BRIGHT'S DISEASE OF MALARIAL ORIGIN. 
I. E. ATKINSON, M. D.. 
PKOFESSOR OF PATHOLOGY IN THE UNIVERSITY OF MARYLAND. 
FROM 
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES. 
July, 1884. Extracted from the 
American Journal of the Medical Sciences for July, 1884. 
BRIGHT'S DISEASE OF MALARIAL ORIGIN.1 
Professor of Pathology in the University of Maryland. 
By I. E. ATKINSON, M.D., 
The liver and spleen are the only viscera upon which paludal intoxica- 
tion can be said to exert a constant and specific influence. The patho- 
logical changes induced by it in other organs are, for the most part, 
inconstant, and have received but comparatively little consideration from 
medical writers; and yet in the kidneys the alterations almost attain 
the characters of specificity in those results of malarial fever more com- 
monly encountered in warm climates, and more especially in our own 
Southern States, and which have received of late considerable notice from 
intelligent observers. I refer to those paludic fevers in which hiematuria 
and haemoglobinuria, with the, probably, invariable accompaniment of 
albuminuria, constitute a characteristic feature of the attack. The unmis- 
takable evidences of renal derangement in this form of the disorder-of 
which, however, it is not designed to speak in this paper-would lead, 
a priori, to the conclusion that renal alterations of more permanent 
character may, likewise, occasionally depend upon the same influence, 
when brought to bear upon the kidneys under different circumstances and 
in diminished intensity, though with frequent recurrence. Indeed, nearly 
all systematic writers upon Bright's disease agree in attributing a certain 
influence in its production to malarial disorders, though they are usually 
content to dismiss the subject with a very few words. That renal de- 
rangements, thus arising, should frequently escape attention may be 
explained, to some extent, by the fact that they are often confounded with 
the dropsies so very frequently resulting from malarial fever, commonly 
entirely independent of renal disorder, and due to causes that must pro- 
bably be sought for as direct results of the malarial poison upon the blood 
and vascular system. 
The first mention of albuminuria occurring in the course or as a result 
of malarial fever, is said to have been by Blackball, who described it as 
1 Read before the Clinical Society of Maryland, May 15,1884. 
1 2 
occurring after intermittent, in 1818 (Calmette, Recueil de memoires de 
medecine et de chirurgie milit., 36, 1880). In 1845, Clienouard {Rec. 
des trav. de la Soc. Med. du depart, d'Indre-et-Loire, 1845, p. 101) 
expressed the opinion that intermittent fever, so frequent in the depart- 
ment, was one of the principal causes of nephritis and albuminuria. Cases 
were also described by Neret in 1847 {Arch. Gen. de Med., xv. 509); and 
Martin Solon (Gaz. Med., 1848, p. 618) declared that albuminuria was to 
be detected in one-fourth of all intermittent fever cases. In his inaugural 
dissertation, Lenz also claimed that intermittent fever was a very frequent 
cause of diffuse nephritis {De diffusa nephritide chronica, prcecipue 
respecto decursu morbi post inter mittentem febrim, 1865, Gryphiae). 
Rosenstein {Pathologie u. Therap. der Nierenkr., Berlin, 1870, p. 215, 
and Virchow's Arch., B. 14, 110) saw in Dantzic, on the Baltic Sea, 23 
per cent, of renal disease, definitely attributable to preceding malaria. 
Bartels (German Clinical Lectures, N. Syd. Soc. Trans., vol. Ixvi.), 
while admitting that he had not been able to trace the granular contract- 
ing kidney to malaria, says, " chronic inflammatory enlargement of the 
kidney may, in isolated cases, originate from acute nephritis following a 
severe chill or scarlet fever. But, in my experience, malaria is the most 
frequent amongst the well-established causes of this disease." Hertz 
{Ziemssen's Cyclop., vol. ii. p. 641) asserts that "it is no very uncommon 
thing to find albumen present in considerable quantities. This may cor- 
respond with the hyperaemia of pernicious and remittent fevers, and is 
then usually accompanied with an abundant admixture of blood ; but it 
appears that even simple malarial fevers may show a highly albuminous 
condition of the urine, and even renal hemorrhage during their course. 
. . . . Albumen is to be found in the urine, either only on the fever 
days, or during the intermission as well, .... and disappears on re- 
covery. Still, cases do occur which pass into a chronic diffuse nephritis." 
An evidence of the occasionally great frequency of renal affections is also 
afforded by the observations of Soldatow, who detected derangements 
of the kidney at 350 necropsies of soldiers of the Russian army dead 
of malaria in East Roumelia, during the summer of 1878 {Petersburg, 
med. Wochenschr., 1878, No. 42). Cases have also been recorded by 
Devalechi {Arch. Beiges de Med. Mil., xxiii. 20), Verhaige {ibid., xxvi. 
31), Schmid {Deutsche Klinik, iv. 442), and others on the continent of 
Europe. 
As might be expected, English authors, doubtless, on account of the 
the rarity of malarial diseases in England, have but little to say upon 
this subject. Roberts has not met with any case of renal disorder occur- 
ring as a sequela of ague ; but Dickinson felt compelled to admit that he 
had seen more than one instance of persons who had returned from India 
with persistent albuminuria, and symptoms of the granular kidney, after 
having, while there, severely suffered from malarious fever. McLean, 3 
likewise {Reynolds's System, i. 613), speaking of intermittent fever, says, 
"Albumen is found in an uncertain number of cases during the fit, with 
blood and renal cylinders. I can confirm, from personal observation, Dr. 
Parke's remark, that chronic Bright's disease is a consequence of ague. 
Many 'old Indians,' who have suffered from malarial fevers, die of this 
disease." Other English authors refer to the conditions under discussion. 
In America, renal disease as a result of malaria has attracted the atten- 
tion of a number of writers. Woodward, in his Camp Diseases (1863, 
p. 185), says of the results of chronic malarial poisoning: " Disorder of the 
kidneys frequently complicates the condition under consideration. Scanty, 
more or less albuminous urine is often observed, and those cases which 
occasionally perish with the symptoms of acute uraemic toxaemia, not un- 
frequently terminate in chronic Bright's disease, with confirmed albu- 
minuria, oedema, or general anasarca, and the whole train of symptoms of 
that disorder." Busey (Am. Jour. Med. Sci., Jan. 1873, and Transact. 
