Intervene
ISSUE 7 CASE STUDY ILLUSTRATIONS Using Data to Manage Behaviour
This entity was described in Nigeria by Hen& 1 27, and other researchers in the tropics (Habib 1 973'8, Kibukamusoke, 197 1 2Q, Morel Maroger et al. 1 9 7 P ) . The evidence in support of causal relationship between P. Malariae and the nephri~ic syndrome was based on epidemiologic. experimental and clinico-pathological ions by various researchers. The epidemiological evidence deril ly from the observation of Giglioli (1962b) f 1 who pointed UUL LUG vinual disappearance of the nephritic syndrome in Guiana after the eradication of malaria. This view was supported by Hendrickse " who found a highly 5i~nilicant increase in P. malaline parasitaemia in the nephritic childl.cn. It has however been argued that this may be due to an increased susceptibility of thr rlc-:phritic child to P. mnlariae infection.
observat {es large1
A , . * ,.ld
~cd essentially focal glo~i~erulosclerosis
In. mononuclear cell proliferation and .e\.alence of renal disease in HIV .- a
: \courgc.- and the high risk for ESRD, cilities for renal replacement therapy in
~nity sti~dies of the prevalence and risk RD will inform appropriate preventive
7'112 c x p e s i n ~ c ~ i ~ i ~ i e\!idence is based on rile M-ork of'\'oller et al ( 1973 )'' u.ho clescrihed nephritic syndrome in one ~plenectomised ~nonkey ba hour 20 weeks after infection with P. malariite.
I'CI.II~IJS the backhone of the body of data establishing the c.ns~i:lI
1 r.cl:tt ionship lii.~\\.ccn P.m:llariae and the nephritic s\:ndrome is h e sirnil:u'it!
I ol'glomei-\~l;i~- I~istolog!~ in cases of nephritic sqndmme associated with P.
malrlriae pnsa\i!:lcrnia. and also those largely eni.oiunrtxed in the P. malari;!e endemic regions 0-Iendrickse et a1 1072) ". This has been it~~rther corroborated by the demonstration of P. malariae antigen along the glomerular basement rnembrrine in up to 3G percent of cases". The
possibility of P. malariae triggering off other immunopathopenetic mechanism like Deoxyribonucleic acid (DNA) anti DNA immune complexes has been entertained in case3 where I? malariae antigen could not be demonstrated.
F? malariae nephmpathy is characterized by a progressive seg:nental and focal glomrulosclerosis. The basic lesion is a thickening of the capillary wall which in the earliest cases affects only few glomeruli in a segmental fashion, This thickening involves the subendothelial aspect of the baqement membemm, giving rise to a double contour of periodic acid Schiff (PAS) -positive, &@rophilic fibrils. There is messangial expansion with immune complex deposits mostly 1 gCa and C3.
. ,
Benefit5
frwn
p ~ w l o n e or immunosuppressive drugs have been reported in a few children especially those with highly sensitive proteinuria. mild histologic lesions and short duration of symptoms. (Adeniyi et rd 1970").Figure 12: Showing Quartan Malarial Nephropathy. P malariae GN:
PA!.!
stainning of the glomerulus showing focal segmental sclerosis (in an %year old child).:ring off other immunopathogenetic leic acid (DNA) anti DNA immune
I case5 where l? malariae antigen could
lerized by a progressive segmental and ,ic leion is a thickening of the capillary kcts only few glomeruli in a segmental ne subendothelial aspect of the basement e contour of periodic acid Schiff (PAS)
le is rnessangial expansion with immune
ld C3.
no suppressive drugs have been reported with highly sensitive proteinuria. mild In of symptoms. (Adeniyi et a1 I 9703?).
