WORLD KIDNEY FORUMCKD in Aboriginal Australians

Wendy E. Hoy, FRACP,1 Priscilla Kincaid-Smith, FRACP,2 Michael D. Hughson, MD,3

Agnes B. Fogo, MD,4 Rajalingam Sinniah, MD,5 John Dowling, MBBS,2 Terrence Samuel, MBBS,6

Susan A. Mott, MPH,1 Rebecca N. Douglas-Denton, BSc,6 and John F. Bertram, PhD6

ved.

World Kidney ForumAdvisory Board

Rashad S. BarsoumCairo, Egypt

Christopher R. BlaggMercer Island, Washington

John BoletisAthens, Greece

Garabed EknoyanHouston, Texas

Tazeen H. JafarKarachi, Pakistan

Feature edited byJohn T. HarringtonBoston, Massachusetts

In this review, we summarizesome findings about kidney

disease in Australia’s Aboriginalpeople. A review more than 5years ago described most of thesefacts up to that point.1

The 2006 census categorized455,028 Australian people as in-digenous.2 That designation is byself-assignment and can varyamong individuals and within in-dividuals over time. AustralianAborigines are a very heteroge-neous group, differing in migra-tory origin, heritage, language,nonindigenous admixture, socio-economic status, health status,birth weight, mortality, education,empowerment, lifestyle, and ac-cess to services. It is scientificallyand strategically unsound to painta homogeneous picture of theirhealth status and needs.

Ancestors ofAboriginal people

(population, �407,000) derive

American Journal of Kidney Diseases, Vol

from Micronesian migrations,whereas Torres Strait Islanders(population, 29,515) are ofMelanesian origin. This reviewaddresses Aboriginal peopleonly. Only one-third of them(�120,000) live in remote orvery remote areas, althoughthose regions constitute most ofAustralia’s land mass (Fig 1),and their nonindigenous admix-ture generally is less.About two-thirds live in and around popula-

Chronic kidney disease (CKD) isdisease in Aboriginal Australians. CKDrenal failure and nonrenal natural dearegion and are much higher in remocharacteristics and circumstances of Aand early-life influences (notably low bircoccal glomerulonephritis), metabolic/genetic factors probably contribute. CKlar risk. Albuminuria progresses over tpathologic levels of albuminuria in afindings are found in renal biopsy specnotable in individuals from remote regiocenters. Glomerulomegaly probably repby low nephron number, which probablrenal disease. In the last decade, heaaccommodate systematic chronic diserelentless increase for 3 decades, rates otherapy, as well as chronic disease deaOfficial endorsement of these system cdence of low birth weight and infections,Am J Kidney Dis 56:983-993. © 201Published by Elsevier Inc. All rights reser

1From the Centre for Chronic Dis-ease, The University of Queensland,Brisbane, Queensland; 2University ofMelbourne, Melbourne, Victoria, Aus-tralia; 3The University of Mississippi,Jackson, MS; 4Department of Pathol-ogy, Vanderbilt University MedicalCenter, Nashville, TN; 5The Univer-sity of Western Australia, Perth, West-ern Australia; and 6Department ofAnatomy and Developmental Biology,Monash University, Melbourne, Victo-

ria, Australia.

56, No 5 (November), 2010: pp 983-993

tion centers, designated as“major cities, inner and outerregional” by ARIA� (Accessi-bility/Remoteness Index of Aus-tralia).3

Most remote-living mainlandAboriginal people live in theNorthern Territory and WesternAustralia, largely in small com-munities that formed forcibly orspontaneously around religiousmissions and services introducedby colonizers and often involved

omponent of a spectrum of chronicarked by albuminuria, which predictsates vary greatly by community andas. This reflects the heterogeneousinal people. CKD is multideterminant,ight), infections (including poststrepto-dynamic parameters, and epigenetic/ssociated intimately with cardiovascu-with a high incidence of new onset of

groups. All the usual morphologic. However, glomerular enlargement isut not those living closer to populationnts compensatory hypertrophy causederlies the accentuated susceptibility tore services have been transformed tourveillance and management. After ariginal people starting renal replacementppear to be stabilizing in some regions.es, plus ongoing reductions in the inci-romise for continued better outcomes.the National Kidney Foundation, Inc.

Originally published online as doi:10.1053/j.ajkd.2010.05.010 on Au-gust 23, 2010.

