Attenuation of renal injury by depleting cDC1 and by repurposing Flt3 inhibitor in anti-GBM disease.

Previous studies found cDC1s to be protective in early stage anti-GBM disease through Tregs, but pathogenic in late stage Adriamycin nephropathy through CD8+ T cells. Flt3 ligand is a growth factor essential for cDC1 development and Flt3 inhibitors are currently used for cancer treatment. We conducted this study to clarify the role and mechanisms of effects of cDC1s at different time points in anti-GBM disease. In addition, we aimed to utilize drug repurposing of Flt3 inhibitors to target cDC1s as a treatment of anti-GBM disease. We found that in human anti-GBM disease, the number of cDC1s increased significantly, proportionally more than cDC2s. The number of CD8+ T cells also increased significantly and their number correlated with cDC1 number. In XCR1-DTR mice, late (day 12-21) but not early (day 3-12) depletion of cDC1s attenuated kidney injury in mice with anti-GBM disease. cDC1s separated from kidneys of anti-GBM disease mice were found to have a pro-inflammatory phenotype (i.e. express high level of IL-6, IL-12 and IL-23) in late but not early stage. In the late depletion model, the number of CD8+ T cells was also reduced, but not Tregs. CD8+ T cells separated from kidneys of anti-GBM disease mice expressed high levels of cytotoxic molecules (granzyme B and perforin) and inflammatory cytokines (TNF-α and IFN-γ), and their expression reduced significantly after cDC1 depletion with diphtheria toxin. These findings were reproduced using a Flt3 inhibitor in wild type mice. Therefore, cDC1s are pathogenic in anti-GBM disease through activation of CD8+ T cells. Flt3 inhibition successfully attenuated kidney injury through depletion of cDC1s. Repurposing Flt3 inhibitors has potential as a novel therapeutic strategy for anti-GBM disease.

Exposure to Violence in Social Unrest, Resilience, and Mental Health of Older People in Hong Kong.

OBJECTIVE: Older adults are prone to the negative effects of exposure to violence on their mental health. This study aimed to examine the impact of exposure to violence during social unrest and the role of resilience in the mental health of older people. DESIGN: A total of 1,203 people aged 65 years or older were randomly selected for a telephone survey using the random digit dialing numbering method in Hong Kong. MEASUREMENTS: A 13-item scale was developed to measure exposure to violence. The Chinese versions of the Connor-Davidson Resilience Scale and the Startle, Physiological Arousal, Anger, and Numbness scales for measuring mental health status were adopted in the survey. RESULTS: The results showed that the more frequently older people were exposed to information, the more negative mental health status they had. However, exposure to witnessing and experiencing violence was not significantly associated with mental health status. Older adults' level of resilience had a moderating effect between exposure to information and mental health, whereas the effect of exposure to information on mental health was stronger for respondents with lower resilience. CONCLUSION: This study showed that emotional problems caused by exposure to related information among older people should be properly addressed during massive social unrest and conflict. Their resilience capacity is an important moderating factor. Future interventions and support services should focus on enhancing the resilience of older people to better equip them with overcoming problems related to macro-social issues.

Trends in elder abuse and age discrimination during the COVID-19 pandemic in Hong Kong: Findings from a two-wave representative telephone survey study.

OBJECTIVES: Empirical evidence about the heightened risks of elder abuse and age discrimination during the COVID-19 pandemic is scarce. This study aimed to track the changes in rates of both, and investigated their associated factors in the community-dwelling older population in Hong Kong. METHODS: In this two-wave, cross-sectional telephone survey, we interviewed a population-based sample of individuals (≥55 years), and captured the situation of elder abuse and age discrimination before the COVID-19 outbreak (n = 1209, Wave 1: October-December 2019) and during the pandemic (n = 891, Wave 2: December 2020-January 2021). Participants reported their experiences of different types of abuse and discrimination, financial health, subjective well-being, satisfaction with environment, health and social services, and resilience. RESULTS: Abuse was reported by 20.2% of the sample before the outbreak and 17.8% during the pandemic; while discrimination was reported by 24.6% and 29.8% at the two time points, respectively. A drop in physical abuse was observed, but it was accompanied by a rise in discrimination in the form of harassment or refusal of services. Findings of logistic regression analysis show that abuse during the pandemic was associated with younger age, poorer subjective well-being, and lower resilience; while discrimination was associated with female gender, being married, and poorer subjective well-being. CONCLUSIONS: Elder abuse and discrimination were prevalent across time points. The pandemic has highlighted the marginalization of older persons in our communities. There is an urgent need for development of effective interventions to end abuse and discrimination.

