The wind of change in the management of autosomal dominant polycystic kidney disease in childhood

Abstract

Significant progress has been made in understanding the genetic basis of autosomal dominant polycystic kidney disease (ADPKD), quantifying disease manifestations in children, exploring very-early onset ADPKD as well as pharmacological delay of disease progression in adults. At least 20% of children with ADPKD have relevant, yet mainly asymptomatic disease manifestations such as hypertension or proteinuria (in line with findings in adults with ADPKD, where hypertension and cardiovascular damage precede decline in kidney function). We propose an algorithm for work-up and management based on current recommendations that integrates the need to screen regularly for hypertension and proteinuria in offspring of affected parents with different options regarding diagnostic testing, which need to be discussed with the family with regard to ethical and practical aspects. Indications and scope of genetic testing are discussed. Pharmacological management includes renin-angiotensin system blockade as first-line therapy for hypertension and proteinuria. The vasopressin receptor antagonist tolvaptan is licensed for delaying disease progression in adults with ADPKD who are likely to experience kidney failure. A clinical trial in children is currently ongoing; however, valid prediction models to identify children likely to suffer kidney failure are lacking. Non-pharmacological interventions in this population also deserve further study.

Zystennieren im Kindes- und Jugendalter

“…Ein fehlender Zystennachweis schließt erst ab einem Alter von 40 Jahren eine ADPKD aus 11 . In der Regel ist in der Konstellation mit unauffälligem Ultraschallbefund bei Kindern und Jugendlichen eine genetische Abklärung nicht zwingend notwendig und eine sonografische Kontrolle nach 1–3 Jahren ausreichend 6 , 13 .…”

Translational research approaches to study pediatric polycystic kidney disease

“…Major clinical variability has been described in ADPKD that can only partially be explained by the underlying genetics. It was for a long time believed that children of patients with ADPKD should not be examined but a "wind of change" has recently been noted in this field [28]. More attention has been given to a concept of prevention of disease progression by early modification of ADPKD risk factors.…”

“…Thus, urinary MCP-1 may become an easilyobtainable marker of disease severity for subgroups of pediatric ADPKD patients [30]. It may in the future be complemented by radiological findings obtained by both novel MR techniques or 3D-ultrasound [28,30].…”

Germline Mutations for Kidney Volume in ADPKD

“…8,9 Although TKV and Mayo imaging classification are clinically important, valid prediction models to identify children with ADPKD and therefore likely to suffer kidney failure are still lacking, as the radiological features in children are different from those in adult patients. 14 As TKV changes with aging, Mayo imaging classification is only applicable from 16 years of age. 7 This situation is unfavorable, because 20% of children with ADPKD have hypertension, 15 and the pediatric stages of ADPKD have been recognized as important stages for disease understanding and treatment.…”

“…7 This situation is unfavorable, because 20% of children with ADPKD have hypertension, 15 and the pediatric stages of ADPKD have been recognized as important stages for disease understanding and treatment. 14 Considering that beneficial effects of early treatment for slowing the increase in TKV have been reported in children with ADPKD 16 and that valid prediction models to identify children with ADPKD likely to suffer kidney failure are lacking, 14 it is important to identify a high-risk group among patients with ADPKD, who are candidates for early intervention. The lack of early prognostic markers for kidney prognosis is still a concern for both physicians and patients; 17 Mutations in PKD1 and PKD2 are responsible for ADPKD.…”