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Rates of chronic kidney disease of unknown etiology are high in Aguascalientes, Mexico. Kidneys of adolescents are small by ultrasonography, compatible with oligonephronia, whereas proteinuria and higher estimated glomerular filtration rates and blood pressures among those with relatively higher kidney volumes probably flag relatively greater degrees of compensatory hypertrophy. Glomerulomegaly and podocytopathy, and later segmental glomerulosclerosis in biopsies, suggest a cascade driven by nephron deficiency. Better measures of glomerular number and volume should improve understanding, facilitate risk assessment, and guide interventions., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin., Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model., Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17-49 ml/min) and 3 pediatric cohorts (median eGFR range of 26-45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7-6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R 2 7%-44% across cohorts)., Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations., (© 2023 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Introduction: We have previously showed that albuminuria was associated with low birthweight in young adults in a remote Australian Aboriginal community that has high rates of kidney disease. Here we describe the association of birthweight with incidence and progression of kidney disease over time., Methods: Among 695 members of an Aboriginal community with recorded birthweights, urine albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured at ages 5 to 40 years, and follow-up values were measured or imputed again a median of 11.6 years later. Prevalence of markers on each occasion and change over time were evaluated in the context of birthweights and other potentially significant factors., Results: On the second screen, ACR was inversely and significantly correlated with birthweight and eGFR was directly correlated with birthweight. Increases in ACR and in proportions of persons who developed new-onset (incident) albuminuria between screens were higher in those of lower birthweights (<2.5 kg). Proportions of persons who lost ≥20% of their baseline eGFR were higher in the lower birthweight groups. Lower birthweights also amplified elevations of ACR associated with other risk factors, specifically higher body mass indexes (BMIs) and a prior history of poststreptococcal glomerulonephritis (PSGN). At both screens, progressively higher levels of ACR beyond the mid-microalbuminuria range were correlated with lower levels of eGFR., Conclusions: Lower birthweight contributes to an excess of kidney disease and its progression in this population. Because an excess of low birthweight and episodes of PSGN are eminently preventable, substantial containment of kidney disease is feasible., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Antecedents of the high rates of chronic kidney disease in Australian Indigenous peoples may originate early in life. Fourteen percent of Australian Indigenous infants are born preterm (under 37 weeks gestation) and, therefore, at risk. Here, our observational cohort study sought to determine the impact of preterm birth on renal function in Australian Indigenous and non-Indigenous infants. Renal function was assessed between 4-29 days postnatally in 60 Indigenous and 42 non-Indigenous infants born at 24-36 weeks gestation. Indigenous ethnicity was associated with impaired renal function, with significantly higher serum creatinine (geometric mean ratio (GMR) 1.15 [1.06, 1.25]), fractional excretion of sodium (GMR 1.21 [1.04, 1.39]), and urine albumin (GMR 1.57 [1.05, 2.34]), β-2 microglobulin (GMR 1.82 [1.11, 2.98]) and cystatin C (GMR 3.27 [1.54, 6.95]) when controlling for gestational/postnatal age, sex and birth weight Z-score. Renal injury, as indicated by high urine neutrophil gelatinase-associated lipocalin levels, was associated