Cigarette smoking and adverse health outcomes in patients treated with maintenance dialysis.

BACKGROUND: The association of smoking with new-onset cardiovascular disease, chronic lung disease, malignancy and mortality in dialysis is well-known. The smoking prevalence and its association with clinical outcome was assessed. METHODS: Multicentre cohort study using 'ANZDATA' Registry, 57 838 adults who commenced dialysis (>3 months) between 1990 and 2016 were included. Patients' demographics, initial dialysis modality, presence of comorbidities and smoking history are predictors. The primary outcome was all-cause mortality. Secondary outcomes were smoking prevalence, cause-specific mortality, non-skin cancers, cardiovascular and chronic lung diseases. RESULTS: Of the 57 838 patients, 56 512 (mean age of 58.9 ± 15.1 years, 40.1% female, 43% diabetic), had data on smoking history with 13.6% current, 40.7% former and 45.6% never smokers. Former and current smokers had 10% (HR 1.10; 95% CI: 1.08, 1.13) and 22%(HR 1.22; 95% CI: 1.18, 1.26) higher risk of all-cause mortality. They were 13% (HR 1.13; 95% CI: 1.09, 1.18) and 23% (HR 1.23; 95% CI: 1.17, 1.29) for CVD mortality. Smoking was associated with higher mortality from respiratory failure (HR 1.59; 95% CI: 1.13, 2.23, p = .073 and HR 1.33; 95% CI: 1.01, 1.74, p = .042) for current and former smokers. Current and former smokers had higher risk for non-skin cancer (HR 1.30; 95% CI: 1.19, 1.42 and HR 1.24; 95% CI: 1.17, 1.32). Smoking was associated with a higher rate of death from cancer (HR 1.26; 95% CI 1.19-1.33) and chronic lung disease (HR 1.48; 95% CI 1.15-1.92). Former and current smokers had a higher adjusted risk for de novo vascular disease (PVD, CVD), CAD (adjusted RR 1.1; 95% Cl: 1.09-1.12). CONCLUSIONS: In dialysis patients, smoking was associated with higher rates of all-cause mortality, cardiovascular mortality, respiratory failure, chronic lung disease and malignancy along with higher risks of non-skin cancers, de novo vascular disease and chronic lung disease.

Establishing community mental health facilities: a comparative review of Hong Kong and international jurisdictions.

BACKGROUND: The establishment of mental health facilities in the community has been hindered by opposition from local residents in Hong Kong. Through a comparative review, this study aimed to compare the issues related to the process of establishment of community-based mental health facilities between Hong Kong and selected overseas countries and regions. It will better inform the strategies and best practices that can be adopted for the establishment of mental health facilities in Hong Kong. METHODS: Three electronic databases (PubMed, Scopus, and PsycINFO) were used to examine literature on nine jurisdictions in Asia and western societies from 2005 to 2019. In addition, we conducted a number of in-depth interviews with overseas experts to gain in-depth insights and clarify information that was unavailable or unclear. A total of 19,248 articles were identified through the initial search. 71 of them met the inclusion criteria. In addition, 20 articles about the establishment of other types of community facilities or sensitive facilities were identified from supplementary sources. RESULTS: Most Western countries and Singapore have adopted regulations or laws to reduce public discrimination against particular groups, giving them corresponding human rights and legislating to demarcate the use of land in the community. Regions close to Hong Kong emphasize communication with community leaders to obtain support for sensitive services or facilities. CONCLUSIONS: Hong Kong may consider strengthening the land zoning ordinance in relation to community sensitive facilities, as well as increasing communication with the community and considering the possibility of locating facilities in government buildings.

Back to the campus: Lifelong experience of older learners in a university setting.

