A CLINICO-PATHOLOGICAL STUDY OF …adc.bmj.com/content/archdischild/39/206/313.full.pdf · A...

Arch. Dis. Childh., 1964, 39, 313.

A CLINICO-PATHOLOGICAL STUDY OF ACUTEGLOMERULONEPHRITIS IN EAST AFRICAN CHILDREN

BY

M. S. R. HUTT and R. H. R. WHITESFrom the Departments ofPathology and Paediatrics, Makerere Universitv College, Kampala, Uganda

(RECEIVED FOR PUBLICAnON JANUARY 17, 1964)

The assessment of disease incidence in Uganda, anemerging but still young country, presents manyproblems. Information about a disorder such asacute glomerulonephritis, which has a high spontan-eous recovery rate and may present atypical clincalfeatures, is particularly liable to be misleading. Theevidence that already exists is conflicting. Luder(1958) saw no cases of 'Type I' nephritis in Africanchildren during two years' work at Mulago Hospital;on the other hand, Musoke (1961), analysingadmissions to the children's wards during 1959,reported that 8 out of 18 renal admissions were foracute nephritis. In a retrospective survey ofadmissions to the medical wards during 1957, Shaperand Shaper (1958) found only 3 among 131 patientswith renal disease.

In necropsy surveys, Raper (1953) reported only 15instances of Type I nephritis in six years, whileAllison (1962) found no cases of acute nephritis andonly 13 cases of chronic glomerulonephritis among272 necropsies showing renal disease. However, thehigh recovery rate in acute nephritis and the lownecropsy rate among children in Uganda combine torender post-mortem figures misleading. Neverthe-less, the prevalence of 'proliferative glomerulitis' inearlier necropsy surveys (Hennessey, 1939; Davies,1949) suggests that a background of antecedent acutenephritis must exist.With the aid of renal biopsy, Leather (1960) found

that glomerulonephritis was the commonest type ofrenal disease during the first four decades and waspresent in 12 of 13 children studied. Fortunately,the histological features of acute diffuse glomerulo-nephritis are well defined. In this paper we reportthe results of a prospective study, in which a diligentsearch for clinical evidence suggestive of glomerulo-nephritis was combined with the appraisal of renalbiopsy material, undertaken in the hope of obtaining* Present address: Department ofPaediatrics, Guy's Hospital, London,S.E.I.

a better understanding of the incidence, clinicalpatterns, and pathological features of the disease inUganda.

Material and Methods

Between August 1960 and July 1962, 45 negro childrenwith evidence of renal disease, based on clinical andlaboratory findings, were studied by means of percutan-eous renal biopsy: 23, in whom a histologicaldiagnosis of acute diffuse glomerulonephritis was made,are included in this paper, and a further child, in whomthe diagnosis was made at necropsy, has been added(Table 1). Investigations were carried out as follows.

Urialysis. On admission, at least one urine specunenfrom every child was examined by one of us. Quantita-tive 24-hour protein output estimations were attemptedbut failed or were considered unreliable owing to difficultyin collection of specimens. However, the proteinconcentration was estimated in specimens from everychild and the centrifuged deposit was examined micro-scopically.

Bacteriology. Throat swabs were taken from 20children and were cultured on blood agar medium.Later in the series, haemolytic streptococci were groupedwhen isolated.

Serology. Antistreptolysin-O (ASO) titres wereestimated in 20 of the patients.

TABU 1CLINICAL PRESENTATION OF 46 AFRICAN CHILDRENWITH RENAL DISEASE, INCLUDING 24 DIAGNOSED

HISTOLOGICALLY AS ACUTE DIFFUSEGLOMERULONEPHRITIS (AGN)

Number No. of PatientsClinical Presentation of

Biopsies Total LAGNAcute haemorrhagic nephritis 18 15 14Nephrotic syndrome .. 35 23 4Congestive cardiac failure 3 4* 3*Detected on routine urinalysis.. 44 3

* Includes one child diagnosed at necropsy.

313

copyright. on 11 July 2018 by guest. P

rotected byhttp://adc.bm

j.com/

Arch D

is Child: first published as 10.1136/adc.39.206.313 on 1 A

ugust 1964. Dow

nloaded from

http://adc.bmj.com/

HU1T AND WHITE

TABLE 2PRESENTING SYMPTOMS IN 24 CHILDREN WITH AGN

Presenting Symptoms No.

Swelling and dark or bloody urine . 11Swelling only .10Dark or bloody urine only. 2Oliguria 3Fever .... 13Cough. ..9Vomiting ... 2Joint pains I.. .

TABLE 4RELATION BETWEEN ASO TITRE AND CLINICAL

MANIFESTATIONS

ASO titre (units,ml.)Clinical Group

> 200 166 < 166 NotRecorded

Haemorrhagic .. 9 1 1 3'Nephrotic . .. 2 - 2Cardiac failure .. 1 2Urinalysis .. .. 1 1 1

* One child (Case 3) also had acute rheumatism; ASO titre was 100units ml. 98 days from onset when second biopsy showed recovery.

TABLE 3MAIN PHYSICAL FINDINGS IN 24 CHILDREN WITH AGN

Physical Findings No.

Oedema, slight to moderate 17Oedema, gross, with ascites ..... ... .. 5Macroscopic haematuria . .. 15Hypertension (blood pressure recorded in 23) 14Congestive cardiac failure 6Acute tonsillitis 5Non-respiratory sepsis 3Acute rheumatism I

TABLE 5DETAILS OF 4 CHILDREN PRESENTING WITH

NEPHROTIC SYNDROME

Case Case Case Case8(M) 9(M) 13(F) 22(F)

Age (yr.) 2. .. 2 26 days 5 4Nutrition Poor Good Poor PoorHypertension .. + ? + +Macroscopic haematuria - - - +Serum proteims:

Total (g. 100 ml.) . .Albumin (g. 100 ml.)

Serum cholesterol(mi&/lO mL)

Blood urea (mg I100 ml.)

Haemoglobin (g./100 ml.)Hookworm ..Malaria

.. 5.3

.. 1-7

.. 100

.. 36

.. 5-5..

..

