Oligonephronia: another piece in the CKDu jigsaw?

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.

Equitable Expanded Carrier Screening Needs Indigenous Clinical and Population Genomic Data.

Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By comparison, less is known about pathogenic DNA variants in people from other parts of the world. Consequently, inclusion of currently underrepresented Indigenous and other minority population groups in genomic research is essential to enable equitable outcomes in ECS and other areas of genomic medicine. Here, we discuss this issue in relation to the implementation of ECS in Australia, which is currently being evaluated as part of the national Government's Genomics Health Futures Mission. We argue that significant effort is required to build an evidence base and genomic reference data so that ECS can bring significant clinical benefit for many Aboriginal and/or Torres Strait Islander Australians. These efforts are essential steps to achieving the Australian Government's objectives and its commitment "to leveraging the benefits of genomics in the health system for all Australians." They require culturally safe, community-led research and community involvement embedded within national health and medical genomics programs to ensure that new knowledge is integrated into medicine and health services in ways that address the specific and articulated cultural and health needs of Indigenous people. Until this occurs, people who do not have European ancestry are at risk of being, in relative terms, further disadvantaged.

Chronic kidney disease in public renal practices in Queensland, Australia, 2011-2018.

AIM: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland. METHODS: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years. RESULTS: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons mostly had diabetic nephropathy, renovascular disease and multiple diagnoses. Proportions of specific renal diagnoses varied >2-fold across sites. Over the first year, eGFR fell in 24% but was stable or improved in 76%. Over follow up, 10% started KRT, at a median age of 62 yr, most with CKD stages 4 and 5 at consent, while 18.8% died without KRT, at a median age of 80 yr. Indigenous people were younger at consent and more often had diabetes and diabetic kidney disease and had higher incidence rates of KRT. CONCLUSION: The spectrum of characteristics in CKD patients in renal practices is much broader than represented by the minority who ultimately start KRT. Variation in CKD by causes, age, site and Indigenous status, the prevalence of obesity, relative stability of kidney function in many persons over the short term, and differences between those who KRT and die without KRT are all important to explore.

The prevalence of Fabry disease in a statewide chronic kidney disease cohort - Outcomes of the aCQuiRE (Ckd.Qld fabRy Epidemiology) study.

BACKGROUND: Prevalence of Fabry disease amongst Chronic Kidney Disease (CKD) patients on haemodialysis has been shown to be approximately 0.2%. METHODS: We undertook a cross-sectional study employing a cascade screening strategy for Fabry Disease amongst 3000 adult, male and female patients affected by CKD stage 1-5D/T at public, specialty renal practices within participating Queensland Hospital and Health Services from October 2017 to August 2019. A multi-tiered FD screening strategy, utilising a combination of dried blood spot (DBS) enzymatic testing, and if low, then lyso-GB3 testing and DNA sequencing, was used. RESULTS: Mean (SD) age was 64.0 (15.8) years (n = 2992), and 57.9% were male. Eight participants withrew out of the 3000 who consented. Of 2992 screened, 6 (0.20%) received a diagnosis of FD, 2902 (96.99%) did not have FD, and 84 (2.81%) received inconclusive results. Of the patients diagnosed with FD, mean age was 48.5 years; 5 were male (0.29%) and 1 was female (0.08%); 4 were on kidney replacement therapy (2 dialysis and 2 transplant); 3 were new diagnoses. CONCLUSIONS: Estimated overall FD prevalence was 0.20%. Screening of the broader CKD population may be beneficial in identifying cases of FD. TRIAL REGISTRATION: The aCQuiRE Study has been prospectively registered with the Queensland Health Database of Research Activity (DORA, https://dora.health.qld.gov.au ) as pj09946 (Registered 3rd July 2017).

Podocyte endowment and the impact of adult body size on kidney health.

