Posigrad. med. J. (December 1968) 44, 903-907.

Adult nephrotic syndrome in Ibadan, Nigeria:a prospective study of 135 cases

0. 0. AKINKUGBEM.B.Lond., D.Phil.(Oxon), F.R.C.P.Ed.

MOLLIE HUNTONM.B. Newcastle

The Department of Medicine, University College Hospital,Ibadan, Nigeria

SummaryOne hundred and thirty-five adult patients ad-

mitted into the medical wards with the nephroticsyndrome have been studied over a period of3 years.The histopathology in eighty-one renal biop-

sies showed predominantly proliferative glomer-ulonephritis.

Nine patients had filariasis and in six of thesethe microfilaria isolated was Loa loa. Six patientshad malarial parasitaemia; of these, three hadP. malariae infection. Urinary schistosomiasis wasdiagnosed in four patients.Twenty-seven patients were noted to be hyper-

tensive and 104 patients had some degree ofimpairment of renal function. A total of ninedeaths was recorded (6-7%) in the 3-yearperiod.The significance of these results is discussed.

IntroductionThe nephrotic syndrome is an important cause

of morbidity from renal disease in Ibadan,Nigeria. It is approximately ten times more com-mon in local hospital practice than it is inEurope and America, accounting for 2-3 % ofall medical admissions into the adult wards ofthe University College Hospital (U.C.H.) Ibadan(Willis, personal communication 1965). It is,however, less significant a factor in renal mor-tality in this environment (Table 1). The purposeof this study is three-fold: to define the histo-pathology of adult nephrotic syndrome as seenin the wards; to assess the significance of malarialand microfilarial parasitaemia and urinary schisto-somiasis, and to outline the role of hypertension,haematuria and urea retention in the overallprognosis of the disease.

Materials and methodsDuring the 36 months between January 1965

and December 1967, a total of 135 cases of thenephrotic syndrome were personally studied at

the renal unit of the U.C.H., Ibadan. Practicallyall the patients seen were from Ibadan township(population 750,000) or the conglomeration ofvillages in its environs. Patients below 12 yearsof age and those suffering merely from massiveproteinuria but without a substantial fall in theirserum albumin levels were excluded from thestudy. Skin snips were taken for Onchocercavolvulus and D. streptocerca, blood was ex-amined for the microfilariae of Loa loa, D.perstans and Wuchereria bancrofti and a mini-mum of three thick blood smears were taken formalarial parasites. In each patient, on at leasttwo occasions, the urine was examined for thepresence of ova of S. haematobium. Packed cellvolume (PCV) was estimated by the micro-haematocrit method and for the biochemical in-vestigations the standard methods employed areas described in Varley (1962). Following intra-venous pyelography, percutaneous renal biopsywas undertaken in ninety-three patients.

TABLE 1Mortality from renal disease (U.C.H. 1965-66)

No. of %cases Deaths mortality

Acute glomerulonephritis 24 12 50Chronic glomerulonephritis 12 9 75Acute pyelonephritis 19 5 26Chronic pyelonephritis 50 16 32Acute renal failure 9 7 78Nephrotic syndrome 41 4 9.8Miscellaneous (chronic 10 6 60

renal disease)

ResultsOf a total of 135 cases, sixty-four (47-5 %)

were male and seventy-one (52-5 %) female.There were no patients over the age of 70 years.Over 80% were between the ages of 10 and 40(Fig. 1).

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0. 0. Akinkugbe and Mollie Hunton

HistopathologyIn twelve of the ninety-three renal biopsies,

the number of glomeruli present in the sectionswere too few to give conclusive results. The re-maining eighty-one biopsies are analysed inTable 2. It is seen that proliferative glomerulo-nephritis accounts for the majority of cases. Itmust be stated that no attempt has been made toseparate the proliferative into the generalized,localized, diffuse or focal (segmental) types(Dodge et al., 1962), and although it is knownthat the prognosis varies as between the endo-thelial and predominantly epithelial varieties ofproliferative nephritis, it has not been easy todistinguish numerically between these two. Four-teen cases showed thickening, splitting or dupli-cation of the basement membrane component ofthe peripheral capillary wall as the dominantlesion. The miscellaneous group is furtherbroken down to show pyelonephritis accountingfor six cases (Table 3).

