The Treatment of Renal Diseases

All the well-known processes of pathology—acute and chronic inflammation, immune reactions, degenerative changes, etc.—may be found in the kidney, and the forms of therapy required to reverse them are equally diverse. All these processes, however, lead to one thing, destruction of renal tissue. This destruction may be rapid and severe, followed by regeneration in many cases, or a slow but progressive destruction with fibrous overgrowth. Broadly speaking, the kidneys are responsible for maintaining the stability of the body fluids. If acute destruction of renal tissue occurs the body fluids are acutely altered, whereas in chronic renal destruction the disturbance is slowly progressive. The acute upset of normal physiology accompanying rapid destruction is the syndrome known as acute renal failure, and the progressive physiological imbalance known as chronic renal failure is the result of chronic tissue destruction. This leads me to the first and most important point I wish to make. Therapy in renal disease must be two-fold. Firstly, it must deal with the pathological process causing renal destruction. Secondly, it must correct the disordered physiology which the renal disease has created. Whereas the pathological processes are legion, they lead to only two types of physiological upsets—acute or chronic renal failure. Copyright Royal Medical Society. All rights reserved. The copyright is retained by the author and the Royal Medical Society, except where explicitly otherwise stated. Scans have been produced by the Digital Imaging Unit at Edinburgh University Library. Res Medica is supported by the University of Edinburgh’s Journal Hosting Service: http://journals.ed.ac.uk ISSN: 2051-7580 (Online) ISSN: 0482-3206 (Print) Res Medica is published by the Royal Medical Society, 5/5 Bristo Square, Edinburgh, EH8 9AL Res Medica, Spring 1962, 3(2): 38-47 doi: 10.2218/resmedica.v3i2.387 THE TREATMENT OF RENAL DISEASES By JOHN A. CALVERT, B.Sc. Fellow of the Royal M edical Society. Based on a Dissertation read before the Royal Medical Society on Friday, 8th December, 1961. All the well-known processes of pathology— acute and chronic inflammation, immune reactions, degenerative changes, etc.— may be found in the kidney, and the forms of therapy required to reverse them are equally diverse. All these processes, however, lead to one thing, destruction of renal tissue. This destruction may be rapid and severe, followed by regeneration in many cases, or a slow but progressive destruction with fibrous overgrowth. Broadly speaking, the kidneys are responsible for maintaining the stability of the body fluids. If acute destruction o f renal tissue occurs the body fluids are acutely altered, whereas in chronic renal destruction the disturbance is slowly progressive. T he acute upset of normal physiology accompanying rapid destruction is the syndrome known as acute renal failure, and the progressive physiological imbalance known as chronic renal failure is the result of chronic tissue destruction. This leads me to the first and most important point I wish to make. Therapy in renal disease must be two-fold. Firstly, it must deal with the pathological process causing renal destruction. Secondly, it must correct the disordered physiology which the renal disease has created. W hereas the pathological processes are legion, they lead to only two types of physiological upsets— acute or chronic renal failure. In renal failure of either type management consists of either augmenting or completely taking over the functions the kidney normally performs in homeostasis. These functions fall into four groups. First, the e x c r e t io n of non-volatile end-products of metabolism. These pass into the glomerular filtrate and are either not reabsorbed or only partially reabsorbed by the tubules. Second, the maintenance of w a t e r b a l a n c e . The tubules allow only sufficient water to be reabsorbed from the filtered fluid to provide normal tonicity. Thirdly, e l e c t r o l y t e b a l a n c e . Normally the dietary intake provides an excess of Na, K and C l. Na C l is filtered and only the RENAL d i s e a s e s 39 right amount is reabsorbed. T he appropriate amount of K is secreted by the tubular cells. These activities are under the control of the adrenal cortical hormones. Lastly, a c i d b a s e b a l a n c e . Bodily metabolism leads to the production of mainly acid