Amer. Med. Assoc., 1880) records a number of cases of renal disease in 
children, the origin of which he attributed to malaria. Da Costa (N. Y. 
Med. Rec. 17, p. 54) declares that he has "seen a large number of cases 
of Bright's disease following malaria." Observations upon renal altera- 
tions due to malaria, with cases, have also been recorded by Loving 
(Columbus Med. Jour., i. 1883, 289), Berkley (Maryland Med. Jour., x. 
1883, 227), Pepper (Am. Jour. Med. Sci. 1866, li. 405 and 408), Clemens 
(Louisville Med. News, 1880, x. 145), and others. The subject has also 
received consideration from Santiago (Gaz. Med. di Lima, 1866-67, xi. 
42), and in the Tokei Med. Journal, March 27, 1880, from Koike, the 
contents of whose articles I have been unable to avail myself of. 
There are not wanting, however, those who do not admit malaria as a 
cause of Bright's disease, or at least concede that only very rarely does 
it exert such an influence. Among these are Colin (Traite desfievres 
intermittentes), Jaccoud (Pathologic interne'), and Rendu (These d'aggre- 
gation, 1878)-(Calmette). Rosenstein quotes Becquerel as saying: 
" I have had opportunity, in an especially damp and swampy region, to 
observe, every autumn, patients, of whom some had dropsy, but never one 
of them Bright's disease." He also quotes Frerichs, as follows, viz.: 
" Among a large number of dropsies after intermittent, which I observed 
along the North Sea coast, there was not a single case in which the kid- 
neys were diseased." Hirsch (Historisch. Geogr. Pathologie, ii. 342) 
also denies that Bright's disease from malaria occurs with more than the. 
greatest infrequency; and Bamberger (Samml. klin. Vortrdge, No. 
173, Leipzig), in a summary of 2430 necropsies of patients dead of 
Bright's disease, was able to associate paludal toxaemia with but 13, or 
0.5 per cent, of the whole number. He admitted, however, that in his 
locality malaria played but a most insignificant role. This want of agree- 
ment is to be explained, not to the discredit of any of these observers, 4 
but by the fact that the renal complications of malarial intoxication de- 
pend upon varying and not understood conditions of climate, soil, tempe- 
rature, etc. Indeed, they have been known to prevail most unequally in 
different epidemics in one locality. For example, Rosenstein, who saw 
in Dantzic 23 per cent, of all cases of Bright's disease definitely attributable 
to malaria, encountered in Northern Holland, in Groningen, "a fever 
province, much malaria indeed, but only seldom nephritis in 
consequence. And Heidenhain, who observed in Marienwerder a series 
of epidemics of intermittent fever in which neither dropsy nor renal affec- 
tion developed, encountered, in a last epidemic, hardly a case without 
secondary nephritis. 
From the foregoing synopsis of the experiences and opinions of writers, 
it becomes evident that malarial poisoning implicates the kidneys in no 
fixed and definite proportion of cases, and that when a morbific influence 
is exerted upon these organs it cannot be as a result of any characteristic 
and peculiar process. The fact remains, however, that in an indetermi- 
nate number of cases renal disorder will be excited, varying from the 
sudden and intense congestions with hrematuria or haemoglobinuria and 
albuminuria, of pernicious and certain other severe forms of malarial fever, 
to renal inflammations of unequal intensity, resulting in exudations and 
deep structural alteration. It is to the latter form of alterations, those 
associated with extensive structural disorders of the kidneys, that the 
present remarks are devoted. It is to such pathological processes that 
the term malarial Bright's disease may, with propriety, be applied. 
Believing that the subject has not attracted, in this country at least, 
the attention it deserves, I have been led to study with reference to it all 
cases of malarial fever coming under my observation during the late sum- 
mer and early fall of the past two years (1882 and 1883) at Bay view' 
Asylum, the Baltimore Almshouse. The first series of cases numbered 
76, and was recorded in 1882. This series served Dr. Hiram Woods 
and myself a basis for testing the asserted merits of iodine as an anti- 
periodic remedy (see Amer. Jour. Med. Sei., July, 1883) ; and, inasmuch 
as the iodine may possibly have exerted some influence in the production 
of renal disorder, I do not present this series as giving unobjectionable 
evidence in the direction of the present research. In the light of the re- 
sults of the second series of observations, I am inclined to attribute little 
or no influence to this agent in the production of the albuminuria. At 
all events, I give the results of the observations for what they are worth. 
Of the 76 cases of intermittent and remittent fever, albuminuria was 
noted but five times. One case was that of a woman who had suffered 
from irregular attacks of ague for more than two years, and who also 
had chronic Bright's disease. We were unable, however, to discover a 
causative relation between the two disorders. In one case of remittent 
fever albuminuria was present upon a single occasion during the twelve 
days of observation. Another case of quotidian ague developed album i- 5 
nuria after a week's sojourn in the hospital. This symptom disappeared 
after four days, under the administration of sulphate of cinchonidia. 
Albuminuria appeared in another case of quotidian ague after the fifth 
day of treatment. Cinchonidia promptly relieved the chills and the 
renal symptoms, neither occurring during the eighteen days of his rest in 
hospital. These cases, except the first, were evidently dependent upon 
transitory circulatory disturbances. A single case of this series presented 
symptoms that indicated profound renal alterations apparently the direct 
result of malarial toxaemia. An abstract of the notes, taken by Dr. Hiram 
Woods at the bedside, gives the following history :- 
Case IHarris, an Englishman, 26 years old, ostensibly a labourer, 
but manifestly a tramp, was admitted September 21st, with a history of 
tertian malarial fever for eight days. He had the aspect of one who had 
endured many hardships. On the afternoon of the 22d he had a chill. 
