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Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three-SARS, SARS-CoV-2 and MERS-are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.
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Microvasos , Polissacarídeos , SARS-CoV-2 , Animais , Humanos , Enzima de Conversão de Angiotensina 2/metabolismo , Betacoronavirus/metabolismo , COVID-19/metabolismo , COVID-19/virologia , Tratamento Farmacológico da COVID-19 , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Agregação Eritrocítica , Eritrócitos/metabolismo , Eritrócitos/virologia , Microvasos/metabolismo , Microvasos/virologia , Polissacarídeos/metabolismo , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Ligação ViralRESUMO
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.
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Glomerulosclerose Segmentar e Focal , Insuficiência Renal Crônica , Humanos , Adolescente , Glomerulosclerose Segmentar e Focal/patologia , Glomérulos Renais/patologia , Rim/patologia , Néfrons , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/patologiaRESUMO
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 (R2 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.
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Rationale & Objective: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT). Study Design: Retrospective observational cohort study. Setting & Participants: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018. Predictors: Demographic and clinical characteristics of patients with CKD. Outcomes: Hospital admissions. Analytical Approach: We evaluated the association of demographic and clinical features with hospitalizations, length of hospital stay, and cost. Results: Approximately 81.5% of the patients were admitted at least once, with 42,283 admissions, costing Australian dollars (AUD) 231 million. The average number of admissions per person-year was 1.7, and the cost was AUD 9,060, 10 times and 2 times their Australian averages, respectively. Single (1-day) admissions constituted 59.2% of all the hospital episodes, led by neoplasms (largely chemotherapy), anemia, CKD-related conditions and eye conditions (largely cataract extractions), but only 14.8% of the total costs. Approximately 41% of admissions were >1-day admissions, constituting 85.2% of the total costs, with cardiovascular conditions, respiratory conditions, CKD-related conditions, and injuries, fractures, or poisoning being the dominant causes. Readmission within 30 days of discharge constituted >42% of the admissions and 46.8% costs. Admissions not directly related to CKD constituted 90% of the admissions and costs. More than 40% of the admissions and costs were through the emergency department. Approximately 19% of the hospitalized patients and 27% of the admissions did not have kidney disease mentioned as either principal or associate causes. Limitations: Variable follow-up times because of different dates of consent. Conclusions: The hospital burden of patients with CKD is mainly driven by complex multiday admissions and readmissions involving comorbid conditions, which may not be directly related to their CKD. Strategies to prevent these complex admissions and readmissions should minimize hospital costs and outcomes. Plain-Language Summary: We analyzed primary causes, types, and costs of hospitalizations among 7,201 patients with chronic kidney disease (CKD) from renal speciality clinics across Queensland, Australia, over an average follow-up of 3.54 years. The average annual cost per person was $9,060, and was the highest in those with more advanced CKD, higher age, and with diabetes. More than 85% of costs were driven by more complex hospitalizations with longer length of stay. Cardiovascular disease was the single largest contributor for hospitalizations, length of hospital stay, and total costs. Readmission within 30 days of discharge, particularly for the same disorder, and multiday admissions should be the main targets for mitigation of hospital costs in this population.
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Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found that colonoscopy screenings were marginally beneficial, based upon ITT analysis, with only 42% of the intervention group actually undergoing the procedure. However, the study authors themselves concluded that the medical efficacy of that screening was a 50% reduction in colorectal cancer deaths among that 42% PP group. The second RCT found a ten-fold reduction in mortality for a COVID-19 treatment drug vs. placebo by PP analysis, but only a minor benefit by ITT analysis. The third RCT, conducted as an arm of the same platform trial as the second RCT, tested another COVID-19 treatment drug and reported no significant benefit by ITT analysis. Inconsistencies and irregularities in the reporting of protocol compliance for this study required consideration of PP outcomes for deaths and hospitalizations, yet the study coauthors refused to disclose them, instead directing inquiring scientists to a data repository which never held the study's data. These three RCTs illustrate conditions under which PP outcomes may differ significantly from ITT outcomes and the need for data transparency when these reported or indicated discrepancies arise.
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Aim: Anaemia among patients with chronic kidney disease (CKD) leads to poor overall outcomes. This study explores anaemia and its impact on nondialysis CKD (NDD-CKD) patients. Methods: 2,303 adults with CKD from two CKD.QLD Registry sites were characterised at consent and followed until start of kidney replacement therapy (KRT), death, or censor date. Mean follow-up was 3.9 (SD 2.1) years. Analysis explored the impact of anaemia on death, KRT start, cardiovascular events (CVE), admissions, and costs in these NDD-CKD patients. Results: At consent, 45.6% patients were anaemic. Males were more often anaemic (53.6%) than females, and anaemia was significantly more common over the age of 65 years. The prevalence of anaemia was highest among CKD patients with diabetic nephropathy (27.4%) and renovascular disease (29.2%) and lowest in patients with genetic renal disease (3.3%). Patients with admissions for gastrointestinal bleeding had more severe anaemia, but accounted for only the minority of cases overall. Administration of ESAs, iron infusions, and blood transfusions were all correlated with more severe degrees of anaemia. The number of hospital admissions, length of stay, and hospital costs were all strikingly higher with more severe degrees of anaemia. Adjusted hazard ratios (CI 95%) of patients with moderate and severe anaemia vs. no anaemia for subsequent CVE, KRT, and death without KRT were 1.7 (1.4-2.0), 2.0 (1.4-2.9), and 1.8 (1.5-2.3), respectively. Conclusion: Anaemia is associated with higher rates of CVE, progression to KRT and death in NDD- CKD patients, and with greater hospital utilisation and costs. Preventing and treating anaemia should improve clinical and economic outcomes.