end-products. These are buffered in the blood, mainly by the H CO3 ion. Exhalation of the resulting CO2 provides a rapid stabilisation of the pH. However, although the pH is corrected, the blood H C O 3— that is the alkali reserve— is depleted. T he function of the kidney in acid-base balance is, in fact, to maintain the normal plasma H C O 3 level, by producing one H C O 3 ion for every H + ion excreted. C A U S E S O F A C U T E R E N A L F A IL U R E H y p o v o l a e m i c s h o c k commonly arises from loss of blood, and renal com­ plications are especially common after obstetrical haemorrhage. Loss of plasma after burning, and of fluid and electrolytes as in diabetic coma can also lead to renal damage. T he renal failure is thought to be due to ischaemia of the kidneys, following intense vasoconstriction in an attempt to maintain the systemic blood pressure. T h e renal medulla has a poorer blood supply than the cortex, and hence prolonged shock leads first to acute tubular necrosis. I f the state of shock persists for an extreme length of time, cortical damage ensues and irreversible renal cortical necrosis occurs. T he treatment of a shocked patient found to be anuric therefore consists of immediate vigorous resuscit­ ation with the appropriate fluid. In many cases recovery of the blood pressure will be followed by resumption of urine flow. I f oliguria persists, acute tubular necrosis must be assumed to have taken place, and the resultant acute renal failure must be managed along the lines I shall indicate later. Spontaneous regeneration of the tubules leads to resumption of urine flow some ten to twenty days later. If anuria persists much beyond this time, renal cortical


THE TREATMENT OF RENAL DISEASES
By JOHN A. CALVERT, B.Sc.
Fellow of the Royal M edical Society.

Based on a Dissertation read before the Royal Medical
Society on Friday, 8th December, 1961.
A ll the well-known processes of pathology-acute and chronic inflam m ation, im m une reactions, degenerative changes, etc.-may be found in the kidney, and the forms of therapy required to reverse them are equally diverse.All these processes, however, lead to one thing, destruction of renal tissue.T his destruction may be rapid and severe, followed by regeneration in many cases, or a slow but progressive destruction with fibrous overgrowth.
Broadly speaking, the kidneys are responsible for m aintaining the stability of the body fluids.If acute destruction o f renal tissue occurs the body fluids are acutely altered, whereas in chronic renal destruction the disturbance is slowly progressive.T h e acute upset of normal physiology accom panying rapid destruction is the syndrome known as acute renal failure, and the progressive physiological imbalance known as chronic renal failure is the result of chronic tissue destruction.
T h is leads me to the first and most important point I wish to make.Therapy in renal disease must be two-fold.Firstly, it must deal with the pathological process causing renal destruction.Secondly, it must correct the disordered physiology which the renal disease has created.W hereas the pathological processes are legion, they lead to only two types of physiological upsets-acute or chronic renal failure.
In renal failure of either type m anagement consists of either augm enting or com pletely taking over the functions the kidney normally performs in homeostasis.T hese functions fall into four groups.
First, the e x c r e t i o n of non-volatile end-products of metabolism.These pass into the glomerular filtrate and are either not reabsorbed or only partially reabsorbed by the tubules.Second, the maintenance of w a t e r b a l a n c e .T h e tubules allow only sufficient water to be reabsorbed from the filtered fluid to provide normal tonicity.T hirdly, e l e c t r o l y t e b a l a n c e .N orm ally the dietary intake provides an excess of N a, K and C l. N a C l is filtered and only the right am ount is reabsorbed.T h e appropriate am ount of K is secreted by the tubular cells.T hese activities are under the control of the adrenal cortical hormones.
Lastly, a c i d -b a s e b a l a n c e .B odily metabolism leads to the production of m ainly acid end-products.T hese are buffered in the blood, m ainly by the H CO3 ion.Exhalation of the resulting CO2 provides a rapid stabilisation of the pH .However, although the pH is corrected, the blood H C O 3-that is the alkali reserve-is depleted.
