Résumé
Primary nephrotic syndrome (NS) is a common kidney disease in children.Around 80% to 90% of children with NS are sensitive to corticosteroid treatment.Most of the children with NS will relapse after the first remission, and 50% to 70% of them will develop frequent relapse or steroid dependence.The main target of treatment is to prevent relapse while minimizing the adverse effects of medications.The progress of the treatment of steroid sensitive NS is reviewed in order to provide evidence for individualized therapy.
Résumé
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.
Résumé
Resumen: Introducción: En el síndrome nefrótico cortico-sensible (SNCS), la corticoterapia prolongada podría reducir la frecuencia de recaídas. El objetivo de este trabajo fue la comparación de un esquema corticoide prolongado frente al tratamiento habitual del SNCS primario, evaluando los siguientes parámetros: el número de pacientes con recaídas, el número total de recaídas, el tiempo medio transcurrido al iniciar el tratamiento, hasta la remisión y hasta la primera recaída, la dosis acumulada de corticosteroides y la toxicidad esteroide. Métodos: La población se dividió en dos grupos: el grupo A (27 pacientes) recibió 16-β-metilprednisona durante 12 semanas, reduciendo la dosis hasta la semana 24; y el grupo B (29 pacientes) recibió 16-β-metilprednisona durante 12 semanas, y placebo hasta la semana 24. Resultados: La tasa de incidencia acumulada de recaídas (persona/año) fue en el grupo A 36/100, y en el grupo B 66/100 (p = 0.04). El tiempo medio transcurrido (días) hasta la primera recaída fue de 114 en el grupo A y 75 en el grupo B (p = 0.01). Las diferencias de tiempo transcurrido al iniciar tratamiento y hasta la remisión entre ambos grupos no fueron significativas. El total acumulado de recaídas fue de 9 en el grupo A y 17 en el grupo B (p = 0.04), y el total de pacientes con recaídas fue de 3 (grupo A) y 7 (grupo B) (p = 0.17). La dosis media acumulada (mg/m2) por paciente fue de 5,243 en el grupo A y de 4,306 en el grupo B (p = 0.3), y el cortisol sérico (μg/dl) final fue de 14 en el grupo A y 16 en el grupo B (p = 0.4). La toxicidad esteroide fue similar entre ambos grupos. Conclusiones: La duración del tratamiento disminuyó el número de recaídas, sin incrementar la toxicidad esteroide.
Abstract: Background: In the steroid-sensitive nephrotic syndrome (SSNS) the prolonged treatment with steroids could decrease the frequency of relapses. We conducted a comparative study of prolonged steroid scheme and the usual treatment of primary SSNS to assess: the number of patients with relapses, mean time to treatment initiation, to remission and to first relapse, total number of relapses, total cumulative dose of steroids, and the steroid toxicity. Methods: Patients were divided into two groups: group A (27 patients) received 16-β-methylprednisolone for 12 weeks, reducing the steroid until week 24. Group B (29 patients) received 16-β-methylprednisolone for 12 weeks and placebo until week 24. Results: Cumulative incidence rate of relapse (person/years) for group A was of 36/100 and 66/100 for group B (p = 0.04). Average elapsed time to first relapse was of 114 days for group A and of 75 days to for group B (p = 0.01). The difference in time for initial response to treatment and up to achieve remission between both groups was not significant. Total cumulative relapses were 9 for group A and 17 for group B (p = 0.04). Total patients with relapses were 3 for group A and 7 for group B (p = 0.17). Cumulative average dose per patient was 5,243 mg/m2 for group A and 4,306 mg/m2 for group B (p = 0.3), and serum cortisol was 14 μg/dl for group A and 16 μg/dl for group B (p = 0.4). There were no steroid toxicity differences between groups. Conclusions: The duration of the treatment had an impact on the number of relapses without increasing steroid toxicity.
Résumé
Objective To investigate the changes in serum cortisol and adrenocorticotrophic hormone(ACTH) levels in children with steroid-sensitive nephritic syndrome (SSNS) and the clinical significance of intervention.Methods According to whether a child with SSNS would relapse,48 children with SSNS were divided into non-recurrence group(n =19) and recurrence group(n =29),at the same time 14 age-matched healthy children were enrolled as the healthy control group.Serum cortisol and ACTH were measured in patients with SSNS by using electrochemiluminesence methods.In recurrence group,methylpredisolone or methylprednisolone combined with ACTH injection therapy was used on 15 patients with their serum cortisol and ACTH below normal.Results Before standard glucocorticoid treatment,the serum levels of cortisol and ACTH had no difference among 3 groups (all P ＞ 0.05).By the end of remission phase,the serum levels of cortisol and ACTH in recurrence group were statistically lower than those of the non-recurrence group[(113.03 ± 80.02) μg/L vs (251.54 ± 185.05) μg/L,t =-2.925,P ＜ 0.05 ; (12.81 ± 10.14) ng/L vs (23.53 ± 12.05) ng/L,t =-0.885,P ＜ 0.05].Eight to 12 weeks after being adjusted,the serum level of cortisol and the average monthly time of recurrent were both significantly improved in 15 abnormal children in recurrence group [(168.90 ± 133.43) μg/L vs (73.62 ± 58.04) μg/L,t =3.016,P ＜ 0.05 ; (0.09 ± 0.08) times vs (0.35 ± 0.11) times,t =-7.560,P ＜0.05],but as to the serum level of ACTH,there was no significant difference in abnormal children in recurrence group [(14.05 ± 10.99) ng/L vs (8.72 ± 4.11) ng/L,t =1.991,P ＞ 0.05].Conclusions The concentrations of serum cortisol and ACTH can reveal the risk of recurrence for children with SSNS to some extent,and effective intervention can reduce the recurrence rate and shorten the course of disease.