This study focuses on older participants' experiences of and views on a lifelong learning program at the Hong Kong Polytechnic University in Hong Kong. As many third age adults tend not to have the opportunity to receive tertiary education when they were young, this program aims to fulfil their dream of studying at a university and boost their self-esteem and self-confidence. Using qualitative research methods, this research was conducted after the MiniU program (supported by the Institute of Active Aging of the Hong Kong Polytechnic University). Semi-structured interviews were conducted with 32 participants after the program. While participants had acquired knowledge and experience of university life from the Mini-U program, they also reported concerns and difficulties with participation including difficulties in memorizing course content and financial difficulties. The program has offered a unique opportunity for enhancing participants' interpersonal relationships and wellbeing. The research also further informs the development of creative lifelong learning programs aimed at improving the well-being of older people.

Promotion of ß-Catenin/Forkhead Box Protein O Signaling Mediates Epithelial Repair in Kidney Injury.

Fibrosis is characterized by progressively excessive deposition of matrix components and may lead to organ failure. Transforming growth factor-ß (TGF-ß) is a key cytokine involved in tissue repair and fibrosis. TGF-ß's profibrotic signaling pathways converge at activation of ß-catenin. ß-Catenin is an important transcription cofactor whose function depends on its binding partner. Promoting ß-catenin binding to forkhead box protein O (Foxo) via inhibition of its binding to T-cell factor (TCF) reduces kidney fibrosis in experimental murine models. Herein, we investigated whether ß-catenin/Foxo diverts TGF-ß signaling from profibrotic to physiological epithelial healing. In an in vitro model of wound healing (scratch assay), and in an in vivo model of kidney injury, unilateral renal ischemia reperfusion, TGF-ß treatment in combination with either ICG-001 or iCRT3 (ß-catenin/TCF inhibitors) increased ß-catenin/Foxo interaction, increased scratch closure by increased cell proliferation and migration, reduced the TGF-ß-induced mesenchymal differentiation, and healed the ischemia reperfusion injury with less fibrosis. In addition, administration of ICG-001 or iCRT3 reduced the contractile activity induced by TGF-ß in C1.1 cells. Together, our results indicate that redirection of ß-catenin binding from TCF to Foxo promotes ß-catenin/Foxo-mediated epithelial repair. Targeting ß-catenin/Foxo may rebuild normal structure of injured kidney.

Digital health technologies to support medication adherence in chronic kidney disease.

Non-adherence to medications is a critical challenge in the management of people with chronic kidney disease (CKD). This review explores the complexities of adherence in this population, the unique barriers and enablers of good adherence behaviours, and the role of emerging digital health technologies in bridging the gap between evidence-based treatment plans and the real-world standard of care. We present the current evidence supporting the use of digital health interventions among CKD populations, identifying the key research questions that remain unanswered, and providing practical strategies for clinicians to support medication adherence in a digital age.

Exposure to socio-political unrest and wellbeing of older people in Hong Kong.

BACKGROUND: The social unrest in the second half of 2019 in Hong Kong came with conflicts, confrontations, and violence which affected almost everyone in the city. The destruction and disruption of the urban facilities have undoubtedly had a significant impact on the lives and mental well-being of the public, and the older people are even more vulnerable. This study examined the impacts of the social unrest on the wellbeing of older people, an area that was seldomly addressed in the public discourse and literature. METHODS: Narrative interviews were conducted to capture older people's lived experiences and ways of making sense of the unrest in Hong Kong. A total of 63 participants aged 60 and above was recruited through personal networks of the research team, and referrals by participants who took part in the interviews. Qualitative semi-structure interviews was conducted one on one via telephone. RESULTS: Thirty-three male and 30 female participants took part in the interview. The number of participants from different risk zones affected by political unrest was comparable. Three themes were generated. Participants experienced challenges during the social unrest, including disturbance to family and social life, reduced incomes which affect quality of life, and difficulties in socializing with friends and accessing medical services. The social unrest caused emotional disturbance, giving rise to feelings of panic, fear, insomnia, depression, annoyance, and anger. Participants reported different coping strategies, ranging from moving to other places, to avoiding going to risky areas and watching news. CONCLUSION: Social unrest brings emotional distress to older people. In many cases, older people cope with challenges in different ways, whether active or passive. Social workers and other professionals should give more support to older people to encourage them to overcome their difficulties. The stakeholders' awareness of the problem and mental health promotion is required to alleviate the multiple layers of negative impacts.

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).

Cost-effectiveness of a mobile phone text messaging program (KIDNEYTEXT) targeting dietary behaviours in people receiving haemodialysis.