Low birth weight is a risk factor for chronic kidney disease, whereas adult podocyte depletion is a key event in the pathogenesis of glomerulosclerosis. However, whether low birth weight due to poor maternal nutrition is associated with low podocyte endowment and glomerulosclerosis in later life is not known. Female Sprague-Dawley rats were fed a normal-protein diet (NPD; 20%) or low-protein diet (LPD; 8%), to induce low birth weight, from 3 wk before mating until postnatal day 21 (PN21), when kidneys from some male offspring were taken for quantitation of podocyte number and density in whole glomeruli using immunolabeling, tissue clearing, and confocal microscopy. The remaining offspring were fed a normal- or high-fat diet until 6 mo to induce catch-up growth and excessive weight gain, respectively. At PN21, podocyte number per glomerulus was 15% lower in low birth weight (LPD) than normal birth weight (NPD) offspring, with this deficit greater in outer glomeruli. Surprisingly, podocyte number in LPD offspring increased in outer glomeruli between PN21 and 6 mo, although an overall 9% podocyte deficit persisted. Postnatal fat feeding to LPD offspring did not alter podometric indexes or result in glomerular pathology at 6 mo, whereas fat feeding in NPD offspring was associated with far greater body and fat mass as well as podocyte loss, reduced podocyte density, albuminuria, and glomerulosclerosis. This is the first report that maternal diet can influence podocyte endowment. Our findings provide new insights into the impact of low birth weight, podocyte endowment, and postnatal weight on podometrics and kidney health in adulthood.NEW & NOTEWORTHY The present study shows, for the first time, that low birth weight as a result of maternal nutrition is associated with low podocyte endowment. However, a mild podocyte deficit at birth did not result in glomerular pathology in adulthood. In contrast, postnatal podocyte loss in combination with excessive body weight led to albuminuria and glomerulosclerosis. Taken together, these findings provide new insights into the associations between birth weight, podocyte indexes, postnatal weight, and glomerular pathology.

Heterogeneity in patterns of progression of chronic kidney disease.

BACKGROUND: Progression of kidney disease is a deceptively simple word for a complex bio-clinical process, evidenced by the number of definitions in the literature. This has led to confusion and differences in interpretation of studies. METHODS: We describe different patterns of progression, the performance of different definitions of progression and factors associated with chronic kidney disease (CKD) progression in a public renal service in Australia, in a study of patients enrolled in the CKD.QLD Registry with a minimum of 2 years' follow up. RESULTS: Nine patterns of changing estimated glomerular filtration rate (eGFR) over two consecutive 12-month periods were identified. Most common was a stable eGFR over 2 years (30%), and the least was a sustainable improvement of eGFR over both periods (2.1%). There was a lack of congruence between the several definitions of progression of CKD evaluated. More people progressed using the definition of decline of eGFR of >5 mL/min/1.73 m2 /year (year 1 = 30.2%, year 2 = 20.7%) and the least using development of end-stage renal disease (year 1 = 5.4%, year 2 = 9.9%). Age (40-59, ≥80 years), degree of proteinuria at baseline (nephrotic range) and CKD aetiology (renal vascular disease, diabetic nephropathy) were significantly associated with eGFR decline over 2 years. CONCLUSIONS: This is one of the first demonstrations of the great variations among and within individuals in the progression of CKD over even a period as short as 2 years. Findings suggest considerable potential for renal function recovery and stability while demonstrating the importance of using identical definitions for comparisons across datasets from different sources.

Five enablers to deliver safe water and effective sewage treatment to remote Indigenous communities in Australia.

CONTEXT: Safe drinking water and effective sanitation in remotely located Indigenous communities are essential services and their provision is a human right. Yet sustainable provision of these services can be challenging. Risks to human health from inadequate provision include transmission of hygiene-related infections from microbial contamination, and toxic chemicals that may cause kidney damage or dysfunction. This narrative review is conducted in the current context of the United Nations Sustainable Development Goal 6, the 'refresh' of the National Agreement on Closing the Gap in Indigenous inequity, and the 2020 Inquiry of the Australian Productivity Commission into the National Water Reform. ISSUES: Challenges to providing drinking water supplies in remote communities include biological contamination and chemical contamination from naturally occurring elements in groundwater. Monitoring regimes can be challenged by remote location, minimal and/or high turnover of staff and a lack of ongoing maintenance. Unpalatable water can shift consumption to purchased drinks such as sugar-sweetened beverages, with flow-on health impacts of diet-related chronic conditions such as overweight and obesity, and type 2 diabetes. LESSONS LEARNED: By analysing two effective programs from remote areas of New South Wales and the Torres Strait Islands in Queensland, Australia, five enablers were identified: people factors (support, training, cultural competence); cross-agency collaboration (regulators, funders, state and local government); technology that is fit for place, purpose and local people; funding that is sufficient and sustainable; and taking a systems view of water and sanitation.

