scholarly journals Characteristics associated with variation in corticosteroid exposure in children with steroid-sensitive nephrotic syndrome: Results from a Canadian longitudinal study

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0002692021
Author(s):  
Sara Rodriguez-Lopez ◽  
Rahul Chanchlani ◽  
Allison B. Dart ◽  
Catherine J. Morgan ◽  
Anne-Laure Lapeyraque ◽  
...  

Background: Variation in dose and duration of corticosteroids for childhood-onset steroid-sensitive nephrotic syndrome occurs worldwide, likely reflecting the evolving evidence on optimal dosing and variable severity of the disease observed between patients. We conducted a study to determine the associations between site, physician, and patient factors and average daily corticosteroid dose and duration of therapy. Methods: Data were derived from the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project, an observational longitudinal study from 2013 to 2019 of children with nephrotic syndrome involving pediatric nephrologists in 11 sites across Canada. Primary outcome was average daily corticosteroid dose prescribed per episode of proteinuria, reported as mg/m2 prednisone equivalents. Secondary outcome was duration of treatment for each episode of proteinuria in days. Exposure variables were categorized into site-, physician- and patient-level variables. Results: 328 children, median age at enrollment of 4.3 years old (Interquartile range [IQR]: 3.6), participated and were followed for a median time of 2.62 years (IQR: 2.61). The observed variability in average daily corticosteroid dose and in duration of therapy was mostly attributed to the site where the patient was treated. Accounting for between patient, physician and site differences, average daily corticosteroid dose decreased with increasing age (beta coefficient: -0.07 [95% Confidence interval (CI) -0.09, -0.05], p<0.001). African and Indigenous ethnicity was associated with longer treatment duration compared to Caucasian (beta coefficient: African 42.29 [95% CI 7.85, 76.73 p=0.016], Indigenous 29.65 [95% CI 2.79, 56.52 p=0.03]). Conclusions: We found practice variation with respect to corticosteroid prescriptions across 11 Canadian sites, and that variation is mostly explained at the site level. Age and ethnicity are important factors to be considered, as they are significantly associated with average corticosteroid dose and duration of therapy.

2021 ◽  
Vol 36 (11) ◽  
pp. 3799-3802
Author(s):  
Lieke A. Hoogenboom ◽  
Hazel Webb ◽  
Kjell Tullus ◽  
Aoife Waters

Abstract Background Levamisole is frequently used as a steroid-sparing agent in children with steroid-sensitive nephrotic syndrome. Side effects, such as neutropenia, gastro-intestinal upset and skin rash, have been reported. We noted an increase in creatinine in some of our patients, but literature on the effect of levamisole on kidney function is lacking. Methods A retrospective cohort study was conducted, including patients 1–18 years of age, treated for steroid-sensitive nephrotic syndrome with levamisole at Great Ormond Street Hospital for Children between January 2010 and January 2020. Data was collected on clinical observations and serum creatinine values before, during and after treatment. eGFR was calculated using the Schwartz equation. Results In total, 75 children were included in the analysis. The median duration of treatment was 19 (IQR 12–27) months. The median estimated GFR was 134 (IQR 119–160), 101 (IQR 91–113) and 116 (IQR 106–153) ml/min/1.73 m2, respectively, before, during and after treatment with levamisole. The difference between eGFR before and after treatment compared with during treatment was statically significant (P < 0.0001). During the treatment period, the eGFR decrease was not progressive. The median levamisole dose was 2.5 (IQR 2.3–2.6) mg/kg on alternate days, and the dose was not correlated with the decrease in eGFR (r = 0.07, 95% CI − 0.22 to 0.35). Conclusion Levamisole significantly decreases eGFR. However, this decrease is not progressive or irreversible and would not be an indication to discontinue the treatment.


Author(s):  
Anne M. Schijvens ◽  
Nynke Teeninga ◽  
Eiske M. Dorresteijn ◽  
Steven Teerenstra ◽  
Nicholas J. Webb ◽  
...  

