This communication is based upon the study of 250 cases of nephritis which have come under the personal treatment or supervision of one of us. (C.E.S.), and upon the pathological investigation of the last 50 of these (A.T.N.). The figures quoted below refer to 160 of those cases whose records are available.
It is proposed to deal with the subject under the headings of Clinical Aspects and Pathology, and to review the various work which has been done upon its etiology.
Seasonal Incidence.- Our own cases reached their maximum in the months of January and February. This is contrary to the observations of other writers and is probably to be explained by an increase in the military population form which this hospital draws its sick; during these months divisional units were “resting” in the neighborhood.
Age Incidence.- The average age of our last 160 patients was 31 years. The disease was commonest in the decade 25 to 35; 8 per cent. of the cases, in which a history of previous disease could be excluded, occurred over the age of 40.
Previous Renal Disease.- A history of this could rarely be obtained. Of 160 cases, 6 certainly and 2 probably has suffered from a previous attack o nephritis. Of these, 2 gave a history of nephritis while on active service, one six months, the other 12 months previously; 4 had had acute nephritis in civil life; 2 gave histories of scarlet fever with delayed convalescence within the preceding five years.
Nature of the Duties on Which the Patients Were Employed – Of our 160 cases 10 per cent. had never been in the front line; while the remainder had all served at the front, in many cases such services had been discontinued for a period of weeks or months before the onset of nephritis. Three of our 250 cases occurred in officers. The average stay in France of our last 80 cases was 72 months; 5 cases occurred before the fourth month.
Associated Conditions.- Some degree of bronchitis was a constant feature; it was often a serious complication, in tow of the fatal cases was responsible for death. Septic infection of the skin in the form of impetigo or a superficial wound was present in 12 of our cases. Trench – foot was present in two cases. Quinsy preceded the onset of nephritis by five days in one case. (Contrast Citron.6)
Type of Case.- There are all varieties in the severity of the disease, ranging from the slight attack with little or no oedema to the typical and fatal case. It seems possible that slight atypical or abortive cases, who suffer from an undiagnosed, malaise, may recover without admission to hospital.
Mode of Onset.- The appearance of the more striking symptoms is so impressive that it is only occasionally that the patient volunteers the statement that he had been indisposed for any time before he was compelled to “go sick.” Careful inquiry will, however, in large majority of instances, elicit the information that there has been some departure from the normal health for two or three days before the onset of the acute symptoms. Such slight prodromal symptoms include headache, backache, “a cold,” and a feeling of fatigue after slight exertion; some degree of bronchial catarrh is practically constant at this stage.
Alimentary symptoms are rarely mentioned, and it is unusual for complaint to be made of any alteration of urine or micturition during the prodromal period, but some patients speak of “scalding” as having occurred from the very commencement of the illness. The following symptoms and signs are found in every typical case: oedema, dyspnoea, headache. Very common, but not invariable, are backache, limp – pains, slight pyrexia, and scanty micturition. Probably if these patients came under observation at the earliest stage of the disease these symptoms would be more often evidence.
OEdema.- This always affects the face; it may be confined to this situation or involve the whole body. The positions in which it is found are, in order of frequency, face, feet, hands, lumbar region, scrotum, and abdominal wall. Ascites and pleural effusions are uncommon except in those patients in whom the disease tends to run a prolonged course. The duration of the oedema is very variable – usually it disappears rapidly; if the case if not seen during the first three or four days it may already be entirely absent; we have seen it disappear completely within 36 hours of the onset. Associated with the oedema an almost characteristic flush of the skin is often seen; it is not a cyanosis, but a red flush resembling early sunburn. In our experience this appearance has been most noticeable in patients suffering from capillary bronchitis.
Dyspnoea.- Some degree of respiratory distress is constant. Most of the patients describe the onset as quite sudden; the man may parade in full marching order without discomfort, and fall our a few minutes later, quite unable to march after the column has gone a few hundred yards. Many of the men, however, when closely questioned, state that they have noticed gradually increasing shortness of breath for two or three days before the occurrence of the dramatic attack. In a large proportion of cases this shortness of breath, slight and gradual or sudden and severe, may precede the appearance of facial oedema by several days.