with maternal smoking and postnatal antibiotic exposure. Indigenous infants appeared to be most susceptible to the adverse impact of antibiotics. These findings show that preterm Australian Indigenous infants are highly vulnerable to renal dysfunction. Preterm birth may contribute to their increased risk of chronic kidney disease. Thus, we recommended that renal function should be closely monitored life-long in Indigenous children born preterm., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Although blood pressure control is a major goal in chronic kidney disease, no worldwide overview of either its achievement or antihypertensive prescriptions is currently available. To evaluate this we compared crude prevalence of uncontrolled blood pressure among 17 cohort studies, including 34 602 individuals with estimated glomerular filtration rate under 60 ml/min/1.73 m 2 and treated hypertension across four continents, and estimated observed to expected prevalence ratios, adjusted for potential confounders. Crude prevalence of blood pressure of 140/90 mm Hg or more varied from 28% to 61% and of blood pressure of 130/80 or more from 54% to 84%. Adjusted prevalence ratios indicated poorer hypertension control than expected in cohorts from European countries, India, and Uruguay, and better control in patients from North American and high-income Asian countries. Four antihypertensive drug classes or more were prescribed to more than 30% of participants in North American and some European cohorts, but this practice was less common elsewhere. Renin angiotensin-aldosterone system inhibitors were the most common antihypertensive drugs, prescribed for 54% to 91% of cohort participants. Differences for other drug classes were much stronger, ranging from 11% to 79% for diuretics, 22% to 70% for beta-blockers, and 27% to 75% for calcium-channel blockers. The confounders studied explain only a part of the international variation in blood pressure control among individuals with chronic kidney disease. Thus, considerable heterogeneity in prescription patterns worldwide calls for further investigation into the impact of different approaches on patient outcomes., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Enabled by the Chronic Kidney Disease, Queensland (CKD.QLD) Registry, we aim to outline the structure, implementation, and outcomes of telenephrology clinics for the management of patients with chronic kidney disease (CKD) in rural, regional, and remote areas of the Darling Downs region in Queensland, Australia., Methods: This is an observational registry-based study involving adult patients with CKD, attending specialist clinics, and residing ≥50 km away from Toowoomba Hospital. The telenephrology cohort (TC) included those who had their follow-up appointments via videoconference at local Queensland Health facilities, and the standard care cohort (SCC) included those who continue to have their follow-up in Toowoomba Hospital., Results: A total of 234 patients with CKD were seen via videoconference clinics between September 1, 2011 and December 31, 2016, representing 22.2% of the CKD registry cohort from Toowoomba Hospital. The baseline characteristics and comorbid profiles of both groups were similar. The Aboriginal population was overrepresented in the TC (22.2% vs. 5.9%). As a group for each visit, the TC traveled 100,000 km less (both ways) to see a specialist physically. During follow-up, 5.1% of patients in the TC were initiated on dialysis whereas 9.9% were initiated on dialysis in the SCC ( P  = 0.02). There was lower mortality in the TC (11.1% vs. 18.2%; P  = 0.02)., Conclusion: Telenephrology clinics were safe, economical, and efficient for the delivery of specialist care for patients with CKD living at a distance from the main referral hospital. Such care was comparable to standard care delivered at the main hospital but with clear benefits to the patients in terms of reduced travel distance, more independence, and similar outcomes.

