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ABSTRACT: OBJECTIVES: 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. DESIGN: A cohort study. SETTING: A remote Aboriginal region. PARTICIPANTS: 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. RESULTS: 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. CONCLUSIONS: 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.
BMJ open. 01/2013; 3(1).
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ABSTRACT: Background. Chronic kidney disease (CKD) is recog-nized as a major public health problem in Australia with significant mortality, morbidity and economic burden. However, there is no comprehensive surveillance pro-gramme to collect, collate and analyse data on CKD in a systematic way. Methods. We describe an initiative called CKD Queens-land (CKD.QLD), which was established in 2009 to address this deficiency, and outline the processes and pro-gress 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. Results. We have established through early work of CKD.QLD that there are over 11 500 CKD patients at-tending public renal services in Queensland, and these are the target population for our registry. Progress so far in-cludes conducting two CKD clinic site surveys, consent-ing 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 manage-ment are underway. Conclusions. 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.
Nephrology, Dialysis and Transplantation 11/2012;
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Wendy E Hoy,
Terence Samuel,
Susan A Mott,
Priscilla S Kincaid-Smith,
Agnes B Fogo,
John P Dowling,
Michael D Hughson,
Rajalingam Sinniah,
David J Pugsley,
Meshach G Kirubakaran,
Rebecca N Douglas-Denton,
John F Bertram
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ABSTRACT: Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathological findings and terminology, quantify glomerular size, and establish and compare regional biopsy profiles. The relative population-adjusted biopsy frequencies were 16.9, 6.6, and 1, respectively, for Aboriginal people living remotely/very remotely, for Torres Strait Islander people, and for non-remote-living Aboriginal people. Indigenous people more often had heavy proteinuria and renal failure at biopsy. No single condition defined the Indigenous biopsies and, where biopsy rates were high, all common conditions were in absolute excess. Indigenous people were more often diabetic than non-Indigenous people, but diabetic changes were still present in fewer than half their biopsies. Their biopsies also had higher rates of segmental sclerosis, post-infectious glomerulonephritis, and mixed morphologies. Among the great excess of biopsies in remote/very remote Aborigines, females predominated, with younger age at biopsy and larger mean glomerular volumes. Glomerulomegaly characterized biopsies with mesangiopathic changes only, with IgA deposition, or with diabetic change, and with focal segmental glomerulosclerosis (FSGS). This review reveals great variations in biopsy rates and findings among Indigenous Australians, and findings refute the prevailing dogma that most indigenous renal disease is due to diabetes. Glomerulomegaly in remote/very remote Aboriginal people is probably due to nephron deficiency, in part related to low birth weight, and probably contributes to the increased susceptibility to kidney disease and the predisposition to FSGS.Kidney International advance online publication, 29 August 2012; doi:10.1038/ki.2012.307.
Kidney International 08/2012; · 6.61 Impact Factor
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Wendy E Hoy,
Terence Samuel,
Susan A Mott,
Priscilla S Kincaid-Smith,
Agnes B Fogo,
John P Dowling,
Michael D Hughson,
Rajalingam Sinniah,
David J Pugsley,
Meshach G Kirubakaran,
Rebecca N Douglas-Denton,
John F Bertram
Kidney International 08/2012; · 6.61 Impact Factor
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ABSTRACT: Although unusual in western countries and in Australia in general, post-streptococcal glomerulonephritis (PSGN) is still common in Australian Aboriginal children living in remote communities. Here, we evaluated whether episodes of acute PSGN increased the risk for chronic kidney disease in later life in 1519 residents of a remote Aboriginal community (85% of those age eligible), with high rates of renal and cardiovascular disease, who participated in a health screen over a 3-year period. Of these, 200 had had at least one episode of PSGN, with 27 having had multiple episodes, usually in childhood. High levels of albuminuria (albumin/creatinine ratio) with increasing age were confirmed. All PSGN episodes were associated with group A streptococcal skin infections, often related to scabies. In both genders, aged 10-39 years at screening, about one in five had such a history. Among them, PSGN (5 years or more earlier) was significantly associated with higher levels of albuminuria than those without. In women, aged 30-39 years, a history of PSGN was associated with a significantly higher frequency of estimated glomerular filtration rates <60 ml/min. The adjusted odds ratios for an albumin/creatinine ratio over 34 g/mol (overt albuminuria) in males and females with a history of PSGN were 4.6 and 3.1, respectively, compared with those without a history. Thus, PSGN contributes to the very serious burden of chronic kidney disease in this community. Rigorous strategies to prevent scabies and Group A streptococcal infections will reduce this burden.