BACKGROUND: There is little information available to inform the cost-effectiveness of eHealth interventions in improving patient health outcomes. A trial-based economic evaluation was undertaken aiming to inform the feasibility of conducting a mobile phone text messaging programme targeting dietary behaviours in people receiving haemodialysis. METHODS: A trial-based economic evaluation from a health system perspective of a 6-month pilot randomised controlled trial was undertaken. One hundred and thirty patients receiving haemodialysis from six dialysis units across Sydney, Australia, were enrolled into the KIDNEYTEXT study. Usual care (inperson dietary counselling) was compared with usual care plus three semi-personalised dietary mobile phone text messages per week over a 6-month period. The outcomes of this economic evaluation included: cost of intervention, cost-effectiveness and marginal effects on total costs. RESULTS: The cost of developing and maintaining the KIDNEYTEXT intervention was US $110 per participant. Total costs were US $1418 higher in the usual care arm compared to the intervention arm. The incremental benefits for quality-adjusted life adjusted years were 0.01 [95% confidence interval (CI) = -0.03 to 0.06] and dietary adherence (i.e., adherent to three or more dietary guidelines at 6 months) being 0.04 (95% CI = -0.15 to 0.24). The largest component of total costs was related to unplanned admissions to hospital. CONCLUSIONS: Mobile phone text messages targeting dietary behaviours may be cost saving, at the same time as maintaining similar or improved dietary behaviours. A larger trial with a longer follow-up time is warranted.

Aspirin for the prevention of pre-eclampsia in women with pre-existing diabetes: Systematic review.

BACKGROUND: There is a lack of evidence for pre-eclampsia prophylaxis with aspirin in women with pre-existing diabetes mellitus (DM). AIMS: To examine the evidence for aspirin in pre-eclampsia prophylaxis in women with pre-existing DM. MATERIAL AND METHODS: An electronic search using Ovid MEDLINE, Embase, CinicalTrials.gov and the Cochrane CENTRAL register of controlled trials through to February 2021 was performed. Reference lists of identified studies, previous review articles, clinical practice guidelines and government reports were manually searched. Randomised controlled trials (RCTs) of aspirin vs placebo for pre-eclampsia prophylaxis were included. Articles were manually reviewed to determine if cohorts included women with DM. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data from included trials were extracted independently by two authors who also independently assessed risk of bias as per the Cochrane Handbook criteria version 5.1.0. Data were analysed using Rev-Man 5.4. RESULTS: Forty RCTs were identified, of which 11 included a confirmed subset of women with DM; however, data were insufficient for meta-analysis. Meta-analysis of 930 women with DM, from individual patient data included in a systematic review and unpublished data from one of the 11 RCTs, showed a non-significant difference in the outcome of pre-eclampsia in participants treated with aspirin compared to placebo (odds ratio 0.58; 95% CI 0.20-1.71; P = 0.33). CONCLUSIONS: Pre-eclampsia risk reduction with aspirin prophylaxis in women with pre-existing DM may be similar to women without pre-existing DM. However, randomised data within this meta-analysis were insufficient, warranting the need for further studies within this high-risk group of women.

Renal tubular cell binding of ß-catenin to TCF1 versus FoxO1 is associated with chronic interstitial fibrosis in transplanted kidneys.

ß-Catenin is an important co-factor which binds multiple transcriptional molecules and mediates fibrogenic signaling pathways. Its role in kidney transplantation is unknown. We quantified binding of ß-catenin within renal tubular epithelial cells to transcription factors, TCF1 and FoxO1, using a proximity ligation assay in 240 transplanted kidneys, and evaluated their pathological and clinical outcomes. ß-Catenin/FoxO1 binding in 1-month protocol biopsies inversely correlated with contemporaneous chronic fibrosis, subsequent inflammation. and inflammatory fibrosis (P < .001). The relative binding of ß-catenin/TCF1 versus ß-catenin/FoxO1 (TF ratio) was the optimal biomarker, and abnormal in diverse fibrotic transplant diseases. A high 1-month TF ratio was followed by greater tubular atrophy and interstitial fibrosis scores, cortical inflammation, renal impairment, and proteinuria at 1 year (n = 131, all P < .001). The TF ratio was associated with reduced eGFR (AUC 0.817), mild fibrosis (AUC 0.717), and moderate fibrosis (AUC 0.769) using receiver operating characteristic analysis. An independent validation cohort (n = 76) confirmed 1-month TF was associated with 12-month moderate fibrosis (15.8% vs. 2.6%, P = .047), however, not with other outcomes or 10-year graft survival, which limits generalizabilty of these findings. In summary, differential binding of ß-catenin to TCF1 rather than FoxO1 in renal tubular cells was associated with the fibrogenic response in transplanted kidneys.

