Disease relevance of Polycystic Kidney, Autosomal Dominant

• In the absence of osm-5, the C. elegans autosomal dominant PKD (ADPKD) gene products [11] accumulate in stunted cilia, suggesting that abnormal or lack of cilia or defects in IFT may result in diseases such as polycystic kidney disease (PKD) [1].
• An unbalanced submicroscopic translocation t(8;16)(q24.3;p13.3)pat associated with tuberous sclerosis complex, adult polycystic kidney disease, and hypomelanosis of Ito [2].
• Cyclosporine A produced a biphasic response despite delayed graft function in recipients with underlying adult polycystic kidney disease [3].
• CD2-associated protein (CD2AP) is an adapter protein associating with several membrane proteins, including nephrin, mutated in congenital nephrotic syndrome of the Finnish type, and polycystin-2, mutated in type 2 autosomal dominant polycystic kidney disease [4].
• The number of primary renal diseases of uncertain aetiology and of pyelo/interstital nephritis caused by renal stone disease was high (46% and 4.9% resp.), that of diabetic nephropathy (14.8%) not much different from EDTA figures, while adult polycystic kidney disease was seen in only four patients (1.2%, versus EDTA: 5.5%) [5].

Psychiatry related information on Polycystic Kidney, Autosomal Dominant

• Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis [6].

High impact information on Polycystic Kidney, Autosomal Dominant

• Somatic loss of Pkd2 expression is both necessary and sufficient for renal cyst formation in ADPKD, suggesting that PKD2 occurs by a cellular recessive mechanism [7].
• Here we show, in a mouse model of ADPKD (Pkd2(-/tm1Som)), a similar cellular phenotype and response to OPC31260 treatment, with reduction of renal cyclic AMP (cAMP) levels, prevention of renal enlargement, marked inhibition of cystogenesis and protection of renal function [8].
• Polycystin-2, the product of the second gene mutated in ADPKD, modulates the signaling properties of the polycystin-1 CTT [9].
• The search for the adult polycystic kidney disease gene has recently been narrowed to the analysis of candidate loci on chromosome 16, and localization of the gene determining juvenile Batten disease has been further refined by disequilibrium mapping [10].
• Non-PKD1 ADPKD has a much milder phenotype than that linked to PKD1 [11].

Chemical compound and disease context of Polycystic Kidney, Autosomal Dominant

• In the Han:SPRD (cy/+) model for ADPKD, the proximal nephron is primarily affected by the cystic changes [12].
• Treatment of ADPKD cells or ARPKD cells with either Bay K8644, a Ca2+ channel activator, or A23187, a Ca2+ ionophore, caused sustained increases in intracellular Ca2+ levels and completely reversed the mitogenic response to cAMP [13].
• (35S) sulfate incorporation studies revealed that, among various GF, HGF and TGF-beta 1 had the maximal stimulatory effect on the synthesis of PG extracted from ADPKD cells [14].
• Effects of angiotensin converting enzyme inhibition in adult polycystic kidney disease [15].
• The mean SI was not significantly different in patients with renal disease of immune (IgAGN) or non-immune (ADPKD) origin, and it was not correlated with GFR (r = 0.01, P < 0.52), intact PTH (r = -0.23, P < 0.11) or calcitriol concentration (r = -0.03, P < 0.82) [16].

Biological context of Polycystic Kidney, Autosomal Dominant

• We show further that del34 homozygotes continue to produce mutant polycystin-1, thereby providing a possible explanation for increased immunoreactive polycystin-1 in ADPKD cyst epithelia in the context of the two-hit model [17].
• Linkage disequilibrium between D16S94 and the locus for adult polycystic kidney disease (PKD1) [18].
• Our findings are concordant with increasing evidence for a role of polycystin-1 in cell Ca2+ homeostasis and indicate that dysregulated Ca2+ entry might promote Cl- secretion and cyst expansion in ADPKD [19].
• The Han:SPRD rat is the only well-documented animal model of inherited PKD with an autosomal-dominant inheritance pattern and appears to have several features which resemble human ADPKD [20].
• Association of the angiotensin I converting enzyme gene deletion polymorphism with early onset of ESRF in PKD1 adult polycystic kidney disease [21].

Anatomical context of Polycystic Kidney, Autosomal Dominant

• In this study, primary cultures of cyst epithelial cells from autosomal dominant (ADPKD) and recessive (ARPKD) PKD kidneys were used to determine whether controlled addition of Ca2+ could reverse the aberrant mitogenic response to cAMP [13].
• CONCLUSION: In Cy/Cy kidneys with ADPKD, there was an increase of the proform of caspase-9, an increase in cytochrome c release into the cytosol, and an increase in caspase-2 protein and activity demonstrating involvement of the intrinsic pathway [22].
• During the chase, kinetics for the cellular transport of sulfated glycoproteins by secretory vesicles and their assembly into extracellular matrix were comparable in ADPKD and NK cells [23].
• These results suggest that the high incidence of intrapancreatic common bile duct dilatation in ADPKD is a previously undescribed sign of extracellular matrix remodeling in ADPKD [24].
• Cyst expansion in autosomal dominant polycystic kidney disease (ADPKD) requires accumulation of fluid into the cyst lumen, which is probably driven by aberrant chloride secretion by the cyst lining epithelium [25].

Gene context of Polycystic Kidney, Autosomal Dominant

• These data indicated that molecular defects observed in Pkd1(-/-) embryos contributed to the pathogenesis of ADPKD and that thiazolidinediones had a compensatory effect on the pathway affected by the loss of polycystin-1 [26].
• There is no evidence of linkage to PKDL in six ADPKD families that are unlinked to PKD1 or PKD2 [27].
• Although ADPKD is a frequent monogenic disorder affecting approximately 1:1000 individuals in the Caucasian population, progress in understanding its pathology was somewhat slow until relatively recently when the PKD1 and PKD2 genes were mapped and cloned [28].
• Expression of transforming growth factor alpha and epidermal growth factor receptor in adult polycystic kidney disease [29].
• 3. This region is evolutionarily conserved in all vertebrate genomes from the puffer fish (Fugu rubripes) to human, and also contains loci for genes associated with two common multisystemic disorders, adult polycystic kidney disease (PKD1) and tuberous sclerosis (TSC2) [30].

Analytical, diagnostic and therapeutic context of Polycystic Kidney, Autosomal Dominant

• In order to evaluate the impact of ciclosporin in patients with adult onset polycystic kidney disease (ADPKD) following renal transplantation, we performed a single-center study of all (n = 65) patients with this disorder since 1978, 43 of whom received CSA (PC-CSA) with the remaining 22 treated with azathioprine (PC-AZA) [31].
• Using immunofluorescence, we analyzed the distribution of alpha-integrin subunits (alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6) and basement membrane proteins in kidneys of fetuses with autosomal dominant (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD) [32].
• Thus, because ultrasonography now sometimes identifies the cysts of adult polycystic kidney disease in utero or in neonates, the term autosomal dominant polycystic kidney disease is now more appropriate [33].

References