Chronic kidney disease (CKD) was largely a hidden health problem until the publication of an internationally agreed approach to its identification, monitoring, and treatment. The 2002 National Kidney Foundation CKD classification and the subsequent 2006 Kidney Disease Improving Global Outcomes (KDIGO) recommendations are powerful tools for translating thinking about CKD into clinical practice. These guidelines were strongly endorsed by the international community, including Australia, and were incorporated into CKD practice guidelines. In the past, CKD research studies in Australia focused on screening the general population, and more specifically, individuals at risk for CKD. Information from these studies led to the recognition that the CKD burden in Australia is a public health problem and contributed to the development of national health policies and priorities. At present, apart from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) that reports on CKD patients undergoing renal replacement therapy (RRT), long-term surveillance to describe the natural history of the CKD population not on RRT has only recently started. Entities such as CKD. Queensland and the Western Australian Nephrology Database are able to fill the gap and provide opportunities for collaborative research of CKD in Australia. Establishment of a National Health and Medical Research Centre-funded CKD Centre of Excellence in 2015 and the Better Evidence and Translation-Chronic Kidney Disease in 2016 are likely to change the future of CKD surveillance and research in Australia.

Introduction: The relationship of APOL1 renal risk variants to cardiovascular disease (CVD) is controversial and was the subject of this investigation., Methods: Age, cause of death, and nephrosclerosis (the latter defined by glomerulosclerosis) were analyzed in the autopsies of 162 African Americans and 136 whites genotyped for APOL1 risk alleles., Results: Sudden deaths represented >75% of CVD autopsies for both races and all-risk genotypes. The average ages of CVD deaths for African Americans with 1 and 2 APOL1 risk alleles were, respectively, 7.0 years ( P  = 0.02) and 12.2 years ( P  < 0.01) younger than African Americans with 0 risk alleles and 8.7 years ( P  = 0.01) and 13.9 years ( P  = 0.01) younger than whites. Age differences were not significant between African Americans and whites with 0 risk alleles ( P  = 0.61). The younger CVD deaths of African Americans were associated with less severe glomerulosclerosis with 2 ( P  = 0.01), although not 1 ( P  = 0.09), compared with 0 APOL1 risk alleles. Cardiomyopathy was found in 23% of African Americans with 1 and 2 risk alleles and significantly contributed to the lower age ( P  = 0.01). For non-CVD deaths, age differences were not seen by race ( P  = 0.28) or among African Americans by risk allele status ( P  = 0.38)., Conclusion: Carriage of 1 or 2 APOL1 risk alleles in African Americans was associated with earlier age deaths due to coronary artery disease and cardiomyopathy. For 2 risk alleles, the early age was independent of nephrosclerosis.

Objective: Although elevated body mass index (BMI) and waist circumference (WC) have been identified as risk factors for mortality, data from the Australian Aboriginal communities are scarce. This study examined the associations of BMI and WC with all-cause mortality in an Australian Aboriginal community., Methods: A total of 934 Aboriginal adults, aged 18-76 years, who participated in a community-wide screening programme in Australia's Northern Territory from 1992 to 1998, were followed-up prospectively for up to 18 years for death outcomes. The hazard ratios for mortality were estimated by baseline BMI and WC. Age, sex, smoking and alcohol consumption status were adjusted for in multivariable analysis., Results: In 14,750 person-years of follow-up, 216 deaths were recorded. For each standard deviation increase in BMI, the risk of all-cause death decreased by 9% (95% CI: 0.80-1.05); whereas for each SD increase in WC, the risk of all-cause mortality increased by 17% (95% CI: 1.03-1.33). The risk of mortality was lower in the 3rd BMI tertile compared to the 1st tertile for mortality after adjusting for WC, age, sex, smoking and alcohol consumption. Risk of death was higher in WC tertile 3 compared to tertile 1 after adjusting for BMI, age, sex, smoking and alcohol consumption., Conclusions: The risk of all-cause mortality among participants increased with higher WC, while participants with relatively higher BMI had a lower mortality risk. WC had stronger association with mortality than did BMI. The results indicate the importance of assessing WC measures in studies conducted in Aboriginal Australia., (Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

The increased risk of end-stage kidney disease (ESKD) among hypertensive African Americans is partly related to APOL1 allele variants. Hypertension-associated arterionephrosclerosis consists of arteriosclerosis, glomerulosclerosis, and cortical fibrosis. The initial glomerulosclerosis, attributed to preglomerular arteriosclerosis and ischemia, consists of focal global glomerulosclerosis (FGGS), but in biopsy studies, focal segmental glomerulosclerosis (FSGS) is found with progression to ESKD, particularly in African Americans. This is a study of arterionephrosclerosis in successfully APOL1 genotyped autopsy kidney tissue of 159 African Americans (61 no risk alleles, 68 one risk allele, 30 two risk alleles) and 135 whites aged 18-89 years from a general population with no clinical renal disease. Glomerulosclerosis was nearly exclusively FGGS with only three subjects having FSGS-like lesions that were unrelated to APOL1 risk status. For both races, in multivariable analysis, the dependent variables of arteriosclerosis, glomerulosclerosis, and cortical fibrosis were all significantly related to the independent variables of older age (P < 0.001) and hypertension (P < 0.001). A relationship between APOL1 genotype and arteriosclerosis was apparent only after 35 years of age when, for any level of elevated blood pressure, more severe arteriosclerosis was found in the interlobular arteries of 14 subjects with two APOL1 risk alleles when compared to African Americans with none (n = 37, P = 0.02) or one risk alleles (n = 35, P = 0.02). With the limitation of the small number of subjects contributing to the positive results, the findings imply that APOL1 risk alleles recessively augment small vessel arteriosclerosis in conjunction with age and hypertension. FSGS was not a significant finding, indicating that in the early stages of arterionephrosclerosis, the primary pathologic influence of APOL1 genotype is vascular rather than glomerular., Competing Interests: The authors declare that they have no conflicting financial interests.