4-2 3-7 4-22-1 1-6 1-0

1389813-0

106725-6+

185285-0+

+

TABLE 6DETAILS OF 3 CHILDREN PRESENTING WITH

CONGESTIVE CARDIAC FAILURE

Case 18(F) Case 21(M) Case 24(F)

Age (yr.) .. .. .. j 4 3jOCedema (0-3) .. 2 2 3Hypertension ..+ + -

Blood urea(mg./IOOml.) 55 30 109Haemoglobin(g./1OOmI.) 6-7 8-7 7-2Hookworm .. + + -

Blood Cbemistry. Blood urea levels were estimated onadmission in every patient, and were subsequentlyrepeated in children whose initial levels were raised.Serum protein estimations, together with serum proteinpaper electrophoresis. were carried out in 23 and serum

cholesterol in 19 cases.Haemoglobin estimations, reticulocyte counts, blood

smears for malarial parasites, sickling preparations andhaemoglobin electrophoresis if indicated, and stoolconcentrations for parasites and ova were carried out asroutine investigations on all admissions. The results willbe given only in selected cases where they appear toinfluence symptoms.

Percutaeous Renal Biopsy. This was performed on allbut the last patient, who died shortly after admission tohospital and was examined post mortem. In 3 childrentwo biopsies were performed, and in a further 2 childrenthree biopsies, at intervals. The biopsy instrument andtechnique employed have been described elsewhere (White,1962, 1963). No serious complications of biopsy were

TABLE 7DETAILS OF 3 CHILDREN DETECTED ON

ROUTINE URINALYSIS

Case 7(F) Case 17(F) Case 19(M)

Age (yr.) 4 2 3Oedema (0-3) .. 0 1 1Blood urea (mg- 1°OO ml.) .. 28 21 42Haemoglobin (g. 00 ml.) .. 11-7 6-4 7-6Presenting illnss .. Acute Sickl cell Hookworm

tonsilitis anaemia anaemia

encountered in this series, but one patient, a 26-day-oldinfant, died 23 hours later from causes unrelated to theperformance of renal biopsy (White, 1963).The biopsy material was immediately transferred to

Susa fixative and embedded in paraffin. As a routine,serial sections were cut at 2-5 u and stained withhaematoxylin and eosin and by the periodic acid-Schifftechnique. In selected cases Weigert's iron haematoxylinand van Gieson, and Mallory's trichrome stains were alsoused.

Results

Clinial Manifestations. Clinical details of the 24patients, 12 boys and 12 girls, are given in Tables 2-7.Their ages ranged from 1 month to 15 years (Fig. 1),19 (79 %o) being under 5 years.The presenting symptoms are summarized in

Table 2 and the main physical findings in Table 3.Swelling, the commonest complaint, was volunteeredin 21 and oedema was found on examination in 22,

314



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/

ACUTE GLOMERULONEPHRITIS IN EAST AFRICAN CHILDREN

being slight to moderate in 17 and gross in 5 childrenwho also had ascites. The passage of dark or blood-stained urine was not usually volunteered as acomplaint but was admitted on questioning by theparents of 13 children, in 11 of whom there wasassociated swelling. Macroscopic haematuria wasconfirmed on admission in all 13, and was observedin 2 other children in whom its occurrence wasdenied by the mothers. Thus, oedema and macro-scopic haematuria occurred together in 14 patients,oedema alone in 8, haematuria alone in 1, andneither in 1. Hypertension, assessed according tothe figures of Haggerty, Maroney, and Nadas (1956)for children of different ages, was observed in 14 outof 23 children in whom the blood pressure wasrecorded. It was associated invariably with oedemaand in 10 instances with gross haematuria. Con-gestive cardiac failure occurred in 6 children, ofwhom 4 were hypertensive and 3 had gross haema-turia: all had moderate or severe anaemia, withhaemoglobin levels rangingfrom 3 7 to 8 - 8 g./100 ml.Sixteen children gave histories of antecedent illnessuggesting upper respiratory infection, e.g. pyrexia,cough, and abdominal pain, and 6 were found to haveacute tonsillitis on admission. Two had infectedskin lesions, 1 had septicaemia following umbilicalsepsis, and 1 child was originally admitted with acuterheumatism.

Urialysis. Protein, varying from 30 to morethan 1,000 mg./100 ml. of urine, red blood cells, andpolymorphonuclear leucocytes were present in theurine of all the patients on admission, and granularcasts were found in 17.

Bacteriology. P-haemolytic streptococci wereisolated in 8 out of 20 throat swabs: in 6 of these thegroup was not specified, and in the remaining 2 itwasspecified as 'not group-A'. In no instances weregroup-A haemolytic streptococci positively identified.

Serology. ASO titres exceeded 200 units/ml. in 13out of 20 children in whom results were obtained.Cases 10 and 17 had titres of 166 units/ml., which canbe accepted as abnormal levels for children of theirage, since Potter and Lorber (1961) were unable todemonstrate titres as high as 100 units/ml. in healthychildren between 2 months and 2 years of age.Although the numbers are small it is perhaps note-worthy that a higher proportion of raised titresoccurred in patients presenting with macroscopichaematuria than in the other three clinical groups(Table 4).

Blood Chemitry. Blood urea levels were initiallyraised above 40 mg./100 ml. in 12 children, and in

most instances the rise was moderate and transient.However, in Case 12, whose haematuria began eightweeks before admission, the first reading obtainedwas 321 mg./100 ml.The serum proteins showed appreciable variation,

according to the patients' nutrition and the occur-rence of local infections such as hookworm andmalaria. No characteristic electrophoretic patternwas observed, though 11 patients showed a slightrise of am-globulin. Four children presenting withthe nephrotic syndrome showed stiking hypo-albuminaemia (Table 5).Serum cholesterol levels ranged from 61 to 247 mg.,

the mean being 142 mg./100 ml.

Varataos in the Clinical Pattern. Fourteenpatients presented in the classical manner, withmacroscopic haematuria in all cases and slight to

zIJ S_

0 3

do 2

234/

I 4 S 6 7 10 11 I 15AGE Cyrs)

FIG. 1.-The age incidence of 24 children with acute giomenrlo-nephritis.

moderate oedema in 13: 9 were hypertensive, 7 hadurea retention, and 3 had congestive cardiac failure.Four children were found, on admission, to have

gross oedema with ascites, proteinuria of more than1 %, and hypoalbuminaemia, and were thereforeclassified clinically as nephrotics (Table 5). InCases 8, 13, and 22, however, poor nutrition andsevere hookworm infection, with haemoglobin levelsof only 5-6 g./100 ml., undoubtedly contributed tothe hypoproteinaemia and oedema. All three werehypertensive: Case 13 had urea retention and Case 22macroscopic haematuria, a feature that was notvolunteered as a symptom but discovered onadmission. The fourth case (Case 9), on the otherhand, was a breast-fed and well-nourished maleinfant, and had neither hookworm nor malaria.

