Biomedical subjects

M E Robbins

Publications and source records attributed to M E Robbins.

At least 55 records · Page 3Linked to original sources

PubMed1993

Sequential evaluation of radiation-induced glomerular ultrastructural changes in the pig kidney.

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.

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PubMed1993

Capillary endothelium. Target site of renal radiation injury.

BACKGROUND: Therapeutic abdominal irradiation may be accompanied by late occurring progressive renal disease associated with glomerular mesangial sclerosis and tubular degeneration. Pathogenesis of this lesion is disputed. EXPERIMENTAL DESIGN: Kidneys of mature pigs were irradiated with a single dose of 9.8 Gy 60Co gamma-rays; serial individual kidney glomerular filtration rate and renal biopsies were obtained at 3-4-week intervals with death 24 weeks after irradiation. RESULTS: Irradiated pigs displayed a progressive reduction in glomerular filtration rate with minimal values observed 12 weeks postirradiation. Morphologic changes in irradiated glomeruli were characterized by leukocytic attachment to capillary endothelial cells 3-6 weeks after irradiation followed by activation and swelling of endothelial cells and occasional microthrombi formation. Similar changes were noted focally in peritubular capillaries with accompanying tubular degeneration and atrophy. In glomeruli these endothelial cell changes were followed by increased capillary permeability and fluid, erythrocyte, platelet, and leukocytic exudation into the subendothelial/mesangial space resulting in compression of glomerular capillary lumina. By 12 weeks postirradiation mesangial cells showed evidence of activation and proliferation accompanied by progressive mesangial expansion and sclerosis with continued reduction of glomerular filtration rate. CONCLUSIONS: It is concluded that endothelial cell injury represents the primary site of radiation damage in the kidney and that the progressive glomerular mesangial sclerosis and reduced renal function of radiation nephropathy may be associated with exposure of capillary elements to various vasoactive and growth promoting factors that stimulate mesangial contraction and proliferation resulting in reduced glomerular filtration area and glomerular filtration rate.

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PubMed1992

Prevention of X-ray-induced late dermal necrosis in the pig by treatment with multi-wavelength light.

Low-level light from a multi-wavelength array of light sources has been used to prevent late X-ray-induced dermal necrosis in the pig. Skin fields, measuring 4 x 4 cm on the flank, were irradiated with a single dose of 23.4 Gy of X-rays. This X-ray dose was associated with the development of a 100% incidence of dermal necrosis, 10-16 weeks after irradiation. These irradiated skin sites were subsequently exposed to light of 660, 820, 880, and 950 nm wavelengths from a gallium aluminium arsenide multiple wavelength multidiode cluster probe (Biotherapy Medical Laser, 3ML), three times a week, from 4 to 16 weeks or 6 to 16 weeks after X-irradiation. The skin fields were exposed to the light pulsating at either 2.5 Hz or 5 kHz. With light pulsating at 5 kHz, energy densities of 0.22, 0.54, 1.08 2.16, 4.32, and 10.8 J/cm2 were used. Treatment with light pulsating at 2.5 Hz, 6-16 weeks after X-irradiation, or treatment with light pulsating at 5 kHz, 4-16 weeks after X-irradiation, did not have a significant effect on the incidence or the latency for the development of ischemic dermal necrosis irrespective of the exposure time to light at each treatment. With light pulsating at 5 kHz, no effect of light dose was observed. However, the overall incidence of dermal necrosis was significantly reduced (P = 0.001) to 52% in the X-irradiated fields receiving treatment with 5 kHz light, 6-16 weeks after X-irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1992

Long-term studies of cisplatin-induced reductions in porcine renal functional reserve.

