Clinical practice guideline monitoring children and young people with, or at risk of developing autosomal dominant polycystic kidney disease (ADPKD)

No relevant studies were identified for this review question; however, NICE guidance on patient experience in adult NHS services recommends that patients should be provided with information, and the support they need to promote their active participation in care and self-management. This should include information about relevant treatment options and services that they are entitled to, even if these are not provided locally [4]. There was 100% agreement with this recommendation in the Delphi consensus process. Health professionals should be aware of the anxiety suffered by families relating to uncertainty of diagnosis as well as at times of testing for ADPKD.

Health professionals should discuss the limitations of testing modalities for ADPKD. Renal ultrasound cannot effectively exclude ADPKD in children [5]. In a retrospective cohort study of ultrasound assessment in children and young people under the age of 15 at risk of ADPKD, 193/420 CYP were diagnosed with cysts at baseline visit (mean age 8.6 +/− 4.2 years) with 227 having no cysts (8.0 ± 4.1 years). In follow up to age fifteen, 18/77 (23%) of the latter group who underwent repeat ultrasound developed cysts. In other words, 23% of CYP with no cysts visible on initial renal ultrasound who received a further ultrasound, were diagnosed with ADPKD [6]. No standardised criteria for renal ultrasound diagnosis of ADPKD exist for children under the age of 15 years, and even below the age of 30, there is a significant false negative rate. This is particularly so in families carrying a PKD2 mutation, which is typically associated with milder disease. In these families, 16.5% of patients between the ages of 15–29, with no cysts on initial ultrasound scan, go on to a diagnosis of ADPKD later in life [7]. While genetic testing is more definitive, it is most likely to be informative in families of known genotype, as around 10% of families phenotypically affected by ADPKD do not carry a pathogenic mutation of PKD1 or PKD2 that is detected by current technologies [8]. Health professionals (generally nephrologists, geneticists or paediatricians with interest in nephrology) providing information on testing should have a good understanding of these issues.

Low quality evidence identified for this review question was deemed by the committee to be sufficient to make a recommendation without the need for formal consensus. A recent systematic review of 928 children with ADPKD across 14 studies estimated the prevalence of hypertension to be 20% (95% CI 15–27%) [9]. There is also evidence to suggest that children with ADPKD whose BP is high or borderline high have an increased left ventricular mass index on echocardiography, a marker of cardiac target organ damage [10]. Studies have also shown that children with ADPKD who are hypertensive show an increased total kidney volume, compared to those that are normotensive [11‐13]. There are, as yet, no studies assessing long term outcomes for the treatment of hypertension in children with ADPKD. However, there is clear evidence of benefit of treating hypertension in children generally and especially in those with chronic kidney disease [14].

We recommend that both children with a confirmed diagnosis of ADPKD and those at risk of ADPKD through family history should have BP monitored, since some families may choose not to undertake testing for ADPKD in childhood. The risk of developing hypertension in children with ADPKD rises with age [9]. Hypertension under the age of 5 years is uncommon in ADPKD [15] and should prompt a search for an alternative diagnosis. In the absence of any other disease process BP rises slowly in children with ADPKD, therefore monitoring BP every 2 years should be sufficient to detect a rise in BP requiring treatment during childhood.

No relevant studies were identified for this review question. There was 88% agreement with this recommendation in the Delphi consensus process.

Inheriting and passing on a genetic disease may have significant psychological impact, ranging from frank depression through anxiety, guilt, anger, uncertainty and sadness [16]. This genetic anxiety or ‘guilt’ may increase with uncertainty over disease variability and where there is a perceived lack of diagnosis or effective therapy. These are common issues in CYP with ADPKD, which may be further compounded by mixed messages from the medical community, with conflicting opinions as to the clinical significance of ADPKD in childhood. Genetic Counselling and testing for a condition in at risk individuals has been reported to ameliorate the psychological burden for some families and children [17‐19], however, wherever possible, the child or young person should be involved in this decision. Article 12 of the United Nations Convention on the Rights of the Child (1989) states that we must assure ‘the child who is capable of forming his or her own views has the right to express those views freely’ and that ‘the views are given due weight in accordance with the age and maturity of the child’ [20].