Case 9. Swelling began in the scrotum at the age of 8days and extended rapidly. When admitted on thefourteenth day he was found to have gross oedema andascites. The umbilical stump was slightly swollen and

315



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/

316 HUIT AND WHITETABLE 8

SUMMARY OF HISTOLOGICAL FINDINGS IN THE INITIAL BIOPSY SPECIMENS

Glomerular TuftsCase GradeNo. Days From No. of Cell Polymorphs* Scierosist Bowman's Tubules Interstitial

Onset Glomeruli Prolif. Capsulest Tissue

1 49 76 + +- - - - I2 23 63 + + + - + - +II3 8 21 + +- - - - I4 6 97 + + + Occ. + + + III5 12 204 + + + - - + - II6 4 139 + + - - - - I7 21 60 + + + Occ. +(T) - - I8 15 96 + + + - + - III9 18 72 ) - - - -9 19 NecropsyX +10 7 67 + + + - - - II11 24 30 + + - + - H12 90 82 + + + +++ -- IX13 13 73 ++ + Occ. - - - I14 9 18 ++ - - - - I15 7 79 + a + Occ. +(T) - - II16 16 54 + + Occ. - - I17 17 99 - + - - - - I18 14 93 t - + - + t- II19 6 84 - - + - - - - I20 9 32 -+ - - - _ I21 14 57 t -- - - - -I'2 7 83 + - - - I23 9 102 + - - II24 9 Necropsy + + + + Occ. - - I

* + and -+ indicate the intensity of cellular proliferation and polymorphonuckar exudation. all glomeruli being involved to varying degrees.+ +, + , and+++, as applied to glomerular sclerosis and to proliferation of Bowman's capsules are based on the proportion of glomeruliinvolved as well as the severity.Occ. = occasional glomeruli involved. (T) = tubularization of capsular epithelium.Dashes imply insignificant lesions or normal appearance.

inflamed. Both kidneys were easily palpable. Theblood pressure was not recorded. The urine showedprotein 1Oo, red blood cells, and leucocytes. The ASOtitre was greater than 333 units/ml. Biochemical data areshown in Table 5. With a provisional diagnosis ofsepticaemia, secondary to umbilical sepsis and complicat-ed by the nephrotic syndrome, possibly due to renal veinthrombosis, he was treated with intramuscular penicilinand streptomycin, and subsequently oral tetracycline.However, his condition did not improve and on the 24thday he had two convulsions. The right kidney wasbiopsied without difficulty on the 27th day: he died on thefollowing day and necropsy confirned the biopsy findingof acute diffuse glomerulonephritis, while revealing noevidence of operative trauma that could have accountedfor death (White, 1963). There was a collection of pus inthe umbilical vein, from which a coagulase-positiveStaph. aureus was cultured, with metastatic abscesses andextensive pulmonary alveolar haemorrhage, believed tohave been the immediate cause of death.

Three children were admitted on account ofcongestive cardiac failure (Table 6). Oedema wasgross only in Case 24 but all three had ascites.Cases 18 and 21 were hypertensive. All hadproteinuria and microscopic haematuria, andgranular casts were found in the urine of Cases 18and 21. They were all undernourished and anaenic,and Cases 18 and 21 were infected with Ancylostonaduodenale. In Case 24 cardiac failure was severe

enough to cause death on the second day ofadmission, and the diagnosis of glomerulonephritiswas revealed at necropsy.

Three children were found to have protein, redblood cells, and granular casts in their urine onroutine analysis (Table 7). Case 7 was admittedwith acute tonsillitis, and Cases 17 and 19 withanaemia and slight oedema, their provisionaldiagnosis being hookworm infection. This wasconfirmed in Case 19 but not in Case 17, who wasfound to have sickle-cell anaemia All had normalblood pressure levels and the highest blood urealevel recorded was 42 mg./100 ml. in Case 19.

HitgilF in InitalB . Renalbiopsy was performed in 22 patients, necropsy in 1,and both in 1, from four to ninety days after the onsetof the acute attack. In 5 patients more than onebiopsy was done. The changes in the individualpatients are sumarized in Table 8.

GLOMERuLAR TuFIS. The principal histologicalfeature, common to all the patients, was cellularproliferation of the glomerular tuft, which usuallyled to an incrase in the size of the whole glomerulusand frequently to obliteration of the capsular space(Fig. 2). Analysis of the changes in the glomerulartufts in thin sections stained by the periodic acid-



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/


FIG. 2.-Glonerulus showing proliferation of ndothelial and mesangial cells, and extensive infiltration by polymorphonuclear kucocytes.(Case 20.) (Haematoxyin and eosin. x 434).

Schiff technique suggested that the proliferation wasmainly of endothelial cells, although the possibilitythat mesangial cells were also increased could not beexcluded. The increased cellularity, demonstratedby the larger number of nuclei, was accompanied byan excess of pink-staining material in haematoxylinand eosin sections. The appearances suggested thatthis was principally due to swelling of the endothelialcell cytoplasm and, in thin sections, it could often beseen almost filling the lumen of the capillaries. Inmany of the biopsies mitotic figures were seen inoccasional glomeruli. There did not appear to beany gross alteration of the epithelial cells of the tuft,although they were occasionally swollen and some-times contained hyaline droplets. The exceptionsto this were seen in those cases where there wasproliferation of the Bowman's capsules, formingcellular crescents; in these specimens swelling andproliferation of tuft epithelial cells were often seen.The other feature present in all cases was exudation

ofpolymorphonuclear leucocytes into the glomerulartufts (Fig. 2). The appearances suggested that thepolymorphs were adherent to the swollen endothelialcell cytoplasm within the capillary lumens. Thebasement membrane usually showed no abnormality,although occasionally there seemed to be fraying or

oedema, and in the specimen from Case 12, wherethe lesion was progressive, there was a greatlyincreased network of basement membrane fibrils inthe tufts. In some of the biopsies these changes inthe glomerular tufts were the only abnormalitiesfound. Sclerosis of the tufts was a prominentfinding only in Case 12, although occasional scleroticglomeruli were seen in five other specimens.