40

30tn

6 20z

10

0)

Age (years)

FIG. 1. Analysis of 135 cases of adult nephrotic syndronme(1965-67).

Protozoal and hel/ninthic infectionsThe incidence of filarial infection and mal-

arial parasitaemia is shown in Table 4. Micro-filariae were detected in nine patients, two fromskin snips (0. volval/us) and the rest from theblood. Loasis accounts for six (67',/, ) of all thecases of filarial infection. In five of the sixpatients with boasis, eosinophilia was marked(over 10'y,,). In no patient was D. streptocerca orW. hancrofti isolated from the sample taken.There was a total of six patients with malarial

parasitaemia. None of these was pyrexial at thetime of taking the blood sample. Three of the

six had quartan malaria, two tertian and in thesixth both P. malariae and P. falciparium werepresent in the thick blood smear.The presence of urinary schistosomiasis was

confirmed by the detection of ova of S. haemaio-hium in the urine of four patients, all under theage of twenty-five years. Of these, only one hadcomplained of antecedent haematuria.

TABLE 2Histopathology of eighty-one cases of the nephrotic syndronme

in U.C.H.

Minimal change 7Membranous 14Proliferative 35Mixed (membranous,'proliferative) 2Chronic glomerulonephritis 9Miscellaneous group 14

TABLE 3Analysis of fourteen miscellaneous causes of the nephrotic

syndrome in U.C.H.

Renal amyloidosis 3Pyelonephritis 6Toxic tubular necrosis 2Diabetic nephrosclerosis IRenal vein thrombosis IRenal rickets I

TABLE 4Filarial infection and malarial parasitaemia in 135 cases ot

adult nephrotic syndrome

No. of cases

Type of microfilaria0. ColUil/Us 2D. streptocercaLoa loa 6D. perstahis IW. bant roofti

Type of malarial parasiteP. falciparum 2P. mna/ariae 3Mixed P. fu/l iparlini P. ata/ariac I

Hypertension. haernatliria and azotaeniiaHypertension was diagnosed when the recum-

bent blood pressure under basal conditions was140/90 mmHg or over on at least two occasions.Using this criterion twenty-seven patients werehypertensive and of these, twelve were admittedin left ventricular failure. Eighteen of thesehypertensive patients had renal biopsies and inthirteen there was evidence of proliferativeglomerulonephritis with moderate arteriolarsclerosis. In the twenty-seven patients, eight had

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The nephrotic syndrome in Nigeria

had their illness lasting a year or more beforeseeking medical attention. Hypertension and thenephrotic syndrome were then diagnosed simul-taneously. In five others, hypertension had super-vened on a background of the nephrotic syn-drome during several months of outpatientattendance.

In only two patients was a definite history ofmacroscopic haematuria obtained. These oc-curred about 15 months before the onset ofthe illness. Microscopic haematuria was subse-quently detected in both these patients and insix more patients who were reported as havingnumerous red cells in the mid-stream urinaryspecimens.The blood urea level was used as a crude index

of glomerular function. A figure of 40 mg/100 ml was arbitrarily chosen as the upper limitof normal in this population (Edozien, 1958).Employing this parameter, 104 patients hadsome degree of renal impairment at one stage oranother of their illness (Fig. 2). Thirty-eightpatients had severe renal disease as shown by ablood urea of over 100 mg/lO0 ml. Of these,twelve were hypertensive. Histopathologicalstudies could not be correlated with the degreeof urea retention in these cases as intravenouspyelography, a desirable prelude to renal biopsy,could not have been rewarding.A total of nine deaths occurred in the 135

cases (6 7,/',) during the 3-year period understudy. Autopsy was carried out in eight, threeshowed changes of diffuse glomerulonephritiswith epithelial proliferation, one membranousglomerulonephritis and one renal amyloidosis

while in the remaining three patients the kidneyswere small and scarred, with histological changescompatible with chronic pyelonephritis.

35

30

25a)Q.n

u 200

6 1 5z

10

5

Blood urea (mg/ 100 mL)

FicG. 2. Blood urea values in the nephrotic syndrome.

