Childhood Polycystic Kidney Disease

Abstract

Autosomal recessive polycystic kidney disease (ARPKD), historically called infantile PKD, is a major cause of morbidity and mortality in neonates, infants and young adults. Autosomal dominant polycystic kidney disease (ADPKD), historically referred to as adult PKD, is increasingly recognized as a significant cause of morbidity and mortality in children and young adults. ARPKD, a dual-organ disease with hepatic and renal involvement has an incidence of 1: 20,000 to 1: 40,000. All ARPKD patients are invariably afflicted with congenital hepatic fibrosis (CHF) of varying degrees of severity. Improved survival of ARPKD patients has led to recognition of significant clinical complications of CHF and the highly variable age at which it presents, ranging from early childhood to young adulthood. ADPKD, with an incidence as high as 1:400, affects more than 13 million individuals worldwide, and accounts for 7-10% of end stage kidney disease (ESKD) in adults. However, asymptomatic disease is increasingly recognized in infants and children and nearly equivalent numbers of ADPKD and ARPKD patients may be seen in academic pediatric nephrology clinics. The delineation of the basic molecular and cellular pathophysiology of ADPKD and ARPKD has seen remarkable progress in the last decade. This progress has led to the development of promising therapies currently being evaluated in clinical trials. Early diagnosis of ADPKD and ARPKD allows for optimal anticipatory care (for example, early blood pressure control). Given the predicted benefit of early intervention with new disease-specific therapeutics, screening at-risk youth, a previouslydiscouraged strategy, may now be warranted. This chapter will discuss central clinical characteristics essential for diagnosis and the care of children with ARPKD or ADPKD. We will also highlight recent insights in the molecular and cellular pathophysiology of PKD and the clinical translation into new therapies that promise to alter the natural history of disease for children with genetic PKD.

Medullary Cystic Kidney Disease and Focal Segmental Glomerulosclerosis Caused by a Compound Heterozygous Mutation in <i>TTC21B</i>

“…The patient's pathological finding of multiple cysts derived from the medullary distal tubules and collecting ducts was not similar to that of ADPKD, in which renal cysts form in the glomeruli and all tubular segments (9). The finding of medullary cystic kidney disease suggested ARPKD, NPHP, and NPHP-RC.…”

Autosomal Recessive Polycystic Kidney Disease—The Clinical Aspects and Diagnostic Challenges

“…In children with hypoventilation and/or severe feeding intolerance, unilateral or bilateral nephrectomy (with placement of a peritoneal dialysis [PD] catheter) should be taken into consideration. 45,46 Factors affecting the timing of this surgical intervention include age, size, and clinical status of the patients and availability of a potential kidney donor.…”

Emerging Therapies for Childhood Polycystic Kidney Disease

“…Autosomal recessive polycystic kidney disease (OMIM #263200) is characterized by renal cysts and hepatobiliary dysgenesis and is a substantial cause of morbidity and mortality in children (1, 2). ARPKD is caused by mutations in the PKHD1 gene which encodes a protein known as fibrocystin or polyductin (FPC), and both the gene and protein interact with the autosomal dominant polycystic kidney disease (ADPKD) genes and proteins.…”

“…Childhood ADPKD may be indistinguishable from ARPKD, and histological or genetic analysis may be necessary to differentiate the two (2, 8). The prevalence of pediatric patients with ADPKD in our polycystic kidney disease (PKD) clinic is approximately equivalent to the number of ARPKD patients, and both are significant sources of morbidity and mortality in children.…”