Résumé
La incidencia anual del síndrome nefrótico se ha estimado en 1-3 por cada 100,000 niños menores de 16 años de edad. En niños, la causa más común del síndrome nefrótico es el síndrome nefrótico idiopático (SNI), que se define por la presencia de proteinuria e hipoalbuminemia y es, por definición, una enfermedad primaria. En el estudio de la biopsia renal se pueden encontrar alteraciones histológicas renales no específicas que incluyen lesiones mínimas, glomeruloesclerosis segmentaria y focal y proliferación mesangial difusa. En todos los pacientes con SNI se indica el tratamiento con corticosteroides, ya que, habitualmente, no se requiere de una biopsia renal antes de iniciar el tratamiento. La mayoría de los pacientes (80-90%) responden a este tratamiento. Los niños con SNI que no presentan remisión completa con el tratamiento con corticosteroides generalmente presentan glomeruloesclerosis segmentaria y focal, y requieren tratamiento con inhibidores de calcineurina (ciclosporina o tacrolimus), mofetil micofenolato o rituximab, además del bloqueo del sistema renina-angiotensina. En este artículo se revisan las recomendaciones recientes aceptadas para el tratamiento de los niños con SNI.
The annual incidence of the nephrotic syndrome has been estimated to be 1-3 per 100,000 children < 16 year of age. In children, the most common cause of nephrotic syndrome is idiopathic nephrotic syndrome (INS). INS is defined by the presence of proteinuria and hypoalbuminemia and by definition is a primary disease. Renal biopsy study shows non-specific histological abnormalities of the kidney including minimal changes, focal and segmental glomerular sclerosis, and diffuse mesangial proliferation. Steroid therapy is applied in all cases of INS. Renal biopsy is usually not indicated before starting corticosteroid therapy. The majority of patients (80-90%) are steroid-responsive. Children with INS who do not achieve a complete remission with corticosteroid therapy commonly present focal and segmental glomerular sclerosis and require treatment with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil or rituximab, plus renin-angiotensin system blockade. In this article we review the recent accepted recommendations for the treatment of children with INS.
Résumé
Objective:To clarify the dynamics of Th2 related cytokines IL-4、IL-5 and the Treg T cell related cytokines TGF-β、IL-10 in children with primary steroid-sensitive nephrotic syndrome ( SSNS) from the nephrotic phase before steroid treatment to the re-mission phase.Methods:All 36 SSNS patients and 18 healthy controls matched for age , gender, body weight and height were enrolled , and their clinical characteristics were evaluated .Serum cytokine level was measured by ELISA assay .The serum levels of interleukin (IL)-4, IL-5, IL-10 and transforming growth factor (TGF)-βwere compared and correlated with serum albumin and cholesterol .Re-sults:Serum IL-4 and IL-5 levels in SSNS of nephrotic phase were higher than serum IL-4 and IL-5 levels of SSNS of remission phase and the healthy control , respectively .The serum TGF-βlevels of the nephrotic phase were significantly lower than those of remission phase or control group , whereas the serum IL-10 levels showed no significant difference between nephrotic phase and remission phase of SSNS or control group.The serum IL-4 levels had a negative correlation with serum albumin (R2 =-0.694,P=0.000), and a posi-tive correlation with serum albumin levels (R2 =0.658,P=0.000), whereas the serum TGF-βlevels had a positive correlation with serum albumin (R2 =0.838,P=0.000), and a negative correlation with serum albumin levels , had (R2 =-0.722,P=0.000). Conclusion:This study indicates that IL-4, IL-5 and TGF-βlevel is related to the pathogenesis of pediatric SSNS .
