Sequential Evaluation of Radiation-Induced Glomerular Ultrastructural Changes in the Pig Kidney

Abstract

Both kidneys of 12 mature female pigs received either a single dose of 9.8 Gy 60Co gamma rays or sham irradiation. At intervals of 1-4 weeks serial renal biopsies were obtained, followed by sacrifice at 24 weeks after irradiation. Individual kidney glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and the hematocrit (Hct) were measured routinely. Renal irradiation resulted in a progressive decline in GFR, ERPF, and Hct, with minimal values being observed within 12 weeks of irradiation. No change in any of these parameters was noted in the sham-irradiated pigs. The initial morphological change in irradiated glomeruli was leukocyte attachment to capillary endothelial cells 3-6 weeks after irradiation followed by activation and swelling of the endothelial cells. This was followed by pronounced increases in capillary permeability with fluid and erythrocyte, leukocyte, and platelet exudation into the subendothelial/mesangial space. This resulted in compression of glomerular capillary lumina, which occurred concomitantly with the reduction in GFR. By 12 to 15 weeks after irradiation the changes in endothelial cells were less evident. However, mesangial cells exhibited evidence of activation and proliferation accompanied by progressive mesangial expansion and sclerosis. Thus the glomerular capillary endothelial and mesangial cells appear particularly important in the pathogenesis of radiation nephropathy.

Irradiation Induces Upregulation of CD31 in Human Endothelial Cells

“…One of the morphologic changes that endothelial cells are reported to undergo in vivo, after irradiation, is swelling. 3,33 It is conceivable that the upregulated levels of CD31 on irradiated HUVECs may have been due to an increase in cell surface area. However, the data from the flow cytometric analysis of forward scatter, which is proportional to cell size, showed that the increase in CD31 far exceeded any alterations in size.…”

“…1 The blood vessels in irradiated normal tissues often undergo adverse changes that can compromise their functions, and because these changes precede the development of fibrosis, it has been hypothesized that vascular damage could be an important factor in the pathogenesis of late radiation damage. 2 Endothelial cell dysfunction after irradiation can be recognized by morphological changes such as cell swelling, 3 increased leukocyte-endothelial cell adherence and infiltration of leukocytes into tissues, [2][3][4][5][6] platelet adherence to the vascular wall, 7 a loss in vascular wall integrity resulting from reduced endothelial cell numbers, and the formation of tortuous vessels. 8 Recent experimental evidence suggests that radiation-induced expression of the membrane glycoproteins E-selectin and intercellular adhesion molecule 1 (ICAM-1) on endothelial cells is involved in the mechanisms mediating increased leukocyte-endothelial cell interactions after irradiation.…”

Expression of ICAM-1 and Acute Inflammatory Cell Infiltration in the Early Phase of Radiation Colitis in Rats

“…Leukocyte infiltration and accumulation in irradiated pig kidney and rat rectum have been well documented 4,5) . However, the pathological consequences of leukocyte infiltration and accumulation in irradiated normal tissues are not fully understood.…”

Models for the Development of Radiation Countermeasures

“…Systolic blood pressure 46 , blood urea nitrogen (BUN; an excellent surrogate marker for renal injury), serum creatine and clearance, glomerular filtration rate (GFR) 47 and urine protein are some of important functional end points which have been used widely for evaluating agents for their efficacy. Rat (out-bred CD(SD), WAG/Rij) is more reliable model for radiation-induced kidney damage as mouse exhibit radioresistance.…”