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.

Osmoregulation in Polycystic Kidney Disease: Relationship with Cystogenesis and Hypertension

“…Hypertension is a salient feature of both ADPKD and ARPKD [1,9]. Studies in humans with ADPKD indicate that hypertension develops before renal filtration function declines in the majority of patients, suggesting that renal insufficiency is not a primary driver [9,16].…”

“…Autosomal dominant PKD (ADPKD) is more prevalent, affecting approximately 1: 1,000 individuals, and a leading cause of renal failure [1]. Though cysts are observed in children with ADPKD [1], they generally do not impair glomerular filtration until the 5th decade of life [9] (Fig.…”

“…1). Autosomal recessive PKD (ARPKD) is approximately 20 times less common, yet far more aggressive in its clinical presentation, with the majority of affected individuals showing renal insufficiency in the neonatal period [1].…”

“…Polycystic kidney disease (PKD) describes a group of monogenetic disorders characterised by the acquisition of multiple renal cysts and extrarenal abnormalities including hypertension [1]. Impaired urinary concentrating ability is an early clinical presentation of PKD [2][3][4][5].…”

Therapies for Childhood Polycystic Kidney Disease

“…ARPKD is highly variable with a wide clinical spectrum of disease that ranges from the severe classical presentation in utero, or at birth, of massively enlarged bilaterally cystic kidneys to the presentation in older children, teenagers, or young adults with manifestations of hepatic disease and negligible renal disease [4,6]. The variability of organ involvement in ARPKD is not well understood, but it is widely acknowledged [7][8][9][10].…”