BowMAN4's CAPsuLEs. In 9 biopsies the epithelialcells of Bowman's capsules showed swelling andproliferation and in several there were occasionalglomeruli in which this proliferation was sufficient tojustify the term crescent. In 3 patients frank cellularcrescents were seen in numerous glomeruli, and inone child (Case 4) they were noted as early as six daysafter the onset of symptoms. In several otherbiopsies occasional glomeruli contained fibroticcrescents, and in Case 24, who was not biopsied,detailed examination at necropsy showed them inonly 1 in about every 50 glomeruli. In Case 12 manyglomeruli showed adhesions between crescents andfibrils arising from the basement membrane of theabnormal capillary tufts, leading to obliteration ofthe capsular spaces and complete glomerularsclerosis.

317



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/

TABLE 9SUMMARY OF HISTOLOGICAL FINDINGS IN FIVE CHILDREN WHO HAD SERLAL BIOPSIES

Glomerular TuftsGrade Case No.

Days from No. of Cel Polymorphs Sclerosis Bowman's Tubules IntcrstitialOnset Gloncrdli Prolif. Capsuls Tissue

f3 8 21 + + Occ. - - -98 51 Occ. - - - - -

I 1 13 13 73 + + + Occ. - - -65 69 + - - - -_137 33 - - - - - -

21 14 57 ++ ++ - - - +44 94 + - - _ _ _

II 15 7 79 + + + Occ. +(T) + +65 66 + - cc. + - -126 83 + + + _ _

III 8 15 96 + + - + + + +59 71 ++ _ + ++ _ _

Abbrevitxos used are the same as those in Table 8.

In two specimens tubularization of the capsularepithelium was observed, the cells resembling thoseof the proximal tubules.

TUBULES. In 19 of the initial biopsy specimensred blood cells were seen in the tubular lumens.Tubular changes were not usually striking andconsisted principally of dilatation, with flattening ofthe epithelial lining of both proximal and distaltubules. Necrosis was seen in two instances only.Close scrutiny of the tubules showed, however, thatin several patients therewas increased mitotic activity,suggesting regeneration of damaged epithelial cells.

INTERSTnAL TIssuE. Ten cases showed interstitialoedema and patchy infiltration with inflammatorycells. This was usually associated with lesions in thetubules and Bowman's capsules. A fairly constantfeature in this series was the presence offoci ofplasmacells in the interstitial tissue. Occasional eosinophilsand polymorphs were also seen. Except in Case 12,who had rapidly progressive glomerulonephritis,fibrosis was not a notable feature and there were nochanges in the arterioles.

Assessment of Renal Da ge In an attempt tocorrelate the over-all histological features with someof the clinical and biochemical abnormalities, thepatients have been placed into one of four grades ofhistological damage. The grading of the initialbiopsies in individual patients is shown in Table 8.The criteria of assessment, shown below, are depend-ent on changes in the Bowman's capsules, tubules,and interstitial tissues. Cellular proliferation ofglomerular tufts and polymorphonuclear exudationare, of course, common to all grades.

Grade I: No significnt widespread changes inBowman's capsule, the tubules, or interstitial tissue(14 patients).

Grade H: Focal changes in the interstitial tissueconsisting of oedema and inflammatory cell infiltra-tion, usually associated with tubular dilatation and/orproliferation of the cells of Bowman's capsule, form-ing occasional crescents (7 patients).

Grade III: AsH, but with more widespread tubularand interstitial changes, and more numerouscrescents (2 patients).

Grade IV: As I:l, but with numerous crescents andextensive glomerular sclerosis (1 patient).

H1tological Finding in Repeat Biopies Repeatbiopsies were performed on 5 patients (Table 9), 3 ofwhom showed Grade I changes on their initialspecimens. Case 3 was re-biopsied 98 days after theonset of illness, when the specunen was normal apartfrom residual proliferation in occasional glomeruliand the presence of red blood cells in some of thetubules. In Case 13 a second biopsy, at 69 days,showed slight proliferative change in most of theglomeruli while a third, at 137 days, was virtuallynormal. Case 21 had a second biopsy at 44 daysthat showed residual proliferation in the tufts andoccasional foci of inflammatory cell infiltration inthe interstitial tissues. From these findings itappears that resolution of the lesions in those withGrade I damage is complete in about 80-120 daysfrom the onset of the illness.Case 15, who showed Grade H lesions initially,had

biopsies performed at 7, 65, and 126 days, and in thelast specimen there were still significant changesconsisting of minimal proliferation of some of theglomerular tufts, slightly increased cellularity ofBowman's capsules, and occasional sclerosingglomeruli. There was, however, complete resolutionof the tubular and interstitial changes, and ourimpression was that activity was subsiding and thatthe patient would probably survive with a number of

318 HU77 AND WHITE



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/

ACUTE GLOMERULONEPHRITIS IN EAST AFRICAN CHILDRENscarred and functionless glomeruli, although thepossible development of a latent phase, followed bychronic nephritis, could not be ruled out at this stage.Case 8, in Grade Ill, was biopsied after 15 and 59

days. Marked changes were found in both speci-mens and the only significant difference was thegreater frequency of sclerosing glomeruli and fibrouscrescents in the second biopsy, suggesting that aprogressively destructive process was occurring.

Correlation of Structure and Function In anattempt to correlate structure and function we havetabulated the relation between the four grades ofrenal damage and some of the clinical and laboratoryfindings. From Table 10 it can be seen that therewas an even distribution of normal and raised bloodpressures, microscopic and macroscopic haematuria,slight to heavy proteinuria, and insignificant andraised antistreptolysin titres among patients showingGrade I histological changes. Grades H-IV changes,however, were more often associated with hyper-tension, gross haematuria, heavy proteinuria, andraised antistreptolysin titres. Since, however, only 3patients fall into Grades III and IV, caution is neededin drawing any conclusions from the findings.The wide range of blood urea levels seen in patients

with Grade I histological changes overlaps the levelsin Grade II and Ill (Fig. 3), and the highest levelsin these three grades were, in fact, obtained fromtwo Grade I patients, Cases 9 and 24, both of whomdied. The one patient in Grade IV (Case 12) had ablood urea of 321 mg./100 ml. on admission, but itfell gradually and fluctuated between 46 and 60 mg.during her last month in hospital.