An update on chronic kidney disease in Aboriginal Australians.

We provide a brief update on some aspects of chronic kidney disease (CKD) in Indigenous Australians, with CKD referring to all stages of pre-terminal kidney disease, as well as to end-stage kidney failure (ESKF), whether or not a person receives renal replacement therapy (RRT). Recently recorded rates of ESKF and RRT were 6- and 8-fold those recoded for non-Indigenous Australians with age adjustment, while non-dialysis CKD hospitalizations and CKD-attributed deaths were 8-fold and 3-fold higher. The median age of Indigenous people who developed ESKF was ~ 30 years less than for non-Indigenous people, and 84% of them received RTT, while only half of non-Indigenous people with ESKF did so. However, the nationwide average Indigenous incidence rate of RRT appears to have stabilized. The 2012 Australian Health Survey showed elevated levels of CKD markers in Indigenous people at the community level. For all CKD parameters, rates among Indigenous people were strikingly correlated with increasing remoteness of residence and socioeconomic disadvantage, and there was a female predominance in remote areas. The burden of renal disease in Australian Indigenous people is seriously understated by Global Burden of Disease Mortality methodology, because it employs underlying cause of death only, and because deaths of people on RRT are frequently attributed to non-renal causes. These data give a much-expanded view of CKD in Aboriginal people. Methodologic approaches must be remedied for a full appreciation of the burden, costs, and outcomes of the disease, to direct appropriate policy development.

The Ckd. Qld fabRy Epidemiology (aCQuiRE) study protocol: identifying the prevalence of Fabry disease amongst patients with kidney disease in Queensland, Australia.

BACKGROUND: Fabry disease (FD) is a rare, lysosomal storage disorder caused by the absence or deficiency of the enzyme alpha-galactosidase A (α-Gal A) that leads to the abnormal accumulation of the lipid globotriaosylceramide (GB3) in a variety of cell types and tissues throughout the body. FD has an x-linked inheritance pattern. Previously thought to be only carriers, females can also experience FD symptomatology. Symptoms vary in type and severity from patient to patient and tend to increase in severity with age. FD symptoms are non-specific and may be shared with those of other diseases. Misdiagnoses and diagnostic delays are common, often resulting in progressive, irreversible tissue damage. The estimated prevalence of FD in the general population is 1:40,000 to 1:117,000 individuals. However, it is estimated that the prevalence of FD in the dialysis population is 0.12 to 0.7%. Little is known about the prevalence of FD in the broader Chronic Kidney Disease (CKD) population. METHODS: This is an epidemiological study of the prevalence of FD in CKD patents identified from the public renal speciality practices in Queensland, Australia. A cascade approach to screening is being employed with dried blood spot testing for blood levels of alpha-galactosidase A (Alpha-Gal), with follow-up testing for patients with abnormal results by plasma levels of globotriaosylsphingosine (Lyso-GB3) for females and non-definitive cases in males. A diagnosis of FD is confirmed through genetic testing of the GLA gene in cases suspected of having FD based upon Alpha-Gal and Lyso-GB3 testing. DISCUSSION: Expected outcomes of this study include more information about the prevalence of FD at all stages of CKD, including for both males and females. The study may also provide information about common characteristics of FD to assist with diagnosis and optimal management/treatment. Screening is also available for family members of diagnosed patients, with potential for early diagnosis of FD and intervention for those individuals. TRIAL REGISTRATION: Queensland Health Database of Research Activity (DORA, https://dora.health.qld.gov.au) pj09946 (Registered 3rd July 2017).