T h e function of the kidney in acid-base balance is, in fact, to maintain the normal plasma H C O 3 level, by producing one H C O 3 ion for every H + ion excreted.
l a e m ic s h o c k com m only arises from loss of blood, and renal com plications are especially com m on after obstetrical haemorrhage.Loss of plasma after burning, and of fluid and electrolytes as in diabetic coma can also lead to renal damage.T h e renal failure is thought to be due to ischaemia of the kidneys, follow ing intense vasoconstriction in an attem pt to m aintain the systemic blood pressure.T h e renal medulla has a poorer blood supply than the cortex, and hence prolonged shock leads first to acute tubular necrosis.If the state of shock persists for an extreme length of time, cortical damage ensues and irreversible renal cortical necrosis occurs.T h e treatm ent of a shocked patient found to be anuric therefore consists of im m ediate vigorous resuscit ation with the appropriate fluid.In many cases recovery of the blood pressure will be followed by resumption of urine flow .If oliguria persists, acute tubular necrosis must be assumed to have taken place, and the resultant acute renal failure must be managed along the lines I shall indicate later.Spontaneous regeneration of the tubules leads to resum ption of urine flow some ten to twenty days later.If anuria persists much beyond this tim e, renal cortical S e p t i c a e m i a often leads to acute renal failure, and here again the mechanism is thought to involve ischaemia.Bacterial toxins have been shown experiment ally to depress renal blood flow.T he h e p a t o r e n a l s y n d r o m e is an interesting rarity in which a severely jaundiced patient goes into super-imposed renal failure.T his is now thought to be due to an E .coli septicaemia complicating the initial cholangitis.T he treatment for both these conditions is clearly appropriate chemotherapy.

Mechanism
In the c r u s h s y n d r o m e renal failure occurs when the circulation is restored to a region which has had its blood supply occluded for many hours, as after a fall of rock in the mines.Renal damage is caused by the action of toxins liberated from the injured tissue.T h e same applies after i n c o m p a t i b l e b l o o d t r a n s f u s i o n .These two conditions are therefore grouped with the r e n a l p o i s o n s , and really have no specific treatment.

DAYS
B y n e c r o t i z i n g p a p i l l i t i s I mean very virulent forms of pyelonephritis which can cause acute renal failure by direct tubular damage.Treatment again is appropriate chemotherapy.
T he next two conditions cause acute renal failure at the glomerulus by diminishing filtration.Acute g l o m e r u l o n e p h r i t i s has no specific treatment.B y d i f f u s e a n g i i t i s I refer to collagen diseases such as polyarteritis nodosa, which can at least be made to remit (in certain eases) by the exhibition of steroids.
Finally, o b s t r u c t i o n .In cases of total anuria, obstruction is nearly always the cause, whether from prostatism, stricture, pressure from a tumour, and so on.There should never be any hesitation in carrying out cystoscopy and retro grade pyelography in these cases, and surgery may be life-saving.
Across the bottom I have written i n f e c t i o n , in large letters.In an infection, with accom panying pyrexia, tissue catabolism is greatly increased.T h e excretory load on the kidney is therefore increased, and a kidney which is well able to cope with normal conditions may be unable to excrete this addi tional load.Although output is normal the urine is of low specific gravity.T h u s acute renal failure can exist even when quite large urine volumes are being excreted in an infected patient.Infection should always be remembered both as a primary cause of renal failure and as an exacerbating factor in failure from any other cause.
T hese, then, are some of the pathologies leading to acute destruction of renal tissue and the rapid developm ent of oliguria or anuria.T h e renal destruction can rarely be altered by specific therapy, but in time spontaneous regeneration of the renal tubules frequently takes place.B u t during the anuric interval the well-known picture of acute renal failure appears.T h e absence of renal function leads to a rising blood urea and progressive derangem ent of the internal environm ent.T h is acute renal failure can rapidly kill the patient, but if the failure itself is treated, survival can frequently be prolonged until the new renal tissue becomes functional.
As outlined, the kidney performs four functions, and each is impaired or abolished in renal failure.
T h e e x c r e t i o n o f n i t r o g e n o u s e n d -p r o d u c t s virtually ceases, and therefore the production of these must be cut to a m inim um .Protein is excluded from the diet.Secondly, a high caloric intake is given in the form of carbohydrate.T h is reduces endogenous production of urea to a m inim um , as protein cata bolism to provide energy is rendered unnecessary.T h e calories are supplied as dextrose, lactose or glucose.