Treatment, Follow-up, and Prognosis. Bed-rest wasencouraged while gross haematuria continued, butowing to the nursing shortage a strict regime was notpossible and many patients were discharged prema-turely to make room for more seriously ill children.Dietary protein was not usually withheld as nephritiswas often complicated by malnutrition and hook-worm. Intramuscular penicillin was given routinely.Subsequent out-patient attendance was poor anddomiciliary visits were considered impracticable.Only 8 out of 22 survivors were followed up for morethan eight weeks from the onset of illness and furtherrenal biopsies were performed on 5 ofthem (Table 9).Three of these were from patients initially labelled

Grade I. Two were normal and one showedappreciable resolution of the changes. The Grade Hpatient showed minimal abnormalities on her thirdbiopsy and microscopic haematuria continued. Theremaining 15 survivors in these grades wouldprobably have recovered, but limited follow-upprecluded attempts to prognosticate. In Grades Ill

319TABLE 10

CLINICO-PATHOLOGICAL CORRELATIONS

Histological Grade

I II III IV

Blood pressure (23 patients)..Normotensive 7 2 -

Hypertensive 6 5 2 1Haematuria

Microscopic 7 1 1 -

Macroscopic 7 6 1 1Proteinuria (mg 100 ml.)

30-100 .5 1 - -100-300 .4 3 - -> 300 5 3 2 1

ASO titre (units'ml.)< 166 5 -

166 .I I - -> 200 5 5 2 1

Not recorded .3 1 - -

* One patient had acute rheumatism.

and IV, however, the prognosis was clearly poor.Case 4 ran away during a severe, early relapse, andCase 12 had both urinary abnormalities and impairedrenal function. In Case 8 haematuria persisted andthe second biopsy showed deterioration.

DiscussionWhen comparisons are made with previous reports

from Uganda (Luder, 1958; Shaper and Shaper, 1958)there appears to have been a dramatic increase in theincidence of acute nephritis in children in the pastfew years. The problem arises as to whether thisincrease is a real one or reflects better case finding.Symonds (1960) recorded an increasing incidence ofnephritis in Trinidad in 1958, reaching epidemic

00S

wD

a00-J,o

120-

1 10-

100-

90-

70-

60

5o-

40-

30-

20-

1 >j

0

0

S

0

0

0

0

0@00 0

.0

0

0

@00

0

0

1321

i . i

IHISTOLOGICAL GRADE

FIG. 3.-The relation between histological grading and blood urealevels on admission to hospital.



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/

HUIT AND WHITE

proportions and later subsiding. Rammelkamp andWeaver (1953) observed that the attack rate variedfrom year to year and epidemics are occasionallyreported in temperate climates (Siegel, Rammelkampand Griffeath, 1955; George, McDonald, Payne andSlade, 1958; Pleydell and Hall-Turner, 1958).However, in the series reported here there was nosignificant seasonal variation and the geographicaldistribution paralleled the population density.Moreover, there appears to have been no decline inthe occurrence of acute nephritis since the completionof this study. The evidence suggests that this recentincrease might be explained by greater use of themedical services by the local population, betterscreening by medical assistants, increased awarenessof the condition by those informed of our prospectivesurvey, the insistence upon routine urinalysis in thewards and the use of renal biopsy as an infalliblediagnostic procedure.From the published material it appears that the

nephrotic syndrome is commoner than acute'haemorrhagic' nephritis in tropical Africa (Luder,1958; Lauckner, Rankin and Adi, 1961), in contrastto South Africa where, as in the temperate zones ofthe northern hemisphere, acute nephritis is much thecommoner (Furman, 1955: Uys, 1956). This hasrecently been amply confirmed in Nigeria, whereHendrickse and Gilles (1963) collected 156 childrenwith the nephrotic syndrome and only 22 with acutenephritis during the same period. In Uganda, onthe other hand, our own observations (Table I)suggest that the incidence of 'classical' acutenephritis is more than half that of the nephroticsyndrome. However, since the nephrotic syndromeis now recognized as denoting a clinical and bio-chemical pattern rather than a single pathologicalentity, a purely clinical classification of nephritis isno longer sufficient, and racial and geographicalevaluation must, therefore, hinge on both the clinicaland pathological findings.The histological features in the initial renal biopsy

and post-mortem specimens from our 24 cases wereall characteristic of acute, diffuse glomerulonephritis.These findings consist essentially of swelling of theglomerular tufts due to proliferation of the endothel-ial and possibly mesangial cells, swelling of theendothelial cell cytoplasm and infiltration by poly-morphonuclear leucocytes. Several specimensshowed proliferative changes in Bowman's capsules,with crescent formation, and these changes werefrequently associated with evidence oftubular damageand interstitial infiltration or fibrosis. The moresevere capsular changes were usually paralleled bystriking tubular and interstitial lesions. Thesefeatures are similar to those found in renal biopsy

specimens from adults with acute glomerulo-nephritis (Hutt, Pinniger and de Wardener, 1958).It is now generally accepted that the histologicalfeatures described above denote a S-haemolyticstreptococcal aetiology, and it is apparent that thedisease can be recognized at a later stage by thepersistence of endothelial proliferation in the lobularstalk region of the glomeruli (Jennings and Earle,1961; Lawrence, Pollak, Pirani and Kark, 1963).Two specimens also showed striking tubularizationof the capsular epithelium. The significance of thischange is not understood. Hutt et al. (1958)observed it in adults with acute nephritis but Trowell,Davies, and Dean (1954) stated that the capsularepithelium was frequently cubical in East Africanchildren dying from kwashiorkor.