Perinatal and Child Factors Mediate the Association between Preeclampsia and Offspring School Performance.

OBJECTIVE: To determine whether maternal preeclampsia is an independent risk factor for poorer academic school performance in offspring, taking into account important perinatal and child factors. STUDY DESIGN: A population-based cohort study using record-linkage of state-wide data was undertaken. We evaluated children born at 28+ weeks of gestation in New South Wales, Australia who had grade 3 record-linked education outcomes via the National Assessment Program-Literacy and Numeracy (NAPLAN) between 2009 and 2014. Children with in utero preeclampsia exposure were compared with those without exposure. Robust multivariable Poisson models were used to determine adjusted relative risks. RESULTS: Crude models demonstrated an increased risk of scoring below the national minimal standard in all 5 domains (reading, writing, spelling, grammar and punctuation, and numeracy) for children exposed to preeclampsia, ranging from a relative risk (RR) of 1.13 (95% CI, 1.04-1.24) for reading to 1.19 (95% CI, 1.09-1.30) for numeracy. These differences were attenuated once adjusted for perinatal and child factors (RR, 1.07 [95% CI, 0.97-1.18] to 1.11 (95% CI, 0.99-1.22]), with combined perinatal and childhood factors mediating between 35.7% (writing) to 55.1% (spelling) of the association. Gestational age at birth was the most important perinatal factor, explaining 10.5% (grammar and punctuation) to 20.6% (writing) of the association between preeclampsia and poor school performance, followed by small for gestational age. CONCLUSION: The poorer educational performance experienced by children born to women with preeclampsia appears largely attributable to perinatal and childhood factors, suggesting an opportunity to improve school performance in children exposed to preeclampsia by optimizing these perinatal factors, particularly gestational age at birth.

A Text Messaging Intervention for Dietary Behaviors for People Receiving Maintenance Hemodialysis: A Feasibility Study of KIDNEYTEXT.

RATIONALE & OBJECTIVE: An important component of hemodialysis management involves delivery of complex dietary recommendations. The aim of this study was to determine the feasibility of a mobile phone text-message intervention to improve dietary behavior in people undergoing hemodialysis. STUDY DESIGN: Six-month randomized feasibility study. SETTING & PARTICIPANTS: Patients receiving maintenance hemodialysis across 2 health districts in Sydney, Australia. INTERVENTIONS: Participants randomized to the intervention received 3 text messages per week in addition to standard dietary care for 6 months. The usual care group received standard dietary care. OUTCOMES: The primary outcomes were feasibility measured using recruitment and retention rates, acceptability of the intervention, and adherence to dietary recommendations. Secondary exploratory outcomes included information on certain clinical parameters related to dietary management of patients receiving maintenance hemodialysis. RESULTS: 130 people were recruited; 48% of eligible patients (130 of 272) consented to participate, and 88% (115 of 130) completed the study. Semistructured interviews evaluating acceptability identified 5 themes: clear and comprehensive, engaging with consistent and relevant content, maintaining attention with timely reminders, sustaining interest through ongoing care, and generic messages inadequate to prompt dietary change. There was no difference in adherence to dietary recommendations across treatment groups (odds ratio, 1.21 [95% CI, 0.55-2.72]; P = 0.6). Secondary exploratory analyses suggested reductions in dietary intake of single nutrients (potassium, phosphorus, sodium, protein), interdialytic weight gain, and phosphate binder use among intervention participants compared with participants assigned to standard care. LIMITATIONS: Our feasibility study was of short duration. Adherence was based on self-reported data. Generalizability to populations receiving maintenance hemodialysis outside of an urban, Australian setting is unknown. CONCLUSIONS: A simple mobile phone text-messaging intervention was feasible and acceptable to patients. Further investigation of the impact on patient-reported and clinical outcomes is warranted. FUNDING: Funding for the study was provided by a Sydney Medical School Foundation Grant and the Centre for Transplant and Renal Research at Westmead Hospital. TRIAL REGISTRATION: Registered at Australian New Zealand Clinical Trials Registry with study number ACTRN12617001084370.