T h e so-called anabolic steroids have been used to oppose protein catabolism.T h e initial promising results, however, were obtained in patients with renal

Administration of alkali
failure after post-partum haemorrhage, and the effect may be a specific one on the involuting uterus.It has also been found that while these drugs check the rise in blood urea, other end-products such as creatinine continue to accum ulate and clinical deterioration occurs.T h ere is probably n o place for these drugs in the treatment of renal failure at present.Secondly, w a t e r b a l a n c e .T h e anuric patient cannot excrete excess water, and unless fluid intake is restricted he rapidly becomes water intoxicated.T h e insensible water loss through the lungs and skin totals about 500 m l/day, and water adm inistration must therefore be restricted to 500 ml plus the volum e of fluid lost during the previous day, by vom iting or diarrhoea as well as in the urine.If the patient is fevered, an extra ration must be given to replace the volume lost in the sweat.
Successful control of the state of hydration rests on three measures.Accurate fluid balance charts must be kept.T h e usual slap-dash affair is worse than useless.T h e exact quantity of all fluids given must be accurately recorded, and any loss by vomiting, diarrhoea or as urine carefully measured.T h e correct am ount of water for a uraemic patient can only be prescribed on the basis of the previous day's fluid balance.
Secondly, the patient's state of hydration must be assessed clinically each day.A trace of sacral oedema or a few basal crepitations are warning signs of overhydration.
T hirdly, daily weighings are most helpful in indicating gain or loss of total body water.
T h e amount of water which can be allowed as a vehicle governs the number of calories which can be given.If 50% glucose is used an adequate caloric intake is ensured by any volume over 500 ml.A t first this may be given by mouth or intragastric drip, but when the B .U .N .reaches about 100 mg % the incidence of vom iting makes intravenous adm inistration essential.Venous thrombosis can be very troublesome, and some authorities use only 20% glucose intravenously.T h e passage of a plastic cannula into a large vein, frequent change of vein, and heparinisation of the infusion fluid all minimise this problem.
T hirdly, e l e c t r o l y t e b a l a n c e .T h e normal kidney controls this by excreting an appropriate amount of the dietary intake, which is normally excessive.As this excretion cannot occur in anuric patients, no sodium chloride should be given as a rule.Som e salt is lost in the sweat and scanty urine, however, and if vom iting occurs salt loss may be serious.T h e salt lost in this way should be estimated, and a suitable amount of the water ration given as normal saline to correct this.T h e sodium depletion would otherwise lead to a fall in circulatory volume and further deterioration in renal function would ensue.Nevertheless, very slight overtransfusion with saline easily tips over these patients into pulmonary oedema, and salt replacement should be undertaken w ith caution.
W ith potassium the problem is a different one, for cellular catabolism leads to a steady release of the ion into the blood stream.T h e blood level therefore rises in the course of renal failure, and if there has been much cellular damage, this rise is very rapid.T h is is most marked in crush injuries and haemolysis, where cellular breakdown is extensive.Unlike sodium and chloride, high potassium levels are very dangerous, and ventricular fibrillation due to hvperkalaemia is a common terminal event in uraemia.It is important to prevent a high potassium level, as once this is established it is very difficult to lower.Potassium is rigorously excluded from the diet-fruit juice is quite a potent source.Cellular breakdown with potassium liberation is minimised by the high caloric diet already discussed.Depletion of sodium chloride must be corrected, as any diminution of circulating blood volume would allow liberated potassium to cause a correspondingly greater rise in blood potassium con centration.Fin ally, acidosis must be controlled, as it is thought that some of the excess hydrogen ions in acidotic states enter the cells in exchange for potassium ions, thus again causing a high blood potassium level.
If haemolysis or extensive soft tissue injury has occurred, however, the blood potassium will reach dangerous levels despite these precautions.T w o emergency measures may be life-saving in these circumstances.A 50% glucose drip with 20 units of soluble insulin added to every 100 ml has been found to prom ote the passage of some potassium back into the cells.U nfortunately this requires the concom itant adm inistration of quite large volumes of water, which may be dangerous.T h e alternative is the use of an ion exchange resin such as Resonium A , cither by m outh or as a retention enema.T hese non-absorbable resins are saturated with sodium, and in the gut lose som e of this sodium in exchange for an equivalent am ount of potassium, which thus leaves the body per rectum.30 g. of Resonium A may lower the blood potassium level by 1 m.eq/litre, and can be repeated thrice daily.
