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

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

European Society of Pediatric Nephrology survey on current practice regarding recurrent focal segmental glomerulosclerosis after pediatric kidney transplantation

Introduction: Primary FSGS is an important cause of ESRD in children. FSGS recurrence after kidney transplantation is associated with early graft loss. No guidelines for treatment of FSGS recurrence exist. We conducted a survey to gain insight into variation of treatment between centers. Methods: A survey was sent to all members of the ESPN on behalf of the “Renal Transplantation” and “Idiopathic Nephrotic Syndrome” working groups. Results: Fifty-nine nephrologists from 31 countries responded, reporting 807 FSGS patients, with 241 (30%) FSGS recurrences after transplantation. Recurrence varied from 0% to 100% between respondents. Native nephrectomy before or during transplantation was performed, respectively, always (37%), never (39%), or on clinical indication (17%). Half of the respondents started preventive treatment before transplantation, using PF (n = 10); R (n = 4); PF or IA, plus R (n = 9); cyclosporine (n = 2); or unknown (n = 4). Immunosuppressive therapy for patients without known mutations consisted of a combination of steroids, tacrolimus/cyclosporine, and MMF, with or without IL-2R-blockade in, respectively, 61% and 86% of the respondents. Sixty-three percent applied a similar regimen to patients with known mutations. FSGS recurrence was treated with PF or IA, plus R by 66% of respondents; 54% observed no response. Complete remission in >50% of patients was reported by 41% of the respondents. Discussion: FSGS recurrence after transplantation is common, but varies greatly between centers. We found great variability in preventive and therapeutic treatment regimens. Future research should focus on predisposing factors, including biopsy findings and genetic mutations, and standardized treatment

Levamisole causes a transient increase in plasma creatinine levels but does not affect kidney function based on cystatin C

Background: In pediatric patients treated with levamisole to prevent relapses of idiopathic nephrotic syndrome (INS), a transient and non-progressive rise in creatinine levels has been observed. It has been suggested that levamisole affects tubular secretion of creatinine. However, other potential mechanisms — nephrotoxicity and interference with the analytical assay for creatinine — have never been thoroughly investigated. Methods: In three steroid-sensitive nephrotic syndrome (SSNS) patients with elevated plasma creatinine levels, treated with levamisole 2.5 mg/kg every other day, serum cystatin C was determined. The glomerular filtration rate (GFR) was estimated using the full age spectrum for creatinine and the full age spectrum for cystatin C equations. Interference of levamisole with the enzymatic creatinine assay was tested using spare human plasma of different creatinine concentrations spiked with levamisole (4, 20, and 100 µM). Results: Three patients who received levamisole with elevated plasma creatinine levels had normal serum cystatin C levels and corresponding estimated GFR. There was no assay interference. Conclusion: Levamisole increases plasma creatinine levels, which is most probably due to impaired tubular secretion of creatinine since there was no assay interference and patients had normal eGFR based on serum cystatin C. However, interference of metabolites of levamisole could not be excluded. To monitor GFR, cystatin C in addition to creatinine should be used and be measured before and during levamisole use

Correction to: Levamisole causes a transient increase in plasma creatinine levels but does not affect kidney function based on cystatin C (Pediatric Nephrology, (2022), 37, 10, (2515-2519), 10.1007/s00467-022-05547-9)

The original version of this article unfortunately contained a mistake. During the process of typesetting, the institutional author attribution “on behalf of the LEARNS consortium” was left out of the author group. The correct attribution is as shown above. The publisher apologizes for this mistake. The original article was updated

The Use of Patient-Reported Outcome Measures in Daily Clinical Practice of a Pediatric Nephrology Department

(1) Background: Health-related quality of life (HRQoL) is lower in patients with chronic kidney disease (CKD) compared to the general population. In 2011, the KLIK PROM portal was implemented in the Emma Children’s Hospital to monitor and discuss HRQoL in daily care. This study describes and assesses the implementation and use of the KLIK PROM portal in the pediatric nephrology department. (2) Methods: CKD patients (self-report, if 8–18 years of age) and their parents (proxy-report, if 1–8 years) were invited to complete HRQoL patient-reported outcome measures (PROMs): TNO-AZL Preschool children Quality Of Life (TAPQOL) or Pediatric Quality of Life Inventory for Children (PedsQL). The PROMs were completed before and discussed during outpatient consultations. The adaptation rate—the proportion of patients/parents who were invited and completed at least one PROM—was calculated. Reported HRQoL scores of CKD patients were compared to the general population. (3) Results: In total, 142 patients (proxy-and self-report) were invited, 112 patients completed at least one PROM (adaptation rate 79%). Patients (n = 84 with informed consent for scientific use) with CKD reported lower HRQoL and HRQoL was more often impaired compared to the general Dutch population. (4) Conclusions: The implementation of KLIK was successful and its use is feasible for daily care. Using KLIK, HRQoL problems can be easily identified and monitored

Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)

INTRODUCTION: Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome). METHODS AND ANALYSIS: An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2-16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores. ETHICS AND DISSEMINATION: The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NL6826, 2017-001025-41.status: publishe

Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: Study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)

INTRODUCTION: Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome). METHODS AND ANALYSIS: An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2-16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores. ETHICS AND DISSEMINATION: The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NL6826, 2017-001025-41

Incidence and Relapse of Idiopathic Nephrotic Syndrome: Meta-analysis

CONTEXT: Idiopathic nephrotic syndrome (INS) in children is a disease with considerable morbidity, yet the incidence and risk for relapse have not been systematically reviewed. OBJECTIVE: To estimate the overall pooled weighted incidence and risk for relapse of INS in children. DATA SOURCES: Medline and Embase (until December 2020). STUDY SELECTION: All studies reporting incidence (per 100 000 children per year) and/or risk for relapse (the proportion of patients who experience $1 relapse) of INS in children (age: <18 years) were eligible. DATA EXTRACTION: After quality assessment, data were extracted: study (design, localization, and sample size) and patient (age, sex, steroid response, and ethnicity) characteristics, incidence, and risk for relapse. RESULTS: After screening, 73 studies were included for analysis (27 incidence, 54 relapse). The overall pooled weighted estimate and corresponding prediction interval (PI) of the incidence was 2.92 (95% PI: 0.00–6.51) per 100 000 children per year. Higher incidences were found in non-Western countries (P < .001). Incidence tended to be lower in white children, but this was not significant. The overall pooled weighted estimate of the risk for relapse was 71.9% (95% PI: 38.8–95.5). Between 1945 and 2011, incidence did not change (P 5 .39), yet the risk for relapse decreased significantly (P 5 .024), from 87.4% to 66.2%. LIMITATIONS: There was no full-text availability (n 5 33), considerable heterogeneity, and limited studies from Africa, Latin America, and Asia. CONCLUSIONS: INS has a low incidence with ethnic variation but high risk for relapse. Although corticosteroids have significantly reduced the risk for relapse, it remains unacceptably high, underscoring the need for alternative treatment strategies

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)