Effectiveness of Microcurrent Stimulation in Preserving Retinal Function of Blind Leading Retinal Degeneration and Optic Neuropathy: A Systematic Review.

OBJECTIVES: To systematically identify and summarize the effectiveness and the parameters of electrical stimulation (ES) for the preservation of visual function in major retinal degeneration and optic neuropathy. MATERIALS AND METHODS: A systematic review of clinical studies, using ES therapy in patients with blind leading retinal degenerations, including retinitis pigmentosa (RP), age-related macular degeneration (AMD), glaucoma, retinal vein occlusion (RVO), retinal artery occlusion (RAO), and optic neuropathy was conducted. PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant interventional studies including randomized controlled trials (RCTs) and observational studies. RESULTS: A total of 10 RCTs and 15 observational studies were included. Transcorneal ES (TcES), transpalpebral ES (TpES), transdermal ES (TdES), and repetitive transorbital alternating current stimulation (rtACS) were used for the treatment of the patients. ES using 20 Hz biphasic pulses with current strength at 150%-200% of individual electrical phosphene threshold (EPT) for RP patients showed improved retinal function detected by visual acuity (VA), visual field (VF), or electrical retinal graphs (ERG). rtACS on patients with optic neuropathy showed significant preservation of VA and VF. Clinical studies on AMD, RAO, and glaucoma indicated promising protective effects of ES on the visual function, though the amount of evidence is limited. CONCLUSIONS: ES treatment has promising therapeutic effects on RP and optic neuropathy. More large-scale RCT studies should be conducted to elucidate the potential of ES, especially on AMD, RAO, and glaucoma. A comparison of the effects by different ES methods in the same disease populations is still lacking. Parameters of the electric current and sensitive detection method should be optimized for the evaluation of ES treatment effects in future studies.

Regulatory innate lymphoid cells suppress innate immunity and reduce renal ischemia/reperfusion injury.

Innate lymphoid cells are a recently recognized group of immune cells with critical roles in tissue homeostasis and inflammation. Regulatory innate lymphoid cells are a newly identified subset of innate lymphoid cells, which play a suppressive role in the innate immune response, favoring the resolution of intestinal inflammation. However, the expression and role of regulatory innate lymphoid cells in kidney has not been reported. Here, we show that regulatory innate lymphoid cells are present in both human and mouse kidney, express similar surface markers and form a similar proportion of total kidney innate lymphoid cells. Regulatory innate lymphoid cells from kidney were expanded in vitro with a combination of IL-2, IL-7 and transforming growth factor-ß. These cells exhibited immunosuppressive effects on innate immune cells via secretion of IL-10 and transforming growth factor-ß. Moreover, treatment with IL-2/IL-2 antibody complexes (IL-2C) promoted expansion of regulatory innate lymphoid cells in vivo, and prevent renal ischemia/reperfusion injury in Rag-/- mice that lack adaptive immune cells including Tregs. Depletion of regulatory innate lymphoid cells with anti-CD25 antibody abolished the beneficial effects of IL-2C in the Rag-/- mice. Adoptive transfer of ex vivo expanded regulatory innate lymphoid cells improved renal function and attenuated histologic damage when given before or after induction of ischemia/reperfusion injury in association with reduction of neutrophil infiltration and induction of reparative M2 macrophages in kidney. Thus, our study shows that regulatory innate lymphoid cells suppress innate renal inflammation and ischemia/reperfusion injury.

Lipid profiling in maternal and fetal circulations in preeclampsia and fetal growth restriction-a prospective case control observational study.