His urine, examined after the paroxysm, was acid, of specific gravity 
1012, and without albumen. He was ordered to take thirty drops of 
tincture of iodine four times daily. He missed the expected chill on the 
24th, but had one on the 25th, at midday. He had no chill from this 
time. On the 28th his dose of iodine was reduced to ten drops, and on 
the 29th was discontinued. He felt very badly, however, but had no 
elevation of temperature. Swelling of the ankles and some ascites now 
developed. An examination of his urine gave specific gravity 1008 ; no 
albumen. Two days later there was marked ascites, general anasarca; 
and on October 3d his urine contained a large amount of albumen with 
hyaline, finely and coarsely granular tube-casts. His temperature, how- 
ever, did not exceed 99° F. He was pale and puffy, his pulse was weak 
and frequent, bowels constipated, tongue pale and coated. There was 
much dyspnoea from pulmonary oedema, and decided abdominal discomfort. 
The urine was much reduced in amount, though the exact quantity was 
not ascertained. Infusion of digitalis in half-fluidounce doses thrice 
daily, with drachm doses of compound jalap powder once daily, were now 
ordered. On the 6th the amount of urine passed during the twenty-four 
hours was two quarts. On the 9th the patient passed four pints of urine. 
Nevertheless, his condition became alarming, dyspnoea being very urgent. 
On the 10th he passed seven pints of urine of specific gravity 1012, albu- 
minous, and showing abundant tube-casts. The temperature did not 
exceed the normal during these days, but on the 13th the morning tem- 
perature was 99.2° F. The strength was now much reduced; and, 
notwithstanding the free micturition, the dropsy increased. Abdominal 
pain became very distressful. For the relief of this, one-sixth gr. of sul- 
phate of morphia was injected hypodermically. The morning tempera- 
ture of the 14th was 100° F.; pulse, 80. Evening temperature, 100° F.; 
pulse 88. Upon this date the urine was free from albumen. 15Z/z. Morn- 
ing temperature, 98.8° F.; pulse, 100; urine passed during twenty-four 
hours, three pints. Oct. 20. The urine w'as again highly albuminous. 
The albumen nowr rapidly disappeared, and at the examination of 26th 
not a trace of it was found. It did not reappear, though the patient re- 
mained under observation for several months. There was no return of 
fever, and the dropsy slowdy disappeared, though the face remained pallid 
and swollen. Tincture of the chloride of iron, with dilute acetic acid and 
spiritus mindereri, was the only remedy employed during convalescence. 6 
The cases observed during the late summer and fall of the past year 
(1883) enabled me to observe more exactly the effects of malaria upon 
the kidneys, since attention was more especially turned toward these 
points, and since there could be no question of the ingestion of remedies 
that might possibly irritate the urinary organs. The cases were placed 
upon appropriate anti-periodic treatment (the sulphate of quinine or of 
cinchonidia) as soon as the diagnosis was determined and cured with all 
possible dispatch. They numbered 45, and suffered principally from inter- 
mittent fever, though some examples of remittent fever were observed. 
For the most part, they were Germans, employed about the canning 
establishments of Harford County, where, although sufficiently fed, their 
ignorance of hygienic laws exposed them to the violently malarious influ- 
ences of the localities in which they worked. As a test for albumen, 
picric acid was first adopted, but it soon became evident that the quinine 
taken by the patients vitiated the test (see article on " The value of 
picric acid as a test for albumen, by Drs. Cook and Watkins, Medical 
News, Oct. 27, 1883), and the ordinary heat and nitric acid or the float- 
ing nitric acid test, after Heller's method, was employed as certainly 
reliable and very handy. 
Of 45 cases of malarial fever, carefully examined with respect to their 
renal organs, six presented evidences of albuminuria during their attack. 
Three of these were affected to a slight and transitory extent. One, a 
German, 52 years of age, had had daily chills for twelve days. . Upon 
admission a faint precipitate of albumen was detected in his urine. Albu- 
minuria to very slight extent was also present two days later and hyaline 
tube-casts were observed. There was no anasarca and after the cessation 
of the chills the albuminuria disappeared. The second case wras also of a 
German, 41 years old, who had had quotidian ague for ten days. His 
chills were promptly relieved by cinchonidia sulphate, but his urine ex- 
amined on the third day after admission was faintly albuminous, acid, and 
of specific gravity, 1017. No tube-casts could be found upon microscopic 
examination. There was some headache with nausea and vomiting, but 
no dropsy. Five days later there was still a very faint amount of albu- 
minuria, but without cedema. The patient now eft the hospital, but was 
evidently improving, w'ith every promise of ultimate perfect recovery. 
The third of these cases was of an Irishman 58 years old, wrho had had quo- 
tidian ague for two weeks. Upon admission his urine was acid, sp. gr. 
1022, and contained a decided amount of albumen. The ague was imme- 
diately stopped by sulphate of cinchonidia and the albuminuria ceased at 
the same time. The urine, though carefully examined several times pre- 
vious to his discharge, remained normal. The remaining three cases had 
well-marked nephritis w'hich evidently depended upon malarial toxaemia. 
Case 2Hochstadt, German, 29 years old, was admitted September 
14th. He had been w orking in a canning house at Aberdeen, in Harford 7 
County, and was quite well until the beginning of his present attack, thir 
teen days previously. Since then he had had quotidian intermittent 
fever. When admitted he was in the midst of a paroxysm. He was an- 
asarcous and profoundly anaemic. His urine was acid, of sp. gr. 1012, 
and loaded with albumen. The anasarca had first been noticed one week 
previously, and had involved both upper and lower extremities. There 
was, however, no ascites. His tongue was pale, tremulous, and slightly 
furred. Subcrepitant rales could be heard over both lungs posteriorly, 
with diminished resonance and vocal fremitus. Slight left pleural effusion 
was diagnosticated. His pulse was 108; his temperature was normal. 
He was ordered to take ten grains of sulphate of cinchonidia thrice daily. 