Mature Large White female pigs aged approx. 10 months received single intravenous doses of 1.5, 2, or 2.5 mg/kg cisplatin. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) in individual kidneys were measured prior to and at 4-week intervals for up to 24 weeks after cisplatin administration by renography using [99mTc]-diethylenetriamminepentaacetic acid (DTPA) and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated pig and that of three age-matched control pigs was then removed, and GFR and ERPF values were measured in the remaining kidney at 4-week intervals for a further 24 weeks after unilateral nephrectomy (UN). Pigs treated with cisplatin showed no significant reduction in GFR or ERPF for up to 24 weeks after drug infusion. As measured using inductively coupled plasma mass spectrometry, the mean renal platinum concentration in the left kidney removed at UN was 77.5 +/- 9.1 ng/g kidney per mg/kg cisplatin. Histological evaluation of these kidneys revealed narrow interconnecting rays of interstitial fibrosis in the deep cortex and medulla; in these areas, glomeruli exhibited thickened Bowman's capsules and occasionally shrunken sclerotic capillaries. In cisplatin-treated pigs, UN was associated with a marked reduction in the ability of the remaining kidney to increase its function in terms of GFR and, to a lesser extent, of ERPF. The increase seen in GFR following UN in the cisplatin-treated pigs was only ca. 50%-70% of that seen in age-matched UN controls. Histologically, these kidneys revealed resolution of the peritubular fibrosis observed at UN; occasional sclerotic glomeruli were also evident. Platinum remained detectable in these kidneys, the mean levels being 18.8 +/- 4.9 ng/g kidney per mg/kg cisplatin. These findings confirm previous observations and illustrate the need for caution in considering further treatment of patients who have previously received cisplatin along with a second potentially nephrotoxic agent.

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PubMed1992

Functional changes in the pig kidney following irradiation with fractionated doses of fast neutrons (42 MeVd-->Be).

The right kidney of female Large White pigs, approximately 14 weeks old, was irradiated with fractionated doses of fast neutrons (42 MeVd-->Be). The total doses used were 6.6-9.2 Gy. Changes in kidney function, assessed as the functional index (FI, where FI = irradiated kidney function/unirradiated kidney function) or as individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), were serially determined up to 104 weeks after irradiation using 99Tcm-DTPA and 131I-hippuran renography. The animals were then euthanized, the kidneys removed and weighed. A dose-dependent reduction in FI was seen within 13 weeks of irradiation. Measuring individual kidney function revealed a hyperaemic response in both irradiated and unirradiated kidney 4 weeks after irradiation. This was followed by a dose-dependent reduction in irradiated kidney GFR and particularly ERPF. The ED50 value for the impairment in ERPF, assessed as the percentage of irradiated kidneys exhibiting a > or = 50% reduction in ERPF, was significantly lower than that for GFR, i.e. 7.20 +/- 0.10 Gy compared with 8.44 +/- 0.07 Gy (p < 0.001). A dose-related reduction in irradiated kidney weight was also observed. These fast neutron-induced changes in renal function and weight are qualitatively similar to those observed following photon irradiation of the pig kidney.

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PubMed1991

The effect of unilateral nephrectomy on the subsequent radiation response of the pig kidney.

The left kidney of 14 Large White female pigs, approximately 14 weeks of age, was surgically removed. Thirty weeks after unilateral nephrectomy (UN) the remaining kidney was irradiated with a single dose of between 11.9 and 15.6 Gy of 60Co gamma-rays; three pigs received sham irradiation. Following irradiation glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and haematocrit (Hct) were determined for up to 48 weeks after irradiation. Irradiation resulted in a dose-dependent decline in GFR, evident 8 weeks after irradiation. This was followed by a gradual improvement in GFR, although after doses of 14.0 Gy GFR remained below control values throughout the study. A similar pattern of response was seen in terms of ERPF, but this was not dose-related. Doses of greater than or equal to 14.0 Gy also caused a significant reduction (p less than 0.001) in Hct within 4-8 weeks. Minimal levels were evident 16 weeks after irradiation; Hct then increased, but remained below preirradiation values. Dose-effect curves were obtained by determining the percentage of irradiated kidneys which showed a greater than or equal to 50% reduction in GFR and ERPF, fitted by probit analysis, and ED50 values (+/- SE) were calculated for each parameter. The ED50 values for GFR and ERPF were 14.49 +/- 0.27 Gy and 12.56 +/- 0.98 Gy, respectively. These values were not significantly different from those obtained from intact age-matched pigs in which the right kidney alone was irradiated; UN did not compromise or alter the radiation response of the kidney to irradiation. However, the ED50 values obtained for the UN pigs were significantly greater (p less than 0.001) than the values of 9.76 +/- 0.17 Gy and 6.19 +/- 0.93 Gy, seen for GFR and ERPF in intact age-matched pigs in which both kidneys were irradiated. Thus although both experimental situations involved irradiating the entire renal tissue, the relative radiosensitivity of the kidneys varied considerably. These findings show that the radiosensitivity of the pig kidney can vary markedly, depending on the physiological status of the kidney at the time of irradiation.

