The causes of polycystic kidney disease
Polycystic kidney disease is a common hereditary nephropathy, polycystic kidney disease is mainly genetic factors. There may be three mutant genes that cause polycystic kidney disease in adults. PKD1, PKD2 and PKD3, respectively, which have been identified as PKD1 and PKD2 genes have been cloned. PKD1 is the most important cause of adult polycystic kidney disease, accounting for about 85%, and the most serious symptoms. PKD1 gene located in 16p13.3-p13.12, long 52kb, containing 46 exons, of which exon 1 to 34 for the multi-copy area, exon 35 to 46 for the single copy area, accounting for 70% And 30% of the region, the protein product consists of 4302 amino acid residues of a glycoprotein, known as polycystin-1. The content of G and C in the gene sequence was 62.5%, and exon 22 and intron 21 were enriched with a long 2.5kb and 0.5kb polypuronine-polypyrimidine sequence, which was easy to form three strands of DNA. The 1-33 exons contain the number of Alu repeats (2-11), and there are 6 homologous sequence regions in other parts of the chromosome. It is estimated that more than 80% of the pkd1 gene mutations occur in the repetitive sequence of the gene. There are few types of gene mutations in the region, most of which are concentrated in the 3 'end-specific fragment (the repeat region), and the remaining mutations may spread throughout the gene , There are missing, shift code, no sense and missense mutation. PKD2 gene located in 4q21-q23, gene length 68kb, composed of 15 exons, encoding polycystin-2 is composed of 968 amino acid residues in the membrane channel protein. PKD2 gene mutations are both germ cell and somatic. These mutations include small deletions, insertions, and single base substitutions that lead to early termination of translation, as well as missense mutations and mutations in the cleavage site.
Although most of the symptoms occurred in adults, but in the fetus began to form. Cysts originated in the renal tubules, the liquid properties with the origin of different parts, originated in the proximal tubules, cyst fluid components such as Na +, K +, CI-, H +, creatinine, urea and plasma similar to the origin; The concentration of Na +, K + in the cysts was lower, and the concentrations of CI-, H +, creatinine and urea were higher.
Abnormal proliferation of intraepithelial epithelial cells is one of the significant characteristics of ADPKD, in a mature incomplete or re-development state, highly suggestive of the development of mature regulation of bacteria obstacles, so that cells in an immature state, which shows strong proliferation Sex. The abnormality of this cell is another significant feature of ADPKD, which is manifested as the subunit combination, distribution and activity of Na + -K + -ATPase, which is closely related to cell transport, and changes in cell signaling abnormalities and ion transport channels. Abnormal proliferation of extracellular matrix is the third significant feature of ADPKD. Many studies have shown that these abnormalities are involved in cell growth-related activity factors. But the key part of the unusual links and the way is not yet clear. In short, due to genetic defects caused by cell growth changes and interstitial abnormalities, one of the important pathogenesis of this disease.
Clinical studies have shown that , regardless of type 1 or type 2 diabetes, the average glycosylated hemoglobin (HbAlc) levels below 7%...