Renal dysfunction is already evident within the first month of life in Australian Indigenous infants born preterm.

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]), ß-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.

Considerable international variation exists in blood pressure control and antihypertensive prescription patterns in chronic kidney disease.

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 m2 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.

Biopsy-based estimation of total nephron number in Japanese living kidney donors.

BACKGROUND: Increasing evidence suggests that individuals with low nephron number have an increased lifetime risk of renal insufficiency, thereby emphasizing the importance of evaluating total nephron number in each individual. In recent years, new methods have been described for estimating human total nephron number using a combination of image analysis and renal biopsy, though the reproducibility and accuracy of these methods remain uncertain. This study estimated total nephron number in healthy Japanese subjects using such a method. METHODS: Implantation biopsies from 44 living kidney donors were analyzed. Using pre-donation contrast CT angiograms, transplantation donor kidneys were three-dimensionally reconstructed, and total renal cortical volume was estimated. Total nephron number was estimated based on glomerular density in biopsy specimens and total renal cortical volume. The obtained results were analyzed in relation to clinical variables and compared with those of a previously reported Japanese autopsy study. RESULTS: The estimated non-sclerotic and total numbers of glomeruli in this cohort were 650,000 ± 220,000 and 710,000 ± 220,000 (mean ± SD) per kidney. Non-sclerotic glomerular number ranged from 280,000 to 1,220,000 per kidney (4.4-fold) and correlated directly with eGFR (r = 0.328, p = 0.030) and inversely with age (r = - 0.355, p = 0.018). CONCLUSION: The estimated total nephron number obtained in the present study was 25% less than that reported in American living kidney donors obtained using the same procedure and similar to that obtained in a previous Japanese autopsy study using the disector/fractionator method. These results confirm the feasibility of a combined CT angiography and biopsy-based method to estimate total nephron number in humans.

Chronic kidney disease, Queensland: Profile of patients with chronic kidney disease from regional Queensland, Australia: A registry report.

BACKGROUND: Chronic kidney disease, Queensland (CKD.QLD) is a multidisciplinary, collaborative research platform for CKD in Queensland. Most public renal services contribute towards the CKD Registry, including Toowoomba Hospital, which is a referral hospital for Darling Downs Health serving a largely regional population in Queensland. We aim to present the profile of the CKD cohort recruited to the CKD.QLD Registry from Toowoomba Hospital, the first comprehensive report on a pre-dialysis population from regional Australia. METHODS: Study subjects were patients in the Darling Downs Health Service who consented to be included in the CKD.QLD registry from June 2011 to December 2016. Those who were on renal replacement therapy (RRT) were excluded. Patients were followed until date of RRT, death, discharge or loss to follow up or a censor date of 30th June 2017. RESULTS: Overall 1051 subjects, representing 13% of all CKD.QLD Registry patients gave consent of whom, 42.7% were ≥70 years of age. The mean age was 63.8 ± 15.1 years (median age 67 years) with male predominance (55.4%). The majority were born in Australia (86.4%). Aboriginal and Torre Strait Islanders (A&TSI) constituted 9.6% of the cohort. The predominant CKD stages were 3b (28.9%) and 4 (27.7%). Hypertension and diabetes were noted in 91% and 44% of subjects, respectively. Diabetic nephropathy was the leading cause of CKD (26.7%) followed by renovascular disease (17.3%) and glomerulonephritis (14.8%). In 12%, the diagnosis was uncertain. Major co-morbidities included coronary artery disease (24.7%) chronic lung disease (14.8%), cerebrovascular disease (11.6%) and peripheral vascular disease (8.9%). Non-vascular co-morbidities included arthritis (24.6%), gout (23.6%) and gastro-oesophageal reflux disease (19%). The multi-morbidity profile was differed by gender, diabetic status and age. Over a follow-up period upto 72 months, 93 (8.8%) started RRT and 175 (16.6%) died. Of those 82% died without RRT and 18% died after RRT. CONCLUSION: This CKD Registry cohort from regional Queensland consisted mainly of older Caucasians with male predominance. A&TSI patients were overrepresented compared to the overall population. A significant proportion had cardio-vascular disease and multiple co-morbidities which differed by gender, diabetic status and age. This report provides valuable data for health services planning and delivery in regional Queensland.