T h e final feature of acute renal failure is a c i d o s i s , as the anuric kidney is unable to excrete hydrogen ions, and the damaged tubules cannot m anu facture bicarbonate.I have already m entioned the dangers of potassium intoxication which are intensified by acidosis.T h e bicarbonate level must be m onitored, and if it falls seriously an appropriate am ount of the daily water ration should be given as 1 /6 molar lactate.
T hese measures constitute the basic regime in acute renal failure.T h e general medical care of these patients must maintain a very high standard, and extensive laboratory facilities are required.T h e blood chem istry must be analysed at least once every day.T hese patients rapidly becom e profoundly anaem ic due to toxic depression of the bone marrow, and transfusion of packed cells may be required.T h e most im portant general measure, however, as I mentioned earlier, is the prevention of infection.T h is is im portant firstly because these patients are particularly susceptible, and secondly because if infection occurs the build-up of renal failure is much more rapid.N ursing in isolation is the ideal plan, but where this is not possible strict hygiene and the use of antiseptic creams, etc. can be rigorously enforced.If an infection does arise, antibiotics must be used with the greatest precision.N o antibiotic must be used without the sensitivity of the organism being known.T o make this possible routine daily cultures of blood, urine and sputum , should always be carried out.If this is done, by the time an infection becomes apparent clinic ally, the infecting organism is known and its sensitivity is being determined.T h e circumstances in which an antibiotic must be used " blind " therefore never arise.
Infection is the crucial factor in acute renal failure.If it is prevented, the patient can usually be tided over until urine flow is resumed by the conserv ative measures I have outlined.If infection occurs, renal failure progresses rapidly to a fatal stage despite these measures.Fig. 1 shows the rate of rise of B U N in infected patients com pared with a non-infectcd group.It is in the treatm ent of this infected group that the so-called " artificial kidney " plays a principal part.

THE ARTIFICIAL KIDNEY
In the artificial kidney the patient's blood is led through a coil in which it is separated by a semi-permeable dialysis membrane from a bath containing the plasma electrolytes in their normal concentrations.T h e patient's blood is thus allowed to equilibrate by sim ple diffusion with normal ionic con centrations.Blood urea and potassium levels are rapidly lowered, whilst bicarbonate ion passes from the bath into the blood to restore the alkali reserve.A fter some 4 to 6 hours of circulation through this coil, the blood chem istry will have been radically improved.T h e normal solution in the bath will of course have been altered, and must be changed at least once during dialysis.
C ertain fixed biochem ical criteria have been established as indications for dialysis.T h u s if the blood urea level exceeds 350 mg % dialysis should be undertaken.T h is level is reached in a very few days in severely infected cases.A blood potassium level higher than 7-5 m. eq./litre (usually associated with soft tissue injury or haemolysis) or a bicarbonate level below 14 m.eq./l, calls for im m ediate dialysis.
Apart from these three fixed criteria, dialysis is undertaken if signs of undue clinical deterioration occur, such as mental confusion or the onset of twitching.Dialysis is also undertaken early in severely infected cases when it is obvious from the outset that conservative measures will be inadequate.
T h e only contra-indication to use of the kidney lies in the necessity for anticoagulants.In certain patients this is obviously a risk, but as dialysis is a life-saving procedure this risk must be taken.It must also be adm itted that in using extra-corporcal dialysis we are interfering with physiological m echan isms which are far from being fully understood, and many unexplained sudden deaths occur shortly after the blood chem istry has been rendered apparently normal.T hese deaths occur, however, in patients who were extremely ill before dialysis, and thus they perhaps constitute an argument for using dialysis early rather than for not using it at all.
It should be remembered that the anuric phase of acute tubular necrosis is follow ed by a diuretic phase.During diuresis the patient can becom e dehyd rated, and due to delay in the recovery of tubular reabsorptive powers serious urine loss of sodium, chloride and potassium can occur.Indeed, before treat m ent of renal failure became effective, over 2 5 % of the deaths occurred not in the oliguric phase but during the subsequent diuresis.A plentiful water intake must therefore be ensured.Salt losses can be estimated by m onitoring the serum electrolytes and also by measuring the quantities of the various ions lost in the urine.Supplem ents of these ions m ay be required until normal renal concentrating power is regained.