Address correspondence to WendyE. Hoy, FRACP, Health Sciences Bldg,Level 8, Royal Brisbane & Women’sHospital, Herston, Queensland, 4029Australia. E-mail: w.hoy@uq.edu.au

© 2010 by the National Kidney Foun-dation, Inc. Published by Elsevier Inc. Allrights reserved.

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983

Hoy et al984

amalgamation of several differ-ent tribal groups. Very few aretruly nomadic today. They are inepidemiologic transition, mar-ginalized and poor, with substan-dard living conditions, poor edu-cation, few employmentopportunities, and inadequateservices of all types. Their healthprofile reflects lingering “ThirdWorld” conditions as well as life-style diseases considered part ofwesternization. Standardizedadult mortality rates are 3-8times those of non-AboriginalAustralians, with cardiovasculardisease the leading cause,4,5 andrenal failure rates are very high.

Aboriginal people who liveless remotely are very hetero-geneous. The largest numberslive around population centersin New South Wales andQueensland. In general, theyhave had longer exposure toWestern influences and have a

more non-Aboriginal genetic

admixture. Although they havemany unmet needs, their mortal-ity and renal failure rates aresignificantly lower than those ofremote Aboriginal people.4-10

This review addresses chronickidney disease (CKD), a com-ponent of the chronic diseasespectrum (cardiovascular dis-ease, type 2 diabetes, hyperten-sion, and CKD), which has ap-peared in Aboriginal peoplesince the early 1980s.

END-STAGE RENAL DISEASEAND RENAL

REPLACEMENT THERAPY

Australia and New ZealandDialysis and Transplant Regis-try (ANZDATA) data show thatthe incidence nationwide ofAborigines with end-stage re-nal disease (ESRD) resultingin renal replacement therapy(RRT), with age adjustment, is

about 10 times that of non-

Aboriginal Australians.6 Pa-tients with ESRD are youngerthan their non-Aboriginal coun-terparts, there is overall a fe-male predominance, and theyhave high rates of comorbidconditions. However, there isvast variation by region amongAboriginal people across Aus-tralia, as shown further by Casset al7,9 from 1993 to 1998, andconfirmed 10 years later byPreston-Thomas et al.8 In someremote regions in the NorthernTerritory, the incidence of RRTin Aboriginal people is morethan 20-fold that of non-Ab-original Australians, whereasrates in Aboriginal people inmajor metropolitan centers arescarcely higher than those ofnon-Aboriginal Australians.7,8

In relation to today’s state andterritory jurisdictions, rates arehighest where a greater propor-tion of Aboriginal people live

Figure 1. Representation ofAustralian remoteness classifi-cations. Australian Bureau ofStatistics ARIA� (Accessibility/Remoteness Index of Australia)measure of remoteness (2006).Source: Australian Bureau ofStatistics.3

remotely (Northern Territory

World Kidney Forum 985

and Western Australia) andlowest where most indigenouspeople live in and around cities,such as New South Wales andQueensland (Fig 2). Regionalrates also correlate strongly withsocioeconomic disadvantage, as-sessed by using indices of housecrowding, low birth weight,poor educational attainment,low employment, and low in-come.9,10 Regional mortalityfollows a similar pattern.4,5 Theproportion of Aborigines withterminal renal failure who donot receive RRT is under study.

In the last 10 years, dialysisunits have been constructed inmany remote locations. How-ever, many Aboriginal peoplestill need to relocate or travellong distances to access RRT.Relocation poses serious hous-ing, social, and emotional diffi-culties that compound the alien-ation and disempowermentattendant on dependence on ahighly medicalized technicalform of life support away fromfamily and community sup-ports. Their median survivalon dialysis therapy is short,they are less likely to be re-ferred for or receive a kidney

Figure 2. Recent annual incidenc

replacement therapy by state/territory, peRegistry 2009 Report.6

transplant, and they have lowertransplant and patient sur-vival.7,11,12 Furthermore, manyAboriginal living transplant do-nors later develop renal insuffi-ciency.13 This is compatiblewith high background rates ofCKD in some regions, the re-lentless increase in clinicalmanifestations with increasingage (discussed later), and fam-ily clustering of CKD. Stan-dard donor evaluation cur-rently is inadequate to identifysuch susceptibility to renal dis-ease. Living donation should beapplied cautiously until thesematters are understood better.