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PubMed1991

Delirium in an elderly woman possibly associated with administration of misoprostol.

Misoprostol has been associated with adverse reactions, including gastrointestinal symptoms, gynecologic problems, and headache. Changes in mental status, however, have not been reported. We present a case in which an 89-year-old woman in a long-term care facility became confused after the initiation of misoprostol therapy. The patient's change in mental status was first reported nine days after the initiation of therapy. Her delirium significantly improved after misoprostol was discontinued and her mental status returned to normal within a week. Because no other factors related to this patient changed significantly, the delirium experienced by this patient possibly resulted from misoprostol therapy.

Aged↗

PubMed1991

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues in the pig. IV. Effects on renal function.

The effects of fractionated doses of fast neutrons (42 MeVd----Be) on the radiation response of the pig kidney have been assessed and compared with those observed after X irradiation. Following X irradiation there was a marked increase in the total dose at which renal function was preserved with decreasing fraction size. The rate of this increase was dependent on the overall treatment time; for fractionated irradiation given over 18 or 39 days the exponents related to fraction number, N, were 0.36 +/- 0.03 and 0.48 +/- 0.003, respectively. In contrast, there was no significant change in the iso-effect dose for renal injury following fractionated irradiation with fast neutrons where there was also little effect of varying the overall treatment time. Analysing these data by means of the linear-quadratic (LQ) model, using both an Fe-plot and the Tucker test, gave alpha/beta ratios of 2.42 +/- 0.06 Gy and 2.99 +/- 0.16 Gy, respectively, for X-ray doses given in 18 days. For fractionated doses of X rays given in 39 days the alpha/beta ratios were 0.40 +/- 0.01 Gy and 0.47 +/- 0.02 Gy, respectively. The alpha/beta ratios for renal tissue following fast neutron irradiation obtained by the two methods were also similar, i.e. 15.00 +/- 0.60 Gy and 15.72 +/- 3.76 Gy, respectively. The pronounced fractionation effect seen with X irradiation, particularly for doses administered over 39 days as opposed to 18 days, coupled with the absence of any such effect with fast neutrons, resulted in a marked increase in relative biological effectiveness (RBE) with decreasing X-ray dose/fraction. The slopes of the resulting regression lines were -0.73 +/- 0.05 and -0.33 +/- 0.02, respectively. The lack of dose sparing associated with fractionation, or variation of the overall treatment time for fast neutron irradiation, suggests that doses administered to tumours adjacent to the kidney can be given as a few relatively large dose/fractions in a short overall treatment time without an increased risk of complications related to renal tissue. This may be of therapeutic advantage in the treatment of rapidly proliferating tumours where dose may be wasted using more conventional protracted fractionated irradiation schedules.

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PubMed1991

Time-related changes in lymphatic clearance in pig skin after a single dose of 18 Gy of X rays.

The early and late effects of X rays on lymphatic microcirculatory function have been investigated in pig skin. Paired estimates of lymph clearance were performed in irradiated and unirradiated sites on the flank skin of anaesthetized Large White pigs at 3, 6, 9, 12, 26, 39, 52, 64 and 78 weeks after a single dose of 18 Gy of X rays. The dermal clearance of 99Tcm-colloid was used to assess lymph flow. The results demonstrated two waves of impaired lymphatic clearance which correlated well with the gross morphological changes observed. The first wave occurred between 6 and 12 weeks after irradiation and corresponded to a period of ischaemia and oedema. The second wave, at 52 weeks, corresponded with dermal thinning and subcutaneous atrophy. X irradiation resulted in an impairment of lymph drainage both within and outside the field of irradiation. Impaired lymphatic drainage probably contributes to the gross and histological changes observed in the skin after X irradiation.

Animals↗

PubMed1991

Residual radiation-induced damage to the kidney of the pig as assayed by retreatment.

