CYP were published in 2019 (164).
ABPM is considered the gold standard for measuring BP in CYP, including those on dialysis (18, 166). However, normative data do not exist for those <120 cm in height or <5 years of age. Furthermore, achieving compliance in younger patients may not be possible. Compared with in-centre haemodialysis measurements, ABPM enhances the predictability for identifying BP as a risk factor for target organ damage (167, 168). Our suggestion is that an ABPM monitor should be fitted at the end of a mid-week haemodialysis session to allow for standardisation of measurement. Data on the use of HBPM are lacking in CYP on dialysis, but it may be a useful adjunct alongside ABPM to provide measurements that are less affected by the white coat phenomenon (for both patients on haemodialysis and peritoneal dialysis), by pre-dialysis fluid overload, and by BP fluctuations secondary to acute fluid removal.
This guideline suggests targeting BP to <90th percentile for age, height and sex as a measure of minimising long-term risk of hypertension-mediated organ damage. However, our recommendations remain weak as data are not available to suggest that accepting or targeting higher BP values, such as in the range of the 90th-95th percentiles, confers worse prognosis in CYP on dialysis. The evidence base for recommendations in CYP on peritoneal dialysis are even weaker owing to a lack of published research in this area. One small study, involving 87 children, demonstrated improved preservation of residual kidney function in patients on peritoneal dialysis when SBP and DBP were maintained ≤95th percentile (169).
Within the confines of our literature search, no RCTs analysing CYP on dialysis in groups according to BP target were identified. The current evidence related to BP control in CYP is derived from several studies that have looked at BP as either a primary or secondary outcome measure following:
- Commencement of antihypertensive therapies (170, 171)
- Implementation of a blood volume monitoring algorithm to guide ultrafiltration (172, 173)
- Implementation of a haematocrit-guided ultrafiltration algorithm to guide ultrafiltration (174)
- Implementation of a bioimpedance analysis algorithm to guide ultrafiltration (175)
- Assessment of interdialytic weight gain (IDWG) and categorisation into groups according to percentage increase in IDWG (176, 177)
- Commencement of HDF compared with standard haemodialysis (178, 179)
Guidance on the upper limit of recommended daily intake (RDI) for salt is provided by the 2008 KDOQI Guideline for Nutrition in Children with CKD (180). Age-related RDI ranges are: 3.8 grams (1-3 years); 4.8 grams (4-8 years); 5.6 grams (9-13 years); 5.8 grams (14-18 years). This guidance is supported by studies in adults demonstrating that limiting salt intake in hypertensive dialysis patients allows for optimised volume status and BP control (50, 181, 182). A meta-analysis of paediatric trials demonstrated that salt reduction of 42% was associated with a significant reduction in both SBP and DBP in hypertensive CYP without CKD (183). One study identified a positive simplified sodium balance (i.e. the difference between daily sodium intake and daily urinary sodium losses) to be an independent predictor of IDWG in CYP on both haemodialysis and peritoneal dialysis, although there was no correlation with SBP and DBP standard deviation scores (184). However, salt intake remains important for growth in CYP on dialysis, particularly for those who are polyuric (185) and where dialysis prescription and modality may increase sodium removal and put the patient at risk of hyponatraemia (186). The support of dietetic colleagues is therefore vital to develop an individualised approach for each patient.
No single antihypertensive agent, or drug class, has been demonstrated to be more effective, or have an improved safety profile, in CYP on dialysis. Data on antihypertensive therapies remain limited to those with CKD stages 2-4. Prospective analysis of 478 CYP enrolled in the Chronic Kidney Disease in Children (CKiD) study demonstrated renin-angiotensin system (RAS) antagonists were associated with reduced odds of developing LVH compared with other antihypertensive agents, although this did not reach statistical significance (187). Data from the International Pediatric Peritoneal Dialysis Network (IPPN) registry showed lower incidence of LVH in those on RAS antagonists (159). Alongside its antihypertensive effect, ramipiril has been demonstrated to improve serum levels of inflammatory mediators and biomarkers of endothelial dysfunction compared with placebo in CYP on dialysis (171). A clinical practice questionnaire, conducted in the US, demonstrated that dihydropyridine-CCBs and angiotensin converting enzyme inhibitors (ACEis) were the most commonly prescribed antihypertensives in CYP on both haemodialysis and peritoneal dialysis (188). In terms of the mechanism of action, RAS antagonists are likely to be of limited benefit in anephric patients. Although there is a theoretical risk of reduced urinary excretion of potassium, or potassium accumulation in those with anuria, adult data suggest that RAS antagonists in those on maintenance haemodialysis are not associated with an increased incidence of hyperkalaemia (189). As per the adult pharmacological recommendations in this guideline, we suggest a consistent evening dosing schedule for antihypertensives where they are implicated as a contributory factor to the development of IDH and when dialysis sessions are delivered during the day. Additionally, pharmacokinetic profiles need to be considered when determining dosing schedules as drugs that are readily dialysed by either haemodialysis and peritoneal dialysis may be unsuitable or may need to be administered after dialysis sessions rather than before.