This treatment was continued without return of ague. On the 18th his 
urine was acid, 1013 sp. gr., and contained considerable albumen. Micro- 
scopically, amorphous urates, and epithelial, and finely and coarsely granular 
tube-casts were detected. He was now much better, and left the hospital, 
though dropsy and albuminuria were still present. He was readmitted 
Sept. 27th, complaining of diarrhoea. Anasarca was still present, though 
to a greatly diminished extent. The temperature remained normal. His 
urine, examined October 4th, was without albumen. On the 5th, how- 
ever, the albumen tests gave a faint reaction. On the 11th decided im- 
provement was noted, though some oedema still remained. A very faint 
cloud was shown by the nitric acid floating test (Heller's method). 
Microscopic examination revealed a few hyaline tube-casts. He again 
left the hospital, much better though not entirely free from evidences of 
renal disorder. 
Case 3.-Sheridan, Irish labourer, 30 years old, was admitted Septem- 
ber 26th. He had been ill four weeks. His attack began with " dumb- 
ague," then for two weeks he had had quotidian intermittent. Lately his 
fever had taken on the remittent type. Previous to the present attack, 
he reported his health to have been excellent, and that he had performed 
ordinary farm labouring work. Two days before admission he had noticed 
swelling of his feet. Upon admission he was found to be a stout, well-built 
man, but very pallid and slightly dropsical. His tongue was slightly furred. 
His urine was acid, of sp. gr. 1012. It gave no precipitate with heat or 
nitric acid, but a faint cloud appeared with the picric acid test. (He in- 
formed me that he had taken some quinine on the 21st, four days previ- 
ously ; so that the true significance of this reaction remained undecided). 
No microscopic examination of the urine was made at this time. He had 
an aortic direct murmur of some intensity. Full doses of cinchonidia 
sulphate were now prescribed with the result that his fever was suspended 
on the fourth day. The anasarca increased, however, and slight ascites 
appeared, but albuminuria appeared first October 2d, when a decided 
amount was observed. On the 3d, the entire amount of urine passed was 
three pints. It was acid, of sp. gr. 1010, and highly albuminous. Tube- 
casts, finely and coarsely granular, hyaline and epithelial, were present in 
great numbers. Dyspnoea had now appeared and was marked. Slight 
double pleural effusion had developed. He was now ordered to take in- 
fusion of digitalis in half-ounce doses in addition to a ferruginous tonic 
thrice daily in lieu of all other treatment. On the 10th he had a new 
access of ague of rather intense character. Sulphate of quinia, 15 grains, 
daily was added to his other remedies. After this there was no renewal 
of his febrile attacks. The albuminuria persisted, however, slowly dimin- 
ishing with the improvement of the patient's general condition, though 8 
when he was last seen there was still some anasarca and albuminuria. 
The aortic direct murmur also persisted. 
Case 4-Lock, 56 years old, born in London, widower, was admitted 
October 16, 1883, for an irregular and obstinately recurring intermittent 
fever associated with pronounced renal disease. I was fortunate in being 
already acquainted with the antecedents of this patient, having had him 
under my care shortly after the beginning of his illness, at the University 
Hospital, Baltimore (in April, 1882). The patient was of small and 
delicate physique and by occupation a baker. In the fall of 1881, he 
had been seized, for the first time, with intermittent fever at his home in 
Harford County. This was at first quotidian, became tertian, and finally 
irregular, and although large quantities of quinine were given, relief could 
only be secured for brief periods. Having been a perfectly healthy man, 
he now began to decline in general health, and after several months he 
noticed that his body had swollen. Gradually he became incapacitated 
for work, and finally was admitted to the hospital, where he came under 
my care. He was at this time very anasarcous, and had much peritoneal 
dropsy and was extremely debilitated. He had albuminuria. Under the 
administration of quinine and ferruginous diuretics his health slowly im- 
proved until his dropsy disappeared ; and he ultimately became able to work 
about the wards. His chills persisted irregularly, and his albuminuria 
remained constantly, with greater or less intensity. After several months 
he felt well enough to go to work again, and he was lost sight of until his 
admission to Bayview. In the interval he had wandered about between 
Washington, Philadelphia, and New York, spending his time partly at his 
trade and partly in hospital. He was now extremely reduced, and was pro- 
foundly affected by uraemia, which, however, was alleviated after a few days' 
treatment in hospital. He improved sufficiently to ask,for his discharge, 
when he started again upon his travels. He entered the University again 
in March of this year, when I found him upon taking charge of my ser- 
vice on the 15th of the month. He was then suffering from a quotidian 
intermittent quickly but temporarily relieved by cinchonidia sulphate. 
His condition, in so far as concerns his dropsy, has improved. This has 
become very muchless, though his urine is never free from albumen and tube- 
casts. His face is puffy and pallid, and he remains feeble. It would seem 
that the large white kidney, from which he originally suffered, without 
doubt, has passed gradually into a contracted kidney, from interstitial 
fibrosis, which has now assumed the dominating role in the morbid pro- 
cesses, as the parenchymatous changes did in the beginning. 
All four of these cases seem to have depended upon that pathological 
condition that has been called the " large white kidney," the morbid pro- 
cess in each being tubal and diffuse nephritis. That neither of the men 
was the subject of acute tubal or parenchymatous nephritis may be con- 
cluded from the nature of the attack. In the absence of the malarial 
attacks, fever was not present, or was so only to a very slight extent and 
during a brief interval ; the development of the inflammation was insidious, 
the appearance of dropsy more or less gradual. There was no chill as 
distinct from that of the malarial seizure ; there was not the continuous 
high temperature, the flushed countenance, the injected conjunctivae, the 
creamy coating to the tongue, the pain in the baok, the extreme reduction 9 
in the amount of urine passed, the intensely albuminous condition nor 
the very high specific gravity of the more acute form of the disease. 
Even in Case 4, whose history I have been able to trace for two years, 
the symptoms were constantly such as one would expect in the course of 
''large white kidney" gradually undergoing contraction ; not the primary 
contraction of ordinary granular or fibrotic kidney, but such as, gradually 
adding to the tubal changes cellular proliferation and interstitial connec- 
tive-tissue formation, may ultimately terminate in true contraction ; usually 
bearing, however, such characters as will serve to differentiate it from 
primary fibrosis, characters that have induced writers to bestow upon it 
the term " small fatty kidney" or " fatty granular kidney." 