Kidney International 02/2012; 81(10):1026-32. · 6.61 Impact Factor
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American Journal of Kidney Diseases 08/2011; 58(4):685-7. · 5.43 Impact Factor
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ABSTRACT: Chronic kidney disease (CKD) is a major public health problem. The classification of CKD by KDOQI and KDIGO and the routine eGFR reporting have resulted in increased identification of CKD. It is important to be able to identify those at high risk of CKD progression and its associated cardiovascular disease (CVD). Proteinuria is the most sensitive marker of CKD progression in clinical practice, especially when combined with eGFR, but these have limitations. Hence, early, more sensitive, biomarkers are required. Recently, promising biomarkers have been identified for CKD progression and its associated CVD morbidity and mortality. These may be more sensitive biomarkers of kidney function, the underlying pathophysiological processes, and/or cardiovascular risk. Although there are some common pathways to CKD progression, there are many primary causes, each with its own specific pathophysiological mechanism. Hence, a panel measuring multiple biomarkers including disease-specific biomarkers may be required. Large, longitudinal observational studies are needed to validate candidate biomarkers in a broad range of populations prior to implementation into routine CKD management. Recent renal biomarkers discovered include neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and liver-type fatty acid-binding protein. Although none are ready for use in clinical practice, it is timely to review the role of such biomarkers in predicting CKD progression and/or CVD risk in CKD.
Kidney International 06/2011; 80(8):806-21. · 6.61 Impact Factor
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ABSTRACT: Nephrogenesis is ongoing at the time of birth for the majority of preterm infants, but whether postnatal renal development follows a similar trajectory to normal in utero growth is unknown. Here, we examined tissue collected at autopsy from 28 kidneys from preterm neonates, whose postnatal survival ranged from 2 to 68 days, including 6 that had restricted intrauterine growth. In addition, we examined kidneys from 32 still-born gestational controls. We assessed the width of the nephrogenic zone, number of glomerular generations, cross-sectional area of the renal corpuscle, and glomerular maturity and morphology. Renal maturation accelerated after preterm birth, with an increased number of glomerular generations and a decreased width of the nephrogenic zone in the kidneys of preterm neonates. Of particular concern, compared with gestational controls, preterm kidneys had a greater percentage of morphologically abnormal glomeruli and a significantly larger cross-sectional area of the renal corpuscle, suggestive of renal hyperfiltration. These observations suggest that the preterm kidney may have fewer functional nephrons, thereby increasing vulnerability to impaired renal function in both the early postnatal period and later in life.
Journal of the American Society of Nephrology 06/2011; 22(7):1365-74. · 9.66 Impact Factor
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ABSTRACT: Several studies have shown that total nephron (glomerular) number varies widely in normal human kidneys. Whereas the studies agree that average nephron number is approximately 900,000 to 1 million per kidney, numbers for individual kidneys range from approximately 200,000 to >2.5 million. Several studies have shown loss of glomeruli due to age-related glomerulosclerosis. The rates of loss vary among individuals depending upon blood pressure, diseases affecting the kidney, and other attributes of health, but most of the variation in nephron number is present at birth and is therefore developmentally determined. For example, in a relatively small study of nephron number in 15 children <3 months of age, we found that nephron number ranged from approximately 250,000 to 1.1 million. Given that no new nephrons are formed in human kidneys after approximately 36 weeks' gestation, much interest has focused on renal function and health in individuals born with relatively low nephron endowment. Several studies have reported a direct correlation between birth weight and nephron number and an indirect association between nephron number and blood pressure. Associations between low birth weight and cardiovascular disease, including hypertension, have also been widely reported. This report provides an update on our current knowledge of human nephron number and the associations with adult health and disease.