When at rest the condition is one of hurried respiration rather than a true dyspnoea; it lasts for several days and may persist after the disappearance of oedema. Cheyne – Stokes respiration is not seen except in conditions of severe uraemia. Urgent respiratory distress while the patient is at rest may occur if the disease is complicated by severe bronchitis or as a manifestation of uraemia. Two of our seven deaths were due to sudden uraemic dyspnoea.
Headache.- All our patients suffered from dull headache, most commonly frontal, often occipital, rarely vertical. This is one of the earliest symptoms and is often of long duration. An increase in its severity has been noted as a herald of uraemia. We were unable to demonstrate a definite relationship between the degree of the headache and systolic blood pressure. Its disappearance is accompanied by a sense of well – being which cannot, in our opinion, be entirely due to the relief from a moderate though persistent pain.
Cough.- All our patients suffered to some extent from cough, often accompanied by a considerable of expectoration, the sputum being usually frothy and liquid, except in those cases which were complicated by purulent bronchitis.
Backache.- This is practically constant; rarely severe, it persists for several days. It is localized to the loin, and does not radiate; it is variously described as a dull ache, a weight or a load on the loins.
Abdominal pain is occasionally complained of; in our experience chiefly in those patients who suffer from uraemic symptoms. It is transient and variable in intensity and position.
Limb – pains.- These are common but transient. Nothing approaching in severity or persistence the “shin – pains” of trench fever has been met with. This point is of some clinical importance, for in many cases of trench fever albuminuria occurs during the first few days. The limb – pains of nephritis are present only in the early stage of the disease; they disappear with the return of the temperature to normal.
Urine.- In the first days oliguria of suppression is the rule this is usually of a few days duration only, and is frequently followed by polyuria which persists after all obvious oedema has disappeared. Frequency and scalding are not uncommon during the first few days. Incontinence of urine in non – comatose patients occurred in two cases in our series. This symptoms has been noted by a German observer. In 250 cases true dysuria with hypogastric and penile pain was present; these may have been “lower tract” affections as described by Abercrombie.8 They recovered without special medication.
Albuminuria is constant at first but may be remarkably transient; it has a tendency to vary from day to day irrespective of diet changes. No information as to its ultimate persistence is given by the cases of our series, for they were too short a time under observation.
Hematuria – Naked eye examination reveals the presence of blood in rather less than half the cases. Its amount is even more variable than the albumin, but it may be most persistent. The microscopical characters of the urine are described under the heading of “Pathology.”
Temperature.- Moderate pyrexia for a few days is the rule; its duration is brief and relapse uncommon. In the presence of associated disease, such as sepsis or severe bronchitis, the pyrexia is more definite and sustained; but with these exceptions war nephritis may, after the few days at the onset, be regarded as an afebrile disease.
Pulse.- The pulse – rate is little altered. It may rise to 90 or 100 and remain at this figure of a week or 10 days, but persistent tachycardia has been a very rare symptom. In two cases it occurred without any other apparent cause.
Blood – Pressure.- The haemodynamometer was not used in all cases, and experience has convinced us of the fallacy of relying upon digital impressions in estimating blood pressure. The highest record obtained was 210 mm.: this was met with in a uraemic case, in the presence of which complication readings of 150-180 were not uncommon. In mild and quiescent cases no striking rise of blood pressure was met with.
Eye Changes.- Captain R.Graham Brown, R.A.M.C., kindly reported upon 35 consecutive cases. The fundus was normal in 29, while in 6 sight blurring of a portion of the disc margin or papilloedema was present. All these patients had facial oedema. The retinal change and the facial oedema appeared to clear up at the same time. No case was under observation at a sufficiently late stage for chronic changes to be manifest. Transient blindness occurred in 2 cases as one of several uraemic symptoms. Difficulty in reading was complained of by a few patients early in disease, and some of these had slight blurring of the disc; but it is doubtful whether this disability could not be explained by general causes.
Complications.- Only two serious complications were met with – bronchitis and uraemia. The importance of the former is very great, and its presence has a very adverse influence upon prognosis.
Uraemia is seen in about 8 per cent. of the cases. Its onset is usually early in the disease; it may afford the first manifestation. In only 2 cases of our 160 did it occur after the tenth day. The common manifestations of uraemia are torpor, severe headache, nausea, vomiting (always to be regarded as a danger – signal), and convulsions. Uraemic convulsions in this disease present several interesting features.
