RADIATION NEPHROPATHY

81 with community aspects of medical care one session a week throughout the third year is devoted to the primary-medical-care aspects of that discipline to which the student is at that time attached in hospital. In the fourth year, apart from one mandatory day of clinical work each week, the student spends the whole of his time studying a subject of his choice. Students are encouraged, but not obliged, to choose an area of investigation with clinical as well as laboratory or epidemiological aspects. At the end they are expected to write an original dissertation, and many of these have been of high standard. The 5 students who elected to study immunology and alimentary disease have contributed to three papers (in press or published) in the British Medical Journal, one in Gut, one in the Quarterly journal of Medicine, and one in The Lancet. The fourth year allows students to recognise the limitations of existing knowledge and of experimental method in human biology, and to set the pattern for life-long learning. How this type of learning can be organised for a class of 130 students remains to be seen. The fifth year is a year of clinical apprenticeship, with students being given the maximum responsibility under supervision. Most of the work in this year is undertaken in district general hospitals in the Wessex Region outside Southampton, providing a population base of 2*million. While this should certainly make it easier to guarantee that no patient is overwhelmed by the needs of undergraduate teaching, Southampton students have much more extensive opportunities than, for example, those in McMaster for contact with patients on a one-toone basis. The establishment of Southampton medical school was proposed by the Royal Commission on Medical Education. It was sanctioned by the Government in 1967, and the school was inaugurated in 1971. Whether its graduates will recognise and respond to the needs of society more appropriately than those of other institutions cannot yet be judged. Perhaps, by the middle of the 1980s, the enthusiasm of the young faculty will be rewarded by a demonstration that this has been achieved.

RADIATION NEPHROPATHY SINCE 1904, when Baerman and Linser1 described the ill-effects of irradiation on the kidney, evidence has accumulated alerting radiotherapists to this hazard. Luxton,23 reporting a large clinical study, defined five categories of disease--acute radiation nephritis, chronic radiation nephritis, benign hypertension, malignant hypertension, and symptomless proteinuria. Luxton and his co-workers4 deduced that doses of greater than 2300 rads in less than five weeks would probably cause renal damage. Acute radiation nephritis accounts for most of the other reported cases with adequate histological information. The onset of hypertension and proteinuria may be delayed for up to 12 months; hæmaturia is uncommon. Untreated, most patients die of renal fail1. Baerman, G , I. ser, P Münch med Wschr. 1904, 7, 996. 2. Luxton, R. W. Q. Fl Med. 1953, 22, 215. 3 Luxton, R. W. Lancet, 1961, ii, 1221. 4. Kunkler, P. B., Farr, R. F., Luxton, R. W. Br. J. Radiol. 1952,

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within the subsequent year. A few patients go on to late malignant hypertension (Luxton group iv), from 18 months to 11 years after radiotherapy. Again, without treatment there is rapid deterioration. Keane and his associates5 have lately described the renal microstructure and ultrastructure in acute radiation nephritis. They investigated two women with hitherto normal renal function in whom nephritis arose 8 and 10 months after radiotherapy for disseminated ovarian cancer. Radiation doses were 2500 rads and 2700 rads over 4 and 5 weeks. The most striking changes were glomerular, with increase in mesangium and thickening and cleavage of capillary basement membrane. Intimal proliferation was seen in medium and small arteries; interstitial fibrosis and tubular damage were prominent. Fluorescent studies, using immunoglobulins, C3, and fibrinogen, were negative. Neither patient had an abnormal urinary sediment. In relation to the degree of glomerular damage, proteinuria was modest (1 g/24 h) though non-selective.6 How is the damage caused ? After irradiation, replication of capillary endothelial cells (which usually happens every 2-3 months) is delayed.7-9 Capillary-wall damage would allow activation of the coagulation system and further vascular damage. This theory has experimental support, 1012 and the non-specific histological appearances certainly resemble other nephropathies in which coagulation derangement is implicated. The lack of fibrinogen on fluorescent staining requires explanation. Vascular changes and interstitial fibrosis suggest an ischasmic ætiology—maybe a direct effect of irradiation on juxtaglomerular cells or (again) a coagulopathy causing thrombosis in the renal microcirculation. Radiation also increases the susceptibility of renal arteries to hypertensive damage,14 " perhaps compounding the damage. Drug toxicity must be borne in mind: cortisone causes glomerular changes in irradiated rat kidneysl6 and chemotherapy may sensitise the kidney to irradiation-especially in children.17 18 Associations exist between nephrotic syndrome and lymphomas19 and other cancers.20 21 Radiotherapy might activate latent disease; but the immunological evidence is lacking. Radiation nephropathy is now uncommon, since damaging radiation levels can be predicted. For cases of overdosage, anticoagulation would be a logical approach 10 22—providing that it was started early enough. Treatment of the established nephropathy is along conventional lines for renal insufficiency. ure

W. F., Crosson, J. T., Staley, N. A., Anderson, W. R., Shapiro, F. L. Am. J. Med. 1976, 60, 127. 6. Gang, N. F., Sarophin, M E., Madrazo, A., Churg, J. Am. J. Path. 1973,

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Engerman, R. L., Pfaffenbach, D., Davis, M. D. Lab. Invest. 1967, 17, 738. Tannock, I. F., Hayashi, S. Cancer Res. 1972, 32, 77. DeGowin, R. L., Lewis, L. J., Hoak, J. C., Mueller, A. L., Gibson, D. P. J. Lab. clin. Med 1974, 84, 42. 10. Kinzie, J., Studer, R., Perez, B., Potchen, E. J. Science, 1972, 175, 1481. 11. Fajardo, L. F., Stewart, J. R. Lab. Invest. 1973, 29, 244. 12. Khan, M. Y., Okanian, M. Am. J. Path. 1974, 74, 124. 13. Ljungquist, A., Unge, G, Lagergren, C., Notter, G. Acta path. microbiol. scand. 1971, 79(A), 629 14. Wilson, C., Ledingham, J. M., Cohen, M. Lancet, 1958, i, 9. 15. Asscher, A. W., Wilson, C., Anson, S. G. ibid. 1961, i, 580. 16. Berdjis, C. C. Archs Path. 1960, 69, 431. 17. Sagerman, R. H. J. Urol. 1964, 91, 332. 18. Arneil, G. C., Emmanuel, I. C., Flatman, G. E., Harris, F., Young, D. G., Zachary, R B. Lancet, 1974, i, 960. 19. Player, J. Stutzman, L Am. J. Med 1971, 50, 56. 20. Cantrell, E. G. Br. med J. 1969, ii, 739. 21. Loughridge, L. W., Lewis, M G. Lancet, 1971, i, 256 22. George, C, Slichter, S., Quadracei, L., Striker, G., Harker, L. New Engl. J. Med 1974, 29, 1111. 7. 8. 9.