Katrina Chau

Background and Objectives: Renin-angiotensin system inhibitors (RASIs) are recommended to preserve residual kidney function (RKF) in patients on peritoneal dialysis (PD); however, evidence of benefit is inconsistent. This study evaluated the effect of RASI on RKF decline among patients undergoing PD. Materials and Methods: We conducted a retrospective cohort study among PD patients at a large metropolitan dialysis centre in Australia. RKF was assessed using residual Kt/V and urine volume from PD adequacy tests. Time zero was PD initiation. RASI exposure was modelled as a time-dependent variable to avoid immortal-time bias. Linear mixed-effects models were fitted for each outcome, including random intercepts and slopes for time (years since PD start) with unstructured covariance. Fixed effects included time, RASI(t), time × RASI(t), age, sex, baseline RKF, PD modality, PD infection episodes, loop diuretic use, and comorbidities. Results: Of 307 PD patients, 231 met the inclusion criteria; 111 (48.1%) received RASI. RASI users were younger than non-users [65 years (IQR 56–74) vs. 72 years (IQR 61–77); p = 0.014]. Residual Kt/V declined by 0.26 units/year; RASI exposure showed no significant effect on urine volume trajectory and a borderline slower Kt/V decline (interaction β = +0.038, p = 0.069). Hospitalisation and PD-related infection rates were similar between groups. Conclusions: RASI therapy was not associated with meaningful RKF preservation in PD patients in this cohort. While earlier studies suggested renoprotective effects of RASI while on PD, our findings align with recent evidence of mixed efficacy. Larger prospective trials are needed to clarify the role of RASI in maintaining RKF and improving long-term outcomes in PD.

Introduction: Incremental peritoneal dialysis (PD) may confer environmental benefits compared to full-dose PD due to reduced resource use. We aimed to quantify and compare carbon emissions, water consumption, and waste generation between incremental and full-dose PD in a cohort of incident PD patients. Methods: We compared environmental metrics, including carbon emissions, water consumption, and waste generation between incremental and full-dose PD, using prospectively collected data between June 2019 and May 2024 at the Western Renal Service, Sydney, Australia. Carbon emissions were quantified using standardized coefficients from a published life-cycle analysis, while water and waste volumes were estimated using literature-based assumptions. Group comparisons were conducted using the Mann–Whitney U test, with a two-sided p -value p < 0.001). Incremental PD yielded estimated savings of 201,087 kg carbon dioxide equivalent emissions, over 5 million liters of blue water, 1.8 million liters of gray water, 27,223 kg of landfill waste, and 16,219 kg of recyclable materials. Conclusion: Incremental PD was associated with a lower environmental impact than full-dose PD, highlighting its potential contribution to environmentally sustainable dialysis care.

Declining kidney function contributes to the accumulation of uraemic toxins produced by gut microbiota, leading to the uraemic syndrome. This study aimed to identify associations between uraemic toxins, diet quality, symptoms and the gut microbiota in individuals initiating peritoneal dialysis. A cross-sectional analysis of baseline data from participants in a longitudinal study was conducted. Symptom scores using the Integrated Palliative Care Outcomes Scale-Renal were recorded. Plasma p-Cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide were measured using liquid chromatography-mass spectrometry. Gut microbiota was determined using 16S rRNA sequencing. Multivariate linear models examined associations across the cohort. Data from 43 participants (mean age 61 ± 13 years; 70% male; median eGFR 7 mL/min/1.73 m²) were analysed. Diabetes was the primary cause of kidney disease (51.2%). Patients were classified into ‘high’ (n = 18) and ‘low’ (n = 26) uraemic toxin groups using K-means clustering. The ‘high’ group had a lower eGFR (p < 0.05) but no differences in diet quality or symptom scores. Significant differences in alpha and beta diversity were observed between the groups (p = 0.01). The ‘high’ group had increased Catenibacterium, Prevotella, Clostridia, and decreased Ruminococcus gnavus abundances. Multivariate models identified 32 genera associated with uraemic toxins, including positive associations of Oscillospiraceae UCG-002 and UCG-005 with p-cresyl sulfate, and negative associations with Actinomyces and Enterococcus. Patients with kidney failure initiating peritoneal dialysis have distinct uraemic toxin profiles, associated with differences in microbial diversity. This phenotype was also associated with differences in residual kidney function but not with diet or symptom severity. Longitudinal studies are required to determine causality and guide therapeutic interventions.