Figure 13: P malariae GN with glomerulus showing non uniform thickening of the gl. capillary wall with splitting in places, sparse mesangial cellularity & matricial expansion (Masson Trichome stain).
larial Nephropathy. Pmalariae GN:
s showing focal segmental sclerosis
Our effort ro implicate P. ~nalariae in adult glomenllonephritis and chronic kidney discasc has been relentless. The prevalence and density of rnalarial parasiitnema in adult nephrotic syndrome and chronic kidney disease is not sipiticantl y different from controls. EL8i.n though the renal hisrological I?nttelii oi ic~c:11 segmental Glomen~los~:ler-osis and mesangiocapillnry GN sccn commonly' in adult GN appears si:nilar- to rhose reporreti in childhood i P. inaltuiae iiephsc>pathy. it is conceiv:~hlc dlar it is areflectior~ of the li~nited
I
responses oi'tlle kidney to injury-
whate\.er the inju~y - a i d not specific to P. malasiac illt'cctinn. We have hon.evcr occasionally encountred cases of older chiltlren with the classical histological finding of P. malariae nenlironnthv I Firure 12 & 13). Ir is however possible that this may be a reflccric:!~ (,I I ~ I L li~nitecl ~.+sponse of the kidney to injury rather than a specific to malaria.Ilaemoglobin-S disease and GN
The prevalence of HB-S is 25% in the Nigerian population, and it occurs predominantly in theheterozygous state AS, and lebs frequently as SC or SS. st-Iaemoglobin-S has been implicated in somt: cases of primary glomerulonephritis but this association is infrequent ;n adult nephrology practice in Nigeria. The distribution of Haemoglobirl genotypes among the G N patients is not ~ i , ~ m t l y different from the normal population.
We have occasionally seen some SC or SS patients withglomen~lonephritis, complicated by chronic renal failure. The commonly encountered histopathology 1 rative GN.
SLE Nephritis
Systemic lupus erythematosus and its renal complications art: reco_gniixd to be common in black world wide but very uncommonly encountered in our practiceu. We have identified only 12 patients (in 10 years) fulfillin$
American College of Rheumatology d i a p o s ~ i c criteria. All were females.
age range 15
-
52 yrs, with 7 presenting in CRF. The classical butterfly rash wac observed in 2, Discoid rash in 2.Renal histopathology revealed Diffuse Proliferative GN in 3; MCGN 1 and Minimal Change in 1.Hypertensive Nephrosclerosis:
The etiological role of hypertension for renal disease in rhe clinical entity called Hypertensive nephrosclerosis is not in c i o r d 3 1 . hile its major contrihi~tio~l to ESRD particularly in blacks has been \? ~tlcly repolled. I11
a land mark 16 year prospective study of 36 1.662 incn. aged 35-57 years who participated in the multiple risk factor inten,en~ional trial. it \vat
uhscr\.ed I har
Ci) 8 14 died ol'rennl faihu-e/ESRD (49% ciue to hypertension).
(ii) age adjusted rate of ESRD per 100.000 persons w a ~ 205.6 cornpared to 5.3 in individuals with SPB2180. DPB
1 10 lnmtIg and SRP of < l20/80 respectively
1 1 in the Nigerian population, ancl it occurs
PU.: <tateAS, and le>s frequently as SC or
p implicated in some cases of primary hciation is infrequent in adult nephrology Iution of Haemoglobin genotypes among
hily different from the ncmnal popilation.
1 SC or SS patients with glornenllonephritis, Il failure. The commonly encountered 3N.
I and its renal complications are r e c o g i 7 ~ d wide hilt very u n c o m 3 d y encountered in
led only 12 patients (in 10 years) fulfilling ology diagoslic criteria. All were females,
I
presenting in CRF. The classical butterfly lid rash in 2.Renal histopathology revealedMCGN I and Minimal Change in 1.
I
bnsion for renal disease in the clinical entity ,\clerosis is nor ill t l o ~ h ~ . Ilile it< major bial.1) in black, ha\ been \! rtlcly rcpt)iled. In tctive \tu& of 36 1.662 r1k.n. aged 35-57
~nrlltiple ri\k factor mten~enrional tlid. it
(iii) absolute risk of ESRD was highest for those with a baseline BP in the highest category of SBP and
DBP,
and(iv) the relationship of BP and renal damage was positive and continuous through the blood pressure range. In another study of 1 1 12 males followed up for 13.9 years in the Veterans Atlmin hypertensive screening and treatment regimen. baseline BP predicted ESRD and 15 years later (Table 13)".