Important issues to be discussed in counselling before deciding to test for ADPKD include:

A recent European ADPKD Forum multidisciplinary position statement states that ‘Individuals with ADPKD should have access to lifelong, multidisciplinary, specialist and patient-centred care, with information and support to help patients and their families act as fully informed and active partners in care [21].

No relevant studies comparing outcomes in CYP at risk of ADPKD undergoing genetic versus ultrasound testing for ADPKD were identified for this review question. There was 70% agreement with this recommendation (statement) by the Delphi panellists, i.e. consensus not reached. Areas for disagreement largely related to concerns about the utility of ultrasound, particularly in younger children with no standardised criteria for renal ultrasound diagnosis of ADPKD under the age of 15 years and significant false negative rates [22]. The importance of involving CYP in the decision making process was also noted in the Delphi responses. The committee believed that to offer genetic but not ultrasound testing to asymptomatic children and young people at risk of ADPKD could result in a significant change in practice in the absence of evidence and that the importance of individual choice between the two testing modalities should be emphasised given the lack of clear superiority of one over the other. The committee also noted that, although not reaching consensus, the majority (70%) of panellists supported offering a choice of kidney ultrasound or genetic testing to asymptomatic CYP at risk of ADPKD, where testing has been agreed by parents or carers and health professionals (and, wherever possible, the young person) and agreed to make a weaker ‘we suggest’ recommendation.

No relevant studies assessing outcomes in asymptomatic children at risk of ADPKD undergoing repeated ultrasound testing for ADPKD, compared with those not undergoing repeated ultrasound testing, were identified for this review question. There was 70% agreement with this recommendation (statement) by the Delphi panellists, i.e. consensus not reached. Areas for disagreement largely related to the age of the child at the time of the first negative ultrasound scan and a preference to perform more regular ultrasound scans if requested by parents. There may also be concern by health professionals about the risk of missing very early onset ADPKD, however, these children comprise less than 1% of cases and are likely to be genetically distinct from typical ADPKD, perhaps with multiple compound mutations combining to generate such an aggressive phenotype [23, 24]. This recommendation does not apply to these children, who undergo diagnostic testing for symptomatic disease (e.g. severe renal enlargement, hypertension) and are found to have radiological abnormalities at presentation.

Repeated ultrasound testing is not routinely undertaken in adults with ADPKD where significant progression usually occurs over decades. In the absence of evidence of benefit of repeated ultrasound testing in asymptomatic CYP, together with its resource implications, and the importance of considering the wishes of the young person in the decision making process where possible, the committee was of the view that a recommendation for repeated ultrasound testing prior to adolescence could not be made. The committee considered whether repeated ultrasound testing might help to alleviate parental anxiety, but noted in their experience that repeated ultrasound testing may also add to the psychological burden for families.

The committee also noted that, although not reaching consensus, the majority (70%) of panellists supported deferring further ultrasound testing until adolescence (15–18 years, or later if preferred by the young person) in asymptomatic children at risk of ADPKD who do not have cysts on initial ultrasound. The committee therefore agreed to make a weaker ‘we suggest’ recommendation.

No relevant studies were identified for this review question. There was 88% agreement with this recommendation in the Delphi consensus process. ADPKD is associated with a wide range of mutations in the genes PKD1 and PKD2, many of which occur only in one family [25]. As a result, genetic testing of PKD1 and PKD2 can find sequence variations that have not been previously described, and it can be difficult to determine the pathogenicity of these changes. First identifying the mutation in the affected adult family member allows for the use of segregation analysis to help assign pathogenicity to any mutations identified in the child or young person. Furthermore, up to 10% of ADPKD is not associated with detectable mutations in PKD1 or PKD2 [8]. This means that failure to identify a PKD1 or PKD2 mutation in a predictive genetic test cannot reliably exclude ADPKD, unless the familial mutation is known be in those genes.