BACKGROUND: While many risk factors for preeclampsia, such as increased body mass index, advanced maternal age, chronic hypertension, diabetes, are now established in clinical practice, maternal lipid profile has not been included in the risk assessment for preeclampsia. We aim to characterize the serum levels of Total Cholesterol (TC), High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglycerides (TG), Apolipoprotein A1, Apolipoprotein B and their ratios TC/HDL and ApoB/ApoA1 in the maternal and fetal circulations of normal pregnancy, preeclampsia (PE), fetal growth restriction (FGR) and PE + FGR. METHODS: A prospective cross-sectional case control study was conducted measuring maternal and fetal lipid levels by enzymatic analysis and immune-turbidimetric enzymatic assays. FGR was defined by elevated umbilical artery Doppler resistance in association with estimated fetal weight < 10%. Kruskal Wallis non-parametric analysis of variance was used to test for homogeneity across the clinical groups for each of the variables, Mann-Whitney tests for pairwise comparisons and Spearman rank correlation were used to quantify gestational age-related changes. RESULTS: (1) TG levels were elevated in maternal PE and cord blood PE + FGR groups compared to normal pregnancies. (2) A statistically significant elevation of fetal ApoB levels was observed in PE, FGR and PE + FGR compared to normal pregnancies. Apolipoprotein levels A1 and B were not different between maternal groups. (3) TC, HDL, LDL and TC/HDL levels did not show any significant gestational variation or between clinical groups in the maternal or fetal circulation. CONCLUSIONS: Elevation in maternal TG levels may have a role in the pathogenesis of PE. The implications of elevated maternal and fetal TG levels and elevated fetal Apolipoprotein B levels deserves further exploration of their role in long term cardiovascular risk in the mother as well as the offspring.

Effect of centre- and patient-related factors on uptake of haemodiafiltration in Australia and New Zealand: A cohort study using ANZDATA.

BACKGROUND: The use of haemodiafiltration (HDF) for the management of patients with end-stage kidney failure is increasing worldwide. Factors associated with HDF use have not been studied and may vary in different countries and jurisdictions. The aim of this study was to document the pattern of increase and variability in uptake of HDF in Australia and New Zealand, and to describe patient- and centre-related factors associated with its use. METHODS: Using the Australian and New Zealand Dialysis and Transplant Registry, all incident patients commencing haemodialysis (HD) between 2000 and 2014 were included. The primary outcome was HDF commencement over time, which was evaluated using multivariable logistic regression stratified by country. RESULTS: Of 27 433 patients starting HD, 3339 (14.4%) of 23 194 patients in Australia and 810 (19.1%) of 4239 in New Zealand received HDF. HDF uptake increased over time in both countries but was more rapid in New Zealand than Australia. In Australia, HDF use was more likely in males (odds ratio (OR) 1.13, 95% confidence interval (CI) = 1.03-1.24, P = 0.009) and less likely with older age (reference <40 years; 40-54 years OR = 0.85; 95% CI = 0.72-0.99; 55-69 years OR = 0.79; 95% CI = 0.67-0.91; >70 years OR = 0.48; 95% CI = 0.41-0.56); higher body mass index (body mass index (BMI) < 18.5 kg/m2 OR = 0.62; 95% CI = 0.46-0.84; 18.5-29.9 kg/m2 reference; >30 kg/m2 OR = 1.46; 95% CI = 1.33-1.61), chronic lung disease (OR = 0.84; 95% CI = 0.76-0.94; P < 0.001), cerebrovascular disease (OR = 0.76; 95% CI = 0.67-0.85; P < 0.001) and peripheral vascular disease (OR = 0.77; 95% CI = 0.70-0.85; P < 0.001). No association was identified with race. In New Zealand, HDF use was more likely in Maori and Pacific Islanders (OR = 1.32; 95% CI = 1.05-1.66) and Asians (OR = 1.75; 95% CI = 1.15-2.68) compared to Caucasians, and less likely in males (OR = 0.76; 95% CI = 0.62-0.94; P = 0.01). No association was identified with BMI or co-morbidities. In both countries, centres with a higher ratio of HD to peritoneal dialysis (PD) were more likely to prescribe HDF. Larger Australian centres were more likely to prescribe HDF (36-147 new patients/year OR = 26.75, 95% CI = 18.54-38.59; 17-35/year OR = 7.51, 95% CI = 5.35-10.55; 7-16/year OR = 3.00; 95% CI = 2.19-4.13; ≤6/year reference). CONCLUSION: Haemodiafiltration uptake is increasing, variable and associated with both patient and centre characteristics. Centre characteristics not explicitly captured elsewhere explained 36% of variability in HDF uptake in Australia and 48% in New Zealand.

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).