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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.
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Nefropatias Diabéticas , Insuficiência Renal Crônica , Adulto , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Feminino , Queensland/epidemiologia , Diálise Renal , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/terapia , Austrália , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Obesidade/diagnóstico , Obesidade/epidemiologia , RimRESUMO
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).
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Doença de Fabry , Insuficiência Renal Crônica , Adulto , Estudos Transversais , Doença de Fabry/diagnóstico , Doença de Fabry/epidemiologia , Doença de Fabry/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Diálise Renal , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapiaRESUMO
Chronic kidney disease (CKD) is debilitating, increasing in incidence worldwide, and a financial and social burden on health systems. Kidney failure, the final stage of CKD, is life-threatening if untreated with kidney replacement therapies. Current therapies using commercially-available drugs, such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and calcium channel blockers, generally only delay the progression of CKD. This review article focuses on effective alternative therapies to improve the prevention and treatment of CKD, using plants or plant extracts. Three mechanistic processes that are well-documented in CKD pathogenesis are inflammation, fibrosis, and oxidative stress. Many plants and their extracts are already known to ameliorate kidney dysfunction through antioxidant action, with subsequent benefits on inflammation and fibrosis. In vitro and in vivo experiments using plant-based therapies for pre-clinical research demonstrate some robust therapeutic benefits. In the CKD clinic, combination treatments of plant extracts with conventional therapies that are seen as relatively successful currently may confer additive or synergistic renoprotective effects. Therefore, the aim of recent research is to identify, rigorously test pre-clinically and clinically, and avoid any toxic outcomes to obtain optimal therapeutic benefit from medicinal plants. This review may prove to be a filtering tool to researchers into complementary and alternative medicines to find out the current trends of using plant-based therapies for the treatment of kidney diseases, including CKD.
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Insuficiência Renal Crônica , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Feminino , Fibrose , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico , Masculino , Extratos Vegetais/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologiaRESUMO
PURPOSE: This study tested the hypothesis that progression of chronic kidney disease (CKD) is less aggressive in patients whose primary cause of CKD was nephrectomy, compared with non-surgical causes. METHODS: A sample of 5983 patients from five specialist nephrology practices was ascertained from the Queensland CKD Registry. Rates of kidney failure/death were compared on primary aetiology of CKD using multivariable Cox proportional hazards models. CKD progression was compared using multivariable linear and logistic regression analyses. RESULTS: Of 235 patients with an acquired single kidney as their primary cause of CKD, 24 (10%) and 38 (17%) developed kidney failure or died at median [IQR] follow-up times of 12.9 [2.5-31.0] and 33.6 [18.0-57.9] months after recruitment. Among patients with an eGFR < 45 mL/min per 1.73m2 at recruitment, patients with diabetic nephropathy and PCKD had the highest rates (per 1000 person-years) of kidney failure (107.8, 95% CI 71.0-163.8; 75.5, 95% CI 65.6-87.1); whereas, patients with glomerulonephritis and an acquired single kidney had lower rates (52.9, 95% CI 38.8-72.1; 34.6, 95% CI 20.5-58.4, respectively). Among patients with an eGFR ≥ 45 mL/min per 1.73m2, those with diabetic nephropathy had the highest rates of kidney failure (16.6, 95% CI 92.5-117.3); whereas, those with glomerulonephritis, PCKD and acquired single kidney had a lower risk (11.3, 95% CI 7.1-17.9; 11.7, 95% CI 3.8-36.2; 10.7, 95% CI 4.0-28.4, respectively). CONCLUSION: Patients who developed CKD after nephrectomy had similar rates of adverse events to most other causes of CKD, except for diabetic nephropathy which was consistently associated with worse outcomes. While CKD after nephrectomy is not the most aggressive cause of kidney disease, it is by no means benign, and is associated with a tangible risk of kidney failure and death, which is comparable to other major causes of CKD.
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Nefropatias Diabéticas , Glomerulonefrite , Insuficiência Renal Crônica , Rim Único , Nefropatias Diabéticas/complicações , Progressão da Doença , Taxa de Filtração Glomerular , Glomerulonefrite/complicações , Humanos , Nefrectomia/efeitos adversos , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Rim Único/complicaçõesRESUMO
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.
