Perceptions
Most kidney patients probably see their nephrologist as an expert (we hope!) in chronic renal failure and dialysis, with some also specialising in transplantation. If this were true, we wouldn’t need to know much at all about how the normal kidney works; we could simply regard it as a “black box” which we replace with dialysis or transplantation if it fails. However, there are numerous kidney diseases which alter the functions of the kidneys without causing complete kidney failure, and there is also a lot we can do to stop some types of kidney disease progressing to cause end-stage renal failure. This means that nephrologists also need to know how the normal kidney works, how diseases which may cause progressive kidney damage start, and how these diseases may be combated at an early stage.
In this article I will try to describe some of the recent advances in this field. The choice of subjects is personal. The amount of research going on in the field is enormous, so I have chosen to concentrate on those which I think will be of general interest. This article is based on one written for a medical readership in the British Medical Journal (BMJ 2000; 320; 98-101, 8 January 2000)
In the last few years we have learnt how the passage of water molecules across cell membranes is controlled by large molecules called aquaporins which act as water channels. The action of these channels is particularly important in the renal tubules, where the control of urine concentration takes place. For instance, there is a rare congenital disease (nephrogenic diabetes insipidus) which causes inability to concentrate urine, resulting in a tendency to severe dehydration in affected infants; we now know that this is caused by abnormalities in the control or production of the aquaporin which controls movement of water molecules in the renal tubule. Although this may seem obscure, these discoveries may lead to better treatment of more common conditions, including those associated with water retention in heart failure.
Similarly, we now know that the glands which control serum calcium concentration (including the parathyroid glands, which sometimes have to be surgically removed in dialysis patients because of persistent overactivity causing bone disease; and the kidneys themselves) detect changes in serum calcium concentration by means of a receptor on the cell surface. Very rare alterations in the way this receptor functions leads to congenital diseases associated with abnormalities in serum calcium concentration. Again, these discoveries are leading to the development of drugs which are already under trial for the treatment of parathyroid gland overactivity, and which may become part of the routine treatment of some dialysis patients in the future, helping to prevent bone disease and the need for surgical removal of the parathyroid glands.
High blood pressure is an extremely common abnormality in the developed world and is a major cause of heart attacks, heart failure and strokes. Several genetic diseases have been discovered recently which cause hypertension by affecting the kidneys’ ability to excrete dietary salt, so that a balance is only achieved at a higher blood pressure than normal. Some experts believe that even the more common forms of high blood pressure are also caused by an inborn tendency only to be able to excrete excessive salt at the expense of high blood pressure, which would explain why high blood pressure is so much commoner in Westernised societies, where salt intake (mostly from processed foods) can be over 50 times that in more primitive societies.
We still know depressingly little about how to prevent glomerulonephritis, which is one of the commonest causes of end-stage renal failure. However, advances are being made in the understanding of IgA nephropathy, one of the commonest types of glomerulonephritis, in which Immunoglobulin A (the type of antibody molecule normally active in the saliva and the gut) gets stuck in the glomeruli (the structures which sieve the blood to make urine) and cause inflammation and progressive damage. We now know that the IgA which gets stuck in glomeruli is made in the bone marrow, and is abnormal in the way that sugar molecules are attached to one part of the IgA molecule. We do not yet know what causes this abnormal attachment of sugar molecules or how to prevent it.
One of the causes of end-stage kidney failure in many elderly people is atherosclerosis of the blood supply to the kidneys. Atherosclerosis is the disease of arteries which causes heart attacks, poor circulation in the legs, and some strokes. The renal circulation is usually involved only when the disease is widespread, so many patients with this type of renal failure also have heart disease, a history of stroke, or peripheral vascular disease.
Prevention, as for heart attacks, lies in attacking the root causes - cigarette smoking, high cholesterol levels, obesity, lack of exercise, high blood pressure, etc. It is currently extremely difficult to predict which patient’s renal function will be improved by bypass surgery or balloon dilatation of narrowed segments of artery, and there is much research going on in this area.
In the last few years the genetic alterations which result in adult polycystic kidney disease have been identified. We know that these alterations affect the functioning of proteins present on the surface of many cells which affect signalling between adjacent cells, but we do not yet know how these alterations lead to progressive enlargement of cysts or to renal failure. Again, there is rapid progress in this field, but it is anyone’s guess whether - or how soon - this research may lead to treatments which might prevent progressive kidney damage in those who have inherited one of these genes.
These are just some of the exciting advances that researchers have made in the last few years. There will, we hope, be many more, each having a small but significant impact on the treatment of kidney patients in the future. We will probably never be able to prevent end-stage kidney failure altogether, but even preventing it in a few patients will be well worthwhile.
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Page created: 13 January 2001
Last updated: 27 February 2011