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1.  Kidney disease in Aboriginal Australians: a perspective from the Northern Territory 
Clinical Kidney Journal  2014;7(6):524-530.
This article outlines the increasing awareness, service development and research in renal disease in Aboriginal people in Australia's Northern Territory, among whom the rates of renal replacement therapy (RRT) are among the highest in the world. Kidney failure and RRT dominate the intellectual landscape and consume the most professional energy, but the underlying kidney disease has recently swung into view, with increasing awareness of its connection to other chronic diseases and to health profiles and trajectories more broadly. Albuminuria is the marker of the underlying kidney disease and the best treatment target, and glomerulomegaly and focal glomerulosclerosis are the defining histologic features. Risk factors in its multideterminant genesis reflect nutritional and developmental disadvantage and inflammatory/infectious milieu, while the major putative genetic determinants still elude detection. A culture shift of “chronic disease prevention” has been catalyzed in part by the human pain, logistic problems and great costs associated with RRT. Nowadays chronic disease management is the central focus of indigenous primary care, with defined protocols for integrated testing and management of chronic diseases and with government reimbursed service items and free medicines for people in remote areas. Blood pressure, cardiovascular risk and chronic kidney disease (CKD) are all mitigated by good treatment, which centres on renin-angiotensin system blockade and good metabolic control. RRT incidence rates appear to be stabilizing in remote Aboriginal people, and chronic disease deaths rates are falling. However, the profound levels of disadvantage in many remote settings remain appalling, and there is still much to be done, mostly beyond the direct reach of health services.
PMCID: PMC4240408  PMID: 25503952
2.  Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race 
Nephrology Dialysis Transplantation  2013;29(7):1399-1409.
African Americans have more severe hypertensive nephrosclerosis than white Americans, possibly at similar levels of blood pressure. Glomerular volume is increased in African Americans relative to whites, but it is uncertain how this relates to nephrosclerosis and whether it contributes to or compensates for glomerulosclerosis.
Stereological disector/fractionator estimates of glomerular number (Nglom) and average glomerular volume (Vglom) were obtained on autopsy kidneys of 171 African Americans and 131 whites. Eighty-eight African Americans and 49 whites were identified as hypertensive. Nephrosclerosis was measured morphometrically as the percentage of glomerulosclerosis, proportion of cortical fibrosis and interlobular artery intimal thickness, and analyzed with Vglom by age, race, gender, body mass index (BMI) and blood pressure.
African Americans were more frequently hypertensive (58.5%) than whites (35.8%) and when hypertensive had higher levels of blood pressure (P = 0.02). Nglom was significantly lower in hypertensive compared with non-hypertensive subjects among white women (P = 0.02) but not white males (P = 0.34) or African American females (P = 0.10) or males (P = 0.41). For each race and gender, glomerulosclerosis, cortical fibrosis and arterial intimal thickening were statistically correlated with age (P < 0.001) and hypertension (P < 0.001) and increased Vglom with hypertension (P < 0.001) and BMI (P < 0.001). In multivariate analysis, African American race was associated with increased Vglom (P = 0.01) and arterial intimal thickening (P < 0.01), while interactions between race and blood pressure indicated that the severity of nephrosclerosis including increased Vglom was linked most directly to hypertension without significant contributions from race. The hypertension-associated enlargement of Vglom was present with mild degrees of glomerulosclerosis and changed little as the severity of glomerulosclerosis increased.
Glomerular hypertrophy was identified as an integral feature of hypertensive nephropathy and appeared to precede rather than compensate for glomerulosclerosis. An effect of race on Vglom and arterial intimal thickening seemed to be related to the more frequent and more severe hypertension among African Americans.
PMCID: PMC4071048  PMID: 24327566
gender; glomerulomegaly; glomerulosclerosis; hypertension; race
3.  Age-dependent decline of association between obesity and coronary heart disease: a cohort study in a remote Australian Aboriginal community 
BMJ Open  2013;3(11):e004042.
To determine whether the association between obesity and coronary heart disease (CHD) in Aboriginal adults depends on age.
Design, setting and participants
A cohort study with up to 20 years of follow-up of 849 participants aged 18–76 years in a remote Aboriginal community in the Northern Territory of Australia.
Main outcome measures
Newly diagnosed CHD cases were identified through hospital records according to ICD codes during the follow-up period. Cox proportional hazard model was used to assess whether the association between obesity and CHD depends on age.
