Disease relevance of Polycystic Kidney Diseases

• A DNA-specific dye, Hoechst 33258, was used to detect morphologic apoptosis in renal samples from patients with normal kidneys, polycystic kidney disease, and other kidney diseases [1].
• Genetic identification of two major modifier loci of polycystic kidney disease progression in pcy mice [2].
• Reversible renal failure associated with angiotensin-converting enzyme inhibitors in polycystic kidney disease [3].
• Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene have been shown to cause autosomal recessive polycystic kidney disease (ARPKD), but the cellular functions of the gene product (PKHD1) remain uncharacterized [4].
• Our previous demonstration that c-myc is overexpressed in human autosomal polycystic kidney disease (ADPKD) prompted us to investigate the pathogenetic role of c-myc in the induction and progression of the cystogenic phenotype in our mouse model [5].

Psychiatry related information on Polycystic Kidney Diseases

• Pancreatitis was significantly more common in those with alcohol abuse, systemic lupus erythematosus (SLE), and polycystic kidney disease [6].
• 3. This band is rich in deletion mutants of genes involved in several human diseases, notably polycystic kidney disease, alpha-thalassemia, tuberous sclerosis, mental retardation, and cancer [7].
• Our results suggest that phenotypic expression of the pcy gene in the mouse depends on genetic background, and that variations in the severity of human polycystic kidney disease may be explained, at least in part, by individual differences in genetic background [8].

High impact information on Polycystic Kidney Diseases

• The oral-facial-digital type I (OFD1) syndrome (OMIM 311200) is a human developmental disorder; affected individuals have craniofacial and digital abnormalities and, in 15% of cases, polycystic kidney [9].
• Somatic inactivation of Pkd2 results in polycystic kidney disease [10].
• Mice heterozygous and homozygous for this mutation, as well as Pkd+/- mice, develop polycystic kidney and liver lesions that are indistinguishable from the human phenotype [10].
• The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains [11].
• Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease--a contiguous gene syndrome [12].

Chemical compound and disease context of Polycystic Kidney Diseases

• The mean arterial pressures measured in the supine and upright positions and the plasma aldosterone concentrations measured in the upright position were significantly higher in the normotensive patients with polycystic kidney disease than in the normal subjects [13].
• It is thought that cysts in polycystic kidneys originate from nephron segments and function in a manner similar to the segment or origin [14].
• Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease [15].
• Cyclic AMP concentration was higher in distal than in proximal cysts (663 vs 6.0 pmol/L). mRNA of HGF and Met were co-expressed in cyst walls from cases with polycystic kidney disease [16].
• Polycystic kidney disease and angiotensin-converting enzyme inhibitors [17].

Biological context of Polycystic Kidney Diseases

• These studies are the first direct evidence for active transport of cysts from human polycystic kidney and provide strong evidence to support the concept that cysts function in the same manner as the nephron segment of origin [14].
• Presymptomatic diagnosis of polycystic kidney disease 1 (PKD1) is possible by genetic linkage analysis with markers from both sides of the disease locus [18].
• We previously have described a mouse model for polycystic kidney disease (PKD) caused by either of two mutations, kat or kat(2J), that map to the same locus on chromosome 8 [19].
• Forty-one Spanish families with polycystic kidney disease 1 (PKD1) were studied for evidence of linkage disequilibrium between the disease locus and six closely linked markers [20].
• A translation frameshift mutation induced by a cytosine insertion in the polycystic kidney disease 2 gene (PDK2) [21].

Anatomical context of Polycystic Kidney Diseases

• Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella [22].
• Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney [23].
• The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton [24].
• Apical plasma membrane mispolarization of NaK-ATPase in polycystic kidney disease epithelia is associated with aberrant expression of the beta2 isoform [25].
• Abnormally high levels of SGP-2 mRNA were found in the cyst wall epithelium of polycystic kidneys [26].

Gene context of Polycystic Kidney Diseases

• PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein [27].
• Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene reveals six novel mutations [28].
• Reduced PKHD1 levels in pck rat kidneys and its colocalization with polycystins may underlie the pathogenic basis for cystogenesis in polycystic kidney diseases [4].
• In light of the focal nature of liver cysts in ADPLD, the apparent loss-of-function mutations in PRKCSH, and the two-hit mechanism operational in dominant polycystic kidney disease, ADPLD may also occur by a two-hit mechanism [29].
• The polycystic kidney disease 1 gene product mediates protein kinase C alpha-dependent and c-Jun N-terminal kinase-dependent activation of the transcription factor AP-1 [30].

Analytical, diagnostic and therapeutic context of Polycystic Kidney Diseases

• These results show that both dietary protein source and level significantly affect polycystic kidney disease in pcy animals, with the effects of dietary soy protein being most pronounced in female animals fed the low protein diets and the effects of protein reduction being most pronounced in animals fed soy protein-based diets [31].
• The presence of messenger RNA for the mouse homologue of the polycystic kidney disease 1 gene (PKD1) was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) methods in mouse embryo messenger RNA [32].
• We used a human renin antiserum and an immunoperoxidase method to investigate the distribution of renin-containing cells in 19 adult polycystic kidneys: 9 autopsy and 10 nephrectomy cases [33].
• Those patients with both PCLD and polycystic kidney disease who are not dialysis dependent can be managed for several years with isolated liver transplantation and then receive kidney transplantation if needed [34].
• To study the role of TGF alpha in cyst formation, we analyzed nine anatomically diagnosed adult polycystic kidneys and four normal kidneys using immunohistochemistry [35].

References