They come on with very little warning, they are very violent, they usually occur quite early in the course of the illness, and, paradoxical as it may seem, are to be regarded on clinical experience as of good prognosis provided they are not fatal within the first few hours. Our experience has been that those patients who have had severe uraemic convulsions calling for active measures and causing considerable alarm have, after a few days of semi – coma, passed on rapidly towards almost complete recovery; their albuminuria has ceased, the flow of urine has been re – established, and there has been a speedy return of a sense of well – being. Chronic uraemia, giving rise to a prolonged state of cheerful busy delirium bordering on mania, occurred in two cases who ultimately returned to apparently normal mental health. TREATMENT.
Treatment has been mainly expectant or aimed at the removal of complications as they arose. Diuretics were rarely used and seemed of no value. Diaphoretics were employed in a few cases, but it is doubtful whether they had any influence on the course of the disease. It is remarkable how these patients sweat without drug treatment. It is the exception to find the skin dry after the first few days. How packs were rarely used; they seemed of doubtful benefit and, by adding to risk of chill, a real danger.
Fluids were not restricted, but the patients were not encouraged to drink more than they desired. No attempt to wash out nitrogenous material by flushing the system was made. A reason for avoiding copious drinks is the effect which the intake of large quantities of fluid has upon the blood pressure. Purgation was used, but was never drastic. Calomel gr. iii. at night followed by a saline purge in the morning was the routine. Occasionally an enema was employed at the commencement of the treatment.
All cases were kept for three days at least on a rigid milk diet. Three pints per diem were allowed. After this time if the albumin showed signs of diminishing, if blood was no longer visible to the naked eye in the urine, if the quantity of urine was normal, if the blood pressure was not raise, an if headache was not troublesome, an increase in the diet was allowed – toast, biscuits, a flavoring of tea in the milk, rice – milk (a fluid form of rice pudding made without eggs). In no case did the patients condition for a return to strict milk diet.
While uraemic danger – signs were present the strict milk diet was enforced. The treatment of uraemia followed the usual lines – venesection, intravenous infusion of saline, and lumbar puncture. The last operation is of the greatest benefit; it is necessary to perform it under chloroform anaesthesia on account of the uncontrolled movement of the patient; the removal of six or seven drachms of fluid is followed by a striking improvement. The fluid is usually under slightly increased pressure, but it is possible that this is due to the anaesthesia.
Opium in the form of morphia or omnopon was given freely and with benefit in uraemic cases; its diaphoretic effect was very noticeable. In the chronic form of excitement bromide, even in large doses, had little or no effect; opium had to be substituted.
Our observation of these cases has been too short to allow any opinion as to their ultimate prognosis to be formed, but certain points bearing on their immediate prognosis have been noted. The coexistence of a severe degree of bronchitis is of bad omen; four cases died and the partial recovery of others was delayed greatly. The coexistence of sepsis did not seem to have any adverse influence. The presence of uraemic symptoms varied in significance. The cases that showed great sleepiness during the first few days did as well as those who did not show this sign.
Uraemic convulsions, as has already been noted, if not immediately fatal, were shown by experience of several cases of be of good prognosis. Persisting mental changes, which may be regarded as uraemic in origin, however, were associated with persistence of albuminuria and haematuria long after the normal date for their disappearance. The blood pressure in the early stages gave little guidance. Some patients with a systolic pressure of 180 mm. Hg. made as rapid a recovery as those in whom the pressure was not raised. As a herald of approaching uraemia sustained high blood pressure may be regarded as of importance.
Pressure – readings during or immediately after a convulsion are probably of little value, as they must be influenced by the muscular exertion involved in the seizure. As no patient was allowed to get up before his evacuation from his hospital no information is available as to the possible return of albuminuria in non – albuminous cases after apparent recovery and on the resumption of the erect posture. Temporary increase of the albumin occurs commonly in cases still confined to bed without change in general symptoms and appears to be independent of changes in the diet.
The urine from 50 cases of war nephritis have been examined since February of this year. Concurrently with these, 44 urines, both from normal individuals and from men who were patients in hospital, have been examined as a control.