In this series serological evidence of recent5-haemolytic streptococcal infection was obtained in15 out of 20 patients (75%) in whom the ASO titrewas estimated; a further child, whose ASO titre wasnot estimated, also had acute rheumatism. ASOtitres of 200 units/ml. or more have been reported in94% ofNorth American children suffering from acutenephritis (Lyttle, Seegal, Loeb and Jost, 1938) and in620% of South African children of non-Europeanorigin (Levin and Yoffe, 1960). However, a titre ofless than 200 units ml. of blood does not precludestreptococcal infection; this has been substantiatedby Jennings and Earle (1961) who demonstratedraised titres of antistreptokinase, antihyaluronidaseand streptococcus type 12 antibodies in the serum inthe presence of low ASO titres. The site of strepto-coccal infection in the cases reported here isuncertain; in our experience throat swab culturetechniques in routine use proved unreliable. Twochildren had impetiginous skin lesions which mayhave been the source of infection. Blumberg andFeldman (1962) found impetigo in 680% of childrenwith acute nephritis while only 3 out of 63 throatswabs gave positive cultures. Davies (1949) andSymonds (1960) have drawn attention to the skin asa likely source of streptococcal infection in negrochildren.The age incidence in the present series is unusually

low; 790% of the children were under 5 years old.Levin and Yoffe (1960) found that 630% of non-European children in South Africa were under 6years old, while about 600% of Symonds' (1960)Trinidad negroes were under 5 years. In British andNorth American children, on the other hand, theincidence rises steeply at 3 years and falls at 9 to 10years, less than 50% of cases occurring in childrenunder 5 years old (Payne and Illingworth, 1940;Burke and Ross, 1947; Lewis, 1955; Blumberg andFeldman, 1962). The higher frequency of young

320



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/


patients in underdeveloped countries parallels theage incidence of infectious diseases such as polio-myelitis (Gear, 1958), presumably reflecting earlyexposure to ,-haemolytic streptococcal infection.Neonatal glomerulonephritis is very rare.

Thompson (1951) described an infant dying at 29days with oedema, cardiac failure, and albuminuria,and Collins (1954) reported a neonatal death at 90hours, associated with oedema and jaundice. Atnecropsy the kidneys in both cases showed similarfeatures, consisting principally ofincreased cellularityand hyalinization of the glomerular tufts which werefrequently adherent to capsular crescents, andtubular dilatation with vacuolation of the proximaltubular epithelium. Claireaux and Pearson (1955)suggested that these were probably cases of intraut-erine pyelonephritis and gave a detailed descriptionof a further infant who died with respiratory distress10 hours after birth. The kidneys showed strikingtubular dilatation, with colloid casts, and theglomeruli, which were reduced in number to one-third, showed considerable atrophy and pericapsularfibrosis. Some contained crescents that obliteratedthe capsular spaces. Inflammatory cell infiltrationand interstitial fibrosis were conspicuous only in thecortex. They claimed that this was another exampleof chronic pyelonephritis, but were able to provideneither bacteriological support nor a convincingexplanation of the extensive glomerular changes.They also remarked that the infant's mother had hada sore throat twice during pregnancy and that herASO titre was 200 units ml. three months afterconfinement.

Kunstadter and Rosenblum (1954) described ababy with the nephrotic syndrome, beginning at 9days and associated with severe anaemia: this infantdied at 72 days and, at necropsy, the glomerulishowed hyperaemia and increased cellularity, withoccasional capsular proliferation and adherence tothe tufts. In the only newborn infant in our series,x-ho also presented clinically as a nephrotic, thekidneys showed, on biopsy and at necropsy, thetypical appearance of acute diffuse glomerulo-nephritis including polymorphonuclear exudation,a feature not mentioned in previous reports.Although the ASO titre exceeded 333 units ml.. it isunlikely that he could have manufactured his ownantibodies to this extent (Lippard and Johnson, 1935:Potter and Lorber, 1961). It is, however, knownthat antistreptolysins are capable of crossing theplacental barrier, and cord blood levels usuallycorrelate with the mother's titres (Lippard andWheeler, 1936). In our case the mother"s titre wasunfortunately not estimated. It is tempting tospeculate that streptococcal antibodies that has-e

entered the foetal circulation transplacentally mayplay a role in the aetiology of intrauterine glomerulo-nephritis.The commonest presenting symptom in our

patients was swelling of the body; oedema wasconfirmed in 22 children (91 7°%). In tropicalAfrica, the mortality associated with oedema inchildren is well known to parents, although know-ledge of the main causes, i.e. kwashiorkor and hook-worm disease, eludes them, and medical advice isnowadays sought increasingly for this symptom.Four patients showed features of the nephroticsyndrome and, although there were atypical featuressuch as haematuria, hypertension, and azotaemia, aswell as other contributory factors, such as poornutrition and hookworm infection, these cases mightwell have been diagnosed as 'nephrosis' or 'Type IInephritis' before the advent of renal biopsy. Wilsonand Heymann (1959) reported five children sufferingfrom acute nephritis who presented as nephroticsand, in the 22 children recently described byHendrickse and Gilles (1%3), marked oedema andhypoalbuminaemia were constant features. It isevident that, in a country where there are multiplecauses of hypoproteinaemic oedema, careful clinicaland laboratory assessment is necessary beforeclassifying oedema, proteinuria, and hypoprotein-aemia simply as 'Type II nephritis'.

Haematuria was volunteered as the sole complaintin only two instances and was actually denied by themothers of two children in whom it was observed inhospital. The two probable explanations are, first,the local custom of micturating on the soil (which inUganda is red) or, less often, into pit latrines; andsecondly, the belief, prevalent amongst the Bagandatribe, that the simultaneous occurrence of oedemaand haematuria is due to gonorrhoea in the father(F. J. Bennett, 1963, personal communication).

Congestive cardiac failure has long been recognizedas a feature of acute nephritis (Goodhart, 1879;Burke and Ross, 1947; Davies, 1951). Levy (1930),Brod (1949), and Sharpey-Schafer (1955) have drawnattention to its occurrence in the absence of leadingsymptoms such as haematuria, and indeed occasion-ally with normal urine. Histological proof of thediagnosis in such cases has recently been provided byHutt et al. (1958) and Blumberg and Feldman (1962),as well as in 3 patients in this series. Congestivecardiac failure was a feature of the illness in 3 otherchildren who, however, also had haematuria. Ofthe 6 with heart failure, 4 were hypertensive. Hook-worm anaemia was presumably a contributory factorin 4 who were found to be infected, but only Case Ihad a haemoglobin level of less than 4 0 g. i 00 ml.,as in the patients of Somers (1959) in whom hook-

321



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/

322 HU7T AND WHITE

worm was the sole cause of reversible cardiac failure.The urine of symptomless patients convalescent

from scarlet fever and acute tonsillitis is frequentlyfound to contain an increased amount of protein,cells, and casts (Lyttle, 1933; de Wesselow, Goadby,and Derry, 1935), and it has been suggested that miildattacks of post-streptococcal nephritis are common.Siegel et al. (1955) have correlated these findings withproof of type 12 haemolytic streptococcal infection.Our biopsy findings demonstrate that the character-istic histological picture of acute, diffuse glomerulo-nephritis may sometimes occur with minimal urinaryabnormalities and in the absence of symptoms. Intropical Africa, where oedema is such a commonsymptom, it is even more likely that mild cases ofnephritis will be overlooked unless urinalysis becomesestablished as a routine investigation of sick children.Hendrickse and Gilles (1963) have remarked uponthe difficulties which this theoretically simpleprocedure may entail in an underdeveloped country,and our experience has been similar.

