HYPERTENSION IN UROLOGICAL CONDITIONS

By CLIFFORD WILSON, M.A., D.M., F.R.C.P. The London Hospital

IT is now well recognised that hypertension may complicate a number of renal diseases which fall within the sphere of genito-urinary surgery. By far the most important, for a number of reasons, is the hypertension associated with unilateral renal disease. I t is important because it is not uncommon, and because it is one of the few hypertensive diseases in which the cause of the high blood-pressure is known and can be removed. But of still greater importance is the light it has thrown and is likely to throw on our knowledge of the genesis of renal hypertension. It is this aspect which I would like to illustrate by reference to the experimental work we have been carrying out at the London Hospital for many years. This work started in collaboration with Dr F. B. Byrom before the war and has been continued by Dr Ledingham and Dr Floyer up to the present time.

There are many methods of causing unilateral renal damage in animals. We have worked with rats and have produced hypertension by partial occlusion of one renal artery with a silver clip-a modification of the technique Goldblatt used in dogs. Blood-pressures are taken on the tail by the plethysmographic method which first made possible long-term blood-pressure measurements in the rat. The rat was found to differ from the dog in that persistent hypertension could be produced by clipping only one renal artery, so that it resembles man and differs from other animals in sustaining chronic hypertension after unilateral renal damage.

I have already said that in man removal of a diseased kidney may be followed by the return of blood-pressure to normal, but in many cases, the proportion varying in different series from 20 to 60 per cent., the blood-pressure remains high after removal of the diseased kidney. A similar phenomenon is observed in the rat, and much time and thought have been devoted to the explanation of this persistent hypertension after the primary cause has been removed. In man various reasons have been suggested to explain this phenomenon ; for example, that the patient might have unsuspected infection, such as pyelonephritis on the other side, or that essential hypertension might also be present, or that some extrarenal factor had come into play to sustain a hypertension once produced. By chance our early experiments revealed a possible explanation for this persistent hypertension in unilateral renal disease, for when the blood-pressure had been raised for some time ; histological examination of the opposite kidney showed a very remarkable picture. The clipped kidney was in most cases remarkably normal; the opposite kidney, on the other hand, which had not been touched, showed arterial, glomerular, and interstitial changes identical with those which occur in malignant hypertension in man. It was concluded that in these experiments hypertension was producing the vascular changes of malignant hypertension ; the absence of these lesions from the clipped kidney was explained by the fact that the clip protected the renal vessels from the high blood-pressure.

In our experiments the animals with persistent hypertension after removal of the clipped kidney were in general the ones which showed severe vascular damage in the remaining kidney. We therefore postulated not only that hypertension may produce renal vascular changes but also that these in turn may cause and perpetuate hypertension. Dr Floyer in an ingenious experiment recently showed that if, instead of removal of the clipped kidney, the clip was removed from the renal artery, hypertension persisted in some animals. Then, if the opposite kidney was removed, the blood-pressure returned to normal. This observation provided conclusive evidence that in these experiments some abnormality in the opposite kidney was responsible for the persistent hypertension.

These findings are of great interest for they offer an explanation of various features occurring I Read at the Thirteenth Annual Meeting of the British Association of Urological Surgeons at London on

28th June 1957. 34 8

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i n the natural course of hypertension in many forms of renal disease, particularly the chronicity of hypertension and the tendency to progressive increase in blood-pressure with the passage of time. They also explain the similarity in the clinical and histological changes in different forms of hypertensive renal disease. The implication in unilateral renal disease is that persistent hypertension after nephrectomy may well be due to secondary hypertensive lesions in the opposite kidney. There is plenty of evidence to support this hypothesis from autopsy studies, where one kidney is found to be greatly contracted and the other enlarged ; for the large kidney often shows the lesions of malignant hypertension.

An interesting example of this same phenomenon, to which attention has been drawn recently, is provided by the (unavoidable) irradiation of one kidney in the treatment of seminoma of the testis. Malignant hypertension may develop following irradiation and may subsequently be reversed by removal of the irradiated kidney, but some degree of hypertension persists and may be attributable to secondary vascular changes in the opposite kidney. We have carried out renal irradiation studies in rats and have shown that hypertension results from irradiation of one kidney, the rest of the body being shielded. After the hypertension has persisted for some time, lesions develop in the opposite kidney identical with those found in the renal artery constriction experiments, and typical of malignant hypertension. Severe fibrinoid lesions of arteries were also found in the irradiated kidney-which in these experiments was not protected by a clip on the renal artery. If the irradiated kidney was removed after a short interval of hypertension the blood-pressure returned to normal.

These various experiments provide good grounds for believing that hypertension which persists after removing the clipped kidney is due to some form of dysfunction in the opposite kidney which is secondary to the high blood-pressure. Whether the actual vascular lesions are themselves responsible or whether it is some associated renal disturbance which maintains the high blood-pressure cannot yet be decided, but certainly the experimental evidence indicates that some form of secondary renal damage is to blame.

Before nephrectomy is carried out in patients with hypertension it is therefore desirable to use every available diagnostic test to exclude the possibility of structural damage in the opposite kidney. A new diagnostic technique which is of undoubted value for this purpose is renal biopsy. The following case illustrates the application of this. Pyelography combined with air studies showed a unilateral contracted kidney in a patient with hypertension with normal renal function. N o obvious abnormality was present in the opposite kidney which was greatly enlarged, although a trace of albumin was present in the urine from that kidney. Renal biopsy was carried out on the enlarged kidney and showed very obvious chronic lesions probably in the nature of pyelonephritis, but with some evidence of hypertensive vascular damage. It was decided that nephrectomy was contraindicated in such a case.

Similar in many respects to the problem of unilateral renal disease is hypertension secondary to phaochromocytoma of the adrenal medulla. Here, again, removal of the tumour sometimes abolishes the hypertension, but more often there is a persistent high blood-pressure which cannot be attributed to continued secretion of adrenaline or noradrenaline. Here, also, we have an example of chronic hypertension persisting when the original cause has been removed-that is, evidence of a dual atiological mechanism for high blood-pressure in the same patient. Phaochromocytoma is rare, and evidence for a renal origin of chronic hypertension is difficult to obtain in these patients, but I would ask any of you when removing such phaochromocytomas to perform a renal biopsy at the time of operation. A recent patient of mine in whom this was done and who had a chronic hypertension showed unequivocal evidence of hypertensive renal changes in the kidney.

It appears, therefore, that a careful study of high blood-pressure in urological conditions can afford valuable information which may give us a lead in the investigation of chronic high blood-pressure in man. Such information is urgently needed because this problem has hitherto eluded all attempts at its solution.