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Background: Australian Aborigines in remote areas are experiencing an epidemic of renal and cardiovascular disease. In November 1995, we introduced a renal and cardiovascular treatment program into the Tiwi community, which has a three- to fivefold increase in death rates and a recent annual incidence of treated end-stage renal disease (ESRD) of 2760 per million. Our previous study described an estimated 50% reduction in renal failure and all-cause natural deaths in the treatment group through December 31, 1998. We now describe a reduction in these events through mid 2000., Methods: People eligible for treatment were those with confirmed hypertension, diabetics with microalbuminuria or overt albuminuria, and people with overt albuminuria, regardless of blood pressure and diabetes. Treatment centered around the use of perindopril (Coversyl, Servier), with additional agents as needed to reach defined blood pressure goals, attempts at control of glucose and lipid levels, and health education. Two hundred and sixty-seven people, or 30% of the adult population, have been enrolled, with mean follow up of 3.39 years. Rates of terminal endpoints were compared on an intention-to-treat basis with those of 327 historical controls matched for baseline disease severity, who were followed for a mean of 3.18 years in the pre-treatment program era, against a background of no treatment or inconsistent changing treatment., Results: Terminal events occurred in 38 controls and 23 people in the treatment group. The estimated rate of natural deaths in the treatment group was 50% that of the controls, (P=0.012); the rate of renal deaths was 47% (P=0.038) and the rate of non-renal deaths was 54% that of controls (P=0.085). Survival benefit in the treatment group was observed at all levels of overt albuminuria, in non-diabetics and diabetics, in normotensive as well as hypertensive people, and in people who had been taking angiotensin converting enzyme-inhibitors (ACEi) in the pre-program era, as well as those who had not. Benefit was absent among the low death rates of people without overt albuminuria, and questionable among people with glomerular filtration rates (GFRs) <60 mL/min. The number of people needed to treat (NNT) to avoid one terminal event of natural causes was calculated at only 11.6., Conclusions: Falling rates of deaths and renal failure in the whole community support marked benefit of the program. Millions of dollars have been saved, based on avoidance of dialysis alone, but the reduction in premature death is the greater benefit. Chronic disease programs like this are enormously effective, and should be introduced into to all high-risk communities as a matter of urgency.

Objective: To examine the relationship between self-reported tobacco smoking and urinary cotinine concentrations in the setting of a remote Aboriginal community., Methods: In a remote Northern Territory (NT) Aboriginal community the relationship between self-reported tobacco smoking and urinary cotinine concentrations was examined as part of a cross-sectional survey of cardiovascular risk factors. Current tobacco smoking was assessed as part of a questionnaire. The concentration of cotinine and cotinine/creatinine ratio (CCR) in a spot urine sample were used as a biochemical marker of nicotine exposure., Results: A total of 237 people took part in the survey, although completed questionnaires and urine results were available for 184 people. Current tobacco smoking was reported by 161 (69 [95% CI 63 to 75]%) people, with higher rates among males (84/104, 81 [95% CI 72 to 88]%) than females (77/129, 60 [95% CI 51 to 68]%, p < 0.001). There was good agreement of self report with current tobacco smoking using categories based on urinary cotinine (agreement 94%, kappa = 0.84) and urinary CCR (agreement 94%, kappa = 0.86). Quantitative agreement between cotinine measures and self-reported number of cigarettes per day was better for CCR than cotinine, but the correlation was relatively weak for both., Conclusions: Self-reported cigarette smoking is a valid qualitative measure in this environment. The relatively weak correlation between the biomarker and number of reported cigarettes smoked illustrates problems both with questionnaire and urinary markers of nicotine exposure., Implications: As a qualitative measure of tobacco smoking in this setting, self-report appears adequate but the validity of quantitative self-report is unclear.