Pediatric Nephrology 05/2011; 26(9):1529-33. · 2.52 Impact Factor
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Wendy E Hoy
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ABSTRACT: In the next Australian Health Survey, Indigenous people under 18 years of age will be excluded from direct clinical measurements and laboratory tests. Indigenous people of all ages were to be excluded from the opportunity, offered to other Australians, to donate blood and urine samples to a national repository. This component has now been abandoned for the whole cohort. This sets perilous precedents of exclusion from opportunities available to all other Australians, and deprives the medical community of information that could inform strategies to improve health profiles and outcomes in this seriously disadvantaged group.
The Medical journal of Australia 05/2011; 194(10):509-10. · 2.81 Impact Factor
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ABSTRACT: This review discusses current understandings of variability in glomerular number and size, and the implications for renal health.
The quantitative microanatomy of the normal human kidney varies widely. Of greatest significance, total nephron number varies at least 13-fold, and several genes and environmental factors that regulate human nephron endowment have been identified. Full or partial deletion of more than 25 genes in mice has been shown to result in renal hypoplasia and, when measured, reduced nephron endowment. Many more will likely be identified. As would be expected, some gene abnormalities increase nephron endowment above that found in control mice. Glomerular volume also varies widely, both between and within kidneys, and increased heterogeneity of glomerular volume within kidneys is associated with risk factors for kidney disease, including birth weight, age, race, body size and hypertension.
Data from several human populations indicate that the quantitative microanatomy of the human kidney varies considerably: total glomerular number varies at least 13-fold, mean glomerular volume varies up to seven-fold and the volumes of individual glomeruli within single kidneys can vary as much as eight-fold. Human glomerular number, size and size distribution are being found to correlate with risk factors for kidney disease. The genetic and fetal environmental regulators of nephrogenesis, and thereby nephron endowment, are being rapidly identified and will provide the bases for future clinical interventions. In contrast, the molecular regulation of glomerular size remains unclear.
Current opinion in nephrology and hypertension 01/2011; 20(1):7-15. · 3.96 Impact Factor
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ABSTRACT: We have demonstrated considerable variability in the volumes of different glomeruli in given individuals (individual glomerular volume: IGV) in a stereologic study of kidneys at forensic autopsy performed to investigate sudden or unexpected death in people without manifest kidney disease. We review some important associations of IGV by subject characteristics and by ethnic groups. IGVs were measured by the Cavalieri method in 30 glomeruli in each of 111 adult males who belonged to 4 ethnic groups, i.e. US Whites, African-Americans, Africans from Senegal, and Australian Aborigines. Correlations of pooled IGV values with certain subject characteristics were evaluated in the US Whites. Pooled IGV data were compared in subjects across the 4 ethnic groups. In US Whites, mean IGV and its variance were greater with higher age, lower nephron number, lower birth weight, and with gross obesity, hypertension and cardiovascular death. In comparisons by ethnic group, mean IGV and IGV ranges were higher in African-Americans and Australian Aborigines than in US Whites and African Senegalese subjects. We conclude that glomerular enlargement with volume heterogeneity marks more advanced age, relative nephron deficiency, lower birth weight, obesity, hypertension, and advanced cardiovascular disease. The findings in African-Americans and Australian Aborigines suggest that larger IGVs and volume heterogeneity might mark populations with accentuated susceptibility to hypertension and kidney disease, but the data need to be further examined in the context of the determining characteristics defined in the US Whites.