The costs of RRT for indig-enous people and treatment oftheir intercurrent complicationsand comorbid conditions arevery high.14 That expenditurecompetes with primary healthcare for resources within a finitehealth care budget that alreadyis strained by the extra costs ofhealth care delivery in remoteareas. The relative responsibili-ties of states/territories versusfederal government for fundingprimary care, specialist services,hospitalizations, and RRT in-creasingly are debated.15

indigenous Australians starting renal

rson per million. Source: ANZDATA

Until recently, the incidenceof treated RRT in indigenouspeople had been increasing re-lentlessly. However, higher num-bers of people developing ESRDmean higher costs because ofhospitalizations and RRT, butthey do not always mean wors-ening population health status.Decreases in competing mortal-ity, such as deaths in low-birth-weight infants and children andall-cause deaths in adults, createa larger pool of patients at riskby increasing longevity. Thewell-recognized decreases in in-fectious deaths are one consider-ation, but improved managementof diabetes and cardiovascular dis-ease also is extending adult life,potentially allowing progressionof coexisting nephropathy to endstage.That said,numbersand ratesof people starting RRT in someremote regions seem to have lev-eled off in the last few years (Fig2). There also seems to be a de-crease in all-cause deaths andchronic disease deaths gener-ally.5,16-19

EPIDEMIOLOGIC STUDIES

Reports of renal and relatedchronic diseases in indigenouspeople in Australia are increas-ing. Discrete research studiesare being supplemented by sur-veillance data from health ser-vices. A unified approach tochronic disease surveillance na-tionwide and ongoing evalua-tion through well-resourced in-formation systems ultimatelyshould eliminate the need forsurveys, unless community par-ticipation is deficient and/orspecial testing is required. In-troduction of a unique healthcare number for each Austra-lian ultimately will permit link-

e of

ing of profiles and episodes of

missi

Hoy et al986

service use to individuals andlinkage of service use of indi-viduals across the health carecontinuum.

In all regions, rates of hyper-tension, renal disease, andtype 2 diabetes in indigenouspeople are high, but vary byregion and community. Ratesincrease with age, and hyper-tension and proteinuria ap-pear much earlier in the lifecourse and at higher rates thantype 2 diabetes, as shown inFig 3.20-23 Figure 4 shows theextent of risk exacerbation in3 remote communities in oneregion of the remote North-

Figure 3. Increase in prevalenccommunity in the Northern TerritorReproduced from Hoy et al22 with per

ern Territory relative to thosein the contemporaneous Aus-Diab (Australian Diabetes,Obesity and Lifestyle) study,which was conducted inlargely nonindigenous Austra-lians.24 Reasons for differ-ences in rates are poorly un-derstood, although variouscommunities are composed ofdifferent mixes of tribal groupsin different stages of epidemio-logic and health transition andhave different types of bodyhabitus.

Much has been learned fromdetailed studies in 2 remotecommunities in the Top End of

morbidities by age in one remotebreviation: CI, confidence interval.on of Elsevier.

the Northern Territory that are�700 km apart.25-29 Both usedalbumin-creatinine ratio (ACR;grams per mole) on a randomurine specimen as the primaryrenal disease marker. ACRproved to be very robust; itwas stable under various condi-tions of diuresis and glucoseloading, albumin levels werestable up to 10 years of storageat �80°C,30 and albumin levelsassayed using both immuno-nephelometry and high-perfor-mance liquid chromatographyhad identical cross-sectionalcorrelations with clinical pro-files and identical predictivevalues for terminal outcomeswhen examined along thecontinuum of their own val-ues.31 Furthermore, urine pro-tein excretion using dipstickcorrelated fairly well withACR, with more than tracecorrectly identifying 76% ofpeople with ACR �3.4 g/mol(microalbuminuria threshold)and dipstick �1� correctlyidentifying 82% of peoplewith ACR �34 g/mol. This

Figure 4. Odds ratios (95%confidence intervals [CIs]) forselected conditions in adults in3 remote Northern Territorycommunities relative to rates inthe AusDiab (Australian Diabe-tes, Obesity and Lifestyle) studyadjusted for age and sex. Re-produced from Hoy et al24 with

e ofy. Ab

permission of John Wiley &Sons.

World Kidney Forum 987

supports the use of dipstickswhen ACR is not available.