During the follow-up period, 171 participants were diagnosed with CHD. On an average, the incidence rate of CHD increased with the increasing baseline BMI, 11.3%, 16.3% and 20.2% for normal weight, overweight and obese groups, respectively. HR of CHD for obesity were 2.6 (95% CI 1.1to 6.3), 1.2 (0.7 to 2.0) and 0.5 (0.1 to 2.1) for those <40, 40–59 and 60+ years, respectively. HRs corresponding to 1 SD increase in BMI were 1.4 (1.0 to 2.0), 1.2 (1.0 to 1.5) and 0.8 (0.5 to 1.2) for those <40, 40–59 and 60+ years, respectively. The interaction terms between age and BMI as category variables or as a continuous variable were statistically significant.
The association between obesity and CHD is stronger for younger adults than for older adults in Aboriginal Australians in the remote community. Our findings suggest that weight control efforts may produce more beneficial effects in CHD prevention in young adults than in older adults.
PMCID: PMC3845075  PMID: 24282250
4.  The correlates of urinary albumin to creatinine ratio (ACR) in a high risk Australian aboriginal community 
BMC Nephrology  2013;14:176.
Albuminuria marks renal disease and cardiovascular risk. It was estimated to contribute 75% of the risk of all-cause natural death in one Aboriginal group. The urine albumin/creatinine ratio (ACR) is commonly used as an index of albuminuria. This study aims to examine the associations between demographic factors, anthropometric index, blood pressure, lipid-protein measurements and other biomarkers and albuminuria in a cross-sectional study in a high-risk Australian Aboriginal population. The models will be evaluated for albuminuria at or above the microalbuminuria threshold, and at or above the “overt albuminuria” threshold with the potential to distinguish associations they have in common and those that differ.
This was a cross-sectional study of 598 adults aged 18–76 years. All participants were grouped into quartiles by age. Logistic regression models were used to explore the correlates of ACR categories.
The significant correlates were systolic blood pressure (SBP), C-reactive protein (CRP), uric acid, diabetes, gamma-glutamyl transferase (GGT) (marginally significant, p = 0.054) and serum albumin (negative association) for ACR 17+ (mg/g) for men and 25+ for women. Independent correlates were SBP, uric acid, diabetes, total cholesterol, alanine amino transferase (ALT), Cystatin C and serum albumin (negative association) for overt albuminuria; and SBP, CRP and serum albumin only for microalbuminuria.
This is the most detailed modelling of pathologic albuminuria in this setting to date. The somewhat variable association with risk factors suggests that microalbuminuria and overt albuminuria might reflect different as well as shared phenomena.
PMCID: PMC3765271  PMID: 23947772
Albuminuria; Microalbuminuria; Overt albuminuria; ACR; Aboriginal people
5.  Lifetime risk of developing coronary heart disease in Aboriginal Australians: a cohort study 
BMJ Open  2013;3(1):e002308.
Lifetime risk of coronary heart disease (CHD) is an important yardstick by which policy makers, clinicians and the general public can assess and promote the awareness and prevention of CHD. The lifetime risk in Aboriginal people is not known. Using a cohort with up to 20 years of follow-up, we estimated the lifetime risk of CHD in Aboriginal people.
A cohort study.
A remote Aboriginal region.
1115 Aboriginal people from one remote tribal group who were free from CHD at baseline were followed for up to 20 years.
Main outcome measures
During the follow-up period, new CHD incident cases were identified through hospital and death records. We estimated the lifetime risks of CHD with and without adjusting for the presence of competing risk of death from non-CHD causes.
Participants were followed up for 17 126 person-years, during which 185 developed CHD and 144 died from non-CHD causes. The average age at which the first CHD event occurred was 48 years for men and 49 years for women. The risk of developing CHD increased with age until 60 years and then decreased with age. Lifetime cumulative risk without adjusting for competing risk was 70.7% for men and 63.8% for women. Adjusting for the presence of competing risk of death from non-CHD causes, the lifetime risk of CHD was 52.6% for men and 49.2% for women.
Lifetime risk of CHD is as high as one in two in both Aboriginal men and women. The average age of having first CHD events was under 50 years, much younger than that reported in non-Aboriginal populations. Our data provide useful knowledge for health education, screening and prevention of CHD in Aboriginal people.
PMCID: PMC3563122  PMID: 23370013
Epidemiology; Public Health
6.  CKD.QLD: chronic kidney disease surveillance and research in Queensland, Australia 
Nephrology Dialysis Transplantation  2012;27(Suppl 3):iii139-iii145.
Chronic kidney disease (CKD) is recognized as a major public health problem in Australia with significant mortality, morbidity and economic burden. However, there is no comprehensive surveillance programme to collect, collate and analyse data on CKD in a systematic way.