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OBJECTIVE: To explore factors behind inpatient admissions by high-cost users (HCUs) in pre-end-stage chronic kidney disease (CKD). DESIGN: Retrospective analysis of CKD.QLD Registry and hospital admissions of the Queensland Government Department of Health recorded between 1 July 2011 and 30 June 2016. SETTING: Queensland public and private hospitals. PARTICIPANTS: 5096 individuals with CKD who consented to the CKD.QLD Registry via 1 of 11 participating sites. MAIN OUTCOMES: Associations of HCU status with patient characteristics, pathways and diagnoses behind hospital admissions at 12 months. RESULTS: Age, advanced CKD, primary renal diagnosis, cardiovascular disease and hypertension were predictors of the high-cost outcome. HCUs were more likely than non-HCUs to be admitted by means of episode change (relative risk: 5.21; 95% CI 5.02 to 5.39), 30-day readmission (2.19; 2.13 to 2.25), scheduled readmission (1.29; 1.11 to 1.46) and emergency (1.07; 1.02 to 1.13), for diagnoses of the nervous (1.94; 1.74 to 2.15), circulatory (1.24; 1.14 to 1.34) and respiratory (1.2; 1.03 to 1.37) systems and other factors influencing health status (1.92; 1.74 to 2.09). CONCLUSIONS: The high relevance of episode change and other factors influencing health status revealed that a substantial part of excess demand for inpatient care was associated with discordant conditions often linked to frailty, decline in psychological health and social vulnerability. This suggests that multidisciplinary models of care that aim to manage discordant comorbidities and address psychosocial determinants of health, such as renal supportive care, may play an important role in reducing inpatient admissions in this population.
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Pacientes Internados , Insuficiência Renal Crônica , Hospitalização , Humanos , Sistema de Registros , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Estudos RetrospectivosRESUMO
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.
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Diabetes Mellitus Tipo 2 , Serviços de Saúde do Indígena , Austrália , Humanos , Havaiano Nativo ou Outro Ilhéu do Pacífico , New South Wales , Queensland , EsgotosRESUMO
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.
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Tamanho Corporal/fisiologia , Nefropatias/patologia , Podócitos/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Peso ao Nascer/fisiologia , Feminino , Rim/patologia , Glomérulos Renais/patologia , Gravidez , Ratos Sprague-DawleyRESUMO
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.
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Falência Renal Crônica , Insuficiência Renal Crônica , Austrália/epidemiologia , Pré-Escolar , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Proteinúria/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Fatores de RiscoRESUMO
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.
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Metagenômica/métodos , Grupos Populacionais/genética , Austrália , Variação Genética/genética , HumanosRESUMO
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).
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Doença de Fabry/epidemiologia , Insuficiência Renal Crônica/etiologia , Adulto , Protocolos Clínicos , Diagnóstico Tardio , Doença de Fabry/complicações , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Feminino , Glicolipídeos/sangue , Humanos , Masculino , Prevalência , Estudos Prospectivos , Queensland/epidemiologia , Diálise Renal , Insuficiência Renal Crônica/genética , Esfingolipídeos/sangue , alfa-Galactosidase/sangueRESUMO
OBJECTIVE: To assess the performance of cardiovascular disease (CVD) risk equations in Indigenous Australians. METHODS: We conducted an individual participant meta-analysis using longitudinal data of 3618 Indigenous Australians (55% women) aged 30-74 years without CVD from population-based cohorts of the Cardiovascular Risk in IndigenouS People(CRISP) consortium. Predicted risk was calculated using: 1991 and 2008 Framingham Heart Study (FHS), the Pooled Cohorts (PC), GloboRisk and the Central Australian Rural Practitioners Association (CARPA) modification of the FHS equation. Calibration, discrimination and diagnostic accuracy were evaluated. Risks were calculated with and without the use of clinical criteria to identify high-risk individuals. RESULTS: When applied without clinical criteria, all equations, except the CARPA-adjusted FHS, underestimated CVD risk (range of percentage difference between observed and predicted CVD risks: -55% to -14%), with underestimation greater in women (-63% to -13%) than men (-47% to -18%) and in younger age groups. Discrimination ranged from 0.66 to 0.72. The CARPA-adjusted FHS equation showed good calibration but overestimated risk in younger people, those without diabetes and those not at high clinical risk. When clinical criteria were used with risk equations, the CARPA-adjusted FHS algorithm scored 64% of those who had CVD events as high risk; corresponding figures for the 1991-FHS were 58% and were 87% for the PC equation for non-Hispanic whites. However, specificity fell. CONCLUSION: The CARPA-adjusted FHS CVD risk equation and clinical criteria performed the best, achieving higher combined sensitivity and specificity than other equations. However, future research should investigate whether modifications to this algorithm combination might lead to improved risk prediction.