The effect of re-irradiation on the previously irradiated kidney was studied in the Large White female pig. Both kidneys of 14-week-old pigs were initially irradiated with a single dose of 3-7 Gy of 250 kV X-rays. The individual kidney glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and the haematocrit (Hct) were serially measured up to 24 weeks after X-irradiation. Doses of 3 and 5 Gy of X-rays had little effect on the GFR. However, 7 Gy of X-rays caused a marked decline in the GFR up to 12 weeks after irradiation; the GFR then began to recover. A similar pattern of response was seen in the ERPF. In contrast, the Hct was reduced in all pigs 4 weeks after X-irradiation. The extent of the decline and subsequent recovery 24 weeks after irradiation appeared to be related to dose. Twenty-four weeks after X-irradiation both kidneys were re-irradiated with a single dose of 7.9 Gy of 60Co gamma-rays; both kidneys of four age-matched control pigs which had not previously received X-irradiation were similarly treated. Individual kidney GFR, ERPF and Hct were again serially measured up to 24 weeks after gamma-irradiation. Re-irradiation resulted in a significantly greater reduction in the GFR, ERPF and Hct compared with that seen after gamma-irradiation alone. Moreover, the severity of the reduction in the GFR and Hct observed after gamma-irradiation was related, in a dose-dependent manner, to the initial X-ray doses employed. These results indicate that the kidney fails to exhibit complete long-term recovery in function following irradiation. Re-irradiation of the kidney in patients should thus be viewed with extreme caution.

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PubMed1991

A morphological study of radiation nephropathy in the pig.

Both kidneys of mature pigs received a single dose of 9.8 Gy 60Co gamma rays. Pigs were killed between 2 and 24 weeks after irradiation and the kidneys examined histologically. Glomerular and tubular changes were observed within 2 weeks of irradiation. Neutrophils and other leukocytes were seen within glomerular capillary loops; mesangial matrix and cell number increased. A progressive increase in thickening of the basement membrane and a decrease in capillary lumina were then noted. Basement membrane duplication occurred within 12 weeks. By 24 weeks these lesions had increased in severity, sclerotic endstage glomeruli, predominantly subcapsular or juxtamedullary, being evident. Tubular lesions initially consisted of focal areas of tubular atrophy in the juxtamedullary region. By 6 weeks subcapsular foci of tubular degeneration, regeneration, and necrosis were found; these appeared to resolve 12 weeks after irradiation. At later times the severity of the tubular lesions varied between pigs, with some exhibiting interstitial fibrosis involving a complete band of subcapsular tissue, while others showed relatively mild changes. There was no apparent change in the vasculature. These findings indicate that (a) there is no one target or dose-limiting cell, and (b) the vasculature does not play a primary role in the development of radiation nephropathy.

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PubMed1990

Cisplatin-induced reductions in renal functional reserve uncovered by unilateral nephrectomy: an experimental study in the pig.

Groups of mature Large White female pigs, approximately 10 months of age, received single intravenous infusions of 1.5, 2 or 2.5 mg/kg body weight (equivalent to approximately 90, approximately 120 and approximately 150 mg/m2) cisplatin. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured before and at 4 weeks after cisplatin infusion by renography using [99 mTc]-DTPA (diethylenetriamminepentaacetic acid and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated animal plus that of four age-matched control pigs was then removed surgically, and GFR and ERPF were measured in the remaining kidney at 4 weekly intervals for up to 24 weeks after unilateral nephrectomy (UN). The pigs treated with cisplatin exhibited no consistent change in either GFR or ERPF at 4 weeks after treatment. A histological evaluation of kidneys from animals treated with greater than or equal to 2 mg/kg cisplatin that had been removed at UN revealed both tubular and glomerular lesions. The latter consisted of cell proliferation on the parietal surface of the urinary space; damage to the S1 portion of the proximal convolution was also noted. Following UN there was a pronounced dose-dependent reduction in the functional status of the remaining kidney such that the increase in GFR and ERPF in pigs initially receiving 2.5 mg/kg cisplatin was less than 50% of that seen in age-matched UN controls. Moreover, the glomerular lesions observed at 4 weeks after cisplatin infusion had apparently progressed to glomerular hyalinisation by 24 weeks after UN. Thus, prior treatment with cisplatin may cause a permanent reduction in renal functional reserve that may be clinically "silent" until exposure to an additional nephrotoxic insult.