We describe an initiative called CKD Queensland (CKD.QLD), which was established in 2009 to address this deficiency, and outline the processes and progress made to date. The foundation is a CKD Registry of all CKD patients attending public health renal services in Queensland, and patient recruitment and data capture have started.
We have established through early work of CKD.QLD that there are over 11 500 CKD patients attending public renal services in Queensland, and these are the target population for our registry. Progress so far includes conducting two CKD clinic site surveys, consenting over 3000 patients into the registry and initiation of baseline data analysis of the first 600 patients enrolled at the Royal Brisbane and Women's Hospital (RBWH) site. In addition, research studies in dietary intake and CKD outcomes and in models of care in CKD patient management are underway.
Through the CKD Registry, we will define the distribution of CKD patients referred to renal practices in the public system in Queensland by region, remoteness, age, gender, ethnicity and socioeconomic status. We will define the clinical characteristics of those patients, and the CKD associations, stages, co-morbidities and current management. We will follow the course and outcomes in individuals over time, as well as group trends over time. Through our activities and outcomes, we are aiming to provide a nidus for other states in Australia to join in a national CKD registry and network.
PMCID: PMC3484715  PMID: 23115138
chronic kidney disease; registry; surveillance
7.  Towards a definition of glomerulomegaly: clinical–pathological and methodological considerations 
Nephrology Dialysis Transplantation  2010;26(7):2202-2208.
Background. Glomerulomegaly, the abnormal enlargement of glomeruli, has been related to an increased risk of glomerulosclerosis, but the degree of enlargement that constitutes glomerulomegaly has not been defined.
Methods. The principal stereological methods for estimating glomerular volume are [1] the disector/Cavalieri method that is considered the ‘gold standard’ for measuring individual glomerular volume (IVglom) and [2] the disector/fractionator technique that estimates average glomerular volume (Vglom) together with total glomerular number (Nglom) for the entire kidney. The two methods produce different estimates with Vglom consistently exceeding IVglom. This study compares glomerular volumes obtained by the two methods in autopsy kidneys of 39 African American and 34 US white adult males, and correlates the values with Nglom, body mass index (BMI), hypertension, glomerulosclerosis and race, factors known or thought to influence glomerular volume.
Results. For the smallest glomeruli, Vglom was 25% larger than IVglom with the difference increasing to over 50% for kidneys with the largest glomeruli. Both Vglom and IVglom showed significant inverse correlations with Nglom and significant direct correlations with BMI and hypertension. African Americans had larger IVglom and Vglom than whites, but only IVglom was significant. The 90th percentile for IVglom was 6.81 μm3 × 106 and 13.10 μm3 × 106 for Vglom, but larger glomerular size did not separate hypertensive from non-hypertensive subjects nor did it show any significant relationship to glomerulosclerosis. While Vglom overestimated glomerular size compared with IVglom, both measurements demonstrated similar relationships to factors influencing glomerular volume.
Conclusions. With neither method could glomerulomegaly, the abnormal enlargement of glomerular size predisposing to glomerulosclerosis, be determined.
PMCID: PMC3164445  PMID: 21115671
body mass index; glomerular number; glomerulomegaly; hypertension
8.  A comparison of nephron number, glomerular volume and kidney weight in Senegalese Africans and African Americans 
Nephrology Dialysis Transplantation  2010;25(5):1514-1520.
Background. Low nephron number is determined in utero and is a proposed risk for essential hypertension. Glomerular volume is inversely correlated with nephron number, and genetic and environmental factors that determine nephron number are thought to determine glomerular volume. This study compared total glomerular (nephron) number (Nglom), mean glomerular volume (Vglom) and kidney weight in two geographically separated black populations with significant common genetic ancestry.
Methods. Unbiased stereology was used to determine Nglom and Vglom in kidneys collected at coronial autopsy in an age- and sex-matched sample of 39 adult Africans from Dakar in Senegal, West Africa and 39 African Americans from Mississippi in the USA.
Results. African Americans were taller and heavier than their Senegalese counterparts. Nglom was remarkably similar—with a geometric mean of 937 967 in Senegalese and 904 412 in African Americans (P = 0.62). Vglom was correlated inversely with Nglom and directly with body surface area in both groups, but Vglom was 54% greater in African Americans than in Senegalese Africans [8.30 ± 2.92 (SD) and 5.38 ± 1.25  μm3 × 106, respectively] and remained significantly larger (38%) after adjustment for body size. Vglom increased with age in African Americans, but not in the Senegalese. Kidney weight was larger in African Americans (P < 0.0001), but kidney-to-body weight ratio was not different between groups.