DiscussionThe exact incidence of the nephrotic syndrome

in the community at large still has to be estimated.It seems hardly surprising that there should be,as most authors have demonstrated, a disparityin figures for outpatient attendance, inpatientadmissions and autopsy records in a disease com-plex characterized by a protracted course(Table 5).The histopathological classification of the renal

lesions in the nephrotic syndrome has always

TABLE 5Renal disease in U.C.H. (data from five studies)

Lauckner,Rankin & Adi

(1958)Clinical: adult

Acute renal failureAcute glomerulonephritisChronic glomerulonephritisAcute pyelonephritisChronic pyelonephritisNephrotic syndromeMiscellaneous

Total number of cases

93842

24Unclassified

88

*Subacute glomerulonephritis.tlncludes detailed study of twenty cases.

905

Edington &Mainwaring(1958-62)A utopsy

102

104125124*

Amyloid 12Ca kidney 10Schisto, 7

Unclassified 20282

Hend rickse& Gilles(1959-63)Clinical:paed iatric

22

7156

Unclassified11

196

Akinkugbe(1965-66)Clinical:adult andpaediatricin-patients

I 12412184965t

Unclassified14

193

Akinkugbe(1965-66)Clinical:adult

out-patients

23

2952

Unclassified27

113

7

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906 0. 0. Akinkugbe and Mollie Hunton

been bedevilled by lack of uniformity in nomen-clature. Thus, minimal change on light micros-copy is grouped under the proliferative headingby some (Kibukamusoke & Hutt, 1967) whilstother workers prefer to classify it separately(Blainey et al., 1960). Confused terminology isepitomized in the use of the word 'focal' as threedifferent authors proffer separate meanings:Edington & Mainwaring (1966) using Dodge'sclassification (Dodge et al., 1962) describe in-volvement of part of a glomerulus butKibukamusoke & Hutt (1967) restrict the use ofthe term to abnormal involvement of someglomeruli, whilst others are spared. Spear (1965),however, denotes as focal, changes involving'specific glomeruli and only specific tufts withinan afflicted glomerulus-thus focal within thekidney and focal within the glomerulus'. It iswith these difficulties in mind that we find our-selves unable to categorize the histologicalchanges in our specimens any further than asessentially minimal change, and as proliferativeand membranous glomerulonephritis. It must bestated that the majority of cases of proliferativenephritis were of the localized diffuse variety.It is also noteworthy that these appearancesdiffer somewhat from those classically found inchildren in the same environment. Hendrickse &Gilles (1963) and Edington & Mainwaring (1966)describe biopsy findings in children in Ibadanwith the nephrotic syndrome as falling into twomain groups: the localized focal proliferative(simulating post-streptococcal nephritis) and thelocalized focal membranous. Both groups ofworkers agree that diffuse membranous changesare extremely rare in this environment.

Filariasis was noted in nine of the 135 casesand the majority of those so infected turnedout to be loasis. A significant link has beenrecently contested, on both epidemiological andimmunological grounds between endomyocardialfibrosis and loasis (Ive et al., 1967). Our figuresare too small to draw any valid conclusions as tothe causal relationship between loasis and thenephrotic syndrome in the tropics. It is possiblethat any relationship between these two condi-tions is fortuitous.

Nearly 40 years ago, a striking association wasemphasized between the occurrence of massiveproteinuria and P. malariae infection (Giglioli,1930). The same worker subsequently went onto prove (Giglioli, 1962) the virtual disappear-ance of the nephrotic syndrome with eradicationof malaria in Guyana. This relationship has beenamply confirmed in childhood nephrosis in bothWest and East Africa (Gilles & Hendrickse,1960; Hendrickse & Gilles, 1963; Kibukamu-

soke, 1966b). The same association has beensuggested in adults in East Africa by Kibu-kamusoke (1966b). It has been suggested that theantigenic response to infection by P. malariae'sets the stage' for vulnerability of the glomerulusto a wide variety of potentially toxic agents. Alimited study of eleven patients by Kibu-kamusoke (1966a) in Lagos, Nigeria showed thepresence of P. malariae in seven adult nephroticsas compared to only two in controls. Whetherthe same association can be proved in adultswith the syndrome in West Africa remains amatter for speculation but our present resultsdo not point in the affirmative. It is, of course,possible that the initial renal damage occurs dur-ing infection with P. malariae in childhood, leav-ing a legacy of proteinuria that becomes obviousin later years, long after the malarial para-sitaemia has disappeared.