Careful observation of the recorded cases of malarial Bright's disease 
discloses the fact that in by far the greater number, the symptoms 
are those attributable to tubal and diffuse nephritis. Rosenstein 
unhesitatingly pronounces this to be the usual variety. It should be borne 
in mind, however, that I am now referring to such cases as present 
evidence of pronounced renal alterations. It is undoubtedly true that 
the sudden and transitory albuminurias of ordinary malarial attacks are 
quite common. These, however, either result from renal hypertemias 
that pass away so rapidly that no permanent structural alterations are 
produced, or from those pernicious cases in which death occurs before 
structural changes in the kidneys have time to develop, or, finally, 
frequently repeated, tend to run into more pronounced and permanent 
changes. It has already been stated that in malarial haematuria or 
haemoglobinuria, albumen is always present. In many cases of ordinary 
malarial fever, albuminuria is present only during or immediately succeed- 
ing the attack. It may even be present upon the " ague" days, the urine 
remaining normal during the days of intermission. (Neret, Arch. Gen. 
de Med., xv. 1847, p. 509. Hertz, Ziemssen's Cyclop., vol. ii. p. G41.) 
As a rule the alterations in the kidneys under these circumstances are 
only temporary, and speedily subside upon the removal of the exciting 
cause. Dropsy generally does not appear in these cases. It sometimes 
happens, however, that extensive structural changes are lighted up 
from the very first. Fortunately, the albuminurias due to transitory 
hyperemia of the kidney from attacks of malarial fever are very much 
more common than that attributable to extensive renal inflammation ; but 
it need hardly be stated that between the mildest grade of hyperaemia and 
the highest grade of inflammation of the organ, all possible degrees of 
morbid change may be encountered, and that, although nephritis to the 
extent developed in my above-described cases may justly be considered 
uncommon, the possibility of its occurrence in affections capable of so 
readily lighting up milder renal hypersemias and inflammations is by no 
means remote. That the kidney can and does, far more frequently than 
is generally recognized, suffer both from the intense and the frequently 10 
repeated hyperaemias to which all the viscera are subjected in malarial 
fevers is shown in the haematuric and haemoglobinuric forms of malarial 
attacks on the one hand, and on the other, in very many simple intermit- 
tent and remittent fevers, in which the albuminuria disappears with the 
cessation of the malady. In some cases, however, of intense or long- 
persisting ague, the renal hyperaemia continues, structural alterations 
develop, and the transitory albuminuria becomes chronic and confirmed. 
Tubal and diffuse nephritis is then the ordinary form encountered in those 
cases that exceed the limits of simple inflammatory hypertemia, and attain 
the dignity of true renal inflammation. 
Although, as Rosenstein remarks, cases usually get well or die before 
granular kidney develops, there can be no doubt that this form of 
kidney may result from malarial poisoning. It has been encountered by 
Rosenstein, Soldatow (Petersburg, med. Wochenschr. 1878, No. 42), 
Kiener and Kelsch and others. Dickinson admits its rare occurrence, 
as does also Axel Key. Hertz will not venture to say whether the con- 
tracted kidney occurs after intermittent fevers ; and Bartels, while recog- 
nizing " malaria as the most frequent amongst the well-established causes," 
does not admit that the contracting kidney may result from it. There 
seems to be indeed no evidence showing that that form of renal inflam- 
mation in which the changes are interstitial from the beginning, which is 
known by the name of fibrotic, granular, cirrhotic, true contracting kidney, 
etc., can ever be attributed to malaria; but without doubt, cases are not 
so very unfrequent in which tubal and diffuse nephritis passes after a time 
into fibrotic contraction. Of such, I take Case 4 of this paper to be an 
example. 
It is difficult to determine whether there are definite conditions of 
malarial intoxications that more especially predispose to structural alterti- 
tions of the kidneys. Rosenstein, who speaks more definitely than any 
other of the predisposing conditions of malarial poisoning (Patholog. it. 
Therapie der Nierenkr., Berlin, 1870, p. 217), claimed that the fever 
in consequence of which the renal affection developed most commonly 
appeared under three conditions: viz., 1. The attacks were incomplete. 
The patients suffered during a long time (usually from the tertian type) 
with the cold and hot stages, but never the sweating stage; or 2. The 
attacks were complete, of tertian or quartan type and only few in number. 
Upon three or four similar attacks, succeeded several weeks, during which 
the patient, in consequence of the marked form of the fever, experienced 
only slight disturbance of general health ; they attended to their work 
until dropsy appeared. This developed simultaneously with albuminuria or 
preceded it ; or 3. The intermittent type of the fever persisted almost 
without interruption for months-in one case for two years-and the 
dropsy appeared for the first time upon the cessation of the attacks. 
Rosenstein declares that dropsy is a constant symptom in nephritis from 11 
intermittent fever, and that it here may reach a higher grade than in any 
other form. He, moreover, asserted that the urine showed the peculiarity 
that it never contained blood, but generally much albumen with relatively 
much urates and uric acid. This, however, is certainly incorrect as ap- 
plied to the urine of malarial nephritis generally. Cases of renal hemor- 
rhage in simple malarial fever have been reported by Hertz, Griesinger, 
Keiner and Kelsch, and others. Da Costa considers bloody urine one 
of the characteristic features of the malady. It thus appears that, 
although bleeding from the kidneys may be vastly more common in per- 
nicious and severe remittent fevers, its absence from the kidneys of per- 
sons with simple ague cannot be assumed as of unvarying rule. 