American Journal of Nephrology 01/2011; 33 Suppl 1:15-20. · 2.54 Impact Factor
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ABSTRACT: Chronic kidney disease (CKD) is one component of a spectrum of chronic disease in Aboriginal Australians. CKD is marked by albuminuria, which predicts renal failure and nonrenal natural death. Rates vary greatly by community and region and are much higher in remote areas. This reflects the heterogeneous characteristics and circumstances of Aboriginal people. CKD is multideterminant, and early-life influences (notably low birth weight), infections (including poststreptococcal glomerulonephritis), metabolic/hemodynamic parameters, and epigenetic/genetic factors probably contribute. CKD is associated intimately with cardiovascular risk. Albuminuria progresses over time, with a high incidence of new onset of pathologic levels of albuminuria in all age groups. All the usual morphologic findings are found in renal biopsy specimens. However, glomerular enlargement is notable in individuals from remote regions, but not those living closer to population centers. Glomerulomegaly probably represents compensatory hypertrophy caused by low nephron number, which probably underlies the accentuated susceptibility to renal disease. In the last decade, health care services have been transformed to accommodate systematic chronic disease surveillance and management. After a relentless increase for 3 decades, rates of Aboriginal people starting renal replacement therapy, as well as chronic disease deaths, appear to be stabilizing in some regions. Official endorsement of these system changes, plus ongoing reductions in the incidence of low birth weight and infections, hold promise for continued better outcomes.
American Journal of Kidney Diseases 11/2010; 56(5):983-93. · 5.43 Impact Factor
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ABSTRACT: 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.
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 (IV(glom)) and [2] the disector/fractionator technique that estimates average glomerular volume (V(glom)) together with total glomerular number (N(glom)) for the entire kidney. The two methods produce different estimates with V(glom) consistently exceeding IV(glom). 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 N(glom), body mass index (BMI), hypertension, glomerulosclerosis and race, factors known or thought to influence glomerular volume.
For the smallest glomeruli, V(glom) was 25% larger than IV(glom) with the difference increasing to over 50% for kidneys with the largest glomeruli. Both V(glom) and IV(glom) showed significant inverse correlations with N(glom) and significant direct correlations with BMI and hypertension. African Americans had larger IV(glom) and V(glom) than whites, but only IV(glom) was significant. The 90th percentile for IV(glom) was 6.81 μm(3) × 10(6) and 13.10 μm(3) × 10(6) for V(glom), but larger glomerular size did not separate hypertensive from non-hypertensive subjects nor did it show any significant relationship to glomerulosclerosis. While V(glom) overestimated glomerular size compared with IV(glom), both measurements demonstrated similar relationships to factors influencing glomerular volume.
With neither method could glomerulomegaly, the abnormal enlargement of glomerular size predisposing to glomerulosclerosis, be determined.
Nephrology Dialysis Transplantation 11/2010; 26(7):2202-8. · 3.40 Impact Factor
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ABSTRACT: We assessed the independent contribution of C-reactive protein to the risk of cardiovascular disease in Aboriginal Australians.
High sensitivity CRP levels were measured in 705 Aboriginal participants aged 20-74 years free from CVD at baseline. Participants were followed for a median of 11 years. Cox proportional hazards models were used to assess the association of CRP with the risk of developing CVD events.
A total of 114 participants were diagnosed with CVD. Incidence rates were 5.4 and 21.4 per 1,000 person-years for the lower (<3 mg/l) and the higher (>or=3 mg/l) CRP groups, respectively. After adjusting for age, sex, total cholesterol, systolic blood pressure, smoking status, diabetes, BMI and waist circumference, the association between CRP and CVD remained significant, with a hazard ratio of 2.40 (95% CI: 1.25, 4.62) for the higher CRP group relative to the lower CRP group. The population attributable risk was 52% (95% CI: 14%, 74%).
CRP is an independent predictor of CVD in Aboriginal people. A large proportion of CVD cases are associated with elevated CRP levels. Therefore, controlling the conditions that cause inflammation may be beneficial to cardiovascular health in Aboriginal communities.
Australian and New Zealand Journal of Public Health 07/2010; 34 Suppl 1:S25-9. · 1.20 Impact Factor
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The Medical journal of Australia 05/2010; 192(10):566. · 2.81 Impact Factor
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ABSTRACT: To report the short-term experiences and outcomes of a program to support chronic disease management in three remote communities in Top End Northern Territory and in two Aboriginal Medical Services (AMSs) in Western Australia, and to discuss the implications of findings for health service delivery and policy.