Problem: To evaluate the associations of different anthropometric measurements on earlier exam with subsequent gestational diabetes mellitus (GDM) in Aboriginal women., Methods: This is a nested case-control study. Anthropometric measurements were conducted at baseline from 1992 to 1995 in a remote Aboriginal community. All subsequent pregnancies among the original participants were identified through review of hospital records of 20 years. Thirty-two women developed GDM and 99 women were hospitalised for pregnancy-related conditions other than GDM. The association between body mass index (BMI), weight, height, waist circumference, hip circumference, waist-to-hip ratio and waist-to-height ratio with subsequent GDM was examined., Results: Our results showed an increased risk of GDM with increase in one standard deviation of BMI (OR=2.0; 95% CI: 1.3, 3.1), weight (OR=1.7; 95% CI: 1.1, 2.7), waist circumference (OR=1.8; 95% CI: 1.1, 3.0) and waist-to-height ratio (OR=2.3; 95% CI: 1.4, 3.9). High BMI (BMI≥25kg/m(2)) was associated with subsequent GDM (OR=2.8; 95% CI: 1.0, 7.8)., Conclusions: BMI and waist-to-height ratio are better predictors than other anthropometric indices of GDM in Aboriginal women. Given that these measures are associated with future GDM, interventions to reduce BMI, weight and waist circumference in young women need to be assessed for their potential to prevent GDM., (Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Objective: To estimate the lifetime risk of developing hospital-diagnosed chronic obstructive pulmonary disease (COPD) in Aboriginal people living in remote areas., Methods: A total of 1,374 participants in a remote community were followed up to 20 years. Individuals with hospital-diagnosed COPD were identified through hospital records. The lifetime risk of hospital-diagnosed COPD was estimated using a modified technique of survival analysis., Results: Of the 1,374 participants, 164 were identified as having incident hospital-diagnosed COPD during 21,614 person years of follow-up. After adjusting for the presence of competing risk of death from non-COPD causes, the lifetime risk of COPD was 53% for the overall population, higher in women (61%) than in men (45%). Adjusting for baseline age and smoking status, women had a significantly higher risk of COPD than men with a hazard ratio (HR) = 1.55 (95%CI 1.13-2.14), while men were more likely to die from non-COPD causes than women before being diagnosed as having COPD, HR = 2.30 (95%CI 1.64-3.23)., Conclusions: These Aboriginal people have a high lifetime risk of COPD, and one in two have hospital-diagnosed COPD during their lifetime. Our findings warrant further efforts and resources to combat this condition in remote Aboriginal communities., (© 2014 Public Health Association of Australia.)

Chronic kidney disease is now recognized to be a worldwide problem associated with significant morbidity and mortality and there is a steep increase in the number of patients reaching end-stage renal disease. In many parts of the world, the disease affects younger people without diabetes or hypertension. The costs to family and society can be enormous. Early recognition of CKD may help prevent disease progression and the subsequent decline in health and longevity. Surveillance programs for early CKD detection are beginning to be implemented in a few countries. In this article, we will focus on the challenges and successes of these programs with the hope that their eventual and widespread use will reduce the complications, deaths, disabilities, and economic burdens associated with CKD worldwide.

Aim: To examine chronic disease (CD)-related clinical activity and outcomes associated with introduction of a more systematic approach to chronic disease care in a remote Aboriginal community, using data from Communicare patient record management system., Methods: We examined CD process measures, outcomes and clinical profiles in adults age 15+ years from Communicare data and compared results for two intervals. Process measures were clinic visits and proportions of eligible patients with recorded CD-related procedures or diagnostic tests. Outcome measures were results of CD care items and CD morbidities. Data in the interval 2007-2009 were compared with data from 2009 to 2011, in which an intensified CD program was conducted in the clinic by its own staff., Results: About one-third of adult visits were related to CD care; CD-cycle of care encounters increased significantly in the second interval, from 3.2% to 9.1%, and proportions of adults having CD-related procedures or tests were also higher. For already commonly performed items, like blood pressure, weight and lipids, proportions of adults tested were 30-50% higher in the second interval, while proportions tested for more recently emphasised items, like waist, HbA1C, urine ACR, rose by more than 200%. Levels of SBP, DBP, HbA1c and HDL-C significantly improved in the second interval. Proportions of adults with clinical values outside normal ranges decreased for at least half of observations., Conclusions: Parameters of CD care activities and outcomes have increased significantly over the last four years in this setting, accompanied by stabilisation of or improvement in outcomes., (© 2014 The Authors. ANZJPH © 2014 Public Health Association of Australia.)