Blood pressure management in hypertensive people with non-dialysis chronic kidney disease in Queensland, Australia.

BACKGROUND: High blood pressure is the most significant risk factor for the development and progression of chronic kidney disease (CKD). Lowering blood pressure is a goal to prevent CKD progression. This study of adults with CKD who have hypertension aimed to determine blood pressure control rates and the treatment patterns of hypertension and to explore factors associated with control of hypertension. METHODS: This cross-sectional study included all non-dialysis people with CKD stages 3A to 5 under nephrology care in three public renal clinics in Queensland, who joined the CKD.QLD registry from May 2011 to Dec 2015 and had a history of hypertension. Demographic information, other health conditions, laboratory markers and anti-hypertensive medications in use at consent were extracted from the registry. RESULTS: Among 1814 CKD people in these three sites in the registry who were age ≥ 18 years and had CKD stage 3A to 5, 1750 or 96% had a history of hypertension. Of these, the proportion with BP control to < 140/90 mmHg was 61.7% and to < 130/80 mmHg was 36.3%. With target BP < 140/90 mmHg or < 130/80 mmHg, participants aged ≥65 years were 1.23 (95% CI 1.06-1.42) or 1.12 (1.03-1.22) times more likely to have uncontrolled BP compared to those < 65 years old. Participants with severe albuminuria or proteinuria were 1.58 (1.32-1.87) or 1.28 (1.16-1.42, p < 0.001) more likely to have uncontrolled BP compared to those without significant albuminuria or proteinuria. Participants who had cardiovascular disease (CVD) were less likely to have uncontrolled BP compared to those without CVD (0.78, 0.69-0.89 or 0.86, 0.80-0.92). Factors associated with use of more classes of antihypertensive medicines among participants with uncontrolled BP (> 140/90 mmHg) were older age, diabetes, CVD, obesity and severe albuminuria/proteinuria (p < 0.05). Renin Angiotensin Aldosterone System inhibitors were the most frequently used medicines, regardless of the number of medicine classes an individual was prescribed. CONCLUSIONS: Blood pressure control rates in these hypertensive people with CKD was still far from optimal. People with CKD and hypertension aged 65 or older or with severe albuminuria or proteinuria, a group at risk of progression of kidney disease, have higher rates of uncontrolled BP.

BMI and its association with death and the initiation of renal replacement therapy (RRT) in a cohort of patients with chronic kidney disease (CKD).

BACKGROUND: A survival advantage associated with obesity has often been described in dialysis patients. The association of higher body mass index (BMI) with mortality and renal replacement therapy (RRT) in preterminal chronic kidney disease (CKD) patients has not been established. METHODS: Subjects were patients with pre-terminal CKD who were recruited to the CKD.QLD registry. BMI at time of consent was grouped as normal (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), mild obesity (BMI 30-34.9 kg/m2) and moderate obesity+ (BMI ≥ 35 kg/m2) as defined by WHO criteria. The associations of BMI categories with mortality and starting RRT were analysed. RESULTS: The cohort consisted of 3344 CKD patients, of whom 1777 were males (53.1%). The percentages who had normal BMI, or were overweight, mildly obese and moderately obese+ were 18.9, 29.9, 25.1 and 26.1%, respectively. Using people with normal BMI as the reference group, and after adjusting for age, socio-economic status, CKD stage, primary renal diagnoses, comorbidities including cancer, diabetes, peripheral vascular disease (PVD), chronic lung disease, coronary artery disease (CAD), and all other cardiovascular disease (CVD), the hazard ratios (HRs, 95% CI) of males for death without RRT were 0.65 (0.45-0.92, p = 0.016), 0.60 (0.40-0.90, p = 0.013), and 0.77 (0.50-1.19, p = 0.239) for the overweight, mildly obese and moderately obese+. With the same adjustments the hazard ratios for death without RRT in females were 0.96 (0.62-1.50, p = 0.864), 0.94 (0.59-1.49, p = 0.792) and 0.96 (0.60-1.53, p = 0.865) respectively. In males, with normal BMI as the reference group, the adjusted HRs of starting RRT were 1.15 (0.71-1.86, p = 0.579), 0.99 (0.59-1.66, p = 0.970), and 0.95 (0.56-1.61, p = 0.858) for the overweight, mildly obese and moderately obese+ groups, respectively, and in females they were 0.88 (0.44-1.76, p = 0.727), 0.94 (0.47-1.88, p = 0.862) and 0.65 (0.33-1.29, p = 0.219) respectively. CONCLUSIONS: More than 80% of these CKD patients were overweight or obese. Higher BMI seemed to be a significant "protective" factor against death without RRT in males but there was not a significant relationship in females. Higher BMI was not a risk factor for predicting RRT in either male or female patients with CKD.