In acute renal failure specific treatment is rarely able to influence the causative pathology.T h e im portant procedure is to treat the physiological dis location and maintain the patient until spontaneous recovery of renal function takes place.C hronic renal failure however is caused by progressive fibrosis of the kidney, and no regeneration of renal tissue takes place.T h e most important step in chronic failure is therefore to determ ine the underlying cause of the condition and attem pt to arrest the pathological process.
T able 3 shows a few of the more com m on causes of chronic renal failure.T h e order looks haphazard because I have placed the conditions which can be treated with most success at the top of the list.A chronic obstruction to the urinary tract as from prostatism can usually be eradicated.C hronic pyelonephritis is particularly liable to linger on, progressively destroying renal tissue, in the pre-sence of obstruction.Rem oval of the obstruction followed by isolation of the organism and appropriate intensive chem otherapy may arrest this process.Tuberculous infection may also be eradicated.Hydronephrosis will regress after removal of the obstruction.T h e renal lesions in hyperparathyroidism, diabetes, and even amyloid disease may regress with treatm ent of the underlying con dition.C ontrol of the blood pressure will arrest the progressive renal sclerosis which accompanies hypertension.T reatm ent for polyarteritis, D .L .E ., the leukaemias and so on can only delay the inevitable fatal outcome.W h en these potentially treatable conditions have been ruled out, we are left with a hard core of cases due to chronic nephritis and polycystic disease which are not am enable to treatment.O ther treatable factors affect the course of C .R .F .I make no apology for returning once again to infection.A ny systemic infection places an additional strain on the kidneys and intensifies the degree of renal failure.If the infection is eradicated, failure will becom e less marked, and the patient m ay continue tolerably well for a further indefinite period.A ll the causes of acute renal failure are particularly liable to occur in the course of chronic failure, and again if the acute phase is energetically treated the patient may regain rea sonable health.
T H E NEPHROTIC SYNDROME I have grouped certain causes of chronic renal failure separately because they are often associated with the clinical picture known as the nephrotic syndrome.T h e hallmark of this syndrome is massive proteinuria, with marked lowering of the plasma proteins and consequent' gross oedema.It can occur when the kidneys are involved by any of these processes, but conversely any of them may progress to chronic renal failure without ever presenting a nephrotic picture.O ften the proteinuria w ill regress spontaneously, and the oedema clears.W h ilst recovery may be perm anent, most cases present again some years later with chronic failure.Indeed, some cases go on to extensive renal fibrosis with renal failure whilst proteinuria and oedema still persist.
In children the nephrotic syndrome is nearly always due to type II nephritis.T h at is, its onset is insidious, and no underlying cause such as diabetes exists.

Palliative therapy only
T h e histology of the kidney presents a typical appearance.There is now good evidence that steroid therapy is of benefit in these cases.A rneil in G lasgow reviewed his patients at a date two years after the onset of the disease.Previous to the use of steroids only 6 2% of his patients survived this period.Using prednisolone the two year survival rate is 9 1 % .Regression of proteinuria is quicker and more of the patients are symptom-free after two years.T here is some evidence that under steroids the electron-microscopic appearances of the kidney sometimes return com pletely to normal.Although steroids have proved far from com pletely successful their use is thus a real therapeutic advance.

. Administration of alkali
In the adult presenting with the nephrotic syndrome one of the other causative factors, such as diabetic nephropathy is com m only found, and treat m ent is aimed at the basic disease.Even with diagnosis by renal biopsy, how ever, a certain number of so-called idiopathic cases do present, in which no specific abnorm ality is found, and which may be benefited by steroids.

T H E T R E A T M E N T O F C H R O N IC R E N A L F A I L U R E
A s in acute failure, all the functions of the kidney are impaired.T h e ability to concentrate and dilute the urine is lost, and large volumes of urine isotonic with plasma arc excreted.Excretion of urea is impaired and as in acute failure a low protein, high caloric diet is essential.Anorexia is com mon, but the disease may run on for several years and it is essential to insist on a good diet being taken.V itam in supplements are com m only prescribed.
