TY  - JOUR
AU  - E Sweeney, William
AU  - D Avner, Ellis
AU  - Patil, Ameya
PY  - 2018
DA  - 2018/12/23
TI  - Therapies for Childhood Polycystic Kidney Disease
JO  - OBM Genetics
SP  - 056
VL  - 02
IS  - 04
AB  - Renal cysts are present in a wide variety of hereditary renal diseases in children. The term polycystic kidney disease (PKD) refers to two specific hereditary diseases, distinguished by the usual age of onset and genetic cause: autosomal recessive polycystic kidney disease/congenital hepatic fibrosis (ARPKD/CHF, MIM *606702) and autosomal dominant polycystic disease (ADPKD-OMIM *601313 and OMIM *173910).
ARPKD/CHF is characterized by cystic dilations of the renal collecting ducts and developmental defects of biliary ductal plate remodeling, resulting in varying degrees of congenital hepatic fibrosis. ARPKD/CHF is commonly diagnosed in utero or at birth but can remain silent well into adolescence and rarely into adulthood. 
 ADPKD, the most common inherited renal disease is characterized by slow, progressive enlargement of fluid-filled cysts leading to renal failure by the fifth to sixth decade of life in addition to various extrarenal manifestations. ADPKD can manifest in utero, infants, and children and can be a significant cause of morbidity and mortality in this age group.
The genetic basis of ARPKD and ADPKD has largely been identified but continues to evolve. Despite remarkable advances in understanding the basic molecular and cellular pathophysiology, the development of targeted therapies has proven difficult.  
The complex structure of the genes and proteins, the tremendous allelic heterogeneity, complex inheritance patterns, and functional interactions of both the genes and proteins products of ARPKD and ADPKD complicate diagnostic and prognostic assessments. None the less, multiple therapeutic interventions are being tested in clinical trials, two clinical trials aimed at pediatric PKD patients are underway and one therapy, Tolvaptan, has been approved for adults use in Japan, Europe and recently in the USA. This review will discuss: 1) the clinical manifestations and genetics of childhood PKD; 2) how our understanding of the molecular and cellular pathophysiology of PKD is guiding current therapies; and 3) how recent discoveries may shape future therapies.
SN  - 2577-5790
UR  - https://doi.org/10.21926/obm.genet.1804056
DO  - 10.21926/obm.genet.1804056
ID  - E Sweeney2018
ER  -