Objective: To determine trends in health status over a 10-year interval in a high-risk remote Australian Aboriginal community., Methods: Two health surveys were performed, one between 1992 and 1997 and the other between 2004 and 2006, on people aged five years or older. Outcomes were compared across age-matched and sex-matched pairs., Results: There were 1,209 matched pairs. In the second survey, birthweights tended to be higher, and there were significant increases in heights of adolescents and young adults, and high density lipoprotein cholesterol (HDL-C) levels generally. Young adult males were lighter, had lower measurements for waist circumference and blood pressure and less frequently had overt-albuminuria, while elevated blood pressure was less common in older males. However, females≥15 years had higher measurements for waist circumference, waist to hip ratio (WHR), body mass index (BMI) and diastolic blood pressure and a higher proportion of diabetes, notably in those aged older than 45 years. Males aged 15-24 years were less likely to be smokers while women aged less than 45 years were more often current drinkers., Conclusions: Results indicative of better nutrition among youth, better health of young adult males, stable or lower levels of albuminuria and improved HDL levels are all encouraging. The waist circumference increase in females might reflect better food access. An increase in diabetes in older subjects probably reflects recent enhanced survival of middle-aged and older people with--and at risk for--diabetes., (© 2014 The Authors. ANZJPH © 2014 Public Health Association of Australia.)

Objective: To examine the trends of all-cause natural mortality for people aged 15 years and over in a remote Australian Aboriginal community between 1996 and 2010., Methods: The annual population in the community by gender and age group was obtained from the Australian Bureau of Statistics (ABS). All known deaths and all records of start of renal replacement therapy (RRT) for renal failure were recorded between 1996 and 2010. Five-year aggregated death rates were calculated and the changes in natural mortality over the interval were evaluated. Mortality was compared with those of the Northern Territory (NT) Indigenous and non-Indigenous people as a whole from 1998 to 2006., Results: Rates of natural deaths were lower in the third interval 2006-2010 relative to the first interval 1996-2000, with higher, but more rapidly falling rates for females than males. Reductions were prominent for both sexes in the 65 and over age groups, but death rates in females of earlier middle age also trended lower. The trends applied whether or not the starting of RRT was considered as a natural death. There was a similar trend in rates of natural death in the aggregate Indigenous population of NT., Conclusions: The downward trends probably reflect improvements in risk factor status since the 1960s, all-of-life health interventions, as well as better chronic disease management in the last two decades. The higher death rates in females than males in this community remain unexplained, but the rapid rate of decline of female death rates predicts that this gap will soon be minimised., (© 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.)

Developmental programming of non-communicable diseases is now an established paradigm. With respect to hypertension and chronic kidney disease, adverse events experienced in utero can affect development of the fetal kidney and reduce final nephron number. Low birthweight and prematurity are the most consistent clinical surrogates for a low nephron number and are associated with increased risk of hypertension, proteinuria, and kidney disease in later life. Rapid weight gain in childhood or adolescence further compounds these risks. Low birthweight, prematurity, and rapid childhood weight gain should alert clinicians to an individual's lifelong risk of hypertension and kidney disease, prompting education to minimise additional risk factors and ensuring follow-up. Birthweight and prematurity are affected substantially by maternal nutrition and health during pregnancy. Optimisation of maternal health and early childhood nutrition could, therefore, attenuate this programming cycle and reduce the global burden of hypertension and kidney disease in the future., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

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.

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.

Objectives: We assessed the independent contribution of C-reactive protein to the risk of cardiovascular disease in Aboriginal Australians., Methods: 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., Results: 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%)., Conclusions: 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.