Conclusions. Despite similar nephron numbers, a common genetic constitution, and even in relation to current body size, African Americans have larger Vglom than Senegalese subjects. This may mark exposure to environmental stressors or hereditary traits concentrated in the population's relocation to North America.
PMCID: PMC2910333  PMID: 20154008
African Americans; glomerular volume; kidney weight; nephron number; Senegalese Africans
9.  Incidence of type 2 diabetes in Aboriginal Australians: an 11-year prospective cohort study 
BMC Public Health  2010;10:487.
Diabetes is an important contributor to the health inequity between Aboriginal and non-Aboriginal Australians. This study aims to estimate incidence rates of diabetes and to assess its associations with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) among Aboriginal participants in a remote community.
Six hundred and eighty six (686) Aboriginal Australians aged 20 to 74 years free from diabetes at baseline were followed for a median of 11 years. During the follow-up period, new diabetes cases were identified through hospital records. Cox proportional hazards models were used to assess relationships of the incidence rates of diabetes with IFG, IGT and body mass index (BMI).
One hundred and twenty four (124) new diabetes cases were diagnosed during the follow up period. Incidence rates increased with increasing age, from 2.2 per 1000 person-years for those younger than 25 years to 39.9 per 1000 person-years for those 45-54 years. By age of 60 years, cumulative incidence rates were 49% for Aboriginal men and 70% for Aboriginal women. The rate ratio for developing diabetes in the presence of either IFG or IGT at baseline was 2.2 (95% CI: 1.5, 3.3), adjusting for age, sex and BMI. Rate ratios for developing diabetes were 2.2 (95% CI: 1.4, 3.5) for people who were overweight and 4.7 (95% CI: 3.0, 7.4) for people who were obese at baseline, with adjustment of age, sex and the presence of IFG/IGT.
Diabetes incidence rates are high in Aboriginal people. The lifetime risk of developing diabetes among Aboriginal men is one in two, and among Aboriginal women is two in three. Baseline IFG, IGT and obesity are important predictors of diabetes.
PMCID: PMC2931471  PMID: 20712905
10.  Nephron number and individual glomerular volumes in male Caucasian and African American subjects 
Nephrology Dialysis Transplantation  2009;24(8):2428-2433.
Background. Glomerular hypertrophy has been described in several populations at high risk of chronic kidney disease. Total nephron (and thereby glomerular) number (Nglom) varies widely in normal adult human kidneys and is generally inversely correlated with mean glomerular volume (Vglom). However, little is known about the range of individual glomerular volumes (IVglom) within single human kidneys and the association with Nglom. The aim of the present study was to estimate IVglom in Caucasian and African Americans and identify any associations between heterogeneity in IVglom and nephron number.
Methods. Using unbiased stereological techniques, IVglom was determined for 30 glomeruli in each of 24 adult male kidneys from Jackson, MS, USA (12 Caucasian and 12 African American). Half of each group had ‘high’ Nglom (>1.2 million nephrons per kidney) and the other half had ‘low’ Nglom (<600 000).
Results. Caucasians with high Nglom had a relatively homogeneous distribution of IVglom as well as a relatively low mean value, while those with low Nglom had much greater heterogeneity of IVglom, as well as a larger IVglom (P < 0.0001) compared with those with high Nglom. This disparity was not apparent in African Americans, however, where subjects with both high and low Nglom showed substantial heterogeneity in IVglom and larger mean values (P = 0.95).
Conclusions. High Nglom appeared to protect against glomerular enlargement and volume heterogeneity in Caucasians. However, substantial variation in IVglom and net enlargement in glomerular size in African Americans with high nephron numbers suggest that additional forces, independent of low Nglom, are driving glomerular enlargement and heterogeneity.
PMCID: PMC2727298  PMID: 19297355
African American; Caucasian; glomerular volume; nephron number; stereology
11.  Associations between age, body size and nephron number with individual glomerular volumes in urban West African males 
Nephrology Dialysis Transplantation  2008;24(5):1500-1506.
Background. Glomerulomegaly has been associated with an increased risk of renal disease. Few reports have investigated the heterogeneity of glomerular size within kidneys and associated risk factors. This study measured the individual glomerular volume (IGV) of 720 non-sclerotic glomeruli in kidneys of adult West African males, and investigated associations of IGV with age, total glomerular (nephron) number and body surface area (BSA).
Methods. IGVs were determined in the kidneys of 24 Senegalese males from two age groups (12 subjects aged 20– 30 years and 12 subjects aged 50–70 years). Subjects were randomly chosen at autopsies performed at Le Dantec Hospital in Dakar. Volumes of 30 glomeruli per subject were determined using the disector/Cavalieri stereological method.
