Is Autosomal Dominant Polycystic Kidney Disease Becoming a Pediatric Disorder?

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) affects 1 in 400 to 1,000 live births, making it the most common monogenic cause of renal failure. Although no definite cure is available yet, it is important to affect disease progression by influencing modifiable factors such as hypertension and proteinuria. Besides this symptomatic management, the only drug currently recommended in Europe for selected adult patients with rapid disease progression, is the vasopressin receptor antagonist tolvaptan. However, the question remains whether these preventive interventions should be initiated before extensive renal damage has occurred. As renal cyst formation and expansion begins early in life, frequently in utero, ADPKD should no longer be considered an adult-onset disease. Moreover, the presence of hypertension and proteinuria in affected children has been reported to correlate well with disease severity. Until now, it is controversial whether children at-risk for ADPKD should be tested for the presence of the disease, and if so, how this should be done. Herein, we review the spectrum of pediatric ADPKD and discuss the pro and contra of testing at-risk children and the challenges and unmet needs in pediatric ADPKD care.

The Zebrafish Kupffer’s Vesicle: A Special Organ in a Model Organism to Study Human Diseases

“…An evidence is growing that renal cyst formation starts in utero and that hypertension in childhood correlated well with disease severity. This is changing the old paradigm that considers ADPKD has a late-onset disease [57]. However, renal cysts still become clinically detectable only in adulthood, when the disease is fully established.…”

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

“…ADPKD may lead to both renal and extrarenal manifestations, which are also reported in children: urinary concentration defects, hypertension, left ventricular hypertrophy (LVH), microalbuminuria, proteinuria and haematuria [8–13]. The literature on the clinical presentation of childhood ADPKD has recently been summarized [14]. Some of the features may cause symptoms, while others remain silent and undetected unless actively screened for.…”

“…Also, for individuals <15 years of age, there are no validated diagnostic imaging criteria available [15, 16]. Given the rarity of childhood simple renal cysts [17], children with a family history of ADPKD, having a single cyst, preferably over 1 cm, are assumed to have ADPKD, although this criterion was never fully evaluated [14].…”

“…Additionally, initial cysts are the principal trigger for a snowball effect driving the formation of new cysts, leading to disease progression, including inflammation and fibrosis [23], towards ESKD [24]. Taking together the evidence for early parenchymal destruction and the substantial prevalence of symptoms in children [14, 25], the best chance for preserving long-term renal function may be given by an early therapeutic start [26].…”

“…These predict corresponding median ages at onset of ESKD of 70.6, 56.9 and 49 years, respectively [41]. As both hypertension and urologic events are well-known symptoms in childhood ADPKD [14], it would be interesting to evaluate the applicability of the PRO-PKD score in children. Another validated tool is the Mayo Imaging Classification, in which patients with typical ADPKD are stratified into subclasses 1A to 1E depending on their HtTKV range for age.…”