Since Gelfand (1963) reported fifteen cases ofurinary schistosomiasis in twenty-five consecu-tive African subjects with the nephrotic syn-drome in Central Africa, some attention hasbeen focussed on a possible aetiological relation-ship. We can find no grounds for this in thepresent series. Only four of our 135 patients hadurinary schistosomiasis, an incidence no higherthan one would expect in the rest of the popula-tion, for Ibadan is a well-known endemic areafor urinary schistosomiasis (Cowper, 1963).The incidence of hypertension in this series

was 20%. Majority of the hypertensives showedevidence of proliferative glomerulonephritis. Itis notable that a number of these patients de-veloped hypertension after about a year's follow-up as known cases of the nephrotic syndrome;others admitted to an antecedent history of in-sidious oedema for about a year before thenephrotic syndrome and hypertension weresimultaneously diagnosed. Urea retention ofsome degree was present in 77% of all cases ofthe nephrotic syndrome. This seems a higherfigure than that of Kibukamusoke (1967) whoin a study of fifty-one cases of the nephroticsyndrome found a 'significant degree of urearetention' in twenty-eight. It appears remarkablethat the mortality from this illness for the periodunder review was so low (6-7 %) when one con-siders that thirty-eight patients had blood ureavalues of over 100 mg/100 ml and twelve ofthese (31-6%) had coincident hypertension.

ReferencesBLAINEY, J.D., BREWER, D.B., HARDWICKE, J. & SOOTHILL,

J.F. (1960) The nephrotic syndrome. Quart. J. Med. 29, 235.COWPER, S.G. (1963) Schistosomiasis in Nigeria. Ann. trop.Med. Parasit. 57, 307.

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DODGE, W. F., DAESCHNER, C.W., BRENNAN, J.C., ROSEN-BERG, H.S., TRAVIs, L.B. & Hopps, H.C. (1962) Per-cutaneous renal biopsy in children. Paediatrics, 30,287; 297.

EDINGTON, G.M. & MAINWARING, A.R. (1966) Nephro-pathies in West Africa. Internat. Acad. Path. MonographNo. 6, 488.

EDOZIEN, J.C. (1958) Biochemical normals in healthyNigerians. W. Afr. med. J. 7, 121.

GELFAND, M. (1963) A possible relationship between thenephrotic syndrome and urinary schistosomiasis. Trans.roy Soc. trop. med. Hyg. 57, 191.

GIGLIOLI, G. (1930) Malarial Nephritis. Churchill, London.GIGLIOLI, G. (1962) Malaria and renal disease with special

reference to British Guiana. Ann. trop. Med. Parasit. 56,101; 225.

GILLES, H.M. & HENDRICKSE, R.G. (1960) Possible aetio-logical role of P. malariae in 'nephrotic syndrome' inNigerian children. Lancet, i, 806.

HENDRICKSE, R.G. & GILLEs, H.M. (1963) The nephroticsyndrome and other renal diseases in children in WesternNigeria. E. Afr. med. J. 40, 186.

IVE, F.A., WILLIs, A.J.P., IKEME, A.C. & BROCKINGTON, I.F.(1967) Endomyocardial fibrosis and filariasis. Quart. J.Med. 36, 495.

KIBUKAMUSOKE, J.W. (1966a) The nephrotic syndrome inLagos, Nigeria. W. Afr. med. J. 15, 213.

KIBUKAMUSOKE, J.W. (1966b) M.D. Thesis. University ofEast Africa.

KIBUKAMUSOKE, J.W. (1967) Hypertension and urea reten-tion in proliferative glomerulonephritis. E. Afr. med. J.44, 238.

KIBUKAMUSOKE, J.W. & HUTT, M.S.R. (1967) Histologicalfeatures of the nephrotic syndrome associated withquartan malaria. J. clin. Path. 20, 117.

LAUCKNER, J.R., RANKIN, A.M. & ADI, F.C. (1958)Analysis of medical admissions to University CollegeHospital, Ibadan. W. Afr. med. J. 10, 3.

SPEAR, G.S. (1965) Conjoint Clinic on renal biopsy-per-spective and clinico-pathological correlations. J. chron. Dis.18, 133.

VARLEY, H. (1962) Practical Clinical Biochemistry, 3rd edn.Heinemann, London.

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