Serum suPAR levels help differentiate steroid resistance from steroid-sensitive nephrotic syndrome in children

2014 ◽  
Vol 30 (2) ◽  
pp. 301-307 ◽  
Author(s):  
Zhaoyang Peng ◽  
Jianhua Mao ◽  
Xuejun Chen ◽  
Fengqing Cai ◽  
Weizhong Gu ◽  
...  
2015 ◽  
Vol 7 (1) ◽  
pp. 102-107 ◽  
Author(s):  
O. R. Ramayani ◽  
N. Sekarwana ◽  
P. P. Trihono ◽  
A. H. Sadewa ◽  
A. Lelo

There is no satisfactory explanation as to why some nephrotic syndrome (NS) patients respond to glucocorticoids and others do not. The aim of this study was to investigate an association between single nucleotide polymorphism of the MIF gene -rs755622 and serum MIF concentrations in NS patients. During a period between November 2011 and September 2012, 120 consecutive children divided into three groups [healthy children, steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS)] were examined. Children were defined as healthy when they had a normal estimated glomerular filtration rate and spot urinary albumin creatinine ratio <150 μg/mg creatinine. SRNS was diagnosed in children who did not respond to the usual doses of steroids within 4 weeks of initiating treatment. SSNS patients were defined as those who had remission after usual doses of steroids. The genotype of -173 G to C polymorphism of the MIF gene was determined using polymerase chain reaction restriction fragment length polymorphism methods. Serum MIF concentration was measured using sandwich enzyme-linked immunosorbent assay. The allele frequency of the C allele was higher in SRNS compared with that of SSNS patients (P=0.025). There was a trend toward an association between genotypes and serum MIF disturbances. In conclusion, this study noted elevated circulating serum MIF levels and higher frequency of the C allele of the MIF gene in SRNS patients. The presence of the C allele implies an increased risk for steroid resistance.


2020 ◽  
Vol 7 (6) ◽  
pp. 1304
Author(s):  
Anitha Palaniyandi ◽  
Subramani Palaniyandi

Background: Nephrotic syndrome is a notable chronic disease in children. The objective of this study was to compare the clinical and lab profile between steroid sensitive nephrotic syndrome and steroid resistant nephrotic syndrome at the onset of disease. Certain parameters were tested if they could be significate predictors of developing steroid resistance at the onset of first episode of nephrotic syndrome.Methods: Retrospective observation study done children 1-12 years diagnosed with nephrotic syndrome in Sri Ramachandra Medical College and Hospital, Department of Paediatrics, Chennai. Sample size 150. Period of study Jan 2013- Dec 2015. Variables considered were age at onset, sex, parental consanguinity with essential lab parameters done at the onset of nephrotic syndrome proteinuria, pyuria, microscopic hematuria, urine protein creatinine ratio, serum creatinine, serum triglycerides and serum albumin. Children less than 1 year of age, cases with secondary causes of nephrotic syndrome and steroid dependant nephrotic syndrome, children with incomplete records were not included in this study. 150 cases who fulfilled the study criteria were included in this study.Results: 75 cases of steroid sensitive nephrotic syndrome (SSNS) were compared with an equal number of steroid resistant nephrotic syndrome (SRNS). 85 children had onset of disease before 3 years of age and majority had 3+ proteinuria and males predominated in both the groups. The overall consanguinity rates were higher among SRNS group. Triglyceride level >300 mg/dl predominated in SRNS group along with a higher severity of hypoalbuminemia when compared to SSNS group. None of the parameters tested were significant predictors of developing SRNS subsequently.Conclusions: Comparing steroid sensitive with steroid resistance nephrotic syndrome, no lab parameter could identify the risk of a child developing steroid resistance subsequently. This could be a field of interest in future studies that could predict the development of steroid resistance at the onset of first episode of nephrotic syndrome itself. 


Author(s):  
Ie. A. Burlaka ◽  
I. V. Bagdasarova

Objectives: the objective of this paper was to study the levels of cellular hypoxia, apoptosis controlling factors in children with steroid-sensitive and steroid-resistant nephrotic syndrome. Background: patients with steroid-resistant nephrotic syndrome (SRNS) represent a challenging subset of patients with nephrotic syndrome who often fail standard immunosuppression and have a higher likelihood of progressing to end-stage renal disease. The search of the biochemical markers undergoing the steroid-resistance is under urgent need. Methods: an examination of kidney biopsies and blood of 56 patients (aged 10 to 15 years) with nephrotic syndrome was done. Conventional clinical investigations, immunohistochemistry, immunoblotting were used in this study. Results: patients with steroid-resistant nephrotic syndrome show an increased level of HIF-1 alfa (a marker of cellular hypoxia) as compared to the control group and children with steroid-sensitive nephrotic syndrome. Patients with steroid-resistant nephrotic syndrome show a down-regulation of anti-apoptotic marker BcL-xL as compared to the control group and children with steroid-sensitive nephrotic syndrome. Conclusion: hypoxia-induces disorders and apoptosis activation markers are considered to be included in the complex scheme predicting steroid-resistance in nephrotic children. 


2014 ◽  
Vol 61 (1) ◽  
Author(s):  
Monika Świerczewska ◽  
Danuta Ostalska-Nowicka ◽  
Bartosz Kempisty ◽  
Aleksandra Szczepankiewicz ◽  
Michał Nowicki

Nephrotic syndrome (NS) is the most common reason of proteinuria in children and can be caused by the pathology of renal glomeruli. Steroid therapy is typically used in this disorder. It has been shown that MIF is a cytokine which counteracts the immunosuppressive properties of glucocorticoids. The aim of this study was looking for a correlation between MIF polymorphisms and genetic susceptibility to steroid resistance in children with INS (Idiopathic NS). The study was performed in 71 patients with INS including SRNS (steroid resistance nephrotic syndrome) (41) and SSNS (steroid sensitive nephrotic syndrome) (30) and in 30 control subjects. We employed Sanger sequencing and capillary electrophoresis. Linkage disequilibrium was made using Haploview and PHASE. We didn't observe a statistical significance between SNPs detected in patients with INS and controls. Our studies revealed statistical significance for two polymorphisms: rs2070767C > T and rs2000466T > G between patients with SRNS and SSNS. The results for rs34383331T > A are close to being statistically significant. Statistical significance was revealed for CATT5/CATT6 genotype in SRNS group vs SSNS group (OR=4.604, 95%CI=1.356-15.632, p=0.0168). We found that the frequency of 5/X-CATT genotype compared with X/X-CATT genotype was significantly higher in SRNS patients vs SSNS (OR=3.167, 95%CI=1.046-9.585, p=0.0426). In linkage disequilibrium analysis we didn't show involvement in susceptibility to INS and steroid sensitive phenotype. Our results suggest that the role of MIF polymorphisms in the susceptibility to positive response to steroid therapy is still unresolved. It indicates that MIF may be involved in indirect and complex molecular mechanisms of steroid activity in hormone-dependent metabolic pathways in children with INS. Because of ambiguous findings, pleiotropic features of this cytokine require that more research should be undertaken.


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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