A longitudinal study on the effects of psychological stress on proteinuria in childhood steroid-sensitive nephrotic syndrome.

OBJECTIVE: Steroid-sensitive nephrotic syndrome (SSNS) in children is often complicated by one or more relapses, as manifested by the appearance of proteinuria. Besides health-related triggers, psychological stress might be related to relapse. This longitudinal study examined the link between perceived stress, emotional valence (feeling happy vs. unhappy) and daily reported proteinuria, and investigated the temporal relation between stressful events and proteinuria. METHOD: Sixteen children (4-13 years) diagnosed with SSNS were included. Patients kept an online diary for an average of 124 days, wherein they reported proteinuria (n = 1985 urine samples), perceived stress, emotional valence, medication use and health complaints. Stressful days were determined at the start of the study. Using multilevel analysis, the following associations were tested: (1) the relation between perceived stress, emotional valence and proteinuria, and (2) the temporal relation between stressful days and proteinuria. RESULTS: Appearance of proteinuria was reported in 410/1985 urine samples. Perceived stress and not emotional valence significantly predicted proteinuria (95% CI [0.11, 0.27]), even five days later. There was a significant temporal association between stressful days and proteinuria (95% CI [0.22, 1.14]). The effect sizes of these associations were small, f = 0.04 and f = 0.12, respectively. CONCLUSIONS: Our findings suggest that psychological stress may trigger proteinuria in children with SSNS. Future research in larger samples is needed to support our findings.The funder of this research is the Dutch Kidney Foundation, The Netherlands [SB191]. Lianne Bakkum is supported by the Wellcome Trust [208155/Z/17/Z]

Distress in parents of children with first-onset steroid-sensitive nephrotic syndrome

Background:Steroid-sensitive nephrotic syndrome (SSNS) is associated with a relapsing–remitting course that can be stressful for parents. As little is known of parental distress at the first onset of SSNS, this study aims to describe parental distress and everyday problems in mothers and fathers of a child with newly diagnosed SSNS participating in a randomized controlled trial of levamisole added to corticosteroids. 'Methods: To assess distress, the Distress Thermometer for Parents (DT-P) was used, which includes questions on distress (thermometer score 0–10, ≥ 4 “clinical distress”) and presence of everyday problems in six domains: practical, social, emotional, physical, cognitive, and parenting. The DT-P was completed 4 weeks after the onset of SSNS. Total sum and individual items of everyday problems were compared with reference data from mothers and fathers of the Dutch general population. Results: There was no difference in clinically elevated parental distress between SSNS mothers (n = 37) and fathers (n = 25) and reference parents. Compared to reference fathers, fathers of a child with SSNS scored significantly higher on emotional problems (P = 0.030), while mothers experienced more parenting problems (P = 0.002). Regression analyses showed that lower parental age and having a girl with SSNS were significantly associated with more practical problems and higher distress thermometer scores, respectively. Conclusions: Four weeks after onset, SSNS mothers and fathers experience equal distress as reference parents. However, both parents endorsed significantly more everyday problems. Therefore, monitoring parental distress, even in the first weeks of the disease, could contribute to timely interventions and prevent worsening of problems. Clinical trial registry: Dutch Trial Register (https://onderzoekmetmensen.nl/en/trial/27331 ). Graphical abstract: [Figure not available: see fulltext.]</p

Hydrocortisone-induced increase of PDGF β-receptor expression in a human malignant mesothelioma cell line

The effect of hydrocortisone (HC) on PDGF β-receptor expression was studied in the human malignant mesothelioma cell line Mero-14. HC was found to induce a time- and dose-dependent increase of PDGF β-receptor mRNA. Nuclear run off analysis revealed that HC induced increased transcription of the PDGF β-receptor gene. The expression of PDGF β-receptor protein was also elevated by HC as demonstrated with an immunoblotting assay. However, the number of PDGF-BB binding sites on the cell surface of Mero-14 remained unchanged upon HC treatment. These results suggest that steroid hormones can regulate PDGF receptor expression in vivo

Health-related quality of life of children with first onset steroid-sensitive nephrotic syndrome