Introduction: Incremental peritoneal dialysis (PD) prescriptions, tailored to individual patient needs and residual kidney function, may offer patients greater dialysis-free time than full-dose PD and has the potential to yield substantial cost savings. We aimed to quantify the direct healthcare costs and resource utilization associated with incremental and full-dose PD from a third-party health service payer's perspective and estimate dialysis-free time and dialysis waste saved. Methods: We recruited patients from a large dialysis service provider in Australia. We retrospectively analysed prospectively collected hospital data from 203 incident patients receiving PD over a 24-month period. Incremental PD was compared to full dose, considering costs related to consumables, multidisciplinary reviews, pathology, and in-patient costs. Results: Of the 204 incident patients recruited in the study, 123 (60%) were prescribed incremental PD, with mean age of 62 years, and 66% being male. The total mean monthly outpatient cost ($AUD) for any dose of incremental PD was $339 (95% CI $152, -$526, p< .001) less than full dose, with PD consumables as the greatest contributor to the cost difference. At the end of the study, the mean dwell and exchange procedure times were 5065 h (4222–5908) and 455 h (403–507) lower in incremental PD than full dose, respectively, and incremental PD prescriptions saved >2 million litres of water, >9000 kg plastic and >8000 kg cardboard. Conclusion: Compared to full dose, incremental PD minimizes dialysis time and is associated with lower costs and dialysis waste, driven largely by reduction in consumables use.

(1) Background: Optimal dietary intake is integral to good health in people receiving peritoneal dialysis (PD). We investigated how dietary patterns, dietary adequacy and nutrient intake may change over time in people commencing PD. (2) Methods: Participants were attending the PD training unit for the commencement of peritoneal dialysis, aged ≥18 years and willing to complete food records. Misreporters were excluded from the analysis. Dietary intake was compared at PD commencement and at 12 months. Intake was also compared to reference standards. Dietary patterns were derived using principal component analysis. (3) Results: There were no significant changes between baseline and 12 months for grains, fruit, vegetables and meat. Dairy and added sugar intake was significantly lower (p = 0.01). The intake of energy and protein was adequate and did not change. There was a significant reduction in dietary phosphorus and calcium, and increased vitamin C intake. Three dietary patterns were identified: the ‘Bread and Cereal’ pattern; ‘Milk and Potatoes’ pattern; and the ‘Semi Vegetarian’ pattern. (4) Conclusions: In this longitudinal cohort study, the diet quality was suboptimal and there were limited changes in intake after the commencement of PD. Further exploration of how dietary patterns may impact outcomes and quality of life is warranted.

Chronic kidney disease (CKD) affects > 10% of the global adult population and significantly increases the risk of cardiovascular disease (CVD), which remains the leading cause of death in this population. The development and progression of CVD—compared to the general population—is premature and accelerated, manifesting as coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. CKD and CV disease combine to cause multimorbid cardiorenal syndrome (CRS) due to contributions from shared risk factors, including systolic hypertension, diabetes mellitus, obesity, and dyslipidemia. Additional neurohormonal activation, innate immunity, and inflammation contribute to progressive cardiac and renal deterioration, reflecting the strong bidirectional interaction between these organ systems. A shared molecular pathophysiology—including inflammation, oxidative stress, senescence, and hemodynamic fluctuations characterise all types of CRS. This review highlights the evolving paradigm and recent advances in our understanding of the molecular biology of CRS, outlining the potential for disease-specific therapies and biomarker disease detection.

Background: In autosomal dominant polycystic kidney disease (ADPKD) impaired nitric oxide (NO) synthesis, in part, contributes to early-onset hypertension. Beetroot juice (BRJ) reduces blood pressure (BP) by increasing NO-mediated vasodilation. The aim of this double-blind, randomised, placebo-controlled study is to test the hypothesis that BRJ reduces systolic and diastolic clinic BP in hypertensive adults with ADPKD. Methods: Participants with ADPKD and treated hypertension (n = 60) will be randomly allocated (1:1) to receive a daily dose of either nitrate-replete (400 mg nitrate/day) or nitrate-deplete BRJ for 4 weeks. The co-primary outcomes are change in mean systolic and diastolic clinic BP before and after 4 weeks of treatment with daily BRJ. Secondary outcomes are changes in daily home BP, urinary albumin to creatinine ratio, serum and salivary nitrate/nitrite levels and serum asymmetric dimethylarginine levels before and after 4 weeks of BRJ. Discussion: The effect of BRJ in ADPKD has not been previously tested. BRJ is an accessible, natural dietary supplement that, if effective, will provide a novel adjunctive approach for treating hypertension in ADPKD. Trial registration: ClinicalTrials.gov NCT05401409. Retrospectively registered on 27th May 2022.