Results. IGVs ranged from 1.31 × 106 μm3 to 12.40 × 106 μm3 (a 9.4-fold variation). IGV varied up to 5.3-fold within single kidneys. The trimmed range of IGV within subjects (10th to 90th percentile of IGV) was directly correlated with median glomerular size. The mean and standard deviation (SD) of IGV did not differ significantly between age groups or between subjects with higher (≥1.78 m2) and lower BSA (<1.78 m2). In older subjects the SD of IGV was significantly and directly correlated with BSA. Kidneys with less than 1 million nephrons had significantly larger mean IGV than kidneys with more than 1 million nephrons, and the trimmed range of IGVs within subjects was inversely correlated with total glomerular number.
Conclusion. There was a considerable variation in IGV within kidneys of Senegalese males at autopsy. The heterogeneity of IGV was increased in association with low nephron number and increased BSA, with more pronounced effects in older subjects.
PMCID: PMC2721460  PMID: 19028752
glomerular size; glomerular volume; heterogeneity; nephron number; Senegal
12.  Renal pathology, glomerular number and volume in a West African urban community 
Nephrology Dialysis Transplantation  2008;23(8):2576-2585.
Background. Low glomerular number and large glomerular volume are hypothesized to be risk factors for hypertensive renal disease in adult life. Reports of human glomerular number are based on studies from developed nations and have found single kidney mean values of ∼900 000 per kidney with a roughly 8-fold range matched by a similar range in glomerular volume. Glomerular number and volume have never been investigated in people from a developing country.
Methods. This study analysed the pathology of 81 autopsy kidneys from Dakar, Senegal, and determined total glomerular number and mean glomerular volume in 28 of these kidneys using the physical disector/fractionator method.
Results. Total glomerular number ranged 2.6-fold from 536 171 to 1 394 010, with a mean of 925 485 nephrons. The mean glomerular volume was 5.74 μm3 × 106 with a 2.5-fold variation that was strongly and inversely correlated with total glomerular number. Glomerular number was inversely correlated with age, and age-associated increases in arteriosclerosis, cortical fibrosis and glomerulosclerosis were observed. Arteriolar nephrosclerosis was observed in 34% of adults. Mean glomerular number in this Dakar population was similar to that previously reported for people from developed nations, while the range of glomerular number and mean glomerular volume was much narrower.
Conclusions. The frequency of arteriolar nephrosclerosis in these Senegalese adults was high (34%), suggesting that hypertensive kidney disease could contribute to a large burden of future chronic kidney disease in this population. Unusually low glomerular number or large glomerular volume do not appear to provide a basis for this potential burden of kidney disease.
PMCID: PMC2727292  PMID: 18308771
arteriosclerosis; glomerular volume; nephron number; renal pathology; Senegal
13.  Standard Information Content and Procedures Used in the Formation of a Research Oriented Health Services Database 
This paper describes the process of establishing as automated system for abstraction of computerized healthcare administrative data from a hospital or clinical database (HIS) into a new data structure which has been tailored for research interests. This process involves careful study of the HIS holdings and data collection procedures, means of categorizing and organizing data, and techniques for standardized maintenance of the new database over many years. Benefits of creating and using the new database for specific projects and its limitations are also discussed.
PMCID: PMC2245441
14.  Rates and Causes of End-Stage Renal Disease in Navajo Indians, 1971-1985 
Western Journal of Medicine  1988;149(2):178-182.
The rates of end-stage renal disease are much increased in American Indians, but no longitudinal study of its rates and causes has been undertaken in any tribe. This 15-year study of rates and causes of treated end-stage renal disease in the Navajo, the largest Indian tribe, supplies an important model on which to base projections and plan interventions. Treated end-stage renal disease in Navajos has increased to an age-adjusted incidence 4 times that in whites in the United States. Diabetic nephropathy accounted for 50% of all new cases in 1985, with an incidence 9.6 times that in US whites, and was due entirely to type II disease. Glomerulonephritis caused end-stage renal disease in Navajos at a rate at least 1.8 times that in US whites and afflicted a much younger population. The predominant form was mesangial proliferative glomerulonephritis associated with an immune complex deposition. Renal disease of unknown etiology, which probably includes much silent glomerulonephritis, accounted for 20% of all new cases. The aggregate Navajo population with end-stage renal disease was 9 years younger than its US counterpart.
These observations reflect the genesis of the epidemic of diabetic nephropathy afflicting many tribes. Urgent measures are needed to contain this. In addition, the etiology and control of mesangiopathic, immune-complex glomerulonephritis of unusual severity, a previously unrecognized problem, need to be addressed.
PMCID: PMC1026368  PMID: 3247733

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