Regarding the etiology of malarial nephritis, the above-quoted author 
thinks that, in addition to the collateral hypersemia in the kidney always 
united with the febrile symptom-complex, two other conditions must be 
considered: one is the impoverishment of the blood of its constant con- 
stituents, the red corpuscles, in consequence of the splenic affection 
(hydraemia) ; the other is pigment-formation, to the mechanical signifi- 
cance of which in disorders of the renal circulation Frerichs has directed 
attention. The first of these conditions, however, he considers far more 
important, since cases with marked hydraemia and but little pigment- 
formation show decided alterations of the kidney, and, conversely, there 
is often found in extensive melanaemia long-persistent albuminuria, but 
only slight alteration of the epithelia. He has also observed a high de- 
gree of melanaemia without any sign of albuminuria. Rosenstein's ex- 
planation, however, is not satisfying, since decided renal disorder may 
manifest itself long before the malarial intoxication can have produced 
hydraemia to any extent, as is shown in the acute congestions of per- 
nicious and very intense intermittent and remittent fevers, and also in the 
diffuse inflammations that are sometimes developed quite early in the 
course of the malarial disorder, as, for example, in three of the cases re- 
ported in this paper. It is, indeed, useless at present to attempt to decide 
whether the renal effects are due to a specific influence, to intensity, long- 
continuance and repetition of hyperaemia, or to the causes just mentioned. 
Hydraemia or pigmentary embolisms cannot be unvarying, though they 
may be occasional causes. 
The form of malarial poisoning most prolific of renal inflammation is 
intermittent fever, for in it are to be found the conditions most favourable 
to its production, the often-recurring congestions extending over indefi- 
nite periods, during which the patient's powers of resistance are gradu- 
ally reduced. In regions where pernicious and haematuric or haemoglo- 
binuric malarial fevers prevail, they will be found to excite most fre- 
quently the intense congestion that results in albuminuria, and, doubtless, 
occasionally inflammatory alterations of the kidney. Remittent fever 
may likewise produce identical changes. Although McLean (Reynolds's 12 
System, vol. i. p. 613) says of the urine in remittent fever that it very 
rarely contains albumen, abundant evidence is at hand to show that albu- 
minuria of no small intensity is not so very unfrequent in this form of 
malarial fever. Hertz, for example, declares it to be no uncommon thing 
in the hypertemia of remittent fever, when it may be accompanied with 
an abundant admixture of blood. Kiener and Kelsch found that the 
acute congestions and more acute forms of nephritis might perfectly well 
depend upon remittent fever; and Soldatow's observations resulted in the 
discovery of the alterations described by him only after the "severe forms 
of continuous and remittent malarial fevers." He did not encounter 
them at all after intermittent fevers. This want of agreement amongst 
observers relative to the comparative frequency of nephritis after the 
various forms of malarial fever can only be accounted for upon the theory 
that different epidemics exert unequal influences upon the kidneys, as has 
been stated in the earlier part of this paper. It also demonstrates that 
no particular variety of malarial fever can be said to exert a specific in- 
fluence upon these organs. 
In the transitory albuminuria of ordinary malarial attacks, the prog- 
nosis is favourable, inasmuch as the symptom is usually due to the visceral 
hypertemia alone, and disappears upon the subsidence of this. It is more 
grave in proportion to the intensity of the attack and the persistence of 
the albuminuria. Pernicious and haematuric and htemoglobinuric malarial 
fevers are, of course, most dangerous, apart from their renal complica- 
tions. In less severe but more chronic fevers the danger becomes pro- 
portionate to the extent of the damage to the kidneys. Generally, how- 
ever, even in pronounced diffuse nephritis, the prognosis is favourable. 
Da Costa (W. Y. Med. Rev., 17, p. 54) says: " I have seen a large num- 
ber of cases of Bright's disease following malaria, and am therefore 
moderately familiar with the disease. By malarial albuminuria I mean a 
condition characterized by albumen in the urine, with granular and hya- 
line tube-casts coming on slowly, associated with dropsy, and as gradually 
passing away. In the long run and with proper treatment, such cases 
usually recover." As the symptoms of renal change become more chronic 
and pronounced, the prognosis will not differ from that of ordinary diffuse 
nephritis, and will become graver and more hopeless as the increasing 
structural alterations progressively impair the renal functions. 
Axel Key first studied the pathological anatomy of renal alterations of 
malarial origin. (Cannstatt's Jahresberichte der gessamt. Med., 1862, 
iv. p. 56.) The kidneys examined by him owed their changes to inter- 
mittent fever. They were enlarged. The interstitial tissue was com- 
monly much thickened by cell-proliferation, which was also present in the 
tubules. He found amyloid degeneration constantly in the glomeruli and 
arterite rectte, often also jn the afferent arteries and later in the interlo- 
bular arteries. This latter statement needs confirmation. Kosenstein 13 
could not recognize amyloid degeneration as a constant form of renal dis- 
ease after intermittent. Soldatow makes no mention of this degene- 
ration in kidneys altered by remittent fever; while Kiener and Kelsch 
lay especial stress upon the rarity, possibly the absence of amyloid de- 
generation in malarial nephritis (Arch. de Physiol, norm, et Path. 1882, 
ix. p. 278). Soldatow observed in kidneys after remittent fever en- 
largement reaching sometimes twice the normal size. Scattered through- 
out the cortex w'ere grayish-white nodules, sometimes 1 cm. in diameter. 
In the course of the affection, these nodules would diminish and finally 
disappear, leaving first a depression surrounded by extensive vascular 
injection, and ultimately a contraction of the cortex from scar formation. 
Microscopically, the epithelium was seen to be swollen, in places loosened, 
and later fatty degeneration. There was also extensive cell-infiltration of 
the thickened interstitial tissue. The endothelium of the capillaries was 
granular, its cells much enlarged, making the lumen smaller. Near the 
glomeruli the vessels were filled with white corpuscles, and in places 
plugged by loosened endothelium. Later the elements exuded and under- 
went retrogressive metamorphosis, or new connective-tissue formation 
ensued. In 1873, Cornil reported an examination of the kidneys of two 
children dead of paludal cachexy. In these parenchymatous nephritis 
simply was present; the connective tissue was normal (Calmette, Recueil 
des Alemoires de Med. et de Chir. mil. 36,1880). The most extensive series 
of investigations of renal alterations of malarial origin were those of Kiener 
and Kelsch. The first-named of these authors first published the results 
of his investigations (Paludal Alterations of the Kidney in Algeria, 
Comptes rendus de la Soc. de Biologie, iv. 1879), and, subsequently, the 
results of their combined researches were given in a most elaborate article 
published in 1882 (loc. citj. These investigations, extending as they do 
over the whole field of renal alterations of malarial origin, are such an 
important contribution to the literature of the subject that a somewhat 
extensive synopsis of them may be permitted. 