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PubMed1990

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues in the pig. II. Late effects on cutaneous and subcutaneous tissues.

The late effects of irradiation with single and fractionated doses of X rays (250 kV) and fast neutrons (42 MeVd----Bc), on the cutaneous and subcutaneous tissues of the pig, have been evaluated from measurements of changes in relative field length. These were determined at intervals of 26-104 weeks after irradiation. For fractionated irradiation with X rays the average fractions exponent, N, obtained from a log-log plot of iso-effect dose (ED50) against fraction number was 0.41. This was independent of the period of assessment, with no significant indication of a time factor. However, the exponent N did vary with the level of effect and was in the range 0.33-0.51. It was greatest for a greater than or equal to 10% reduction in relative field length. Assuming the validity of the linear quadratic model of cell survival, the alpha/beta ratio was 1.95 Gy. However, this model fitted the data less well for the least severe levels of damage, and for these the alpha/beta ratios were not significantly different from zero. Irradiation with fast neutrons showed a small effect of fractionation for doses given in greater than or equal to 6 fractions compared with a single dose. There was no significant increase in iso-effect dose when the dose was given in 30 fractions compared with 6 fractions. The relative biological effectiveness for late cutaneous and subcutaneous damage for the energy of fast neutrons used did not vary with the period of assessment, i.e. 26-52 weeks compared with 65-104 weeks, and was not significantly different from that previously obtained for ischaemic dermal necrosis, seen after higher doses, at 12-20 weeks after irradiation.

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PubMed1990

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues. III. Effects on lung function.

The effect of single and fractionated doses of fast neutrons (42 MeVd----Be) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a 133Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 +/- 0.94 for infinitely small X-ray doses per fraction.

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PubMed1990

The effect of acetaminophen on pig kidneys with a 2-bromoethanamine-induced papillary necrosis.

Large White pigs were used to investigate the effects of acetaminophen (paracetamol) on normal kidneys or those with an existing renal papillary necrosis. Pairs of young female animals were treated with either a single iv dose of 50 mg/kg 2-bromoethanamine (BEA), 100 mg/kg/day acetaminophen po for 28 days, or a combination of BEA followed by the acetaminophen treatment. Two pigs served as untreated controls. Kidney length, diameter and parenchymal thickness were measured by ultrasound scans, and glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) assessed by 99mTc-DTPA and 131I-hippuran renography prior to treatment and on day 26. Acetaminophen only caused no renal pathology. Despite the lack of a gross RPN, hyperplasia of the pelvic and ureteric urothelia (with extensive vacuolation) was observed following BEA, but BEA followed by acetaminophen for 28 days did not enhance the lesion. The BEA and BEA-acetaminophen groups (but not acetaminophen only) showed an increased ERPF compared with age-matched controls, but there was no significant difference in the overall GFR between the groups.

Acetaminophen↗

PubMed1989

Nephropathy in the mature pig after the irradiation of a single kidney: a comparison with the immature pig.

The right kidney of 11 mature 10-month-old Large White female pigs was irradiated with single doses of 9.8-14.0 Gy of 60Co gamma rays. Individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured using 99mTc-DTPA and 131I-hippuran renography for periods up to 24 weeks after irradiation. Renal function was assessed either as a functional index, FI (FI = irradiated/unirradiated kidney function), or as the individual kidney GFR and ERPF. The radiation-induced changes after the irradiation of a single kidney (unilaterally irradiated--UI) of mature pigs were compared with those previously observed in 14-week-old immature pigs. Irradiation resulted in a dose-dependent reduction in the FI for both GFR and ERPF. However, these reductions were significantly less than those previously seen in immature pigs. Within 2 weeks of irradiation GFR increased in both the irradiated and the unirradiated kidneys in each animal, compared with unirradiated age-matched control kidneys. No marked changes in renal hemodynamics were seen in mature animals after a single dose of 9.8 Gy. This was in marked contrast to the pronounced reduction in the GFR and ERPF in the irradiated kidney previously observed in immature animals irradiated with an equivalent single dose of X rays. After higher doses, the irradiated kidney in mature pigs showed a dose-dependent reduction in GFR and ERPF. However, the extent of this reduction was significantly less than that seen in immature animals. There was no apparent difference in the response of the unirradiated kidneys in mature or immature pigs. The ED50 values, based on a probit fit to the data for the proportion of functional tests in which the irradiated kidney showed a greater than or equal to 50% reduction in GFR or ERPF, were higher in the mature animals; for example for ERPF the ED50 values were 11.76 +/- 0.28 Gy and 7.67 +/- 0.34 Gy for mature and immature animals, respectively. Thus, the UI kidney in mature pigs appears to be less radiosensitive than the UI kidney in immature animals.