Pathologic albuminuria wasvery common in both commu-nities. Subtle levels were evi-dent in some of the youngestchildren (aged �5 years), andthere was a relentless increasein levels with increasing age(Fig 5). Overall, 28% of adultshad microalbuminuria and 21%had overt albuminuria in com-munity 1,25 and the respectiverates in community 2 were 31%and 13%. A second screen inthe first community 10-14 yearsafter the first screen showed nochange in rates and trends.

ACRs were higher in fe-males than males until middleage. In addition to its associa-tions with age and sex, ACRdirectly correlated with currentbody size, blood pressure,higher triglyceride levels, andlevels of �-glutamyltransferase,C-reactive protein, uric acid,homocysteine, fibrinogen, glu-cose, and hemoglobin A1c.ACR correlated with the pres-ence of skin sores and scabies,persisting antibody to the M

Figure 5. Increase in urine albumin-

protein of group A hemolyticstreptococcus,32 and a historyof poststreptococcal glomeru-lonephritis.33 ACR also corre-lated with high levels of circu-lating immunoglobulins, aswell as high-titer antibodies tocytomegalovirus and Helico-bacter pylori.34 Furthermore,ACR in young adults, and mostmarkedly in females, inverselycorrelated with birth weight;lower birth weights in turnwere associated largely withintrauterine growth restric-tion.35,36 Finally, captured todate by anecdote rather thanmodeling, there is marked fam-ily clustering of renal disease.

Correlations of ACR with“traditional” cardiovascular riskfactors are striking, and asso-ciations with markers of infec-tion and inflammation are an-other shared feature of renaland cardiovascular risk. Thatlink is supported by correla-tions of ACR with carotid inti-mal-media thickness.29 Asso-ciations ofACR with lower birthweights probably are driven inpart by lower nephron numbers,

creatinine ratio (ACR) with age.

which derive from intrauterinegrowth restriction.37 Blood pres-sure also correlated with lowerbirth weights, with the effectmore marked in females.38 Veryrecent data show that cardiovas-cular and renal deaths in youngadults in the same communityare preferentially segregatedamong those of lower birthweight (Fig 6).39 The markeddecrease in mortality of low-birth-weight infants betweenthe 1960s and 1980s, a thera-peutic triumph in itself, thushas illuminated the Barker hy-pothesis in the context ofchronic disease deaths later inlife.40There is a notable defi-ciency of the D allele of theangiotensin-converting enzymegene in one of the communi-ties,41 and a particular polymor-phism in the p53 gene associatesstrongly with albuminuria insmokers in both communities(P � 0.01 for both), as well aswith hemoglobin A1c level.42

Genome typing now is under-way and will be evaluatedagainst a cross-sectional pheno-typic profile of those same indi-viduals, as well as with theircourse over time.

The cross-sectional associa-tion of albuminuria with manyfactors suggests that renal dis-ease in this setting is multide-terminant, a model in whichseveral nephropathic factorsoperating simultaneously pro-gressively amplify the increasein albuminuria and loss of re-nal function that accompanyincreasing age. Specific mod-els have been developed show-ing interactions of anti-groupA hemolytic streptococcus an-tibody and higher body massindex32 and lower birth weights

with higher body mass index.36

Hoy et al988

The models predict a fairly lowprevalence of renal disease inpeople with no risk factors andthe almost inevitable presenceof overt albuminuria by middleage in people with a full menuof risk factors. Nenov et al43

subsequently postulated a“multihit” model of CKD thatembodies the same concept.

Serum creatinine level (di-rectly) and estimated glomer-ular filtration rate (inversely)correlated with albuminuriawith albumin excretion abovethe mid-microalbuminuriarange.25 However, creatinine-based glomerular filtrationrate estimates probably under-estimate renal impairment inremote-living Aboriginalpeople, who often have con-spicuously lower musclemass, at least in the extremi-ties. A study of various glo-merular filtration rate esti-mates versus gold-standardiothalamate clearances in Ab-original people nationwidecurrently is in its third year.44