Background End-stage kidney disease (ESKD) incidence has been increasing over time, contributing significantly to morbidity and mortality. However, there is limited data examining the psychosocial factors affecting people with ESKD and how the social worker fits within the multidisciplinary CKD care. This integrative systematic review aims to summarise the existing evidence on psychosocial determinants of outcomes in ESKD and the role of the social worker in nephrology care. Method The literature search was conducted using PubMed and MEDLINE, targeting articles published from database inception until May 2021. This systematic review was performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The Joanna Briggs Institute tools were employed to assess the quality of included studies. Results Of the 397 citations, 13 studies applicable to 1465 patients met the inclusion criteria. The studies were of cross-sectional, experimental, and exploratory qualitative design in nature. The findings of the studies were summarised into three major themes—psychosocial factors, role of the renal social worker, and impact of the renal social worker. The studies demonstrated that concerns related to adjustment, death and dying, family and social functioning, and loss were common amongst participants of the included studies indicating the need for a social worker. Three studies explored the impact of social workers in ESKD, revealing that people who received support from social workers had an improved quality of life, lower depression scores, and reduced hospitalisations and emergency room visits. Conclusion This review summarizes the multitude of physical and psychological stressors that patients with ESRD face, and highlights the positive role social workers can play in improving the psychosocial stressors in this patient group, and the need for large-scale randomised trials to understand the role of social workers as part of a multidisciplinary nephrology care. Graphic abstract

Placental growth factor (PlGF) is an important angiogenic factor which has an emerging role in the clinical management of suspected preeclampsia. The role of PlGF in normal placental development is not completely understood and it is uncertain whether PlGF influences trophoblast and endothelial cell interactions central to uterine spiral artery remodelling, especially in variable oxygen conditions. A two-cell model of endovascular invasion was used. Tissue culture plates were coated with Matrigel™, on which fluorescent-labelled uterine microvascular endothelial cells (1 × 10⁵/well) and HTR8/SVNeo cells were co-cultured (1 × 10⁵/well) for 20 h. Co-cultures were treated with recombinant human PlGF (rhPlGF) (10 or 100 ng/mL) and incubated at either 21% O₂ or 2% O₂. Images were captured by fluorescence microscopy and analysed using ImageJ (n = 7). Data was analysed using SPSSv24. Treatment with rhPlGF did not improve integration in co-cultures irrespective of oxygen conditions but increased proliferation in 2% O₂ of both trophoblast and endothelial cells. Expression of angiogenic factors VEGF, sFLT-1, PlGF and CXCL12 in both co-cultures and in isolated trophoblast cells was not altered by rhPlGF treatment. Expression of TLR-3 mRNA in co-cultures was increased by rhPlGF 100 ng/mL at 21% O₂ (p = 0.03). PlGF contributes to trophoblast and endothelial cell proliferation in the setting of physiological hypoxia but does not influence trophoblast and endothelial cell interactions in an in vitro model of spiral artery remodelling. Upregulation of TLR-3 expression in co-cultures may indicate a role for PlGF in the placental inflammatory response.

Placental growth factor (PlGF) is decreased in early gestation of pregnant women who subsequently develop preeclampsia. In this study, pre‐emptive treatment with PlGF to prevent preeclampsia was evaluated in an in vivo rodent model of experimental preeclampsia (EPE) induced by TNF‐α and in an in vitro model of human first trimester trophoblast invasion. Pregnant C57/BL6 mice were treated with recombinant mouse placental growth factor‐2 (rmPlGF‐2) 100 μg/kg/day IP from gestational day (gd) 10. Animals had EPE induced by continuous TNF‐α infusion on gd13 and were subject to either continuous blood pressure monitoring by radiotelemetry throughout pregnancy or live placenta T₂ weighted magnetic resonance imaging (MRI) to demonstrate placental function on gd17. There was no difference in BP (p>0.99), proteinuria (p=0.9) or T₂ values on MRI (p=0.9) between control and rmPlGF‐2 treated animals. On gd13, animals treated with rmPlGF‐2 demonstrated increased placenta PlGF (p=0.01) and toll like receptor‐3 (p=0.03) mRNA expression as compared with controls. Fluorescent labelled human uterine microvascular endothelial cells and HTR8/SVNeo cells were co‐cultured on Matrigel^™ and treated with recombinant human PlGF (rhPlGF) (10 ng/mL) and/or TNF‐α (0.5 ng/mL). Trophoblast integration into endothelial networks was reduced by added TNF‐α (p=0.006), as was rhPlGF concentration in conditioned media (p0.9). Although TNF‐α induced EPE was not reversed with pre‐emptive rmPlGF‐2, a further trial of pre‐emptive rhPlGF in vivo is required to determine whether the absence of effect of rhPlGF demonstrated in vitro precludes PlGF as a preventative therapy for preeclampsia.