Aging↗

PubMed1989

Radiation nephropathy in mature pigs following the irradiation of both kidneys.

Both kidneys in mature female Large White pigs, ca. 45 weeks old were irradiated with single doses of 7.8-14.0 Gy of 60Co gamma-rays. Radiation-induced changes in renal function were assessed on the basis of sequential individual measurements of kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) for up to 24 weeks after irradiation. At the same time intervals blood samples were taken to determine plasma renin levels and the haematological status of each animal. Two weeks after irradiation the ERPF and in particular the GFR was increased. This was followed by a pronounced, dose-dependent, decline in renal haemodynamics. Minimal functional levels were observed 8-12 weeks after irradiation. Function then somewhat recovered. There was a significant (r greater than or equal to 0.98; p less than 0.001) inverse relationship between the mean values of GFR and ERPF, determined at 4-24 weeks after irradiation, and the radiation dose. After a dose of 7.8 Gy the reduction in ERPF was greater than that for GFR. However, at higher doses both parameters were reduced to an equal extent. The resulting slope of the dose-effect curve for impaired renal function versus dose was significantly steeper for GFR than that for ERPF (p less than 0.001). There was a significant reduction (p less than 0.002) in the erythrocyte count, the haematocrit and haemoglobin levels within 6-8 weeks of irradiation; this anaemia was characterized as a normochromic normocytic anaemia. There were no marked changes in plasma renin levels as a result of renal irradiation. The pathogenesis of late radiation-induced damage to the kidney is discussed in the light of these findings.

Animals↗

PubMed1989

The effect of age and the proportion of renal tissue irradiated on the apparent radiosensitivity of the pig kidney.

In 14-week-old (immature) and 45-week-old (mature) pigs either the right kidney (unilateral irradiation, UI) or both kidneys (bilateral irradiation, BI) were irradiated. The kidneys of immature pigs received single doses of 7.0-12.6 Gy of 250 kV X-rays; mature pigs received single doses of 7.8-14.0 Gy of 60Co gamma-rays. These were assumed to be approximately equivalent to the X-ray doses using a RBE of 0.9 gamma-rays/X-rays. The glomerular filtration rates (GFR) and effective renal plasma flows (ERPF), were determined for up to 24 weeks after irradiation. From these data dose-effect curves were obtained by determining, at each dose level, the percentage of irradiated kidneys which exhibited a greater than or equal to 50 per cent reduction in GFR and ERPF. 60Co gamma-ray doses were normalised to approximately equivalent X-ray doses. The dose-effect curves were fitted by probit analysis, and ED50 values (+/- SE) calculated for both GFR and ERPF. Similar conclusions could be drawn from the results obtained following the determination of both GFR and ERPF. However, the ED50 values obtained for ERPF were significantly lower than those for GFR (p less than 0.05). In 14-week-old animals the kidney of UI animals was significantly more radiosensitive than that of BI animals, i.e. the ED50 values, in terms of GFR, were 8.74 +/- 0.31 Gy and 10.97 +/- 0.23 Gy, respectively (p less than 0.001). In 45-week-old pigs the reverse was true; the ED50 values were 12.67 +/- 0.34 Gy and 8.78 +/- 0.15 Gy (p less than 0.001) for unilateral- or bilateral-irradiated animals, respectively. The kidney of BI mature animals appeared to be as radiosensitive as the UI immature pigs. Thus the renal response to radiation was markedly influenced by the age of the animals and by the proportion of the renal tissue irradiated.

Aging↗