NATURAL HISTORY

A follow-up study was con-ducted in the first community ata mean of 10.4 years after thefirst. Of 1,466 people in the firstscreen, baseline ACR predicted

the later development of diabe-

tes, clinical ischemic heart dis-ease, and hospital admissions,including but not restricted tothose related to cardiovascularcauses.26,45-47 There were 110nonrenal natural deaths and 32renal deaths in the interim, aswell as 49 deaths of misadven-ture (accidents, suicide, homi-cide, poisoning, etc). Nonrenalnatural deaths were predicted bybaseline ACR over a continuumand renal deaths were predictedby high ACRs (generally �34g/mol) at baseline (Fig 7).26,31,48

In 1,029 survivors who par-ticipated in the second screen,ACR also had progressed.Table 1 lists proportions ofpeople with ACR �3.4 g/molat the first screen who had de-veloped ACR �3.4 g/mol bythe second screen. Such de-

Figure 7. Natural deaths by baseline aa 10-year follow-up. Source: Wang et al.31

compensation was evident evenin the youngest participants andincreased with age. It washigher in female children andadolescents than males, but thedifference was less marked inadult life. Overall, includingchildren, 26.5% of males and35.2% of females had devel-oped that end point during fol-low-up, whereas approximately50% of adults had done so.Proportions of participants whohad developed new-onset dia-betes also were high, but werelower than proportions that de-veloped albuminuria. The ac-tual incidence rates of both out-comes are greater than thosestated, given that the end pointsappeared at some undefinedtime during follow-up andpeople who had died a natural

Figure 6. Hazard ratios(HRs; confidence intervals [CIs])for natural deaths in youngadults (aged 15-37 years), thosewith birth weight less than theirgroup median versus those ofhigher birth weight, adjusted forbirth interval, age, and sex. Re-produced from Hoy and Nicol39

with permission of The MedicalJournal of Australia.

lbumin-creatinine ratio (ACR) during

ine r

World Kidney Forum 989

death in the interim could notbe included in the estimates.Of the simple parameters mea-sured at the first screen, onlyage, female sex, and absolutevalue of baseline ACR pre-dicted such progression.

RENALMORPHOLOGICEVALUATION

In a review of all retrievableand assessable renal biopsyspecimens from native kidneysperformed on Aboriginal peopleacross Australia from 1988 to2004, we found (Table 2) thatthey had higher rates of diabe-

Table 1. Proportion (Percent) of Pg/mol or Diabetes at

Age Group at First Screen (y) M

New On

5-910-1920-2930-39�40All

New

5-910-1920-2930-39�40All

Note: Values expressed as percenAbbreviation: ACR, albumin-creatin

Table 2. Demographic and

Female(%)

Aboriginal, very remote (n � 386) 54.7Aboriginal, remote (n � 65) 60.0Aboriginal, otherc (n � 84) 44.1Nonindigenous (n � 253) 39.9

Abbreviations: GN, glomerulonephaMedian (interquartile range).bGeometric mean (95% confidence

cMetropolitan or inner regional or outer r

tes than non-Aboriginal peopleundergoing biopsy, more fre-quently had heavy proteinuria,and had more advanced dis-ease. Most biopsy specimenswere from people living veryremotely or remotely despitetheir smaller population size.They were younger at biopsythan those living less remotely,females predominated, and asubstantial proportion of thosewith diabetes did not show dia-betic changes in their biopsyspecimens. There were manyfewer biopsy specimens fromAboriginal people living closer

pants With New-Onset ACR �3.4Years of Follow-up

ew Cases Females New Cases

CR >3.4 g/mol

10/93) 21.9 (21/96)21/135) 37.1 (26/70)41/95) 48.1 (25/52)18/36) 35.0 (14/40)9/14) 53.9 (14/26)99/373) 35.2 (100/284)

et Diabetes

1/106) 2.6 (3/117)— 12.4 (11/89)17/139) 22.4 (23/102)14/79) 32.1 (25/78)18/40) 46.2 (30/65)50/515) 20.4 (92/451)

number/total number).atio.

al Features of Indigenous Australians

ge atopsyy)a

Diabeticat Biopsy

(%)

NephroticProteinuria

(%)

RenalFailure aBiopsy

(%)

(20.5) 39.6 43.2 20.7(17.6) 57.4 44.3 31.2(18.6) 48.2 34.6 33.3(23.9) 14.3 21.9 16.7

gA, immunoglobulin A.

val).

egional.

to population centers despitetheir much larger population,they were closer to the age ofnon-Aboriginal people at bi-opsy, and, like them, showed apreponderance of males. In ad-dition, most of those with dia-betes had specific diabeticchanges in their biopsy speci-mens.