AbstractSteroids are the cornerstone of the treatment of childhood nephrotic syndrome. The optimal duration for the first episode remains a matter of debate. The aim of this study is to determine whether the 8 weeks International Study of Kidney Disease in Children (ISKDC) regimen is equally effective as the 12 weeks steroid regimen from the German society of pediatric nephrology (Arbeitsgemeinschaft für Pädiatrische Nephrologie [APN]). An individual patient data (IPD) meta-analysis of randomized controlled trials reporting on prednisolone treatment for a first episode of childhood nephrotic syndrome was conducted. European trials aimed at investigating the ISKDC and/or APN steroid regimen were selected. The lead investigators of the selected trials were requested to provide the IPD of the specific treatment groups. Four trials included European cohorts using dosing schedules according to the regimens studied. IPD of two trials were available. A significant difference was found in time to first relapse after cessation of steroid treatment between the 8 and 12 weeks treatment group with a median time to relapse of 29 and 63 days, respectively. Moreover, relapse rate ratios during total follow-up were 51% higher for the 8 weeks regimen. Finally, younger children have a significantly lower time to first relapse and frequently relapsing nephrotic syndrome.Conclusions: The results of this IPD meta-analysis suggest that the 8 weeks steroid regimen for a first episode of steroid-sensitive nephrotic syndrome may not be equally effective as the 12 weeks steroid regimen. Moreover, this study highlights the importance of using uniform definitions to enable accurate comparison and interpretation of trial results.Trial registration: Registration number: CRD42020199244, date of registration 16-08-2020 What is Known:• Steroids are the cornerstone of the treatment of childhood nephrotic syndrome, however the optimal duration for the first episode remains a matter of debate.• Currently, the 8 weeks ISKDC protocol and 12 weeks APN protocol are among the most frequently used protocols in Europe. What is New:• The 8 weeks steroid regimen for a first episode of steroid-sensitive nephrotic syndrome may not be equally effective as the 12 weeks steroid regimen for the treatment of a first episode of nephrotic syndrome.• Younger children have a significantly shorter time to first relapse and time to frequent relapsing nephrotic syndrome.


Author(s):  
Tetsuro Tamai ◽  
Kaori Kamijo ◽  
Yoshifusa Abe ◽  
Satoshi Hibino ◽  
Shunsuke Sakurai ◽  
...  

Abstract Background Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. This study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS. Methods We sequentially measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 NS patients. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin incuding 51 control subjects. Results The median of total serum adiponectin levels in patients were 36.7, 36.7, and 20.2 μg/mL at the onset, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects. The median values of %HMW, %MMW, and %LMW values were 56.9/27.0/14.1 at the onset, 62.0/21.8/13.4 at the initial remission, and 58.1/21.7/17.5 at during the remission period of NS, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset were high, and the %LMW values at the onset and at initial remission were low. Conclusions In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms change.


2018 ◽  
Vol 34 (4) ◽  
pp. 641-648
Author(s):  
Trine Korsgaard ◽  
René Frydensbjerg Andersen ◽  
Shivani Joshi ◽  
Søren Hagstrøm ◽  
Søren Rittig

2020 ◽  
Vol 36 (7) ◽  
Author(s):  
Gokhan Cakirca ◽  
Ahmet Guzelcicek ◽  
Kenan Yilmaz ◽  
Cemal Nas

Objective: Growing evidence shows that oxidative stress plays an important role in the development and progression of nephrotic syndrome (NS). In this study, we aimed to examine serum IMA levels as an indicator of oxidative stress in children with steroid-sensitive NS (SSNS) in remission and relapse. Methods: This cross-sectional study was carried out at the Pediatric Nephrology Unit of Sanliurfa Training and Research Hospital, Sanliurfa, Turkey, from April 2019 to December 2019. In this study Serum IMA and albumin levels were determined in 70 children with SSNS and 45 healthy controls. Among the children with SSNS, 50 were in remission and 20 were in relapse. Then, adjusted IMA levels were calculated from the IMA/albumin ratio. Results: IMA and adjusted IMA levels significantly increased and albumin significantly decreased in children with SSNS in relapse and remission compared with those of the healthy controls. Moreover, these alterations were more prominent in the relapse group than in the remission group. IMA was inversely correlated with albumin in children with SSNS (r= −0.881, p= <0.001). Conclusions: Our findings demonstrated that elevated IMA and adjusted IMA levels observed in patients with SSNS were associated with increased oxidative stress and could indirectly reflect the degree of oxidative damage in glomerular structures. doi: https://doi.org/10.12669/pjms.36.7.2924 How to cite this:Cakirca G, Guzelcicek A, Yilmaz K, Nas C. Increased ischemia-modified albumin levels in children with steroid-sensitive nephrotic syndrome. Pak J Med Sci. 2020;36(7):---------. doi: https://doi.org/10.12669/pjms.36.7.2924 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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