Effects of Ionizing Radiation on Progressive Experimental Renal Disease: A Hemodynamic Approach

Abstract

In order to evaluate the progression of renal disease, Munich-Wistar rats were submitted to 5/6 nephrectomy and given whole-body x- or γ-irradiation with or without remnant kidney protection or were submitted only to remnant kidney irradiation. All groups received a single 6-Gy dose immediately after surgery. Whole-kidney function, glomerular hemodynamics, 24-hour proteinuria and histopathology were assessed 60 days after surgery and irradiation. The irradiated nephrectomized animals presented whole-kidney function parameters comparable to those of normal rats. In addition, they were less hypertensive and had higher hematocrit. They showed glomerular hyperfiltration and hypertension even greater than their respective nephrectomized controls. However, the interrelations among the glomerular filtration determinants were somewhat different in irradiated animals. Their 24-hour proteinuria was significantly lower and the sclerosis index and tubulointerstitial injury score were markedly smaller. Among irradiated animals, the worst sclerosis index was observed in those with a shielded remnant kidney and the best in those without protection of the remnant kidney. This led us to speculate about a possible influence of resident mesangial cells on the early events following renal mass ablation and on the maintenance of subsequent physiopathologic changes. Therefore, radiation undoubtedly provoked a beneficial change in the course of renal disease when the renal mass ablation model was employed. Many factors could have contributed to this favorable feature including lower levels of systemic arterial pressure, less increment in ΔP, diminished proteinuria, and maintenance of tubulointerstitial space integrity. Our data also suggest that development of glomerulosclerosis seems to be determined by events occurring immediately after injury.

Electroacupuncture and Moxibustion Attenuate the Progression of Renal Disease in 5/6 Nephrectomized Rats

“…stitial fibrosis and tubular atrophy [3,4] , suggesting an ultimate common pathway [5] . Thus, relentless progression of CKD is postulated to result from a self-perpetuating, vicious cycle of fibrosis process that is activated following initial injury [6] .…”

“…Thus, relentless progression of CKD is postulated to result from a self-perpetuating, vicious cycle of fibrosis process that is activated following initial injury [6] . The possible pathophysiological mechanisms of progression of CKD include arterial hypertension, activation of the renin-angiotensin-aldosterone system, neurogenic factors, activation of various cytokines and growth factors, podocyte loss, dyslipidemia, proteinuria, and specific mechanisms of tubulointerstitial fibrosis, such as genetic factors and low nephron number [5][6][7] . Blocking these common mechanisms and modulation of fibrotic agents may inhibit the progression of CKD, independent of the underlying primary disease.…”

Oxidative Stress and the Kidney in the Space Environment

“…According to the model, CIHH resulted in the recession of renovascular hypertension through the facilitation of a baroreflex control [ 83 ]. Moreover, the beneficial impact of radiation was shown in nephrectomized rats that achieved better blood pressure control and proteinuria levels, compared to their controls [ 84 ]. Earlier observations suggest a reduction in both diastolic blood pressure and heart rate in a microgravity environment [ 85 ], while the initial increase in systolic blood pressure observed during a space stay was downregulated after a couple of weeks to preflight levels, and it was accompanied by a new motive in blood pressure control during space travel [ 86 ].…”