Résumé
Background: Nephrotic syndrome (NS) is a common childhood kidney disease caused by impaired glomerular function, characterized by protein leakage from the blood to the urine through the glomeruli, resulting in proteinuria, hypoalbuminemia, hypercholesterolemia and generalized edema. NS is descriptively classified upon the patients’ response to steroid treatment as steroid-sensitive NS (SSNS) or steroidresistant NS (SRNS). Aim: describe and compare different management strategies for SRNS. Methods: This retrospective study included 53 SRNS who were attending the Nephrology Outpatient Clinic, Children's Hospital, and Cairo University for follow-up. Results: out of 53 SRNS patients, 29 (54.72%) patients showed complete response to immunosuppressive therapy, while 14 (25.42%) showed partial response and the remaining 10 (18.87%) showed no response. Conclusion: Partial response to steroids or to first line of immunosuppressive therapy predicts better response to further immunosuppressives in SRNS patient. Cyclophosphamide is a preferable line in MCNS as it gives good results (50% complete response) with the advantage of lower cost and shorter duration of use. In patients with non-minimal change lesions or those who failed to respond to cyclophosphamide, cyclosporine is used.
Résumé
OBJECTIVES: Familial steroid-sensitive idiopathic nephrotic syndrome is rare, and only approximately 3% of patients have affected siblings. METHODS: Herein, we report seven cases of patients with steroid-sensitive idiopathic nephrotic syndrome from three Chinese families. Mutational screening of the Nphs2 gene was performed in all the patients. RESULTS: All seven of the familial steroid-sensitive idiopathic nephrotic syndrome cases in our sample exhibited minimal change disease, and one case also presented with mesangial proliferative glomerulonephritis, according to the renal pathology. No significant was associations were found between Nphs2 gene mutations and the onset of proteinuria and nephrotic syndrome in these familial cases. CONCLUSIONS: The presence of minimal change disease is important, but it is not an unusual finding in patients with familial steroid-sensitive idiopathic nephrotic syndrome, which appears to be clinically benign and genetically distinct from other types of nephrosis. .
Sujets)
Adolescent , Adulte , Enfant , Enfant d'âge préscolaire , Femelle , Humains , Mâle , Protéines et peptides de signalisation intracellulaire/génétique , Protéines membranaires/génétique , Mutation/génétique , Syndrome néphrotique/génétique , Polymorphisme génétique/génétique , Maladies rares/génétique , Chine , Syndrome néphrotique/anatomopathologie , Pedigree , Maladies rares/anatomopathologieRésumé
PURPOSE: Intravenous infusion of albumin has been widely used to relieve severe nephrotic edema in spite of beneficial or harmful effects. The purpose of this study is to examine the harmful effect of albumin on the clinical course of steroid sensitive nephrotic syndrome(SSNS). METHOD: We prospectively randomized the patients with nephrotic syndrome(biopsy proven or clinically compatible to minimal change nephrotic syndrome) into the albumin group(20% albumin 1 g/kg) or control group(5% D/W) between March 1997 and September 1999 at Ewha University Mokdong Hospital. We compared the clinical course of the albumin group(n=13) with the control group(n=13). RESULTS: 1. The duration of steroid therapy until complete remission in the albumin group was significantly longer than the control group(13.7+/-6.4 days vs 7.5+/-2.8 days)(P0.05) and the relapse frequency per year(1.9+/-0.8 vs 1.5+/-0.5) between the albumin and control groups. 3. Spot urine protein/creatinine ratio significantly increased in the albumin group at post-albumin 2, 4 days(P<0.05). There was no significant difference in the change of the daily percent weight loss, blood pressure, serum Na, K concentration between the albumin and control groups. CONCLUSION: Albumin infusion in SSNS delayed the response to steroid and shortened the remission duration to the first relapse. Albumin should be carefully used in nephrotic edema.
Sujets)
Humains , Pression sanguine , Oedème , Perfusions veineuses , Syndrome néphrotique , Études prospectives , Récidive , Perte de poidsRésumé
Objective To investigate the changs of serum and urine vascular endothelial growth factor(VEGF) in children with steroid-sensitive nephrotic syndrome(SSNS) at their active and remission stage.Methods Serum and morning urine levels of VEGF were assayed by Liquichip in 30 patients with SSNS at the active and remission stage and 30 normal age-and sex-matched controls.Results Serum levels of VEGF in patients at the active stage [(186.62?106.21) ng/L] were significantly higher those that at the remission stage [(118.75?73.08) ng/L] and than those in control group [(108.64?54.75) ng/L](P0.05).Morning urine levels of VEGF in patients at the active stage [(201.66?100.46) ng/L] were significantly higher than those at the remission stage [(116.35?55.99) ng/L] and than those in control group [(99.94?42.07) ng/L](P0.05).Conclusions Serum and morning urine levels of VEGF are significantly elevated in patients with SSNS,however they are significantly lower after the treatment of steroid.There is no obvious difference between the patients at the remission stage and healthy controls.VEGF involves pathogenetically and physiologically in SSNS during its onset and growth.