Unmet needs and challenges for follow-up and treatment of autosomal dominant polycystic kidney disease: the paediatric perspective

Abstract

Awareness is growing that the clinical course of autosomal dominant polycystic kidney disease (ADPKD) already begins in childhood, with a broad range of both symptomatic and asymptomatic features. Knowing that parenchymal destruction with cyst formation and growth starts early in life, it seems reasonable to assume that early intervention may yield the best chances for preserving renal outcome. Interventions may involve lifestyle modifications, hypertension control and the use of disease-modifying treatments once these become available for the paediatric population with an acceptable risk and side-effect profile. Until then, screening of at-risk children is controversial and not generally recommended since this might cause psychosocial and financial harm. Also, the clinical and research communities are facing important questions as to the nature of potential interventions and their optimal indications and timing. Indeed, challenges include the identification and validation of indicators, both measuring and predicting disease progression from childhood, and the discrimination of slow from rapid progressors in the paediatric population. This discrimination will improve both the cost-effectiveness and benefit-to-risk ratio of therapies. Furthermore, we will need to define outcome measures, and to evaluate the possibility of a potential therapeutic window of opportunity in childhood. The recently established international register ADPedKD will help in elucidating these questions. In this review, we provide an overview of the current knowledge on paediatric ADPKD as a future therapeutic target population and its unmet challenges.

Demographic and clinical characteristics of children with autosomal dominant polycystic kidney disease: a single center experience

“…Due to the side effects and disappointing results in adults, mTOR inhibitors have no place for treatment in children with ADPKD as well (16). Thus, none of our patients were on routine treatment.…”

“…It is well-known that disease progression can be prevented by modifiable factors including proteinuria and hypertension (2,16). In a meta-analysis, Marlais et al have found that 20% of children with ADPKD have HT (17).…”

Implications of early diagnosis of autosomal dominant polycystic kidney disease: A post hoc analysis of the TEMPO 3:4 trial

“…However, several limitations for such strategies are to be taken into consideration. Although different prognostic indicators have been identified in adults 16,23 , no stratification risk factors for progression are validated for children 10 . Nevertheless, because parenchymal destruction already occurs under the cover of compensated GFR values 27 , such indicators are required in order to accurately identify patients at risk for rapid progression.…”

“…At this point, data on the natural history of and prognostic indicators for childhood ADPKD are both largely lacking and urgently needed [10][11][12] . The Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 trial is one of the largest studies conducted in the field (N = 1445) 6 .…”

Autosomal-dominante polyzystische NierenerkrankungManagement im Kindes- und Jugendalter

“…Ein Teil der Patienten zeigt bei der ADPKD ein rasches Fortschreiten der Erkrankung. Diese Patienten könnten von einer frühen Therapie profitieren [9,17].…”