Unfortunately the lack of follow-up, inevitable ina widely scattered rural population who are not yetfamiliar with the nature of symptomless or latentdisease, did not permit an adequate assessment ofthe prognosis. From our few repeat biopsies it isapparent that the more widespreadthe initial damage,the longer will the histological abnormalities remain.There is also suggestive but not conclusive evidencethat patients with Grades H or IV damage hadprogressive disease.Concepts of streptococcal infections and their

sequelae, in tropical Africa, are now changing.Several decades ago acute rheumatism was regardedas rare in East Africa (Donnison, 1928; Williams,1939) but more recently Shaper and Shaper (1958)claimed that chronic rheumatic heart disease formedthe largest group of cardiac admissions to MulagoHospital in 1957. More than a decade ago Jelliffeand Reed (1953) found a S-haemolytic streptococcalcarrier rate of only 0970% among healthy Nigerianchildren; recently, however, Collard (1961) hasreported an incidence of 100% among patients admit-ted to University College Hospital, Ibadan. Luder(1957), referring to his experience in Uganda duringthe years 1954-56, states that, 'The haemolyticstreptococcus, though present, is relatively avirulent.Tonsillitis and rheumatic fever are rare, and acutenephritis extremely rare'. But a recent communitysurvey conducted in Uganda (G. A. Saxton, 1963,personal communication) has revealed that 20% ofrural African schoolchildren are carriers of >-haemolytic streptococci, while our own observationsindicate that acute post-streptococcal nephritis is byno means uncommon in Uganda. These findings

may have some bearing on the frequency of chronicproliferative glomerulonephritis noted in earliernecropsy reports (Hennessey, 1939; Davies, 1949)and on the more recent observations of Leather(1960) and Hutt and Sood (1963) that the morbidityand mortality from chronic glomerulonephritis ishigh in patients between 10 and 40 years old.

The clinical and pathological features of 24 EastAfrican children suffering from acute diffuseglomerulonephritis, and studied by means of renalbiopsy, are described. The diagnostic histologicalcriteria were (a) diffuse proliferation and swelling ofglomerular endothelial cells, and (b) infiltration bypolymorphonuclear leucocytes.

Serological evidence of ,-haemolytic streptococcalinfection was obtained in 750/ of cases. The ageincidence is lower than that found in temperateclimates. A case of post-streptococcal neonatalnephritis, simulating nephrosis, is described.The clinical pattern was varied; only 14 children

had 'haemorrhagic' nephritis; 4 presented asnephrotic syndrome, and 3 with cardiac failure, butmalnutrition and hookworm infection were contri-butory factors in most cases; 3 were detected only onroutine urinalysis.

Hypertension, macroscopic haematuria, heavyproteinuria, and raised ASO titres were prevalentwhere histological changes were more severe.Widespread interstitial and tubular lesions, associat-ed with numerous epithelial crescents and seen withintwo weeks of onset in two patients, probably denotea progressive lesion.

In contrast to previous reports, it is evident thatacute, post-streptococcal nephritis is common inUganda.

We wish to thank Professor D. B. Jelliffe for hisconstant encouragement and for allowing us to include inthis series patients under his care. The photomicro-graph was kindly produced by Mr. R. Tunnicliffe,Department of Pathology, Makerere University College;and Figures 1 and 3 by the Department of MedicalIllustration, Guy's Hospital, London.

REFERENCES

Allison, S. P. (1962). Renal disease in Uganda: a retrospectiie study.Brit. med. J., 2, 895.

Blumberg, R. W. and Feldman, D. B. (1962). Observations on acuteglomerulonephritis associated with impetigo. J. Pediat., 60, 677.

Brod, J. (1949). Acute diffuse glomerulonephritis. Amer. J. Med..7, 317.

Burke, F. G. and Ross. S. (1947). Acute glomerulonephritis. Areview of ninety cases. J. Pediat., 30, 157.

Claireaux, A. E. and Pearson, M. G. (1955). Chronic nephritis in anewborn infant. Arch. Dis. Childh., 30, 366.



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/

ACUTE GLOMERULONEPHRITIS IN EAST AFRICAN CHILDREN 323Collard, P. (1961). The prevalence of streptococcus pyogenes at

University College Hospital, Ibadan. Dokita, 2, 30.Collins, R. D. (1954). Chronic glomerulonephritis in a newborn

child. A.M.A. Amer. J. Dis. Child., 87, 478.Davies, C. E. (1951). Heart failure in acute nephritis. Quart. J.

Med., 20, 163.Davies, J. N. P. (1949). Pathology of Central African natives,

Mulago Hospital post mortem studies, X. Renal disease inAfricans. E. Afr. med. J., 26, 76.

de Wesselow, 0. L. V. S., Goadby, H. K. and Derry. D. C. L. (1935).Tonsillitis and albuminuria. Brit. med. J.., 1, 1065.

Donnison, C. P. (1928). Valvular heart disease in the African native.Kenva and E. Afr. med. J., 5, 210.

Furman, K. 1. (1955). Nephritis in the Bantu. S. Afr. med. J., 29,590.

Gear, J. (1958). Poliomyelitis. In Diseases of Children in theSubtropics and Tropics, ed. H. C. Trowell, and D. B. Jelliffe,p. 290. Arnold, London.

George, J. T. A., McDonald, J. C., Payne, D. J. H. and Slade. D. A.(1958). Nephritis in North Yorkshire. Bnt. med. J., 2, 1381.

Goodhart, J. F. (1879). On acute dilatation of the heart as a cause ofdeath in scarlatinal dropsy. Guy's Hosp. Rep., 3 ser., 24, 153.

Haggerty, R. J., Maroney, M. W. and Nadas, A. S. (1956). Essentialhypertenasion in infancy and childhood. A.M.A. Amer. J. Dis.Child., 92, 535.

Hendrickse, R. G. and Gilles, H. M. (1963). The nephrotic syndromeand other renal diseases in children in Western Nigeria. E. Afr.med. J., 40, 186.