Body mass index in an Australian population with chronic kidney disease.

BACKGROUND: Obesity emerged as the leading global health concern in 2017. Although higher body mass index (BMI) is a health risk in the general population, its implications for chronic kidney disease (CKD) are not entirely clear. Our aim was to compare BMI in an Australian CKD population with BMI in a sample of the general Australian population, and, in the same group of CKD patients, to describe associations of higher BMI categories with demographic and clinical features. METHODS: A cross-sectional study of BMI in CKD patients was conducted from three major sites who were enrolled in the CKD.QLD registry between May 2011 and July 2015. BMI was categorized according to the World Health Organisation (WHO) guidelines. The prevalence of obesity was compared with a sample of the general Australian population from the most recent National Health Survey (NHS). Associations of BMI with demographic and clinical characteristics of the CKD patients were also analysed. RESULTS: There were 3382 CKD patients in this study (median age 68, IQR 56-76 years); 50.5% had BMI ≥30, the WHO threshold for obesity, in contrast with 28.4% having BMI ≥30 in the NHS cohort. Higher BMI categories were correlated with age < 70 years, male gender, and lower socioeconomic status. After adjustment for age and gender, characteristics which significantly correlated with higher BMI category included hypertension, dyslipidemia, diabetes, diabetic nephropathy, coronary heart disease, other cardiovascular diseases, gout, obstructive sleep apnoea, depression and chronic lung disease. CONCLUSIONS: Patients with CKD in public renal specialty practices in Queensland have strikingly higher rates of obesity than the general Australian population. Within the CKD population, low socio-economic position strongly predisposes to higher BMI categories. Higher BMI categories also strongly correlated with important co-morbidities that contribute to burden of illness. These data flag major opportunities for primary prevention of CKD and for reductions in morbidity in people who already have CKD, which should be considered in public health policy in relation to obesity.

Health service utilisation during the last year of life: a prospective, longitudinal study of the pathways of patients with chronic kidney disease stages 3-5.

BACKGROUND: Chronic kidney disease (CKD) is a growing global problem affecting around 10% of many countries' populations. Providing appropriate palliative care services (PCS) to those with advanced kidney disease is becoming paramount. Palliative/supportive care alongside usual CKD clinical treatment is gaining acceptance in nephrology services although the collaboration with and use of PCS is not consistent. METHODS: The goal of this study was to track and quantify the health service utilisation of people with CKD stages 3-5 over the last 12 months of life. Patients were recruited from a kidney health service (Queensland, Australia) for this prospective, longitudinal study. Data were collected for 12 months (or until death, whichever was sooner) during 2015-17 from administrative health sources. Emergency department presentations (EDP) and inpatient admissions (IPA) (collectively referred to as critical events) were reviewed by two Nephrologists to gauge if the events were avoidable. RESULTS: Participants (n = 19) with a median age of 78 years (range 42-90), were mostly male (63%), 79% had CKD stage 5, and were heavy users of health services during the study period. Fifteen patients (79%) collectively recorded 44 EDP; 61% occurred after-hours, 91% were triaged as imminently and potentially life-threatening and 73% were admitted. Seventy-four IPA were collectively recorded across 16 patients (84%); 14% occurred on weekends or public holidays. Median length of stay was 3 days (range 1-29). The median number of EDP and IPA per patient was 1 and 2 (range 0-12 and 0-20) respectively. The most common trigger to both EDP (30%) and IPA (15%) was respiratory distress. By study end 37% of patients died, 63% were known to PCS and 11% rejected a referral to a PCS. All critical events were deemed unavoidable. CONCLUSIONS: Few patients avoided using acute health care services in a 12 month period, highlighting the high service needs of this cohort throughout the long, slow decline of CKD. Proactive end-of-life care earlier in the disease trajectory through integrating renal and palliative care teams may avoid acute presentations to hospital through better symptom management and planned care pathways.