Figure 14: End stage renal disease and blood pressure
I 1 I I
Optimal I I t i j h - Stage I Stagi. 11 \ i . ~ j c I l l Sragc I V Normal
Opr i rnal )
d sate of ESRD per 100.OC)O persons wak ,red to 5.3 in individuals with SPB2180, DPB , ~ n d SUP of < 120180 respectively
Hypertensive nephrosclerosis accounts for bctwccn 25-50C% of the causes of CFR (our reports and others) in Africa, 22 - 4(!% in the LISA and 8'2 in E ~ ~ ~ ~ ~ I . ~ - 4 3 , 11 has been speculated that a ni~ri7her o f hctors acting in concert with hypertension promote the dt:veloprncnr o f hypertension related CRF. These include age, black race, severity of hypertension:
socio-economic factors, availability and utflization of hospital facilities, compliance with therapy and type of drugs: body Illass index; social hahirs;
alcohol intake; and cigarette smoking: high salt intake and concomitant systemic disease. Dyslipidaernia, oligonephro~iia, preterm birth. It is thus probable that the increased prevalence of hype]-rension induced CRF among the black Americans may be due to a preponderance uf these factors.
An active control of these factors among hypttnensive Nigeriaris wlill certainly translate to reduction in the prevalence ofc,RF and huge savings on renal replacelnent therapy. Obsesvations from our preliminary stildies o n risk factors for hypertensive nephrosclero.;is are in agreement with others elsewhere that
higher blood pressure levels at presentation.
n ~ r l y controlled blood pressure le\.els.
- I-'""'
pool non-
r compliance to therapy.
.. .... -11tili5at.ion of' hospital se~vices,
a higher body mass index, persisrsnr i.! c !.. ! . );[I L~~l~?lintirii~, hypt'rglycacrnia constin~te risk f:rctoss.
M'c h i ~ v e fttl-thes eval~rated the implications of rnicroalhumini~~-i:l anlong
~~ncomplicated hypel~ensives~. Il uras obser\.t.cl thut
. .
m i c r ~ ~ a l b u ~ ~ i i n ~ ~ ~ i a was preserlr in \;a ?in? Ic~cl> in 7(if.'4. ol IX:! ii'T?i>.
Levels colrelated 4ignif'icantly wit4 the prewnce of other tarset organdamage -left vaiirricular hypenrophy by ECG: left ~rentricular mass index (ECHO): retinopathy and a140 glomen~lar fillration rate.
;OI ults for hctwccn 25-50Ck of the causes in Aliica. 22 - 4% in h e LISA atlil 8'/i
~llated thar a nuri-~b~r (sf factors acti~lp iri
,riot? [he dr:~i-l(.,1~1nitW of hypertension
e, hlack race. saerity of hypertension:
lility ant1 ut;lization of hospital facilities,
c of dlu~s: hcdy Inaxs index: social hahirs;
roking: h i ~ h salr intake and concornitar~t u, oligonephmnin, preterm birth. It is thus :valence of huper~ension induced CRF lay he due to a prepontlerance of these
ors among hypenensive Nigerians will n the yrevale,nce ofc,RI: and huge savinss )bser\'ations from our preliminary s~udics e nephroscleroxis are in asreenlent with
:rap\.:
tal seixiccs.
.ndcs, pcrhisterlr I - ! : , . : - ! ; . ~ i h ~ ~ ~ ~ ~ i n u r i i l ,
lute risk frii.tc?r>.
liticantly wit11 thc pre\cr?ce ~i othcr Lasser
~ricular hyp~rophy hy ECG: left \rc~~tricular retinopathy and al\o gloinenilar filtration
Therapy targcted at abo!-tins microalbuminuria in the i~ncomplicated hypertensives should prevent development or evolution to hypertensive nephrosclerosis and CKF.
The institution of (.his strategy presupposes the identification of microalbuminuria as; a marker for onset of nephrosclerosis. Effective mategies should therefore include early detection and goal - focused
LI ~~atrnent of hypertension with drugs that do not only reduce blood pressure but protect the kidney by reducing glomerular hypertension, abort microalburninuria notably ACE inhibitors and calcium channel blockers)
J5. Longitudinal studies of risk factors for hypertensive nephrosclerosis have to be undertaken on a national scale.
Diabetic Nephropathy:
Diabetic Nephropathy is gaining significance as a cause of CRF and it may displace hypertensive nephrosclerosis or CGN as it has done in Europe and in USA46.". Indeed DM has become the leading cause of ESRD in many countries of Western Europe. In the USA, the proportion of patients with DM as the cause of ESRF (incidence) increased strikingly from 27%
in 1988 to 36% in 1992 and 40% in I 99548.J9. It has also been reported that a continuous increase in the number of patients with type 2 DM admitted for RRT has also recently been noted in Europe and Australia (Figure 15). Diabetic Nephropathy is now one of the leading causes of ESRD (exceeding -30-4070) in countries such as Malaysia.
