The etiology, pathogenesis, and treatment of autosomal dominant polycystic kidney disease: Recent advances

被引:118
作者
Grantham, JJ
机构
[1] Department of Medicine, Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS
[2] Department of Medicine, Sudler 4015, Kansas University Medical Center, Kansas City, KS 66160
基金
美国国家卫生研究院;
关键词
renal; cysts; renal failure; heredity; genes; genetics;
D O I
10.1016/S0272-6386(96)90378-9
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in at least three different genes: PKD1, PKD2, and PKD3. ADPKD1 is an inherited disorder that has led to the discovery of a novel protein, polycystin, Polycystin, a 460 kd protein with a host of domains implicating a potential role in cell-cell and cell-matrix regulation, is encoded by a 52 kb gene with a 14 kb mRNA. The PKD2 protein is also large (110 kd) and is thought to interact with polycystin, ADPKD1 is caused by mutated DNA that encodes an abnormal form of polycystin. Polycystin appears to have a normal role in the differentiation of epithelial cells, and when defective, these cells fail to maturate fully, These incompletely differentiated cells proliferate abnormally and express altered amounts of otherwise normal electrolyte transport proteins that result in excessive secretion of solute and fluid into the cysts, The proliferation of ?he cells and the associated apoptosis, end the secretion of the fluid into the cysts created by the enlarging tubule segments appear to be regulated by growth factors, hormones, and cytokines that can alter the extent to which the disease is clinically expressed among individuals, The formation of the cysts is associated with complex changes in the extracellular matrix of the kidneys and other organs that may be directly or indirectly tied to mutated polycystin, The summation of these pathogenetic elements leads to renal interstitial infiltration, with monocytes, macrophages, and fibroblasts culminating in fibrosis and progressive loss of renal function, The modern understanding of cyst pathogenesis opens opportunities to develop treatments that may diminish or halt altogether the progression of this disease. (C) 1996 by the National Kidney Foundation, Inc.
引用
收藏
页码:788 / 803
页数:16
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