They describe as paludal alterations of the kidneys : 1. Inflammatory 
hypercemia; 2. Glomerular or difluse nephritis; 3. Nephritis "d granu- 
lations de Bright4. Inflammatory degenerations of the kidney. 
Under the first heading are included, a. Hcematuric or haemo globinuric 
congestion; b. Hypercemia with tendency toward sclerous induration; 
and c. hypercemia with tendency toward epithelial hypertrophy. 
Hcematuric or hcemoglobinuric congestion of the kidneys of persons 
who had rapidly succumbed to a pernicious attack with blood-corpuscles 
or haemoglobin in the urine. Microscopically, such kidneys were very 
little altered in size or weight. An intense haematic coloration was most 
noticeable, obscuring the parts of the cortex, the glomeruli only being dis- 
tinguishable as dark red points. The pyramids w'ere of a brighter red. 
Microscopically was seen slight and uniform enlargement of the convo- 14 
luted tubes and ascending limbs of Henle's loops, the epithelia being 
enlarged and discoloured. The tubes were filled with casts. The epithe- 
lia of Bowman's capsules of the glomeruli were tumefied and granular, and 
the glomeruli themselves often dilated in places and the seats of small 
hemorrhages. The interlobular veins and those of the limiting zone were 
dilated and their contents commonly thrombosed. The interstitial con- 
nective tissue was but little modified. 
Hypercemia with tendency toward sclerous induration was observed in 
kidneys of subjects dead of remittent fever of bilious or typhoid character 
or a pernicious attack consecutive to several relapses of fever, and whose 
urine had been albuminous and hemorrhagic or hfemoglobinuric. These 
kidneys were larger (300 to 400 grs.), red, smooth, and of almost normal 
consistence. Microscopically, in addition to the changes already noted, 
there were observed conditions which may be briefly summarized as con- 
sisting of three elementary lesions, plus hemorrhagic congestion. These 
were: 1. Cellular proliferation tending toward fibrous transformation in 
the glomeruli ; 2. Epithelial hyperplasia with atrophic tendency in the 
diseased tubules ; 3. Diffuse sclerosis of the stroma. These lesions 
affected the cortical portion and especially the secretory elements. 
Hypercemia with tendency toward epithelial hypertrophy of kidneys 
of subjects dead, likewise, of pernicious fever, or of remittent fever of 
greater or less duration, whose urine had been highly albuminous, of a 
deep-red colour from blood-globules in suspension, and had contained 
" colloid " casts in the sediment. These kidneys were large, smooth, red, 
verging toward gray or yellow, with scattered stellate veins ; the capsules 
tense and easily detached, cortex swollen and paler than the dark red of 
the pyramids. The pyramids of Ferrein were enlarged and of milky 
appearance, merging indistinctly into the convoluted region. Usually the 
colour was uniform, exceptionally pale, and shining patches were notice- 
able. At points the epithelia showed haematic imbibition. Another 
change, however, was predominant. The cells became two or three times 
larger than normal, almost filling the lumen, which was obstructed by 
moulds of colloid substance. There was but little interstitial sclerosis. 
The glomeruli were highly coloured, but did not tend toward fibroid trans- 
formation. 
The second group of renal alterations they describe as diffuse or glome- 
rular nephritis, and divide into acute and chronic forms. The acute form 
was always declared during an early period of the impaludism. It arose 
in the course of intermittent or remittent fever. In some cases the symp- 
toms had been those of acute parenchymatous nephritis, death having 
occurred through increase of dropsy, or by inflammatory or gangrenous 
complications. Other cases had run a more irregular course. The 
chronic form could not be definitely distinguished from the preceding one. 15 
The lesions had developed insidiously in the course of chronic malaria, 
and were sometimes unexpectedly revealed at the necropsy. The kid- 
neys were large, red, firm, and smooth ; in more advanced cases they were 
small, preserving a smooth appearance and uniform red colour, and of 
firmer consistence. In other subjects the kidneys were atrophied, very 
hard, smooth or a little roughened on the surface, and of an opaque brown 
colour. Microscopically, there was shown a tendency of the renal paren- 
chyma to develop an embryonic or fibrous connective tissue. Alteration 
of the glomerular elements was not second to glandular hyperplasia, but 
always independent of this, frequently primary and preponderant. The 
morbid process, rapid or chronic, general or circumscribed, at the start, 
merged from frank inflammation, with active cell-proliferation, to bastard 
and senile forms, in which the sclerous centres resulted from a slow hyper- 
genesis of fibrous tissue with gradual atrophy of the glandular elements. 
There was a tendency of the nephritis to be limited to centres often very 
small and close together, and to produce there profound alterations. 
(Compare with similar changes described by Soldatow.) These centres 
corresponded usually to a glomerulus or group of glomeruli. The sclerosis 
finally became diffused throughout the cortex. " Granulation " was not 
a result. Smooth induration or slight roughening was a persistent char- 
acter of the process. 
Nephritis " a granulations de Bright."-This form they also divide 
into acute and chronic varieties. The acute form is not named from the 
duration of the process, but as marking initial alterations. The authors 
were not sure that the clinical diagnosis between this and the preceding 
form of nephritis is possible. In the more acute cases the kidneys were 
remarkably pale, large, and soft (GOO grs. in weight). The surface 
was smooth, and under the thin capsule showed a yellowish-white color 
with stellate veins. The cortex was very thick, pale yellow, shining, 
and moist. The authors here evidently refer to what is commonly known 
as the "large white kidney." According to them, however, "granula- 
tion" is already indicated at this stage. The peri-granular lesions showed 
the tubuli full, more or less, of indifferent cells, and contracted. The 
glomeruli sustained the same lesions as in glomerular nephritis. The 
intertubular connective tissue gradually thickened at the expense of the 
tubules. The chronic variety is described as having its perfect type in 
the small, red, granular kidney, which the authors consider as related by 
a series of intermediate stages to the big white kidney. 