Turkey. Qatar and the Phillipines. I".
In all European Countries even in those with a relatively Ion prevalence of diabetic nephropathy. the number of patients wit) I type 2 DM admitted for renal replacement therapy has r e c e n t l ~ increased. A high prevalence of DN with ESRD has been obse~--ded among Afro Carribeans and Asian individuals in the UKSn. Surviva 1 and
m$dieM'ke~h6ilHLi;b'K'C;f~~itierits
with tyye 2 DM on renal, I , I :::,,I-- ., ,
replacement therapy is significantly k o r s e than' in non-DM
' patients. It is obvious that in other to stem the tide, intensive efforts are necessary.
Figure 15: Incidence of Diabetes in ESRF Australia 1980-2000
Culled from Ritz et al 47
to inform the medical community about the renal risk of type 2 DM and the striking effectiveness of preventive measures.
(i) to provide better care for diabetic patients and DN-through- antihypertensive treatment with ACE inhibitors, intensified clycaemic control. cessation of smoking, reduction of protein
L -
intake. use of lipid lowering drugs and
(i) to reduce the high prevalence of the western life style all in an effort to mitigate factors that promote the progression of renal damage in diabetic nephropathy viz:
\er to stem the tide, intensive
1 ESRF Australia 1980-2000
Ritz et a1 "
lout the renal risk of type 2 DM and
't' rnensiues.
di:thetic patients and DN-through- :nr 1s ith ACE inhibitors. intensified lion of smoking, reduction of protein ulg drugs and
lence of the western life style - ar promote the progression of renal
Systemic hypertension Microalburniniuia Proteinwia
Hyp~rglyci~emia
Activation of the rennin-angiiotensin system Smoking
111 our published works (Arije, Akinsola & Ladipos', lkem & Akinsola &
others", [brahim, .AKinsola et alp 1 we noted that hypertension, poor glycaemic control and long duration of diabetes were potent risk factors for the development of diabetic nephropathy, while smoking, BMI and hypercholesterolemia surprisingly did not distiiguish between DN and DM without nephropathy. A preventive strategy should be built around detection and adequate treatment of hypertension. glycaemic conbol and iongitudinal follow up.
Figure 16: The relationship between SBP and duration of DM
r=0.284, pd.025.
Dclr.aDun of alabetes (yrs)
Variow drugs ranging from analgesics such a5acetamhophen, non9temidd antiflammatory drugs; antibiotics to a variety of others have been incriminated in renal failure .In traditional societies like Nigeria, drugs are taken in the form of herbal preparations .Some of the herbal preparations contain unknown agents: biological, plant and chemical toxins such as Mercwy(Hg) and Cupper that may be nephroxic. Although the exact magnitude of this problem is not known, our studies as well as others have identified some patients who preserrt in an acute renal failure setting, hut with poor prognosis. In a sig:lificant proportion of patients, herbal therapy may also precipitate acute on chronic renal failureMs5. The inventory of the various herbal preparations is required for a proper understanding of their role in CRF and this calls for collaborative studies between nephrologists/toxicologist/traditional medical practitioners and the drug monitoring agency.
Analgesic nephropathy is recognized as a common cause of CRF in Australia and some European countries, and it occurs more commonly among females who have consumed at least 1.0 kg of analgesic rnixhuesM.
In our study -an epidemiological survey of anal_gesic consumption among labour workers, we observed a remarkably high consumption in a small but significant proportion who also tended to have a higher frequency of symptoms of renal disease5'. A very striking finding was the common practice among many people of ingestion of combined analgesics- paracetamol, phenacetin, codein, non steroidal anti-inflammatory dnigs- what is named power drug"-a potentially kidney damaging 'innovation'.
Proper and effective drug education at the primary healthcare level is mandatory to stem the pervasive practice of self medication in Nigeria Other causes of CRF - o b s t ~ ~ ~ c t i v e uropathy, polycystic kidney disease, hereditary renal diseases, chronic pyelonephritis, renal vascular disease are infrequently encountered.