All the usual morphologic“diagnoses” were otherwise repre-sented to some degree. In additionto diabetic change, postinfectiouschange, lupus, infectious-relatedamyloid, and apparent reflux ne-phropathy were in relative excess,whereas proportions with im-munoglobulin A nephropathywere lower. However, this doesnot imply fewer cases, giventhe overall excess of renal dis-ease in Aboriginal individuals.

Biopsy specimens from Ab-origines in remote and veryremote areas usually showedglomerulomegaly, which wasidentified subjectively at firstand confirmed through formalmeasurement (Fig 8). This con-firms our report 12 years agoof glomerulomegaly and atten-dant focal glomerulosclerosisin biopsy specimens from Ab-original people in the Top Endof the Northern Territory49,50

and supports descriptions of

e Nationwide Biopsy Series

merularolume

�m3 �

106)b

DiabeticChange

(%)

IgANephro-

pathy(%)

Post-infectious

GN(%)

(2.3-2.5) 24.3 12.4 4.7(2.2-2.8) 40.0 7.7 4.6(1.8-2.3) 41.5 12.8 8.5(1.8-2.1) 11.7 22.1 1.6

artici10.4

ales N

set A

10.8 (15.6 (43.2 (50.0 (64.3 (26.5 (

-Ons

0.9 (

12.2 (17.7 (45.0 (9.7 (

tage (

Clinic in th

ABi

(

tGlo

V(

39.8 2.438.6 2.542.9 2.046.0 2.0

ritis; I

inter

spec

Hoy et al990

glomerulomegaly in even ear-lier reports.51,52 However, glo-merular enlargement was notprominent in Aborigines frommajor cities and inner and outerregional areas.

The disproportionately highnumber of biopsy specimensfrom Aboriginal people in re-mote and very remote areasdespite their smaller popula-tion and younger average ageat biopsy reflects their greatersusceptibility to renal disease,which is mirrored in muchhigher ESRD rates. It is likelythat glomerulomegaly marksthis accentuated susceptibility,which is apparently moremarked in females than inmales. Aboriginal people liv-ing in major cities and innerand outer regional centers seemto have patterns and rates morecompatible with those of non-Aboriginal Australians, includ-ing older age at biopsy, excessof males, and less likelihood ofglomerulomegaly.

Obesity, current body sizemore generally, metabolic syn-drome, diabetes, and nephron

Figure 8. Distribution of mean gspecimens from Aboriginal people bywith non-Aboriginal Australian biopsy

number are all determinants of

glomerular volume.53-55 Glo-merular enlargement beyond acritical point predisposes to fo-cal, then global, glomeruloscle-rosis.50 We propose that theglomerulomegaly noted in bi-opsy specimens from remote-and very remote-living Ab-original people is driven largelyby nephron deficiency and thatnephron deficiency underliestheir susceptibility to renal dis-ease and hypertension. This issupported by findings at foren-sic (coronial) autopsy55-59 thatremote-living Aboriginal adultsfrom the Northern Territory tend

rular volume (MGV) in renal biopsygory of remoteness and comparisonimens.

Figure 9. Distribution of glomerularautopsy, Aboriginal versus non-Aboriginal.

to have smaller kidneys thanother adults in the series andhave on average about 180,000fewer glomeruli per kidney: amean of 711,466 (95% confi-dence interval, 571,498-851,433)versus 892,712 (95% confidenceinterval, 857,298-928,127), ad-justed for age and sex (P �0.01457; Fig 9). Glomeruli alsowere larger.55-59 Furthermore,Aboriginal people with thelowest nephron numbers hadhigher rates of hypertension be-fore death, whereas those withrobust nephron numbers in thecontext of body size had lowrates of hypertension.59

Intrauterine growth restric-tion, which is reflected in lowbirth weight and was very com-mon in Aboriginal Australiaseveral decades ago, is almostcertainly a major cause of thisnephron deficiency in remote-living Aboriginal people.60,61

However, some degree of lowerendowment might have beenappropriate in relation to theirbody habitus, growth trajecto-ries, and metabolic needs his-torically. We postulate thatnephron deficits probably areless marked in urban Aborigi-nes, who have much lower

lomecate

number in right kidney at coronial

World Kidney Forum 991

rates of intrauterine growth re-striction60 and greater degreesof ancestral admixture.

