Autosomal Dominant Polycystic Kidney Disease – Clinical and Genetic Aspects

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders in humans. It accounts for 8–10% of the cases of end-stage renal disease worldwide, thus representing a serious medical, economical and social problem. ADPKD is in fact a systemic disorder, characterized with the development of cysts in the ductal organs (mainly the kidneys and the liver), also with gastrointestinal and cardiovascular abnormalities. In the last decade there was significant progress in uncovering the genetic foundations and in understanding of the pathogenic mechanisms leading to the renal impairment. This review will retrace the current knowledge about the epidemiology, pathogenesis, genetics, genetic and clinical heterogeneity, diagnostics and treatment of ADPKD.

Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant

“…The above-mentioned histologic and ultrastructural characteristics of renal cysts in the pc mutant closely resemble those of PKD, particularly autosomal-dominant PKD [12,13] and its murine models [3,4]. Furthermore, the medaka polycystic kidney disorder also resembles autosomal-dominant PKD in its slowly progressive nature, which supported a relatively long life of the affected fish.…”

“…Furthermore, we examined the early stages of cystic formation at the microscopic level, showing that cystic formation occurs in the pronephros and then the mesonephros at larval stages before it can be visualized by the naked eye. Based on these results, we concluded that the kidney disorder in the pc mutant is a mesonephric counterpart of PKD, particularly an autosomal-dominant PKD [12,13]. Thus, the pc mutant is a good mesonephric model for the study of PKD.…”

Neutrophil Gelatinase-Associated Lipocalin in Patients with Autosomal-Dominant Polycystic Kidney Disease

“…Its progression rate varies greatly between patients and about 50% of subjects with ADPKD eventually reach ESRD [9]. The reason for this individual variability is not yet fully understood and can only be partly explained on the basis of various genetic-environmental patterns.…”

Annexin A5 Interacts with Polycystin-1 and Interferes with the Polycystin-1 Stimulated Recruitment of E-cadherin into Adherens Junctions

“…PKD1 mutations cause ADPKD in the majority of cases, leading to severe impairment of kidney function and accompanying systemic damage. 1,2 Both polycystins interact via their cytosolic C-terminal regions 3,4 and are integral parts of a common signal transduction pathway. 1 Polycystin-1 (TRPP1) is the only 11 transmembrane domainscontaining protein that belongs to the superfamily of transient receptor potential channels (TRPs), normally characterized by six transmembrane spans.…”