FIRST Clinical Drug Testing for ARPKD/CHF
Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease.
by Sweeney WE, Frost P, Avner ED
Renal cystic diseases encompass a broad group of disorders with variable phenotypic expression. The term polycystic kidney disease (PKD) explicitly refers to two genetically defined renal cystic diseases: Autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD).
ARPKD (OMIM 263200) belongs to a group of congenital hepatorenal fbrocystic diseases characterized by dual renal and hepatic involvement[1-5]. ARPKD has an incidence estimated at 1/20000 to 1/40000 with a wide spectrum of phenotypic expression[2,4-6]. ARPKD occurs as the result of a mutations in a single gene, polycystic kidney and hepatic disease 1 (PKHD1) [7,8]; encodes a protein called fibrocystin or polyductin (FPC)[9,10]; and is commonly diagnosed in utero through early childhood[2,3,5].
ADPKD is generally an adult-onset multisystem disorder, characterized by bilateral renal cysts, vascular abnormalities including intracranial aneurysms, and cysts in other organs including the liver. ADPKD is increasingly diagnosed in childhood and adolescents[2,11]. Substantial variability in the severity of renal disease and other extrarenal manifestations occurs even within the same family. ADPKD is more common than ARPKD with an incidence of estimated at 1 in 600 and 1 in 1000 live births[12]. ADPKD is a heterogenetic disorder caused by mutations in either the PKD1 gene (85%) (OMIM173900) encoding the protein polycystin 1 (PC1), or in the PKD2 gene (15%) (OMIM173910), encoding polycystin 2 (PC2). The recent report of a third ADPKD gene has been reported but it represents a very small number of ADPKD patients that did not map to PKD1 or PKD2 locus[13]. ADPKD is characterized by the progressive development and expansion of fluid-filled cysts derived from renal tubule epithelia and typically leads to ESRD by late middle age[14,15].
Read more at World Journal of Nephrology World J Nephrol 2017 July 6; 6(4): 168-220