All cases of war nephritis showed casts in the urine. The casts were hyaline, granular, fatty and blood, the first two being the most common. As would be expected, the more definite the clinical symptoms the larger was the number of casts. Again, all cases of war nephritis showed the presence of many degenerate endothelial cells in pronounced distinction to urines obtained from men suffering with other illnesses where endothelial cells were few or absent. The presence of casts and of endothelial cells is, in our opinion, sufficient microscopical evidence on which to diagnose this form of nephritis. The endothelial cells are of all shapes and sizes, but are most commonly spherical, varying from about 10M. to 35 or 40M.
They show vacuoles, one or more nuclei, and are invariably granular in appearance. They are in all stages of degeneration. Occasionally one has been seen to bud, and it is common to find one bursting open and the intracellular protoplasm being distributed into the surrounding fluid. It seems to us that these cells may be similar to the “amoeba urinate granulata,” described by other writers.12 They have never shown any true amoeboid movement, however, and are exactly similar in appearance to endothelial cells from pleural effusions or to those found in the faeces in chronic cases of dysentery.
They stain well in moist preparations, especially if the urine sediment has previously been washed in distilled water. As has been said, their presence in the urine of cases of war nephritis is invariable, nor are they found in any number in other conditions. We had two cases, however, of injury in the loin, where although the kidney was not damaged microscopically endothelial cells were found in the urine. These were, no doubt, due to the fact that the kidney substance was disturbed by the force of the original wound shock or by toxin absorption from the wound. This was confirmed by microscopical examination in one case.
In mild cases of war nephritis a few only of such degenerate cells will be found in the centrifugalized deposit of the urine. In a serious case many may be found in each field of the microscope (objective 6 X eye – piece). One of our cases who at first showed no definite clinical signs gave no endothelial cells in the urine, but as his symptoms of nephritis developed the endothelial cells appeared. These bodies persist in the urine after the patient is apparently well – even when the urine shows no casts; and perhaps they may be of value not only in the diagnosis of a doubtful case, but also in determining whether a man has had war nephritis in the past. How long they persist we are at present unable to say.
Thirty – six out of these 50 cases showed red blood corpuscles in the urine. The amount of blood did not appear to indicate the severity of the attack. One of our most serious cases had very little; other clinically mild cases showed much blood. The determination of the presence of red blood corpuscles was made microscopically on the centrifugalized deposit of a fresh specimen.
Twenty – two men had albumin in the urine, and the urines of the remainder – 28 – failed to give the nitric acid or boiling test for albumin.
A few red blood cells, a few casts and endothelial cells in a low specific gravity urine would hardly be sufficient to give a definite and appreciable chemical test, and here we would like to urge the importance of examining microscopically the centrifugalized deposit of urine, since in the absence of this definite examination it would be possible to miss many slight atypical or convalescent cases. Renal tubule cells and cells from the renal pelvis, in all stages in degeneration, were found in 9 cases out of the 50. Leucocytes, more in number than could be accounted for by the blood in the urine, were present in 3 cases.
Of the series of negative cases taken concurrently with those of war nephritis, none showed either casts, or more than a very few endothelial cells. Five had albuminuria; I, who was possibly suffering from a renal calculus, showed renal pelvis, cells; 5 had blood in the urine; 4 showed excess oxalates, and 7 had leucocytes. Of these 44 cases 7 had definite inflammation of the urinary tract, without, however, the endothelial cells found in the nephritis cases.
No cultural results were obtained aerobically or anaerobically – either from the urines or from two cases whose venous blood was examined.
Blood films were made and differentially counted in 15 cases with the following results: Small mononuclears ranged from 16 to 30 per cent., with an average of 22.2 per cent,; large mononuclears from 8 to 18 per cent., with an average of 13.3 per cent.; finely granular polymorphonuclear leucocytes ranged from 47 to 69 per cent., with an average of 62.1 per cent.; and eosinophiles were from 1 to 5 per cent., with an average of 2.4 per cent. “Mast” cells were not counted differentially, but were present frequently.
No myelocytes changed was noted in the red cells and no parasites were observed. The blood counts individually were typical of the so – called protozoal blood count with large mononuclear increase, and in addition to this most of the cases showed a slight eosinophile increase. Citron6 in his cases records an eosinophilia up to 10 per cent.