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Radiation-induced multi-organ involvement and failure: the contribution of radiation effects on the renal system

¹ Radiation Oncology and ² Nephrology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA

View larger version (22K): [in a new window]   Figure 1. Actual incidence of chronic nephropathy as a function of renal dose. Chronic nephropathy was defined as increased serum creatinine, increased blood urea nitrogen and decreased glomerular filtration rate accompanied by anaemia and hypertension, and without any obvious cause other than radiation [18]. The number of patients at risk are shown in parentheses, and the plots stop when there were fewer than six patients still at risk. Actuarial log rank analysis was done to compare the incidence of chronic nephropathy by renal dose. Trend analysis was done using the Cox proportional hazards model, and a statistically significant trend (p=0.012) exists for decreasing renal dose and decreasing incidence of chronic nephropathy. Adapted with permission from Lawton et al [18].

View larger version (13K): [in a new window]   Figure 2. Dose–response curve for chronic nephropathy after total body irradiation plus bone marrow transplantation from the clinical reports of Lawton et al [18] (•) and Miralbell et al [13] (O). The "equivalent single dose" is derived from the actual fractionated low dose rate regimen by assuming an / ratio of 1.5–4.0 Gy [3, 20, 21] for the fractionation effect, and a dose rate reduction factor of 1.2–1.5 [3, 22] for the dose rate effect. The vertical error bars are standard deviations; the horizontal error bars reflect the biological uncertainty in the "equivalent single dose" calculation.

View larger version (17K): [in a new window]   Figure 3. Treatment of clinical radiation nephropathy with the angiotensin converting enzyme (ACE) inhibitor, captopril. The patient received a bilateral renal dose of 9.8 Gy in 9 fractions at 0.08–0.20 Gy min–1 as part of the total body irradiation used in the preparatory regimen for bone marrow transplantation (BMT). After 7 months, the patient developed BMT nephropathy as confirmed by biopsy (see Figure 2 in Cohen and Robbins [16]). At 12 months, captopril therapy was begun at a dose of 12.5 mg daily and has been continued at that dose. Renal function is shown as 100 x the reciprocal of the serum creatinine. Stabilisation of kidney function is evident from the significant (p<0.001) change in the slope.

View larger version (25K): [in a new window]   Figure 4. Effect of pharmacological interventions on the development of experimental radiation nephropathy after total body irradiation (TBI) plus bone marrow transplantation (BMT). Actual incidence curves are shown for animals that received 17 Gy TBI plus BMT and were treated with: angiotensin converting enzyme (ACE) inhibitors (low dose captopril, high dose captopril, or enalapril); an angiotensin II (AII) Type 1 receptor antagonist (L-158,809); or various other antihypertensives that act by mechanisms not directly related to AII activity (verapamil, hydralazine, hydrochlorothiazide and L-methyl-DOPA). Adapted with permission from Moulder et al [54].