Hennessey, R. S. F. (1939). Observations on nephritis in Ugandanatives. ibid., 15, 329.

Hutts M. S. R., Pinniger, J. L. and de Wardener, H. E. (1958). Therelationship between the clinical and histological features ofacute glomerular nephritis. Quart. J. Med., 27, 265.and Sood. N. K. (1963). An analysis of renal disease as found atpost-mortem at the Mulago Hospital in 1961. E. Afr. Mfed. J-,40. 202.

Jelliffe, D. B. and Reed, F. S. (1953). The incidence of beta-haemoly-tic streptococci in the throats of tropical African children.J. trop. Med. Hyg., 56, 33.

Jennings, R. B. and Earle, D. P. (1961). Post-streptococcal glomer-ulonephritis: Histopathologic and clinical studies of the acute,subsiding acute and early chronic latent phases. J. clin. Invest.,40, 1525.

Kunstadter, R. H. and Rosenblum, L. (1954). Neonatal glomerulo-nephritis and nephrotic syndrome in a 1,320 gm. prematurelyborn infant. A.M.A. Amer. J. Dis. Child., 88, 611.

Lauckner, J. R., Rankin, A. M. and Adi, F. C. (1961). Analysis ofmedical admissions to University College Hospital, Ibadan-1958. 1W .4fr. med. J., 10, 3.

Lawrence, J. R., Pollak, V. E., Pirani. C. L. and Kark, R. M. (1963).Histologic and clinical evidence of post-streptococcal glomerulo-nephritis in patients With the nephrotic syndrome. Afedicine(Baltimore), 42, 1.

Leather, H. M. (1960). Glomerulonephritis in Africans in Uganda.Brit. med. J., 1, 1930.

Levin. A. R. and Yoffe, Y. (1960). Acute nephritis in non-Europeanchildren, with special reference to the treatment of hypertensionwith magnesium sulphate. S. .4fr. med. J.. 34, 921.

Le.v. 1. J. (1930). The cardiac response in acute diffuse glomerulo-nephritis. A4mer. Heart. J., 5, 277.

Lewis, I. C. (1955). The Sch6nlein-Henoch syndrome (anaphylactoidpurpura) compared with certain features of nephritis andrheumatism. Arch. Dis. ChiJd., 30, 212.

Lippard, V. W. and Johnson, P. (1935). Beta hemolytic streptococcicinfection in infancy and in childhood. I. Antifibrinolysin andantistreptolysin response. Amer. J. Dis. Child., 49, 141 1.and Wheeler, G. W. (1936). Beta hemolytic streptococcic

infection in infancy and in childhood. m. Placental trans-mission of antifibrinolysin and antistreptolysin. ibid., 52, 61.

Luder, J. (1957). Some paeditaric problems of Uganda. Brit. med.J.,2, 1143.(1958). Diseases of the kidney and urinary tract. In Diseasesof Children in the Subtropics and Tropics, ed. H. C. Trowell andD. B. Jeiliffe, p. 326. Arnold, London.

Lyttle, J. D. (1933). The Addis sediment count in scarlet fever.J. cdin. Invest., 12, 95.

*, Seegal, D., Loeb, E. N. and Jost, E. L. (1938). The serumantistreptolysin titer in acute glomerulonephritis. ibid., 17, 631.

Musoke, L. K. (1961). An analysis of admissions to the paediatricdivision, Mulago Hospital in 1959. Arch. Dis. Childh., 36, 305.

Payne, W. W. and Illingworth, R. S. (1940). Acute nephritis inchildhood, with special reference to the diagnosis offocal nephritis.Quart. J. Mfed., 33, (n.s. 9), 37.

Pleydell, M. J. and Hall-Turner, W. J. A. (1958). An outbreak ofnephritis in Northamptonshire. Brit. med. J., 2, 1382.

Potter, C. W. and Lorber, J. (1961). Antistreptolysin levels in normalinfants and young children. J. clin. Path., 14, 525.

Raper, A. B. (1953). Nephritis and allied lesion in Central Africans.A contribution from autopsy work. E. Afr. med. J., 30, 49.

Rammelkamp, C. H., Jr. and Weaver. R. S. (1953). Acute glomerulo-nephritis. The significance of the variations in the incidence ofthe disease. J. clin. Invest., 32, 345.

Shaper. A. G. and Shaper, L. (1958). Analysis of medical admissionsto Mulago Hospital, 1957. E. Afr. med. J., 35, 647.

Sharpey-Schafer. E. P. (1955). The response of the heart in acutenephritis. Lancet, 2, 841.

Siegel, A. C.. Rammelkamp, C. H., Jr. and Griffeath, H. 1. (1955).Epidemic nephritis in a school population. The relation ofhematuria to group A streptococci. Pediatrics, 15, 33.

Somers, K. (1959). Acute reversible heart failure in severe iron-deficiency anemia associated With hookworm infestation inUganda Africans. Circulation, 19, 672.

Symonds. B. E. R. (1960). Epidemic nephritis in South Trinidad.J. Pediat., 56, 420.

Thompson. A. C. (1951). Neonatalglomerulonephritis. U: Va med.J., 47, 16.

Trowell, H. C., Dasies, J. N. P. and Dean, R. F. A. (1954).Kwashiorkor, p. 154. Arnold, London.

Uys, C. J. (1956). The pathology of renal disease in the Bantu on theWitwatersrand. Glomerulonephritis. S. 4fr. J. Lab. clin. Med.,2. 232.

White. R. H. R. (1962). A modified Silverman biopsy needie for usein children. Lancet, 1, 673.(1963). Obsersations on percutaneous renal biepsy in children,.4rch. Dis. Childh., 38, 260.

Williams. A. W. (1939). Heart disease in the native population ofUganda. Part Il-Bacterial infections of the heart. E. Afr.med. J.. 16, 2.

Wilson, S. G. F. and Heymann, W. (1959). Acute glomerulonephritisWith the nephrotic syndrome. Pediatrics, 23, 874.



j.com/

Arch D


ugust 1964. Dow

nloaded from

http://adc.bmj.com/

A CLINICO-PATHOLOGICAL STUDY OF …adc.bmj.com/content/archdischild/39/206/313.full.pdf · A...

Documents

Transcript of A CLINICO-PATHOLOGICAL STUDY OF …adc.bmj.com/content/archdischild/39/206/313.full.pdf · A...