Ultrastructure and function of cysts from human adult polycystic kidneys

Abstract

Twenty cysts from five patients with adult polycystic kidney disease were evaluated morphologically by electron microscopy and functionally by cyst fluid chemical analysis in order to correlate the structure with the function of the cyst wall. Thirteen proximal cysts, as defined by cyst fluid/serum sodium ratios of 0.8 to 1.2, were lined by epithelial cells with open or short closed apical junctions that appeared permeable to lanthanum. In contrast, seven distal cysts, as defined by cyst fluid/serum sodium ratios of less than 0.4, were lined by epithelial cells with long closed apical junctions that appeared impermeable to lanthanum. Cell organelles showed no distinction between proximal and distal cysts. Cyst basement membranes appeared abnormal, but there was no consistent pattern. The fluid of proximal cysts contained lower creatinine, potassium, and hydrogen ion, and higher chloride concentrations than did the distal cysts. These studies provide morphologic and chemical evidence consistent with te view that cysts originate from nephrons. Moreover, the maintenance of the epithelial lining and transmembrane solute gradients over many years extending up to and beyond the development of renal insufficiency suggests that the cysts function as nephronsthrughout the life of the patient.

Polycystic disease caused by deficiency in xylosyltransferase 2, an initiating enzyme of glycosaminoglycan biosynthesis

“…In ADPKD patients, renal epithelial tubule BM thickening and lamination with loss of protein homogeneity are postulated to cause cyst development and progression (9,12,14,17,33). In the cystic BM of the Xylt2 Ϫ/Ϫ mice, we observed several consistent ultrastructural abnormalities (Fig.…”

“…ADPKD patients develop decreased renal function, renal tubule dilation, and cysts, and 70% develop liver biliary cysts. Alterations in epithelial cell growth and development, fluid secretion, polarization, and/or apoptosis (7)(8)(9)(10)(11) have all been linked to cyst development and growth and are thought to arise from abnormalities in the extracellular matrix (ECM), basement membrane (BM), and cellular mechanosensing and signaling by the primary cilium (7)(8)(9)(10)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

A model for cyst lumen expansion and size regulation via fluid secretion

“…The lumen volume begins to increase again, following the cell number increase. Cuppage et al (1980) and Huseman et al (1980) found that a balanced state is achieved between proliferation and fluid secretion components of cyst enlargement. This is indicated by the result that hydrostatic pressures within cysts remain close to values observed across the walls of normal renal tubules.…”

Laminin 5 Regulates Polycystic Kidney Cell Proliferation and Cyst Formation

“…Morphological anomalies of the cyst-surrounding ECM have been described in human and animal models of polycystic kidney disease. Pericystic ECM appears thickened and multilaminated in the earliest detectable cysts (10,11). Cystic epithelial cells produce an abnormal basement membrane and have an abnormal proliferative response to ECM proteins (12)(13)(14).…”