The association between C-reactive protein levels and the risk for chronic kidney disease hospitalizations in adults of a remote Indigenous Australian community - A prospective cohort study.

BACKGROUND: Indigenous Australians are significantly burdened by chronic kidney disease (CKD). Elevated levels of C-reactive protein (CRP) have been associated with diabetes and cardiovascular incidence in previous studies. Elevated CRP has been associated with albuminuria and reduced eGFR in cross-sectional studies. This study investigated the long-term predictive association between CRP measured at a baseline exam and the incidence of a CKD-related hospitalization. METHODS: Health screening examinations were conducted in individuals of a remote indigenous Australian community between 1992 and 1998. The risk of subsequent CKD hospitalisations, documented through Northern Territory hospital records up to 2010, was estimated with Cox proportional hazard models in people aged over 18 years at the baseline screen and who had albumin-creatinine ratios (ACRs) less than 34g/mol. RESULTS: 546 participants were eligible for our study. Individuals in the highest CRP tertile at baseline had increased levels of traditional cardiovascular risk factors. They also had almost 4 times the risk of a CKD-related hospitalisation compared with participants in the lowest CRP tertile (HR=3.91, 95%CI 1.01-15.20, P=0.049) after adjustment for potential confounding factors. Participants with CRP concentrations greater than 3mg/L had almost 3 times the risk of CKD hospitalisations than those ≤3mg/L (HR=2.84, 95%CI 1.00-8.00, P=0.049). Furthermore, risk of CKD hospitalisations increased 34% per doubling of baseline CRP (HR=1.34, 95%CI 1.04-1.74, P=0.024). CONCLUSION: In individuals in this remote indigenous community without overt albuminuria at baseline the risk for incident CKD related hospitalisations was predicted by elevated C-reactive protein levels almost a decade earlier. Further research is needed to understand the roles that CRP and systemic inflammation play in CKD risk.

CKD.QLD: establishment of a chronic kidney disease [CKD] registry in Queensland, Australia.

BACKGROUND: Chronic kidney disease [CKD] is recognised as a global public health problem. Until recently, the majority of information informing on CKD has been generated from renal registries reporting on patients with end-stage kidney disease [ESKD] and on renal replacement therapy [RRT]. There has been a paucity of information on pre-dialysis CKD cohorts, and many issues related to these poorly described populations are unresolved. To this end, international organizations have called for CKD surveillance systems across all countries. DESCRIPTION: In Australia, we have responded by developing the Chronic Kidney Disease in Queensland [CKD.QLD] with three main platforms consisting of CKD Registry, clinical trials and development of biobank. This registry which is the core component of CKD surveillance was conceptualized specifically for the pre-dialysis population in the public health system in Queensland, Australia. Recruitment started in May 2011, and to date the Registry has evolved as one of the largest CKD cohorts in the world with recruitment close to 7000 patients. The Registry has had many outcomes, including being the nidus for Australia's first National Health and Medical Research Council [NHMRC] CKD Centre of Research Excellence [CKD.CRE]. CONCLUSIONS: The Registry, with its linkage to Queensland Health datasets, is reporting, and is expected to continue generating, significant information on multiple aspects of CKD, its trajectory, management and patient outcomes. Intent of the CKD.CRE is to facilitate an expanded Registry network that has representation from health services, both public and private, across Australia.