This study assessed HRQoL and emotional and behavioral difficulties (EBD) and associated variables in children with first onset SSNS. While relapsing steroid-sensitive nephrotic syndrome (SSNS) in children is associated with lower health-related quality of life (HRQoL), little is known about first onset. Four weeks after onset, children (2–16 years) and/or their parents who participated in a randomized placebo-controlled trial, completed the Pediatric Quality of Life Inventory 4.0 (PedsQL) and Strengths and Difficulties Questionnaire (SDQ) to measure HRQoL and EBD, respectively. Total and subscale scores and the proportion of children with impaired HRQoL (&gt; 1 SD below the mean of the reference group) or SDQ clinical scores (&lt; 10th and &gt; 90th percentile) were compared to the Dutch general population (reference group). Regression analyses were used to identify associated variables. Compared to the reference group, children 8–18 years reported significantly lower total HRQoL, and physical and emotional functioning. A large proportion (&gt; 45%) of these children had impaired HRQoL. There were no differences in HRQoL between children 2–7 years and the reference group, except for higher scores on social functioning (5–7 years). Similar proportions of SSNS and reference children scored within the clinical range of SDQ subscales. Age, sex, and steroid side-effects were negatively associated with HRQol and/or EBD. Conclusion: This study showed that HRQoL and EBD are affected in children of different ages with first onset SSNS. This calls for more awareness from healthcare providers and routinely monitoring of HRQoL and EBD in daily clinical care to prevent worsening of symptoms. Clinical trial registry: Netherlands Trial Register (https://trialsearch.who.int/ ; NTR7013), date of registration: 02 June 2018. What is Known: • Health-related quality of life (HRQoL) is lower and emotional and behavioral difficulties (EBD) is more affected in children with frequently-relapsing and steroid-dependent nephrotic syndrome. What is New: • HRQoL and EBD are affected in children with first onset steroid-sensitive nephrotic syndrome compared to a reference group of the Dutch general population. • To what extent HRQoL and EBD are affected depends on the age of the patient.</p

Insufficient protection by Neisseria meningitidis vaccination alone during eculizumab therapy

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Rituximab-associated hypogammaglobulinemia in children with idiopathic nephrotic syndrome: results of an ESPN survey.

BackgroundThere is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic nephrotic syndrome (INS).MethodsA survey was distributed by the European Society Pediatric Nephrology to its members. It addressed the screening and management practices of pediatric nephrology units for recognizing and treating RTX-associated HGG and its morbidity and mortality. Eighty-four centers which had treated an overall 1328 INS children with RTX responded.ResultsThe majority of centers administered several courses of RTX and continued concomitant immunosuppressive therapy. Sixty-five percent of centers routinely screened children for HGG prior to RTX infusion, 59% during, and 52% following RTX treatment. Forty-seven percent had observed HGG prior to RTX administration, 61% during and 47% >9 months following treatment in 121, 210, and 128 subjects respectively. Thirty-three severe infections were reported among the cohort of 1328 RTX-treated subjects, of whom 3 children died. HGG had been recognized in 30/33 (80%) of them.ConclusionsHGG in steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) children is probably multifactorial and can be observed prior to RTX administration in children with SDNS/FRNS. Persistent HGG lasting >9 months from RTX infusion is not uncommon and may increase the risk of severe infections in this cohort. We advocate for the obligatory screening for HGG in children with SDNS/FRNS prior to, during, and following RTX treatment. Further research is necessary to identify risk factors for developing both HGG and severe infections before recommendations are made for its optimal management. A higher resolution version of the Graphical abstract is available as Supplementary information

Prophylactic plasma exchange in CD46-associated atypical haemolytic uremic syndrome

Patients with atypical haemolytic uremic syndrome (aHUS) with a mutation in the gene encoding membrane cofactor protein (CD46) are known to have a better prognosis than those with mutations in factor H (CFH) or factor I (CFI), but a small number of the former still proceed to end-stage renal failure. Plasma therapy (PE) is the recommended approach to treat both acute episodes and prevent recurrences in aHUS, but studies have yet to show PE efficacy in aHUS associated with a CD46 mutation. The factors determining failure to treatment are not clear and may be related to the mutation involved or to insufficient treatment. Our experience of PE in a family of three sisters with CFH-associated aHUS suggests that intensive and prophylactic PE allows renal function to be maintained in both native kidneys and allografts. The success of this strategy has led us to use it in all cases of aHUS. Here, we describe the effect of this strategy in a child with aHUS and a CD46 mutation. The initial episode was treated with daily PE, resulting in the recovery of renal function. However, over the next 4 years, there was a progressive decline in renal function to end-stage renal failure, with evidence of an on-going thrombotic microangiopathy despite continuous prophylactic PE. Prophylactic PE does not influence the natural course of aHUS and CD46 mutation