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2010 The Authors. Journal Compilation © 2010 Public Health Association of Australia.)

The International Federation of Kidney Foundations surveyed its members on chronic kidney disease 'prevention' programs in their regions and countries in 2005 and 2007. A profile was developed, representing 28 countries (56% response). Some form of screening activity was reported in 24 of the 28 countries (85.7%). Two countries (7%) had, or anticipated development of, legislated national screening. Programs were conducted by kidney foundations or research groups, and were variously population based, focused on high risk groups or opportunistic. Tests in 63% of responding programs included weight, height, blood pressure, blood glucose, dipstick urinalysis and serum creatinine. Several programs used the USA's Kidney Early Evaluation Program's and International Society of Nephrology's templates. World Kidney Day activities contributed significantly. Stated needs were for more government recognition, firm policies and approaches, and critically, resources. Repeat responders reported progress in 2007, particularly in government interest and education delivery. Despite difficulties, programs are developing in many regions. Most need more resources and some members need substantial and sustained assistance.

Objectives: To quantify Indigenous mortality, compare it with non-Indigenous mortality, and identify causes of excess Indigenous mortality by remoteness in Queensland, 1997-2000., Design: Cross-sectional survey of all deaths of Queensland residents registered in Australia during the study period., Main Outcome Measures: Mortality rates were standardised to the concurrent non-Indigenous population and categorised by age and sex., Results: Death rates in Indigenous people were higher in remote areas. The difference between Indigenous and non-Indigenous mortality was also highest in remote areas. The leading causes of deaths were ischaemic heart disease, diabetes mellitus, respiratory diseases, malignant neoplasms, and injury, which accounted for more than 60% of excess deaths., Conclusions: Despite limitations with Indigenous identification, particularly in urban areas, Indigenous people, compared with the non-Indigenous population, have elevated mortality rates that increase by remoteness. This is in agreement with past work. To the extent that some of the causes of excess mortality can be attributed to lifestyle conditions, the health of Indigenous Australians can be substantially improved.

Objective: To estimate the magnitude of excess risk for proteinuria, high blood pressure and diabetes in Australian Aboriginal adults in three remote communities by comparing them with nationwide Australian data., Methods: Adult volunteers from three remote communities in the Northern Territory were screened for proteinuria, high blood pressure, and diabetes between 2000 and mid 2003. Rates for people age 25 to 74 years were compared with those from the AusDiab study conducted in 1999 and 2000., Results: Compared with AusDiab, rates of these conditions were elevated in all Aboriginal communities, but differed among them. With adjustment for age and sex, rates of proteinuria were elevated 2.5- to 5.3-fold, rates of high blood pressure were elevated 3.1- to 8.1-fold and rates of diabetes were elevated 5.4- to 10-fold (p < 0.001 for all). The risk of having any condition ranged from 3.0- to 8.7-fold and the risk of having two or more conditions ranged from 5.8- to 14.2-fold., Discussion: The data are compatible with the excess morbidity and mortality from cardiovascular disease, diabetes and renal disease in these Aboriginal groups. They reflect the multitude of risk factors operating in these environments. They dictate urgent and systematic intervention to modify outcomes of established disease and to prevent their development. However, the resources required for effective secondary intervention will differ among communities according to the disease burden.

Background: It has been suggested that albuminuria is useful in identifying persons at increased risk of coronary heart disease (CHD). Australian Aborigines have exceedingly high rates of renal failure together with increased CHD mortality. We undertook this prospective cohort study to assess the independent effect of albuminuria on CHD risk in Aboriginal people in the Northern Territory of Australia., Methods: We examined the relation between micro- and macroalbuminuria and incident CHD in a sample of 870 Aboriginal adults aged 20 to 74 years old without prevalent baseline CHD. Cox proportional hazards models were used to assess the association between baseline albuminuria and CHD incidence., Results: During a median of 9.2 years of follow-up, 89 CHD events occurred during the follow-up period (1992 to 2003). The incidence of CHD increased significantly across categories of albuminuria (4.4, 10.9, and 29.8 per 1000 person-years for normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). The multiple Cox proportional hazards regression showed the hazard ratio was 3.4 (95% CI 1.6, 7.3), adjusting for age, gender, body mass index (BMI), blood pressure, total cholesterol, diabetes status, cigarette smoking, and alcohol consumption, for macroalbuminuria group. Hazard ratio for microalbuminuria group was not significantly different from unity during the first 6 years of follow-up but significantly higher during the follow-up period > or = 6 years with adjusted hazard ratio 9.0 (95% CI 2.0, 40.0)., Conclusion: Independent of traditional cardiovascular risk factors, both microalbuminuria and macroalbuminuria may be useful in identifying persons at increased risk of CHD in Aboriginal people.