If the tonicity of the urine is constant it follows that the greater the volume of urine passed, the greater the excretion of waste products.A gener ous water intake should therefore be ensured to promote excretion.A n intake of from 2 -3 litres is also required to preserve water balance, since polyuria is a constant feature.
It is a common misapprehension that salt should be restricted in renal failure.There-, is n o indication for salt restriction in the absence of oedema or cardiovascular disease.These patients become salt depelted, both through renal wasting and by vom iting and diarrhoea.Indeed a supplement of 5 G /d ay of sodium chloride should be given.M uch of the malaise associated with chronic renal failure is in fact due to chronic dehydration from salt depletion and failure to replace the large urinary water loss.Som e rare types of chronic failure do lead to potassium wasting.Usually, however, levels tend to be high, and potassium intoxication is a danger.T h e prevention of this is on the lines suggested in discussing acute failure.T h e calcium loss does not usually require treatment.
Lastly, pH balance.T h e mechanism through which the acidosis occurs in chronic failure is a com plex one.T h e end result, however, is a depiction of the alkali reserve, and oral supplements of sodium bicarbonate arc therefore the correct treatment.
T h e regime which I have merely outlined is suited to most cases of chronic renal failure, but the nephrotic group with gross oedema present a different problem .In the presence of massive proteinuria a high protein, high caloric diet is indicated.T here is no call for water restriction, but sodium intake should be restricted to less than 1 gm /day.W h ere the use of steroids is not applicable, long term treatment with chlorothiazide and potassium chloride supplem ent should be instituted and continued for as long as the drug remains effective.
I have already stressed the dangers of infection, and the likelihood of acute episodes disrupting the normal chronic course.A third hazard is cardio vascular disease.T h e great m ajority of these patients develop hypertension, followed by cardiac failure which com plicates the terminal stages of the disease.Anaem ia is quite intractable, and in general the haemoglobin is kept at about 40 % by periodic transfusions of packed cells.Diarrhoea, vom iting, muscular twitching, mental changes and convulsions all require symptomatic treatment in the terminal stages.
Chronic renal failure always progresses to a stage where despite treatment the blood urea is high and rising, the potassium level is dangerously high and the alkali reserve dangerously low.A t this stage the artificial kidney can be used, but its benefits are short-lived.T h e grafting of perm anent plastic cannulae into the forearm vessels is being developed, through which the patient can be periodically " plugged in " to the artificial kidney.One questions, however, whether it is justifiable to prolong a life, which is an increasing burden to the patient, in this way.T h e main function of the kidney in chronic failure is in the treatm ent of acute episodes when the patient still possesses sufficient renal tissue to continue a useful life afterwards.T h e future cure of chronic renal disease may perhaps com e by a break-through in the field of kidney transplantation.
In all the renal diseases, the many pathologies interfere with a single physio logical unit.M y hope has been that the physiology of the kidney would pro vide a unifying backcloth against which it would be profitable to survey the whole range of its diseases.
m e r u l o n e p h r i t i s ...... None D IF F U S E a n g i i t i s .................... Steroids Back pressure o b s t r u c t i o n ....................... Surgery I N F E C T I O N necrosis must be assumed to have taken place, and the prognosis is hopeless.

R
E F E R E N C E S A R N E IL .G. C. (1961)." T h e N e p h ro tic S y n d ro m e : S te ro id T h e ra p y ."S y m p o s iu m : S o m e A sp e c ts o f R e n a l D isease.R oyal C ollege o f P h y s ic ia n s o f E d in b u rg h .M A C D O N A LD .M. K .(1961)." T h e N e p h ro tic S y n d ro m e : E le c tro n M icro sco p y of th e K id n e y ."ibid.R O B SO N .J .S. (1951)." P a tte r n s o f R e n a l In s u ffic ie n c y ."ibid.P L A T T , R. (1952).B rit. M ed, J " 1 , 1312 a n d 1372.R O B SO N .J .S. e t al. (1959) J .ro y .C oll. S u rg .E d in b .. 5, 206.R ELM A N .A. S. (195G).D is e a s e -a -m o n th .A p ril. S C H W A R TZ & P O L A K ( 1960).J .c h ro n .D is.. 11, 319.