MANAGEMENT ANDHEALTH SERVICES POLICY

Treatment of people with al-buminuria or hypertension withangiotensin-converting enzymeinhibitors reduces progressionof renal disease. It also de-creases rates of renal failureand nonrenal natural death.62,63

In the original demonstrationproject, the number of peoplewith overt albuminuria neededto treat over 3.5 years to avoidone terminal event was only9.5. Treatment saves majorcosts in terms of dialysisavoided or delayed64 and post-ponement of premature death.When systematic screening andtreatment are diminished, goodclinical outcomes are lost.65

These experiences havehelped inform chronic diseasemanagement in Aboriginalhealth care delivery,23,66 result-ing in a groundswell of alteredpractice in the last 10 years.Protocols for regular integratedscreening for chronic disease,including hypertension, renaldisease, diabetes, cardiovascu-lar risk, and chronic lung dis-ease, are embedded in standardhealth care plans within theprimary care structure of mosthealth services for Aboriginalpeople. The federal govern-ment has introduced reimburse-ment for Medicare Australiaservice items for regular (ev-ery 2 years) integrated screen-ing of all adults for chronicdisease and for treatment ofpeople with defined conditions.Medicines for people in re-

mote areas are supplied free

under an additional federalgovernment initiative, Section100,67 and there has been amassive increase in prescrip-tion of chronic disease medica-tions. The central role of theindigenous health care workersin these programs is acknowl-edged. Furthermore, electronicinformation systems are beingintroduced progressively, withprocesses for constant evalua-tion and reporting. Finally, theneed for therapy with multipledrugs is acknowledged, a trial ofa polypill variant is underway,and sustained drug-delivery sys-tems (eg, patches) are at leastunder discussion. Many chal-lenges persist, including lack ofinfrastructure and personnel inremote areas, but there is a realsense of optimism and confi-dence in the government’s com-mitment for ongoing change.Finally, a trial of pharmaco-logic prevention of new-onsetalbuminuria and hypertensionnow is underway. True pri-mary prevention will dependon sustained improvements insocioeconomic circumstancesand community infrastruc-ture, health services, and birthweights.

ACKNOWLEDGEMENTSThe work described in this review

began in 1989 in a project led byProfessor John Mathews, MB BS,PhD, Dr David Pugsley, MB BS, andDr Paul Van Buynder, MB BS, MPH.We thank the laboratory and RenalUnit staff at the Menzies School ofHealth Research, the laboratory staffat the Royal Darwin Hospital andWestern Diagnostic Pathology, and allour multidisciplinary collaborators fortheir efforts; Suresh Sharma, RN, andHilary Bloomfield, RN, for more re-cent field work; Zhiqiang Wang, PhD,Zaimin Wang, PhD, James Scott, BSc

Hons, Karen Andreasyan, BDSc, and

Cheryl Swanson, PhD, for help withdata management and statistical anal-ysis; and especially the Aboriginal par-ticipants in the community-based ele-ments of this program and their LandCouncils and Health Board for sup-port and oversight.

Support: The program has been sup-ported by funds from the NationalHealth and Medical Research Councilof Australia, including an AustraliaResearch Fellowship Award to Dr Hoy;the Stanley Tipiloura fund; KidneyHealth Australia; Rio Tinto; Servier,Australia; Janssen-Cilag; Amgen, Aus-tralia; Territory Health Services, theNew Children’s Hospital in Sydney,Australia; the Office of Aboriginal andTorres Strait Islander Health Servicesand the Colonial Foundation of Austra-lia.

Financial Disclosure: The authorsdeclare that they have no relevant fi-nancial interests.

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3. Australian Bureau of Statistics.The ASGC remoteness structure, 2006.http://www.abs.gov.au/websitedbs/D3310114. nsf/home/ remoteness�structure. Accessed June 2, 2010.

4. The Health and Welfare of Aus-tralia’s Aboriginal and Torres StraitIslander People, 2005. Canberra, Aus-tralia: Australian Bureau of Statisticsand Australian Institute of Health andWelfare; 2005. AIHW cat. no. IHW14: ABS car. no. 4704.

5. Australia’s Health 2008. Can-berra, Australia: Australian Instituteof Health and Welfare; 2008. AIHWcat. no. AUS 99.

6. Indigenous report. Chapter 12:end-stage kidney disease among indig-

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