Autosomal recessive polycystic kidney disease (
ARPKD) is an inherited disease characterized by a malformation complex which includes cystically dilated tubules in the kidneys and ductal plate malformation in the liver. The disorder is observed primarily in infancy and childhood, being responsible for significant pediatric morbidity and mortality. All typical forms of
ARPKD are caused by mutations in a single gene, PKHD1 (
polycystic kidney and hepatic disease 1). This gene has a minimum of 86 exons, assembled into multiple differentially spliced transcripts and has its highest level of expression in kidney, pancreas and liver. Mutational analyses revealed that all patients with both mutations associated with truncation of the longest open reading frame-encoded
protein displayed the severe phenotype. This product, polyductin, is a 4,074-amino
acid protein expressed in the cytoplasm, plasma membrane and primary apical cilia, a structure that has been implicated in the pathogenesis of different
polycystic kidney diseases. In fact, cholangiocytes isolated from an
ARPKD rat model develop shorter and dysmorphic cilia, suggesting polyductin to be important for normal ciliary morphology. Polyductin seems also to participate in tubule morphogenesis and cell mitotic orientation along the tubular axis. The recent advances in the understanding of in vitro and animal models of
polycystic kidney diseases have shed light on the molecular and cellular mechanisms of
cyst formation and progression, allowing the initiation of therapeutic strategy designing and promising perspectives for
ARPKD patients. It is notable that
vasopressin V2 receptor antagonists can inhibit/halt the renal cystic
disease progression in an orthologous rat model of human
ARPKD.