Background: Rates of cardiovascular disease and renal disease in Australian Aboriginal communities are high, as is the prevalence of some 'traditional' cardiovascular (CV) risk factors, such as diabetes and cigarette smoking. Recent work has highlighted the importance of markers of inflammation, such as C-reactive protein (CRP), homocysteine and albuminuria as predictors of cardiovascular risk in urban westernized settings. It is not clear how these factors relate to outcome in the setting of these remote communities, but very high CRP concentrations have been shown in this and other Aboriginal communities., Methods and Results: In a cross-sectional survey including 237 adults in a remote Aboriginal community in the Northern Territory of Australia, we measured carotid intima-media thickness (IMT), together with blood pressure, diabetes, lipid levels, smoking and albuminuria, CRP and fibrinogen, serum homocysteine concentration, and IgG titres for Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus. Median carotid IMT was 0.63 [interquartile range 0.54-0.71] mm. As a categorical outcome, the prevalence of the highest IMT quartile ('increased IMT', > or =0.72 mm) was compared with the lower three quartiles. Increased IMT was associated in univariate analyses with greater waist circumference, systolic BP, fibrinogen and serum albumin concentrations, urine albumin/creatinine ratio and older age as continuous variables. Associations of increased IMT with some continuous variables were not linear; univariate associations were seen with the highest quartile (versus all other quartiles) of CRP and homocysteine concentration and CMV IgG titre. In a multivariate model age, smoking, waist circumference and the highest quartile of CRP concentrations (> or =14 mg/l) remained significant predictors of IMT > or =0.72 mm., Conclusions: Measurement of carotid IMT was possible in this remote setting. Increased IMT (> or =0.72 mm) was associated with increased CRP concentrations over a range that suggests infection/inflammation may be important determinants of cardiovascular risk in this setting. The associations of IMT with markers of renal disease seen in univariate analyses were explained in this analysis by confounding due to the associations of urine ACR with other risk factors.

Background: In the Southeast United States, African Americans have an estimated incidence of hypertension and end-stage renal disease (ESRD) that is five times greater than Caucasians. Higher rates of low birth weight (LBW) among African Americans is suggested to predispose African Americans to the higher risk, possibly by reducing the number of glomeruli that develop in the kidney. This study investigates the relationships between age, race, gender, total glomerular number (Nglom), mean glomerular volume (Vglom), body surface area (BSA), and birth weight., Methods: Stereologic estimates of Nglom and Vglom were obtained using the physical disector/fractionator combination for autopsy kidneys from 37 African Americans and 19 Caucasians., Results: Nglom was normally distributed and ranged from 227,327 to 1,825,380, an 8.0-fold difference. A direct linear relationship was observed between Nglom and birth weight (r = 0.423, P = 0.0012) with a regression coefficient that predicted an increase of 257,426 glomeruli per kilogram increase in birth weight (alpha = 0.050:0.908). Among adults there was a 4.9-fold range in Vglom, and in adults, Vglom was strongly and inversely correlated with Nglom (r =-0.640, P = 0.000002). Adult Vglom showed no significant correlation with BSA for males (r = -0.0150, P = 0.936), although it did for females (r = 0.606, P = 0.022). No racial differences in average Nglom or Vglom were observed., Conclusion: Birth weight is a strong determinant of Nglom and thereby of glomerular size in the postnatal kidney. The findings support the hypothesis that LBW by impairing nephron development is a risk factor for hypertension and ESRD in adulthood.

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.