The final form of renal alteration from malarial influences is described 
as " inflammatory degeneration of the kidneys, with cystic formation." 
This occurred in subjects who were cachectic and had succumbed to the 
effects of slow paludal poisoning with small doses frequently repeated and 
long accumulating. The lesions consisted in sclerous disorders of circula- 16 
tion, " colloid-fatty " degeneration of the epithelium, pigmentation, and 
cysts. The kidneys were atrophied (200-300 grs.). Sclerosis was the 
predominating process, forming bands dense, poor in cells, and but slightly 
vascular. 
The conclusions of these authors are, that if we compare paludal renal 
hypercemia with catarrhal nephritis in general, three facts are notable : 1, 
the tendency toward hemorrhage; 2, the intensity and rapidity of develop- 
ment of inflammatory phenomena, and, notably, of epithelial hyperplasias ; 
and, 3, the rarity of fatty degenerations. Paludal Bright's disease they 
consider not very characteristic. There should be noted, however, 1, the 
tendency toward hemorrhages in all forms and at all periods of the 
nephritis ; 2, the frank character of the inflammation, in contrast with the 
half-fatty, half-sclerous forms often presented by gout and alcoholism ; 3, 
the rarity, possibly the absence, of amyloid degeneration. 
It will be observed that Kiener and Kelsch do not recognize parenchy- 
matous and interstitial nephritis as distinct morbid processes. While it 
is highly probable that granular kidney never occurs as a primary process 
after malarial intoxication, but always when present represents some 
advanced stage of preceding diffuse nephritis, there can be but little 
doubt that one may encounter all gradations from transitory parenchy- 
matous nephritis to chronic contracting interstitial nephritis, now tubal 
predominating over interstitial inflammation, now the latter form pre- 
vailing. In all cases the persistence of inflammatory changes during any 
considerable interval will inevitably lead to the involvement of the other 
renal structures. Therefore it may be concluded, that in the earlier stages 
tubal and diffuse nephritis will more commonly be found when the viscus 
is excited to inflammation by malaria, showing, it is true, a primary 
disposition to affect the glomeruli, but at the same time involving the 
tubules, and that as time elapses without subsidence of the inflammation, 
fibrotic contraction makes steady headway. 
In the treatment of nephritic inflammation of malarial origin, reference 
must always be had to its intensity and duration. In the great majority 
of cases of hamiaturia or haemoglobinuria and of simple albuminuria of 
transitory character, where diffuse renal inflammation has not as yet been 
excited, therapeutic efforts successfully addressed to the cure of the malarial 
poisoning will usually suffice to overcome the renal disorder as well. The 
vigorous use of quinine or other anti-periodic, if sufficient to avert an 
immediately fatal issue, will also restore the healthy condition of the kid- 
neys. Certainly, during the prevalence of the malarial attack, nothing 
can be expected to control the renal hypenemia that does not bring the 
impaludism under subjection. Even in those cases of diffuse nephritis 
where the attacks of ague sometimes assume that almost unmanageable 
form in which they will continue to recur in the most obstinate and 
unaccountable manner, no treatment can hold out promise of cure that does 17 
not strive for the subjugation of this influence, however feebly and 
irregularly it may manifest itself. Where diffuse nephritis persists after 
the malarial influence has been apparently overcome, treatment must be 
conducted as for ordinary diffuse renal inflammation; but regard must 
always be had for the possible survival of the malarial element and its 
possible recrudescence ; and under no circumstance should a case of nephritis 
of malarial origin be treated without efforts to correct malarial toxaemia, not 
by the administration of anti-periodics in the doses and for the intervals 
ordinarily sufficient to overcome a simple attack of malarial fever, but 
persistently and in full doses. Under these conditions but little fear need 
be entertained of any possible injurious influence of the anti-periodic, for 
in the very rare cases where they seem to have exerted this influence over 
the kidneys, it has been by congestive htematuria apparently due to indi- 
vidual idiosyncrasy (Roberts, Urinary and Renal Diseases, Phila., 1872. 
p. 351 ; Brit. Med. Jour., Jan. 1870). In all other respects malarial 
nephritis, whether acute or chronic, should be treated precisely as these 
morbid conditions should be treated, from whatever cause they arise. 
ConclusionsFrom what has preceded the following conclusions seem 
justifiable:- 
1. Transitory albuminuria is not uncommon in the course of malarial 
fevers, and is due to the intense visceral congestions characteristic of these 
affections. It only may endure throughout the height of the congestion, 
recurring with each return of this, or it may persist in the intervals, in 
which event a higher grade of congestion is attained, more nearly ap- 
proaching a condition of acute inflammation. 
2. In a proportion of cases, varying with locality and type of prevailing 
epidemic, or individual conditions, inflammation of the kidney occurs, 
accompanied by dropsy and the usual symptoms of nephritis. 
3. The usual form of malarial nephritis is the tubal and diffuse variety. 
In this the inflammation seems to be most intense in the vicinity of the 
glomeruli. 
4. Contracted kidney may occur as an advanced stage of malarial 
nephritis either from long-continued or frequently repeated attacks of 
malarial fever, or from fibrotic changes such as may ultimately occur in 
ordinary tubal or diffuse nephritis. It is altogether improbable that this 
form of malarial renal disease ever occurs primarily as purely interstitial 
nephritis. 
5. These changes may be induced by any form of malarial fever, 
though they more commonly follow chronic intermittent fever. 
6. The tendency of malarial inflammation of the kidney is toward re- 
covery. But from the persistence of the impaludism or the intensity of 
the inflammation, structural changes may be produced that are charac- 
teristic of chronic Bright's disease, when the gravity of the affection will 
be as that from chronic Bright's disease from whatever cause. 18 
7. Treatment should be directed primarily against the malarial intoxi- 
cation, more especially in recent cases. A correction of this will often 
be followed by a complete, though often gradual, subsidence of the nephri- 
tis. Even in more chronic cases, the malarial factor in the process should 
definitely be destroyed if possible, after which the disease should be 
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