Psychosocial factors in patients with kidney failure and role for social worker : a secondary data audit

Background: People with kidney failure face a multitude of psychosocial stressors that affect disease trajectory and health outcomes. Objectives: To investigate psychosocial factors affecting people with kidney failure before or at start of kidney replacement therapy (KRT) and kidney supportive and palliative care (KSPC) phases of illness and to explore role of social worker during the illness trajectory. Methods: We conducted a secondary data audit of patients either before or at start of KRT (Phase 1) and at the KSPC (Phase 2) of illness and had psychosocial assessments between March 2012 and March 2020 in an Australian setting. Results: Seventy-nine individuals, aged 70 ± 12 years, had at least two psychosocial assessments, one in each of the two phases of illness. The median time between social worker evaluations in Phase 1 and Phase 2 was 522 (116−943) days. Adjustment to illness and treatment (90%) was the most prevalent psychosocial issue identified in Phase 1, which declined to 39% in Phase 2. Need for aged care assistance (7.6%−63%; p < 0.001) and carer support (7.6%−42%; p < 0.001) increased significantly from Phase 1 to Phase 2. There was a significant increase in psychosocial interventions by the social worker in Phase 2, including supportive counselling (53%−73%; p < 0.05), provision of education and information (43%−65%; p < 0.01), and referrals (28%−62%; p < 0.01). Conclusion: Adults nearing or at the start of KRT experience immense psychosocial burden and adaptive demands that recognisably change during the course of illness. The positive role played by the nephrology social worker warrants further investigation

Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease

Augmentation of endogenous nitric oxide (NO) synthesis, either by the classical L-arginine-NO synthase pathway, or the recently discovered entero-salivary nitrate-nitrite-NO system, may slow the progression of autosomal dominant polycystic kidney disease (ADPKD). To test this hypothesis, the expression of NO in human ADPKD cell lines (WT 9-7, WT 9-12), and the effect of L-arginine on an in vitro model of three-dimensional cyst growth using MDCK cells, was examined. In addition, groups of homozygous Pkd1RC/RC mice (a hypomorphic genetic ortholog of ADPKD) received either low, moderate or high dose sodium nitrate (0.1, 1 or 10 mmol/kg/day), or sodium chloride (vehicle; 10 mmol/kg/day), supplemented drinking water from postnatal month 1 to 9 (n = 12 per group). In vitro, intracellular NO, as assessed by DAF-2/DA fluorescence, was reduced by &gt;70% in human ADPKD cell lines, and L-arginine and the NO donor, sodium nitroprusside, both attenuated in vitro cyst growth by up to 18%. In contrast, in Pkd1RC/RC mice, sodium nitrate supplementation increased serum nitrate/nitrite levels by ~25-fold in the high dose group (P&lt;0.001), but kidney enlargement and percentage cyst area was not altered, regardless of dose. In conclusion, L-arginine has mild direct efficacy on reducing renal cyst growth in vitro, whereas long-term sodium nitrate supplementation was ineffective in vivo. These data suggest that the bioconversion of dietary nitrate to NO by the entero-salivary pathway may not be sufficient to influence the progression of renal cyst growth in ADPKD

Effect of placental growth factor on trophoblast-endothelial cell interactions in vitro

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

Effect of placental growth factor in models of experimental pre-eclampsia and trophoblast invasion

Placental growth factor (PlGF) is decreased in early gestation of pregnant women who subsequently develop pre-eclampsia. In this study, pre-emptive treatment with PlGF to prevent pre-eclampsia was evaluated in an in vivo rodent model of experimental pre-eclampsia (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 gd 13 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 gd 17. There was no difference in BP (P > .99), proteinuria (P =.9) or T2 values on MRI (P =.9) between control and rmPlGF-2-treated animals. On gd 13, animals treated with rmPlGF-2 demonstrated increased placenta PlGF (P =.01) and Toll-like receptor-3 (P =.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 =.006), as was rhPlGF concentration in conditioned media (P .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 pre-eclampsia

[In Press] Psychosocial factors affecting patients with end-stage kidney disease and the impact of the social worker

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