Objective: To assess the association between body mass index and the risk of all-cause and disease-specific mortalities in Australian Aborigines in a remote community., Design: A community based cohort study., Participants and Setting: 744 Aboriginal adults aged 20 to 77 years in a remote community in Northern Territory. Eighty-seven deaths occurred during the follow-up period of 5,040.8 person-years., Measures: Mortality data for the period of 1992 and June 2000 were collected. Mortality rate ratios for each body mass index quartile was determined using a Cox proportional hazards model with adjustment for age, sex, and smoking and drinking status., Results: An inverse relationship between BMI quartiles and the risk of all-cause, natural, and non-CVD mortality was found. Adjusted rate ratios (95% CI) of all-cause mortality were 0.92 (0.54-1.59), 0.71 (0.40-1.26) and 0.38 (0.19-0.75) for second, third and fourth BMI quartiles, respectively, with the first quartile as the reference. The fourth BMI quartile had the lowest risk of mortality with adjusted rate ratios of 0.38, 0.28, and 0.16 for deaths from all-cause, natural, and non-CVD, respectively. However, the associations between BMI and CVD and renal deaths did not reach statistical significance., Conclusions: BMI and mortality are inversely associated in Aboriginal adults in a remote community. Individuals with relatively higher BMI have a lower risk of death.

In focal segmental glomerulosclerosis (FSGS), a biphasic change in glomerular size is described in which glomeruli are enlarged with early glomerulosclerosis. Hyperperfusion of larger glomeruli is believed to contribute to progressive glomerular injury. This study was undertaken to investigate whether similar alterations in glomerular size can be found in other renal diseases. Volumes of sclerotic and nonsclerotic glomeruli were estimated in renal biopsy specimens using the Weibel and Gomez method (1962). Glomerulosclerosis was graded on individual glomeruli from 0 to 4, with 0 as no sclerosis and 4 as 76% to 100% sclerosis. Primary and secondary FSGS showed a biphasic change in which grade 2 glomeruli were 50% larger than grade 0 glomeruli and grades 3 and 4 glomeruli were solidified and smaller than grade 0 glomeruli. In essential hypertension, no increase in glomerular size was seen with early glomerulosclerosis, and the latter stages consisted of ischemic obsolescence in which collapsed tufts were 50% smaller than solidified glomeruli of FSGS. Grade 0 glomeruli of membranous glomerulonephritis (MGN) were significantly larger than grade 0 glomeruli of FSGS, and no significant difference in size was seen between grades 0 and 2 glomerulosclerosis. Solidified diabetic glomeruli maintained a large size with grades 3 and 4 sclerosis. Glomeruloscleroses of FSGS, hypertension, MGN, and diabetes have stereologically distinct features. A biphasic change in glomerular size is characteristic of primary and secondary FSGS, but not hypertension, in which tuft collapse supports reduced rather than increased perfusion in the pathogenesis of its glomerular obsolescence., (Copyright 2002 by the National Kidney Foundation, Inc.)

Albuminuria is a widely recognized marker of renal disease and cardiovascular risk. This is especially true in Aboriginal Australians living in remote communities who suffer high rates of end-stage renal disease and cardiovascular mortality. During a survey of risk factors for renal and cardiovascular disease in one such community, an association between a common polymorphism at codon 72 (Arg/Pro) of the p53 gene and markers of renal disease was sought. A cross-sectional community survey including 217 people was performed. Genotypes of the polymorphism were distributed in Hardy-Weinberg equilibrium, with p53Arg allele frequency of 0.45 (range, 0.41 to 0.50). Overall prevalence of albuminuria was high (31% microalbuminuria; 14% overt albuminuria). Urine albumin/creatinine ratio (ACR) was significantly associated with the number of p53Pro alleles (P = 0.01), and there was an interaction with tobacco smoking (P = 0.04). The p53 genotype was also associated with increasing HbA1c, but the relationship between p53 and ACR was independent of this. This is a previously unreported association. This study does not address the mechanism, but this finding, if confirmed, expands the described effects of p53 in cellular proliferation and apoptosis to include a role in the course of renal and possibly cardiovascular disease in this population.