Programs were health-worker centred. They espoused regular screening of all adults for chronic disease, initiation and modification of treatment where indicated and rigorous documentation. Process measures were documented and rates of hypertension, renal disease and diabetes among adults were calculated.
Rates of hypertension, proteinuria and diabetes rose throughout adult life and multiple diagnoses were common. Most people with these conditions were young or middle age adults. Rates were uniformly excessive relative to AusDiab data, but varied greatly among settings. Adherence to protocols improved, many new diagnoses were made, treatments were started or modified and blood pressures in treated hypertensive people fell. In the NT, productivity was seriously limited by lack of health workers and their absenteeism. In the WA AMSs, executive and staff support carried the programs forward to a sustainable future, despite various challenges.
Integrated chronic disease testing must be repeated throughout adult life for timely diagnosis. Health workers can perform all tasks well, with appropriate supports. Blood pressure outcomes alone predict lower cardiovascular and renal mortality. The findings support incorporation of chronic disease into lifetime health care plans.
Australian and New Zealand Journal of Public Health 02/2010; 34(1):11-8. · 1.20 Impact Factor
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ABSTRACT: 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 (N(glom)), mean glomerular volume (V(glom)) and kidney weight in two geographically separated black populations with significant common genetic ancestry.
Unbiased stereology was used to determine N(glom) and V(glom) 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.
African Americans were taller and heavier than their Senegalese counterparts. N(glom) was remarkably similar-with a geometric mean of 937 967 in Senegalese and 904 412 in African Americans (P = 0.62). V(glom) was correlated inversely with N(glom) and directly with body surface area in both groups, but V(glom) was 54% greater in African Americans than in Senegalese Africans [8.30 +/- 2.92 (SD) and 5.38 +/- 1.25 microm(3) x 10(6), respectively] and remained significantly larger (38%) after adjustment for body size. V(glom) 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.
Despite similar nephron numbers, a common genetic constitution, and even in relation to current body size, African Americans have larger V(glom) than Senegalese subjects. This may mark exposure to environmental stressors or hereditary traits concentrated in the population's relocation to North America.
Nephrology Dialysis Transplantation 02/2010; 25(5):1514-20. · 3.40 Impact Factor
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American Journal of Kidney Diseases 01/2010; · 5.43 Impact Factor
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ABSTRACT: To describe associations between birthweight and infant, child and early adult mortality from natural causes in a remote Australian Aboriginal community against a background of rapidly changing mortality due to better health services.
Cohort study of 995 people with recorded birthweights who were born between 1956 and 1985 to an Aboriginal mother in a remote Australian Aboriginal community. Participants were followed through to the end of 2006.
Rates of natural deaths of infants (aged 0 to < 1 year), children (aged 1 to < 15 years) and adults (aged 15 to < 37 years), compared by birth intervals (1956-1965, 1966-1975 and 1976-1985 for infants and children, and 1956-1962 and 1963-1969 for adults) and by birthweight.
Birthweights were low, but increased over time. Deaths among infants and children decreased dramatically over time, but deaths among adults did not. Lower birthweights were associated with higher mortality. Adjusted for birth interval, hazard ratios for deaths among infants, children and adults born at weights below their group birthweight medians were 2.30 (95% CI, 1.13-4.70), 1.78 (95% CI, 1.03-3.07) and 3.49 (95% CI, 1.50-8.09), respectively. The associations were significant individually for deaths associated with diarrhoea in infants, with cardiovascular and renal disease in adults, and marginally significant for deaths from pulmonary causes in children and adults.
The striking improvements in infant and child survival over time must be applauded. We confirmed a predisposing effect of lower birthweights on deaths in infants and children, and showed, for the first time, an association between lower birthweights and deaths in adults. Together, these factors are probably contributing to the current epidemic of chronic disease in Aboriginal people, an effect that will persist for decades. Similar phenomena are probably operating in developing countries.
The Medical journal of Australia 01/2010; 192(1):14-9. · 2.81 Impact Factor
